Nursing Process Specific to Pharmacology — Assessment

Course: Pharmacology and the Nursing Process

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Page 1: Types of Assessment Data

Assessment involves collecting data (both subjective and objective) about the patient, which are used to identify actual and potential health problems. A thorough assessment includes a patient interview, medical and drug histories, physical examination, patient observation, and laboratory testing. Data collection should detail the patient's symptoms and target the organs most likely to be affected by drug therapy.

Subjective Data

Subjective data are based on verbal information from the patient, family members, friends, or other sources, including symptoms described by, and apparent to, the patient. The following are examples of subjective data collected that are related to the drug regimen (McCuistion et al., 2018):

• Current health history (e.g., difficulty swallowing)
• Patient signs and symptoms
• Current drugs, including over-the-counter (OTC) drugs, herbal remedies, and nutritional supplements; doses and frequency of drugs
• Ability to pay for and access prescribed drugs
• Medical and surgical history
• Patient's environment and support system

Objective Data

Objective data are signs that are directly measured or detected by a health care provider (HCP) regarding the patient's health. The following are examples of objective data collected that are related to the drug regimen (McCuistion et al., 2018):

• Data from physical health assessment
• Laboratory and diagnostic tests
• Data from the HCP's notes
• Vital signs
• The patient's body language

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Page 2: Pre-Administration Assessment

Pre-administration assessment allows HCPs to establish the baseline data needed to individually tailor drug therapy. By identifying variables that can affect an individual's responses to drugs, nurses can modify treatment in an attempt to maximize benefit and minimize harm.

Pre-administration assessment has four basic goals. The first three goals are specific to a particular drug. The fourth goal applies to all drugs but may be more critical for some drugs than for others (Burchum & Rosenthal, 2019).

Goal 1: Establish Baseline Measurements

Drugs are administered to achieve a desired response. Baseline measurements of the parameters the drug is being used to modify need to be determined to evaluate whether this response is achieved (Burchum & Rosenthal, 2019).

Example: Taking a patient's blood pressure before administering lisinopril, an angiotensin-converting enzyme (ACE) inhibitor prescribed to control hypertension, will help determine whether the drug is effective.

Goal 2: Anticipate Adverse Effects

All drugs can produce side or adverse effects. Usually, the side effects that a drug can produce are known. Baseline measurements can help HCPs determine whether a side or adverse effect has occurred (Burchum & Rosenthal, 2019).

Example: Furosemide, a diuretic, can lower a patient's potassium level. Checking the potassium level before administration of the drug will help the nurse determine whether this side effect has occurred.

Goal 3: Identify High-Risk Patients

Individual characteristics may put a patient at higher risk for experiencing a side effect or adverse effects. The individual characteristics that predispose a patient to an adverse drug effect depend on the drug under consideration. To identify an at-risk patient, the nurse must understand the pharmacology of the drug (Burchum & Rosenthal, 2019).

Example: African Americans have a higher incidence of angioedema and cough when prescribed ACE inhibitors (e.g., lisinopril) for hypertension than non–African Americans (Williams et al., 2014). Knowing this information helps the nurse prepare for potential side or adverse effects.

Goal 4: Determine Self-Care Capacity

For drug therapy to be successful in the outpatient setting, the patient must be willing and able to self-administer the drug as prescribed. If the nurse determines that the patient is unable to do so, alternative arrangements must be made. A thorough assessment will identify these factors, thereby allowing the nurse to account for them when formulating nursing diagnoses and a plan of care (Burchum & Rosenthal, 2019).

Example: Dulaglutide, for treatment of type 2 diabetes, is only available as an injection; if the patient is not able to self-administer the dulaglutide injection each week, another drug available in a different route must be prescribed.

Nursing Process Specific to Pharmacology — Diagnosis and Planning

Course: Pharmacology and the Nursing Process

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Page 1: Nursing Diagnosis

A nursing diagnosis is made based on analysis of assessment data. Abnormal data serve as the defining characteristics for actual or potential problems (McCuistion et al., 2021).

Multiple nursing diagnoses may be generated. It is important to note that a medical diagnosis is different from a nursing diagnosis. A medical diagnosis identifies a disease condition and the results of diagnostic tests and procedures. Nursing diagnoses guide the development of a patient-centered plan of care that promotes safe and effective nursing care (McCuistion et al., 2021).

Common nursing diagnoses related to drug therapy include the following: acute pain, confusion, decreased adherence, and need for health teaching.

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Page 2: Planning

The planning step involves defining goals, establishing priorities, identifying specific interventions, and establishing criteria for evaluating success. Good planning allows the nurse to promote beneficial pharmacologic outcomes and anticipate side and adverse effects, rather than react to them after the effects occur.

Defining Goals

The goal of drug therapy is to maximize therapeutic response to drugs while preventing or minimizing adverse effects and interactions. The planning step of the nursing process involves formulating ways to achieve this goal (Burchum & Rosenthal, 2019).

Setting Priorities

Planning requires knowledge of the drug prescribed to the patient. It can be difficult to set priorities. Addressing life-threatening conditions such as anaphylactic shock and ventricular fibrillation is considered the highest priority. These conditions may be caused by a disease or may be drug induced. Other conditions given high priority are those that cause severe, acute discomfort and can result in long-term harm (Burchum & Rosenthal, 2019, p. 11). It is not possible to manage all conditions simultaneously; therefore problems that are less severe are deferred. These conditions can be dealt with in other settings and when more time and resources are available for the patient and HCP.

Identifying Interventions

The focus of planning is identification of nursing interventions. These interventions can be divided into four major groups:

• Drug administration
• Interventions to enhance therapeutic effects
• Interventions to minimize side and adverse effects and interactions
• Patient education (which encompasses the first three groups)

Establishing Evaluation Criteria

Therapeutic response to the drug cannot be determined without objective measurement criteria, which includes the following: presence or absence of adverse drug effects, presence or absence of drug interactions, adherence, patient satisfaction with plan of care, and comparison of current status to baseline status (Burchum & Rosenthal, 2019).

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Page 3: Example — Planning for Nursing Diagnosis of Confusion

Scenario: A nurse administered lorazepam (a benzodiazepine, prescribed as needed for insomnia) to her 60-year-old patient 1 hour ago. When she assesses for therapeutic response, she notes the patient has become disoriented and restless and is unable to focus or follow simple instructions. Based on the assessment data, the nurse determines the patient is experiencing confusion secondary to the administration of lorazepam for insomnia.

Goal	Resolution of confusion within 48 hours, return to baseline mental status, and participation in self-care.
Priority	Patient safety during period of resolution.
Interventions	Call the HCP to discontinue the drug; move the patient to a room closer to the nurses' station and assess overall status with hourly rounding; reorient the patient as needed, but do not challenge illogical thinking; ensure the patient has a quiet environment; ensure room is free of clutter; respond to patient needs in a calm manner; provide simple instructions and assist with ADLs as needed.
Evaluation	Patient has remained free of injury; patient is alert and oriented to person, place, and time; patient can dress, feed, and toilet self.

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Page 4: Example — Planning for Nursing Diagnosis Need for Health Teaching

Scenario: Upon completing a home health intake, a nurse determines that a 60-year-old patient is uncertain of the proper administration and follow-up for warfarin, prescribed for new onset atrial fibrillation. Based on the assessment data, the nurse determines that additional health teaching is needed.

Goal	No harmful sequela from warfarin therapy or atrial fibrillation (e.g., stroke); INR remains within therapeutic range.
Priority	Patient safety, appropriate self-administration of drugs, appropriate follow-up with HCP and laboratory for drug monitoring.
Interventions	Determine the patient's preferred method of learning (verbal, written, or multimedia); determine the need for a translator; teach proper dosing of warfarin, its side effects, and potential adverse effects and drug interactions; teach about warfarin's mechanism of action and the need to monitor INR; teach ways to prevent bleeding (e.g., soft bristle toothbrush, electric razor); inform patient about when to call the HCP.
Evaluation	Patient remains free of injury; patient takes warfarin as prescribed and refills on time; INR remains between 2 and 3; patient keeps follow-up appointments.

Nursing Process Specific to Pharmacology — Implementation

Course: Pharmacology and the Nursing Process

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Page 1: Implementation

Implementation of the drug therapy plan of care has four major components: drug administration, nursing actions to enhance the desired effects of the drug, nursing actions to decrease the side/adverse effect of the drug, and patient education. Note that the planning step of the nursing process uses the same four components, indicating the close connection between the two steps. What is planned will be implemented.

Drug Administration

Before the implementation of drug therapy, dosage and route of administration must be considered. The relationship of drug dosing times to mealtimes and administration of concurrent drugs must be taken into consideration (Burchum & Rosenthal, 2019).

Interventions to Promote Therapeutic Effects

Nonpharmacologic interventions can enhance the desired effects of a drug and should be encouraged (e.g., alternating hot and cold packs for arthritic joint pain; Burchum & Rosenthal, 2019).

Interventions to Minimize Side/Adverse Effects

Nursing actions that may decrease or prevent side effects and/or adverse effects of a drug are critical components in the plan of care. When planning these actions, the nurse should recognize the difference between a rapid onset drug reaction and a delayed reaction. A severe (and potentially life-threatening) drug reaction, such as anaphylaxis, will occur quickly after administration. If there is any potential for an anaphylactic drug reaction, the nurse must be sure that emergency equipment and personnel are readily available before administration of the drug (Burchum & Rosenthal, 2019).

Patient Education

Patient education is an ongoing process requiring a dynamic interaction between the nurse and the patient where information is shared. An outline format for patient education may be helpful because teaching is critical to the success of pharmacologic therapy. Adherence, self-administration, diet, side and adverse effects, and cultural considerations need to be addressed (Burchum & Rosenthal, 2019).

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Page 2: Five Rights of Drug Administration

The five rights of drug administration are the foundation for drug safety. They include the right patient, the right drug, the right dose, the right time, and the right route (McCuistion et al., 2018).

Right Patient — Determining the right patient is essential. The Joint Commission (TJC) requires two forms of identification before administration of a drug. Some patients are unable to respond or state their name, so alternate identification must occur.

Right Drug — The nurse must ensure that the right drug is administered. Drug orders may be prescribed by any licensed HCP having authority from the state to prescribe drugs.

Right Dose — The right dose refers to verification by the nurse that the dose administered is the amount ordered and that it is safe for the patient to whom it is prescribed. The right dose is based on the patient's physical status and renal and hepatic functions. The nurse may need to review pertinent laboratory values before administration.

Right Time — The right time is the time the prescribed dose is ordered to be administered. Daily drug dosages are given at specified times during a day, such as twice a day (bid), three times a day (tid), four times a day (qid), or every 6 hours (q6h), so that the plasma level of the drug is maintained at a therapeutic level.

Right Route — The right route is necessary for adequate or appropriate absorption. The right route is ordered by the HCP and indicates the mechanism by which the drug enters the body.

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Page 3: Five-Plus-Five Rights of Drug Administration

Nurses must also address pre-administration assessment, proper documentation, patient education, post-administration evaluation, and the patient's right to refuse (McCuistion et al., 2018).

Right Assessment — The right assessment requires collection of appropriate data before administration of the drug.

Right Documentation — The right documentation requires the nurse to record the appropriate information about the drug administered in a timely fashion. This includes the name, dose, and route (injection site if applicable) of the drug; the time and date the drug was administered; and the nurse's initials or signature.

Right to Education — The right to education indicates that patients receive accurate and thorough information about the drug and how it relates to their condition.

Right Evaluation — The right evaluation refers to an appraisal of a drug's therapeutic, side, and adverse effects.

Right to Refuse — The patient has the right to refuse the drug. The nurse must determine (if possible) the reason for the refusal and, if the reasoning is not sound, take appropriate measures to encourage the patient to take the drug (e.g., informing the HCP).

Nursing Process Specific to Pharmacology — Evaluation

Course: Pharmacology and the Nursing Process

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Page 1: Evaluation

In the evaluation phase of the nursing process, the nurse determines how well goals were met. If goals were not met, nursing interventions and patient education are revised to achieve goal attainment (Burchum & Rosenthal, 2019).

The frequency of evaluation depends on the expected time course of therapeutic and side/adverse effects. Like assessment, evaluation is based on laboratory results, observing the patient, physical examination, and patient interview. The conclusions made during the evaluation phase provide the basis for modifying nursing interventions and the drug regimen (Burchum & Rosenthal, 2019).

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Page 2: Components of Evaluation

Evaluation of patient response to drug therapy is imperative and includes several components.

Therapeutic Responses

The patient's response to drug therapy needs to be evaluated. To adequately and appropriately evaluate the patient's therapeutic response, it is necessary to know the patient's baseline data and anticipated patient outcome. It is also important to know the length of time the patient has been taking the drug compared with the expected onset and duration of action for the prescribed drug (Burchum & Rosenthal, 2019).

Adverse Effects

The nurse must know common adverse effects and evaluate for their presence. In addition, the patient must be evaluated for any unanticipated reaction to drug therapy. Critically analyzing a patient's response to therapy and identifying adverse effects demands a thorough understanding of the pharmacodynamics and pharmacokinetics of drug therapy (Burchum & Rosenthal, 2019).

Adherence

Although important for all patients, evaluation of adherence to prescribed drug therapy is especially valuable when the expected therapeutic response is not achieved or when adverse effects are unexpectedly severe. Adherence can be evaluated by interviewing the patient, counting pills to determine whether the anticipated number has been taken, and/or monitoring for therapeutic plasma drug levels. The patient interview can be used to determine patient understanding of drug use, including purpose, timing, dosage, and method of administration (Burchum & Rosenthal, 2019).

Patient Satisfaction with Drug Therapy

Patient satisfaction with drug therapy is important because it promotes adherence to therapy and increases quality of life. Patient dissatisfaction can lead to nonadherence to pharmacologic therapy. Identification of underlying factors that lead to dissatisfaction is the first step in improving patient adherence; unacceptable side effects, inconvenient dosing schedule, difficulty of administration, and high cost are examples of such factors. Once identified, these factors need to be modified to promote patient satisfaction and achievement of outcomes (Burchum & Rosenthal, 2019).

Pharmacokinetics — Principles of Absorption

Course: Pharmacokinetics

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Page 1: Overview

Absorption is the movement of a drug from the site of administration into the blood. The rate of absorption determines how soon effects will begin. The amount of absorption helps determine how intense effects will be.

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Page 2: Factors Affecting Drug Absorption

Absorption is influenced by the physical and chemical properties of the drug itself and by physiologic and anatomic factors at the absorption site.

Rate of Dissolution — Before a drug can be absorbed, it must first dissolve. Therefore the rate of dissolution helps determine the rate of absorption. Drugs in formulations that allow rapid dissolution (e.g., solutions) have a faster onset than drugs formulated for slow dissolution (e.g., capsules).

Surface Area — The surface area available for absorption is a major determinant of the rate of absorption. The larger the surface area, the faster the absorption. For this reason, orally administered drugs are usually formulated to be absorbed from the small intestine rather than from the stomach. (The small intestine, because of its lining of microvilli, has an extremely large surface area, whereas the surface area of the stomach is relatively small.)

Rate of Blood Flow — Drugs are absorbed most rapidly from sites where blood flow is high because blood containing a newly absorbed drug is rapidly replaced by drug-free blood, thereby maintaining a large gradient between the concentration of the drug outside the blood and the concentration of the drug in the blood. The greater the concentration gradient, the more rapid absorption will be.

Lipid Solubility — As a rule, highly lipid-soluble drugs are absorbed more rapidly than drugs whose lipid solubility is low because lipid-soluble drugs can readily cross the membranes that separate them from the blood, whereas drugs of low lipid solubility cannot.

pH Partitioning — pH partitioning is the process whereby a drug accumulates on the side of a membrane where the pH most favors its ionization. Acidic drugs tend to ionize in basic media, and basic drugs tend to ionize in acidic media. When there is a pH gradient between two sides of a membrane: acidic drugs will accumulate on the alkaline side; basic drugs will accumulate on the acidic side.

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Page 3: Routes of Administration and Effects on Absorption

The route of administration (e.g., enteral or parenteral) affects the ability of the drug to reach systemic circulation.

Intravenous (IV)

• Advantages: Provides rapid onset (drug delivered immediately to bloodstream); allows more direct control of drug level in blood.
• Disadvantages: Irreversibility of drug action in most cases and inability to retrieve medication once administered.
• Nursing Considerations: Continuous IV infusions require frequent monitoring. IV sites should be monitored for redness, swelling, heat, and drainage — all indicative of complications such as thrombophlebitis and infection.

Intramuscular (IM); Subcutaneous

• Advantages: Good for poorly soluble drugs, which are often given in "depot" preparation form and absorbed over a prolonged period; onsets differ depending on route.
• Disadvantages: Slower onset of action compared with IV, although quicker than oral in most situations.
• Nursing Considerations: Selection of the correct size of syringe and needle is key to safe administration, based on thorough assessment of the patient and characteristics of the drug.

Oral

• Advantages: Safer than injection; dosing is more likely to be reversible through induction of emesis or administration of activated charcoal in cases of accidental ingestion.
• Disadvantages: Variable absorption; inactivation of some drugs by stomach acid and/or pH.
• Nursing Considerations: Enteral routes include oral administration and involve a variety of dosage forms (e.g., liquids, solutions, tablets, enteric-coated pills). Some medications should be taken with food, others without. Oral dosage forms should be taken with at least 6–8 ounces of fluid. Other factors include other drugs taken at the same time and concurrent use of dairy products or antacids.

Sublingual; Buccal

• Advantages: Absorbed more rapidly from oral mucosa, leading to more rapid onset of action.
• Disadvantages: Patients may swallow pill instead of keeping under tongue until dissolved.
• Nursing Considerations: Drugs given via the sublingual route are to be placed under the tongue until dissolved. When using the buccal route, medication is placed between the cheek and gum.

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Page 4: Routes of Administration and Effects on Absorption, cont'd

Several additional routes of administration affect absorption.

Rectal

• Advantages: Provides relatively rapid absorption; good alternative when oral route is not feasible.
• Disadvantages: Interruption of absorption by defecation.
• Nursing Considerations: Absorption via this route is erratic and unpredictable, but it provides a safe alternative when nausea or vomiting prevents oral dosing.

Topical

• Advantages: Delivers medication directly to affected area; decreases likelihood of systemic drug effects.
• Disadvantages: Changes in skin thickness and blood flow that vary with age affect absorption.
• Nursing Considerations: Most dermatologic drugs are given via topical route. Maximal absorption is enhanced with skin that is clean and free of debris.

Transdermal Patch

• Advantages: Provides relatively constant rate of drug absorption; one patch can last 1 to 7 days depending on the drug.
• Disadvantages: Rate of absorption can be affected by excessive perspiration and body temperature; patch may peel off.
• Nursing Considerations: Patches should be placed on alternating sites on clean, nonhairy, nonirritated skin, only after the previously applied patch has been removed and the area cleansed and dried.

Inhalational

• Advantages: Provides rapid absorption; drug delivered directly to lung tissues.
• Disadvantages: Rate of absorption can be too rapid, increasing the risk for exaggerated drug effects.
• Nursing Considerations: Inhaled medications are to be used exactly as prescribed to ensure proper drug delivery.

(From Lilley LL, Collins SR, Snyder JJ: Pharmacology and the Nursing Process, ed 8, St. Louis, 2017, Elsevier.)

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Page 5: Nursing Process Related to Absorption

Nurses are responsible for ensuring patient safety during care. Knowledge of the principles of drug absorption is part of that responsibility.

Assessment

• Collect a drug history, including the dates and times drugs were taken.
• Collect patient history to identify factors that may affect drug absorption (e.g., gastric surgery).
• Recognize age-related factors that may affect drug absorption (e.g., body surface area of infants versus older adults).

Implementation

• Advise patient not to eat high-fat food before ingesting an enteric-coated tablet because high-fat foods decrease absorption rate.
• Provide patient education related to drug administration in an environment conducive to learning and in a manner appropriate for the patient's developmental level and cognitive abilities.
• Provide patient education in an environment where the patient feels safe to express anxieties and concerns related to drug administration.

Evaluation

• Evaluate physical, social, and psychological outcomes of education related to pharmacotherapy.
• Evaluate the therapeutic effectiveness of pharmacotherapy.

Pharmacokinetics — Principles of Distribution

Course: Pharmacokinetics

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Page 1: Overview

Distribution is drug movement from the blood to the tissues and into the cells. Three major factors determine drug distribution: blood flow to tissues, the ability of a drug to exit the vascular system, and the ability of a drug to enter cells.

Blood Flow to Tissues — Blood carries drugs to the tissues and organs of the body. The rate of drug delivery is determined by blood flow to the tissues. Because most tissues are well perfused, regional blood flow is rarely a limiting factor in drug distribution. Two pathologic conditions affect this: abscesses (pus-filled pockets of infection with no internal blood vessels — antibiotics cannot reach bacteria within, so the abscess must first be surgically drained) and solid tumors (limited blood supply, with progressively lower blood flow toward the core, making it difficult to achieve high drug levels deep inside tumors — a major reason solid tumors are resistant to drug therapy).

Ability to Exit Vascular System — After a drug has been delivered to an organ or tissue, the next step is to exit the vasculature. Because most drugs do not produce their effects within the blood, the ability to leave the vascular system is an important determinant of drug actions. Drugs in the vascular system leave the blood at capillary beds.

Ability to Enter Cells — Some drugs must enter cells to reach their sites of action, and practically all drugs must enter cells to undergo metabolism and excretion (Burchum, 2019). The factors that determine this ability are the same as those that determine the passage of drugs across all other membranes: lipid solubility, the presence of a transport system, or both.

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Page 2: Protein Binding

As drugs are distributed in the plasma, many bind with plasma proteins. Drugs that are more than 90% bound to protein are known as highly protein-bound drugs (e.g., warfarin, glyburide, sertraline, furosemide, and diazepam); drugs that are less than 10% bound to protein are weakly protein-bound drugs (e.g., gentamicin, metformin, metoprolol, and lisinopril).

The portion of the drug bound to protein is inactive because it is not available to interact with tissue receptors and therefore is unable to exert a pharmacologic effect. The portion that remains unbound is free, active drug. Free drugs can exit blood vessels and reach their site of action, causing a pharmacologic response.

(Diagram note: Albumin is the most prevalent protein in plasma and the most important of the proteins to which drugs bind. Only unbound/free drug molecules can leave the vascular system; bound molecules are too large to fit through the pores in the capillary wall.)

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Page 3: Factors Affecting Protein Binding

Factors affecting protein binding include competition for protein-binding sites when two highly protein-bound drugs are administered together and low plasma protein levels.

Competition for Protein-Binding Sites — When two highly protein-bound drugs are administered together, they compete for protein-binding sites, leading to an increase in free drug being released into the circulation. For example, if warfarin (99% protein bound) and furosemide (95% protein bound) were administered together, warfarin could displace furosemide from its binding site, leading to drug accumulation of furosemide and the potential for toxicity.

Low Plasma Protein Levels — Low plasma protein levels can decrease the number of available binding sites and lead to an increase in free drug available, resulting in drug accumulation and toxicity (McCuistion, 2018). Patients with liver or kidney disease and those who are malnourished may have significantly lower serum albumin levels. Older adults are more likely to have hypoalbuminemia, particularly with multiple chronic illnesses. Nurses should check patients' protein and albumin levels when administering drugs.

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Page 4: Blood-Brain Barrier

Blood vessels in the brain have a special endothelial lining where cells are pressed tightly together (tight junctions); this lining is referred to as the blood-brain barrier (BBB). The BBB protects the brain from foreign substances (McCuistion, 2018). Only drugs that are lipid soluble or have a transport system can cross the BBB to a significant degree (Burcham & Rosenthal, 2019).

Drugs that are highly lipid soluble and of low molecular weight (e.g., benzodiazepines) can cross the BBB through diffusion, and others cross via transport proteins. Water-soluble drugs (e.g., atenolol and penicillin) and drugs that are not bound to transport proteins (free drugs) are not able to cross the BBB, which makes it difficult for these drugs to reach the brain.

(Diagram: The typical capillary wall has pores/fenestrations between cells that allow passage of drugs. Brain capillaries have tight junctions that prevent drug passage.)

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Page 5: Drugs That Cross Placenta

Pharmacologic properties of drugs influence their ability to cross the placenta; lipid-soluble drugs can cross the placenta, but ionic and polar drugs cannot.

During pregnancy, drugs can cross the placenta much as they cross other membranes, affecting both fetus and mother. Drugs taken during the first trimester can lead to spontaneous abortion. During the second trimester, drugs can lead to spontaneous abortion, teratogenesis, or other subtle defects. During the third trimester, drugs may alter fetal growth and development. The risk-benefit ratio should be considered before any drugs are given during pregnancy.

During breastfeeding, drugs can pass into breast milk, which can affect the nursing infant. Nurses must teach women who breastfeed to consult their health care provider before taking any drug — whether OTC or prescribed — or any herb or supplement (McCuistion, 2018).

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Page 6: Nursing Process Related to Distribution

Nurses are responsible for ensuring patient safety during care. Knowledge of the principles of drug distribution is part of that responsibility.

Assessment

• Collect a drug history, including the dates and times drugs were taken.
• Collect patient history to identify factors that may affect drug distribution (e.g., low serum albumin or peripheral vascular disease).
• Assess for signs and symptoms of drug toxicity when administering two or more drugs that are highly protein bound.

Implementation

• Check the literature for the protein-binding percentage of the drugs being administered.
• Provide patient education related to drug distribution in an environment conducive to learning and in a manner appropriate for the patient's developmental level and cognitive abilities.
• Provide patient education in an environment where the patient feels safe to express anxieties and concerns related to drug distribution.

Evaluation

• Evaluate physical, social, and psychological outcomes of education related to pharmacotherapy.
• Evaluate the therapeutic effectiveness of pharmacotherapy.

Pharmacokinetics — Principles of Metabolism

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Overview

Metabolism, or biotransformation, is the process by which the body chemically changes drugs into a form that can be excreted. Most drug metabolism takes place in the liver.

Drug metabolism directly affects pharmacologic responses, so it is important for the nurse to understand how drug properties and diseases affect drug metabolism. For example, a large percentage of drugs are lipid soluble; thus the liver metabolizes lipid-soluble drugs into water-soluble substances for renal excretion. However, some drugs are transformed into active metabolites, causing an increased pharmacologic response. Liver disease can alter drug metabolism by inhibiting drug metabolizing enzymes or creating an influx of medication in the body, both of which are toxic.

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Hepatic Drug-Metabolizing Enzyme

Most drug metabolism in the liver is performed by the hepatic microsomal enzyme system, also known as the P450 system. The term P450 refers to cytochrome P450, a key component of this enzyme system.

Cytochrome P450 is not a single molecular entity but rather a group of 12 closely related enzyme families. Three of the cytochrome P450 (CYP) families — CYP1, CYP2, and CYP3 — metabolize drugs. Each family is composed of multiple forms, each of which metabolizes only certain drugs. Designations such as CYP1A2, CYP2D6, and CYP3A4 identify specific members of these families.

Drug molecules that are the metabolic targets of specific enzymes are called substrates for those enzymes.

Common Liver Cytochrome P450 Enzymes and Corresponding Drug Substrates:

Enzyme	Common Drug Substrates
1A2	Acetaminophen, caffeine, theophylline, warfarin
2C9	Ibuprofen, phenytoin
2C19	Diazepam, naproxen, omeprazole, propranolol
2D6	Codeine, fluoxetine, hydrocodone, metoprolol, oxycodone, paroxetine, risperidone, tricyclic antidepressants
2E1	Acetaminophen, ethanol
3A4	Acetaminophen, amiodarone, cyclosporine, diltiazem, ethinyl estradiol, indinavir, lidocaine, macrolides, progesterone, spironolactone, sulfamethoxazole, testosterone, verapamil

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Factors Affecting Drug Metabolism

The metabolizing capabilities of the liver vary considerably from patient to patient. Factors that can alter biotransformation include genetics, diseases, and the concurrent use of other medications.

• Enzyme inhibitors: Drugs that inhibit drug-metabolizing enzymes, causing decreased metabolism → accumulation of the drug → prolongation of effects → potential drug toxicity.
• Enzyme inducers: Drugs that stimulate drug metabolism, causing decreased pharmacologic effects. This often occurs with repeated administration of certain drugs (e.g., carbamazepine) that stimulate formation of new microsomal enzymes.

Examples of Conditions and Drugs that Affect Drug Metabolism:

Category	Example	Drug Metabolism Effect
Diseases	Cardiovascular disease	Decreased
Diseases	Kidney disease	Decreased
Conditions	Malnutrition	Decreased
Conditions	Obstructive jaundice	Decreased
Genetic constitution	Fast acetylator	Increased
Genetic constitution	Slow acetylator	Decreased
Drugs	Barbiturates	Increased
Drugs	Rifampin (P450 inducer)	Increased
Drugs	Phenytoin (P450 inducer)	Increased
Drugs	Ketoconazole (P450 inhibitor)	Decreased

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Therapeutic Consequences of Drug Metabolism

Drug metabolism has six possible consequences of therapeutic significance:

1. Accelerated renal excretion of drugs
2. Drug inactivation
3. Increased therapeutic action
4. Activation of "prodrugs"
5. Increased toxicity
6. Decreased toxicity

Accelerated Renal Drug Excretion: The most important consequence of drug metabolism. The kidneys cannot excrete highly lipid-soluble drugs, so conversion of lipid-soluble drugs into hydrophilic (water-soluble) forms accelerates renal excretion.

Drug Inactivation: Metabolism can convert pharmacologically active compounds to inactive forms (e.g., conversion of procaine [local anesthetic] into para-aminobenzoic acid [PABA], an inactive metabolite).

Increased Therapeutic Action: Metabolism can increase effectiveness of some drugs (e.g., conversion of codeine into morphine; morphine's analgesic activity is so much greater than codeine's that formation of morphine may account for virtually all pain relief following codeine administration).

Activation of Prodrugs: A prodrug is a compound that is pharmacologically inactive as administered and undergoes conversion to its active form via metabolism (e.g., metabolic conversion of fosphenytoin to phenytoin).

Increased or Decreased Toxicity: Metabolism can decrease toxicity by converting drugs into inactive forms. Conversely, metabolism can increase potential for harm by converting relatively safe compounds into toxic forms (e.g., conversion of acetaminophen into a hepatotoxic metabolite — it is this metabolite, not acetaminophen itself, that causes injury in overdose).

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First-Pass Effect

Most drugs taken orally are absorbed from the intestinal lumen and enter the portal venous system to be conveyed to the liver, where they may be subject to first-pass metabolism and/or excretion in bile.

The first-pass effect refers to the rapid hepatic inactivation of certain oral drugs. If the liver's capacity to metabolize a drug is extremely high, that drug can be completely inactivated on its first pass through the liver, preventing any therapeutic effect.

To circumvent the first-pass effect, drugs that undergo rapid hepatic metabolism are often administered parenterally, temporarily bypassing the liver and allowing the drug to reach therapeutic levels in systemic circulation.

Classic example — Nitroglycerin:

• Orally: largely without effect due to rapid hepatic metabolism.
• Sublingually: very active, because it is absorbed directly into systemic circulation and reaches sites of action before passing through the liver.

Active drugs that enter systemic circulation diffuse (or are actively transported) in and out of interstitial and intracellular fluid compartments. Drug remaining in circulating plasma is subject to liver metabolism and renal excretion. Drugs excreted in bile may be reabsorbed, creating an enterohepatic circulation. First-pass metabolism is also avoided when drugs are administered via buccal or rectal mucosa, or parenterally.

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Nursing Process Related to Metabolism

Assessment

• Collect a drug history, including dates and times drugs were taken.
• Collect patient history to identify factors that may affect drug metabolism (e.g., chronic liver disease or kidney disease).
• Recognize age-related factors that may affect drug metabolism (e.g., liver immaturity in infants; decreased liver volume and blood flow in older adults).

Implementation

• Provide patient education related to drug metabolism in an environment conducive to learning and appropriate for the patient's developmental level and cognitive abilities.
• Provide patient education in an environment where the patient feels safe to express anxieties and concerns related to drug metabolism.

Evaluation

• Evaluate physical, social, and psychological outcomes of education related to pharmacotherapy.
• Evaluate the therapeutic effectiveness of pharmacotherapy.

Pharmacokinetics — Principles of Excretion

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Overview

Drug excretion is the removal of drugs from the body. Drugs and their metabolites can exit the body in urine, bile, sweat, saliva, breast milk, and expired air. The most important organ for drug excretion is the kidney.

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Renal Drug Excretion

The kidneys account for most drug excretion. When the kidneys are healthy, they serve to limit the duration of action of many drugs. Conversely, if kidney dysfunction occurs, both the duration and intensity of drug responses may increase.

Urinary excretion is the net result of three processes:

1. Glomerular Filtration Filtration moves drugs from blood to urine. Protein-bound drugs are not filtered.

2. Passive Tubular Reabsorption Lipid-soluble drugs move back into the blood. Polar and ionized drugs remain in the urine.

3. Active Tubular Secretion Tubular "pumps" for organic acids and bases move drugs from blood to urine.

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Effects of Urine pH

Urine pH influences drug excretion. Normal urine pH varies from 4.6 to 8.0.

Acidic Urine — Promotes elimination of weak base drugs.

• Example: Drugs that acidify the urine (e.g., ascorbic acid, aluminum chloride) can increase renal excretion of weak bases such as amphetamines.

Alkaline Urine — Promotes elimination of weak acid drugs.

• Example: Salicylic acid (aspirin), a weak acid, is excreted rapidly in alkaline urine. Treatment of salicylate toxicity includes IV administration of sodium bicarbonate to increase urine pH to 8.0 or higher; maintaining alkaline urine promotes excretion of salicylate at 18 times the normal rate.

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Effects of Renal Conditions

Prerenal, intrarenal, and postrenal conditions also affect drug excretion. With any of these conditions, drug accumulation may occur, resulting in adverse drug reactions.

Prerenal Conditions: Conditions like dehydration or hemorrhage reduce blood flow to the kidneys and result in decreased glomerular filtration.

Intrarenal Conditions: Conditions like glomerulonephritis and chronic kidney disease (CKD) affect glomerular filtration and tubular secretion and reabsorption.

Postrenal Conditions: Conditions like prostatic hypertrophy, stones, and neurogenic bladder obstruct urine flow and adversely affect glomerular filtration.

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Other Routes of Drug Excretion

Drugs are also excreted through bile, the lungs, and breast milk.

Bile (Biliary Excretion) Drugs eliminated by this route are taken up by the liver, released into the bile, and excreted in the feces. Some drugs undergo enterohepatic recirculation — a repeating cycle in which a drug is transported from the liver into the duodenum (via the bile duct) and then back to the liver (via portal blood). This process is limited to drugs that have undergone glucuronidation (addition of glucuronic acid to the drug molecule), which makes drugs more water-soluble, promoting excretion through urine or feces, or facilitates transport around the body.

Lungs (Pulmonary Excretion) Drugs excreted in part by the pulmonary route include gaseous anesthetics, ethanol, and other volatile organic solvents (e.g., paint, cleaning and polishing fluids, contact adhesives, nail polish removers). The extent to which these drugs are excreted by respiration is correlated with the alveolar concentration of the drug.

Breast Milk Drugs taken by breastfeeding women can be excreted into milk, potentially exposing the nursing infant. The same factors that determine drug passage across membranes govern drug appearance in breast milk: lipid-soluble drugs have ready access to breast milk, while polar, ionized, or protein-bound drugs cannot enter in significant amounts. Because infants may be harmed by drugs excreted in breast milk, nursing mothers should avoid all unnecessary drugs and consult their health care provider if medication is required.

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Nursing Process Related to Excretion

Assessment

• Collect a drug history, including dates and times drugs were taken.
• Collect patient history to identify factors that may affect drug excretion (e.g., kidney dysfunction).
• Recognize age-related factors that may affect drug excretion (e.g., kidney immaturity in children; kidney dysfunction in older adults).

Implementation

• Provide patient education related to drug excretion in an environment conducive to learning and appropriate for the patient's developmental level and cognitive abilities.
• Provide patient education in an environment where the patient feels safe to express anxieties and concerns related to drug administration and excretion.

Evaluation

• Evaluate physical, social, and psychological outcomes of education related to pharmacotherapy.
• Evaluate the therapeutic effectiveness of pharmacotherapy.

Pharmacodynamics — Therapeutic Drug Response, Onset, Peak, and Duration

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Overview of Pharmacodynamics

Pharmacodynamics is the study of the effects of drugs on the body. Once a drug is administered, it goes through two phases:

• Pharmacokinetic phase — what the body does to the drug (absorption, distribution, metabolism, excretion; covered in the Pharmacokinetics lesson)
• Pharmacodynamic phase — what the drug does to the body; involves receptor binding, post-receptor effects, and chemical reactions, resulting in a biologic or physiologic response

Drugs act within the body to mimic the actions of the body's own chemical messengers. Drug response can cause a primary or secondary physiologic effect or both. A drug's primary effect is the desirable response; the secondary effect may be desirable or undesirable.

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Dose-Response Relationships

The dose-response relationship is the body's physiologic response to changes in drug concentration at the site of action. Dose-response relationships determine the minimum amount of drug needed to elicit a response, the maximum response a drug can elicit, and how much to increase dosage to produce the desired increase in response.

The dose-response curve has three phases:

• Phase 1: Dose is too low to elicit any measurable response.
• Phase 2: An increase in dose elicits an increase in response.
• Phase 3: An increase in dose is unable to elicit any further increase in response.

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Efficacy and Potency

Efficacy and potency are independent qualities of a drug.

Efficacy is defined as the drug's ability to produce the desired result.

Maximal Efficacy: The point at which increasing a drug's dosage no longer increases the desired therapeutic response. Maximal efficacy is defined as the largest effect a drug can produce, and is indicated by the height of the dose-response curve. (Example: meperidine has greater efficacy than pentazocine.)

Potency refers to the amount of drug needed to elicit a specific physiologic response. A drug with high potency (e.g., morphine) produces significant therapeutic responses at low concentrations; a drug with low potency (e.g., meperidine) produces minimal therapeutic responses at low concentrations. Achieving pain relief with meperidine requires higher doses than with morphine. Potency is rarely an important characteristic of a drug.

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Minimum Effective Concentration (MEC)

A drug's minimum effective concentration (MEC) is the plasma drug level below which therapeutic effects will not occur — it is the lowest blood level needed to cause the intended action.

• If the body eliminates the drug faster than it enters, the drug level will not be enough to produce the intended action.
• If the body eliminates the drug more slowly than it enters, the drug level could become high enough to increase side effects or reach toxic concentration.

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Onset, Peak, and Duration

Onset is the time it takes for a drug to reach the MEC after administration.

Peak occurs when the drug reaches its highest concentration in the blood; it indicates the rate of drug absorption. If peak drug levels are ordered, they are drawn based on route of administration:

• Oral drugs reach peak in 2 to 3 hours
• Intramuscular drugs reach peak in 2 to 4 hours
• Intravenous drugs reach peak in 30 to 60 minutes

Trough drug level is the lowest plasma concentration of a drug and measures the rate at which the drug is eliminated. Trough levels are drawn just before the next dose, regardless of the route of administration.

Duration of action is the length of time the drug exerts a therapeutic effect. Some drugs produce effects in minutes; others may take hours or days. If plasma concentration decreases below the MEC, adequate dosing has not been achieved; too high a concentration can result in toxicity.

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Drug Half-Life

Drug half-life (t½) is the time it takes for the amount of drug in the body to be reduced by half. The amount of drug administered, the amount remaining from previous doses, metabolism, and elimination all affect half-life. With liver or kidney dysfunction, drug half-life is prolonged and less drug is metabolized and eliminated.

A drug goes through several half-lives before complete elimination occurs, and half-life is used to determine the dosing interval.

Example — Ibuprofen (half-life ~2 hours):

• 200 mg taken → after 2 hrs: 100 mg remains → after 4 hrs: 50 mg remains → after 6 hrs: 25 mg remains → after 10 hrs: ~6.25 mg remains

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Plateau (Steady State)

A steady state occurs when the amount of drug administered equals the amount of drug eliminated — necessary to achieve optimal therapeutic benefit. This takes approximately four half-lives if all doses are the same size.

Example: Digoxin (half-life ~36 hours with normal kidney function) takes approximately 5 days to reach steady state concentration.

Loading Dose: When a drug has a long half-life (e.g., digoxin), waiting to achieve plateau could take many days and adversely affect patient outcomes. An initial large dose — a loading dose — can be given at the onset of therapy to rapidly achieve plateau drug level.

Maintenance Doses: Once plateau is achieved, it can be maintained by giving smaller, regular doses.

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Nursing Process Related to Onset, Peak, and Duration

Assessment

• Examine the patient's history to identify factors relevant to onset, peak, and duration (e.g., kidney dysfunction).
• Collect a drug history, including dates and times drugs were taken.
• Perform a physical examination to identify problems relevant to onset, peak, and duration (e.g., dysphagia resulting in the need for IV versus oral drug delivery).

Implementation

• Provide patient education related to monitoring drug onset, peak, and duration (e.g., fingerstick blood glucose) in an environment conducive to learning and appropriate for the patient's developmental level and cognitive abilities.
• Provide education in an environment where the patient feels safe to express anxieties and concerns.
• Check peak and trough levels for drugs with a narrow therapeutic range (e.g., aminoglycosides). If the trough level is high, toxic effects can occur.

Evaluation

• Evaluate physical, social, and psychological outcomes of education related to pharmacotherapy.
• Evaluate the therapeutic effectiveness of pharmacotherapy.

Pharmacodynamics — Drug Receptors

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Overview of Drug Receptors

Drugs are chemicals, and the only way most drugs produce effects is by interacting with other chemicals. Receptors are the special chemical sites in the body that most drugs interact with to produce effects.

Drugs act by binding to receptors. Binding of the drug may:

• Activate a receptor, producing a response
• Inactivate a receptor, blocking a response

The activity of many drugs is determined by the ability of the drug to bind to a specific receptor. The better the drug fits at the receptor site, the more active the drug is. Drug-receptor interactions are like the fit of the right key in a lock:

• Drugs with complete attachment and response are called agonists
• Drugs that attach but do not elicit a response are called antagonists
• Drugs that attach and elicit a small response but also block other responses are called partial agonists

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Drug Receptor Families

Most receptors, which are protein in nature, are found on cell surface membranes or within the cell itself. Drug-binding sites are primarily on proteins, glycoproteins, proteolipids, and enzymes. The ligand-binding domain is the site on the receptor where drugs bind. There are four receptor families:

Ligand-Gated Channel: The ligand-binding domain for drug binding is on the cell surface. The drug activates the enzyme inside the cell, and a response is initiated.

G Protein–Coupled Receptor Systems: The three components to this receptor response are (1) the receptor, (2) the G protein that binds with guanosine triphosphate (GTP), and (3) the effector, which is either an enzyme or an ion channel.

Cell Membrane–Embedded Enzymes: The channel crosses the cell membrane. When the channel opens, ions flow into and out of the cells. This primarily affects sodium and calcium ions.

Transcription Factors: Found in the cell nucleus on DNA, not on the surface. Activation of receptors through transcription factors regulates protein synthesis and is prolonged.

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Selectivity of Receptors

When drugs interact with a specific receptor and maintain focus on a specific process, the action of the drug is limited because it does not affect multiple receptors — this is defined as selective action. Drugs with selective action are valued because this results in fewer side effects.

If a drug interacts with several receptors (is nonselective), a wide variety of responses are elicited. Note: selective activity does not mean the drug poses no risk to patient safety — highly selective drugs can still be very dangerous.

Relatively Nonselective Drugs: Exert their effect across many tissues or organs. Example: atropine — a therapeutic use includes relaxation of smooth muscle in the GI system for irritable bowel syndrome, but the same dose also causes relaxation of muscles in the eyes and respiratory tract.

Relatively Selective Drugs: Exert a singular effect on a specific target tissue or organ. Example: NSAIDs (aspirin, ibuprofen) — exert their effect on any tissue where inflammation is present.

Highly Selective Drugs: Exert their effect on a single organ or organ system. Example: digoxin — affects electrolyte channels in the heart, resulting in a decrease in heart rate.

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Theories of Drug Receptor Interaction

The theory of drug receptor interaction helps explain relationships and the ability of drugs to mimic or block the actions of receptors.

Term	Definition
Agonists	Drugs that bind to a receptor and produce a desired response by mimicking the body's own regulatory molecules.
Antagonists	Block receptor activation and prevent the receptor from behaving in its normal manner. Have virtually no effects of their own on receptor function.
Partial Agonists	Have moderate intrinsic activity (the ability of a drug to activate a receptor upon binding). Can act as agonists or antagonists.

Affinity refers to the preference a drug has for its receptor. Drugs with high affinity are strongly attracted to their receptors; drugs with low affinity are weakly attracted.

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Drugs that Do Not Act Through Receptors

Although most drug effects result from drug-receptor interactions, some drugs do not act through receptors — instead they act through physical or chemical reactions. These include:

• Antacids: Neutralize gastric acidity by direct chemical interaction with stomach acid.
• Antiseptics: Ethyl alcohol precipitates bacterial proteins.
• Hormones: Work directly on target organs.
• Saline laxatives: Magnesium sulfate acts by retaining water in the intestinal lumen through an osmotic effect.
• Chelating agents: Prevent toxicity by forming complexes with heavy metals.

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Nursing Process Related to Drug Receptors

Assessment

• Examine the patient's history to identify factors that may be relevant to drug receptors (e.g., asthma).
• Collect a drug history, including dates and times drugs were taken.
• Perform a physical examination to identify problems relevant to drug receptors (e.g., cardiac arrhythmia).

Implementation

• Provide patient education related to the receptor properties of prescribed drugs in an environment conducive to learning and appropriate for the patient's developmental level and cognitive abilities.
• Provide education in an environment where the patient feels safe to express anxieties and concerns.

Evaluation

• Evaluate physical, social, and psychological outcomes of education related to pharmacotherapy.
• Evaluate the therapeutic effectiveness of pharmacotherapy.

Pharmacodynamics — Drug Interactions

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Overview of Drug Interactions

Seventy percent of Americans are taking one or more prescription drugs. Drug therapy is complex because of the great number of drugs available. Drug-drug, drug-food, drug-laboratory, and drug-herb interactions are an increasing problem. Nurses must be knowledgeable about drug interactions and closely monitor patient response to drug therapy.

Patients at high risk for interactions include those who have chronic health conditions, take multiple medications, see more than one health care provider, and/or use multiple pharmacies. Older adults are at especially high risk because 20% take five or more medications.

Multiple drug interaction checker websites are available for both health care personnel and consumer use (e.g., Drugs.com, WebMD interaction checker).

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Drug-Drug Interactions

A drug-drug interaction is an alteration in drug effect as a result of interaction with one or multiple drugs. It should not be confused with drug incompatibility, an adverse reaction, or an undesirable drug effect. Drug-drug interactions sometimes increase toxicity.

The most common symptoms of drug-drug interactions include nausea, heartburn, headache, and lightheadedness. The most feared interactions are those that result in a dramatic drop in blood pressure or cause a rapid or irregular heart rate. Also of concern are drug interactions that produce toxins capable of damaging vital organs such as the heart or liver.

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Types of Drug-Drug Interactions

Additive Drug Effects: When two drugs are administered in combination, the response is increased beyond what either could produce alone.

• Desirable example: A diuretic and a beta blocker both given for hypertension — different mechanisms of action result in a more pronounced reduction in blood pressure.
• Undesirable example: Aspirin + alcohol. Aspirin is irritating to the stomach, causes platelet dysfunction, and inhibits protective mucus production. Alcohol disrupts the gastric mucosal barrier and suppresses platelet production. Together, they may result in gastric bleeding.

Synergistic Drug Effects: When two or more drugs are given together, one drug has a synergistic effect on another — the therapeutic effect is substantially greater than that of either drug alone.

• Desirable example: Use of two cytotoxic drugs to treat cancer, reducing the dosing of each and decreasing side effects.
• Undesirable example: Alcohol + a sedative-hypnotic (e.g., diazepam) → increased CNS depression.

Potentiation: Some antibiotics have an enzyme inhibitor added to potentiate the therapeutic effect. Example: amoxicillin with clavulanate, where clavulanate is a bacterial enzyme inhibitor. Without clavulanate, bacterial beta-lactamase would inactivate amoxicillin, causing bacterial resistance.

Antagonistic Drug Effects: When drugs with antagonistic effects are administered together, one drug reduces or blocks the effect of the other. This can be beneficial — for example, in morphine sulfate overdose, naloxone is given as an antagonist to block the harmful effects; in heparin overdose, protamine sulfate is given to block the effects of heparin.

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Drug-Food Interactions

Drug-food interactions sometimes increase toxicity. The most dramatic example is the interaction between monoamine oxidase (MAO) inhibitors (a family of antidepressants) and foods rich in tyramine (e.g., aged cheeses, yeast extracts, Chianti wine). If an MAO inhibitor is combined with these foods, blood pressure can rise to a life-threatening level. Patients taking MAO inhibitors must be warned and given a list of foods to strictly avoid.

Other drug-food combinations that increase toxicity:

Food	Drug or Drug Category	Outcome
Grapefruit juice	Amiodarone, buspirone, carbamazepine, cyclosporine, tacrolimus, felodipine, nifedipine, nimodipine, calcium channel blockers, anticholesterol drugs	Decreased metabolism of drugs and increased effects
Caffeine	Theophylline	Excessive CNS excitation
Salt substitutes	Potassium-sparing diuretics	Dangerously high potassium levels
Citrus beverages (e.g., orange juice)	Aluminum-containing antacids	Excessive absorption of aluminum
Leafy green vegetables	Warfarin	Decreased anticoagulant effect
Dairy products	Tetracycline and fluoroquinolones	Chemical binding of the drug leading to decreased effect and treatment failure

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Drug-Laboratory Interactions

Drugs often interfere with clinical laboratory testing. Drug-laboratory interactions may lead to false positives or false negatives, resulting in additional health care costs from unnecessary repeat laboratory testing or additional testing, and may also lead to missed diagnoses. Nurses should refer to a drug reference text or online database for more information on drug-laboratory interactions for drugs their patients are prescribed.

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Drug-Herb Interactions

Dietary supplements and herbs are used widely, creating the potential for significant interactions with prescription drugs. Of greatest concern are interactions that reduce beneficial responses to prescription drugs and interactions that increase toxicity. These interactions occur through the same pharmacokinetic and pharmacodynamic mechanisms by which conventional drugs interact with each other.

Example — St. John's wort: Reduces the effectiveness of many drugs, including digoxin, warfarin, and oral contraceptives.

• Reduced digoxin effectiveness → may worsen heart failure
• Reduced warfarin effectiveness → increases risk for clot formation, strokes, and pulmonary embolism
• Reduced oral contraceptive effectiveness → may lead to unplanned pregnancies

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Nursing Process Related to Drug Interactions

Assessment

• Examine the patient's history to identify factors relevant to drug interactions (e.g., seeing multiple specialists or using multiple pharmacies).
• Collect a drug history, including dates and times drugs were taken.
• Perform a physical examination to identify problems relevant to drug interactions (e.g., bleeding gums in a patient taking both warfarin and ibuprofen).

Implementation

• Provide patient education related to drug interactions in an environment conducive to learning and appropriate for the patient's developmental level and cognitive abilities.
• Provide education in an environment where the patient feels safe to express anxieties and concerns.

Evaluation

• Evaluate physical, social, and psychological outcomes of education related to drug interactions.
• Evaluate the therapeutic effectiveness of pharmacotherapy.

Pharmacodynamics — Side Effects and Adverse Effects

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Side Effects

Side effects are secondary effects of drug therapy. All drugs have side effects. Side effects are usually predictable, and the patient is told to be aware of effects that could happen while on the therapy. Side effects differ from adverse effects, and many resolve on their own after taking the drug for several weeks.

Examples of common side effects:

• Constipation with the use of opioid analgesics
• Sexual disinterest or impotency with certain antidepressants and antihypertensives
• Diarrhea with penicillin and other antibacterial drugs
• Drowsiness with certain antihistamines
• Decreased blood clotting with aspirin

In some instances, side effects may be desirable — e.g., using diphenhydramine (an antihistamine taken to reduce allergies) at bedtime, when drowsiness is beneficial; or taking aspirin (taken to relieve headache/inflammation) to help prevent heart attack due to its platelet aggregation-reducing side effect.

Chronic illness, age, weight, gender, and ethnicity all play a part in drug side effects. Side effects are one of the primary reasons patients stop taking prescribed drugs. Many side effects can be managed with dosage adjustments, changing to a different drug in the same class, or implementing other interventions.

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Adverse Effects

An adverse effect is an unintended reaction to a drug administered at normal dosage. Adverse effects may be mild to severe and include anaphylaxis (cardiovascular collapse). Adverse effects are always undesirable and must be reported and documented because they represent variances from planned therapy.

Adverse effects are most common in older adults and the very young (patients older than 65 years account for more than 50% of all adverse effect cases). Acute and/or chronic illness also increases risk. Adverse effects are more common in patients receiving multiple drugs than in patients taking just one drug.

Dose-Related Adverse Effects: May result from decreased drug clearance in patients with impaired kidney or liver function, or from drug-drug interactions. Example: a patient with decreased kidney function administered nitrofurantoin develops jaundice and elevated liver function studies.

Allergic Adverse Effects: Not dose-related and usually require prior exposure. Allergies develop when a drug acts as an antigen or allergen. After sensitization, subsequent exposure produces one of several types of allergic reaction. Clinical history and appropriate skin tests can sometimes help predict these. Example: before administering antithymocyte globulin [equine] IV, patients are skin tested to determine likelihood of allergic reaction.

Idiosyncratic Adverse Effects: Unexpected adverse effects that are not dose-related or allergic; occur in a small percentage of patients. Idiosyncrasy refers to a genetically determined abnormal response to a drug.

Paradoxical Effects: An effect that is opposite of the intended drug response. Common examples include excitation (aggression and psychomotor agitation) in some older adults given lorazepam; paradoxical excitation in children given antihistamines; and paradoxical bradycardia in patients administered low doses of atropine (<0.5 mg).

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Therapeutic Index

The therapeutic index (TI) is the ratio between the toxic dose of a drug and the therapeutic dose of a drug. Adverse effects are a big concern when drugs have a narrow TI (e.g., hemorrhage in a patient taking warfarin).

• ED₅₀ = the dose that produces a therapeutic response in 50% of the population
• TD₅₀ = the dose that produces a toxic response in 50% of the population
• The TI is the difference between these two points

If the ED₅₀ and TD₅₀ are close together, the drug has a narrow TI. Drugs with narrow TIs (e.g., aminoglycosides, warfarin, digoxin, lithium, phenytoin) require close monitoring to ensure patient safety. Drugs with a wide TI (e.g., chlorpromazine), while still requiring monitoring, have lethal doses significantly higher than therapeutic doses (e.g., chlorpromazine's lethal dose is 200 times the therapeutic dose).

Drug toxicity occurs when drug levels exceed the therapeutic range; toxicity may occur secondary to overdose (intentional or unintentional) or drug accumulation. Factors influencing drug toxicity include disease, genetics, and age. Examples: profound respiratory depression from morphine overdose; severe hypoglycemia from insulin overdose.

Note: in everyday language, "toxicity" has come to mean any severe adverse effect regardless of dose — e.g., neutropenia caused by anticancer drugs at therapeutic doses may be called a toxicity.

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Nursing Process Related to Side Effects and Adverse Effects

Assessment

• Examine the patient's history to identify factors relevant to side effects and adverse effects (e.g., previous allergic response to penicillin).
• Collect a drug history, including dates and times drugs were taken.
• Perform a physical examination to identify problems relevant to drug side effects (e.g., elevated blood pressure in a person taking an antihistamine).

Implementation

• Teach the patient about a drug's side effects and encourage them to report side effects.
• Provide patient education related to drug side effects and adverse effects in an environment conducive to learning and appropriate for the patient's developmental level and cognitive abilities.
• Provide education in an environment where the patient feels safe to express anxieties and concerns (e.g., erectile dysfunction in a patient prescribed antihypertensives).

Evaluation

• Evaluate physical, social, and psychological outcomes of education related to pharmacotherapy.
• Evaluate the therapeutic effectiveness of pharmacotherapy.
• Evaluate for the presence or absence of side effects, as well as any necessary management of side effects.

Age-Specific Considerations in Pharmacology — Considerations Within the Pediatric Population

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Classification of Pediatric Patients

The term pediatric covers term neonates to adolescents 16 to 18 years of age. Within pediatrics, there is further delineation:

Classification	Age
Term neonate	Birth at 38 or more weeks' gestation to 27 days
Infant	28 days to 12 months
Toddler	12 months to 3 years
Preschool	3 to 5 years
School age	6 to 10 years
Adolescent	11 years to 16 or 18 years (regional difference)

In addition to differing developmental milestones, some drugs prescribed to pediatric patients are dosed differently based on age classification. For example, neonates are prescribed amoxicillin at 20 to 30 mg/kg/day in divided doses every 12 hours.

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Pharmacokinetic Changes in the Neonate and Pediatric Patient

Physiologic differences in body systems between children and adults affect the absorption, metabolism, distribution, and excretion (ADME) of drugs. These differences are most significant in neonates and infants.

Absorption

• Reduced gastric acid production results in a more alkaline environment until age two → decreased absorption of weakly acidic drugs (e.g., aspirin) and increased absorption of basic drugs (e.g., ampicillin).
• Gastric emptying is slowed due to slow or irregular peristalsis.
• First-pass elimination by the liver is reduced due to liver immaturity and reduced microsomal enzyme levels.
• Intramuscular absorption is faster and irregular.

Distribution

• Total body water is 70–80% in full-term infants, 85% in premature newborns, and 64% in children 1–12 years — results in a larger volume of distribution for water-soluble drugs (e.g., phenobarbital) in neonates and infants vs. adults.
• Fat content is lower in young patients due to greater total body water → lower volume of distribution for lipophilic drugs.
• Protein binding is decreased due to decreased protein production by the immature liver.
• More drugs enter the brain due to an immature blood-brain barrier.

Metabolism

• Microsomal enzyme levels are decreased because the immature liver has not yet started producing enough → altered drug metabolism.
• Older children may need increased drug dosages once hepatic enzymes are produced.

Excretion

• Kidney immaturity results in decreased glomerular filtration rate and tubular secretion and resorption in infants and children → increased risk for drug accumulation and toxicity.
• Kidney perfusion may be decreased → reduced renal function, concentrating ability, and excretion of drugs.

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Adverse Drug Effects

Pediatric patients are at increased risk for drug toxicity due to pharmacokinetic differences in body systems compared with adults.

Adverse Drug Reactions Unique to Pediatric Patients:

Drug	Adverse Effect
Androgens	Premature puberty in males; reduced adult height from premature epiphyseal closure
Aspirin and other salicylates	Severe intoxication from acute overdose (acidosis, hyperthermia, respiratory depression); Reye syndrome in children with chickenpox or influenza
Chloramphenicol	Gray syndrome (neonates and infants)
Fluoroquinolones	Tendon rupture
Glucocorticoids	Growth suppression with prolonged use
Hexachlorophene	Central nervous system toxicity (infants)
Nalidixic acid	Cartilage erosion
Phenothiazines	Sudden infant death syndrome
Promethazine	Pronounced respiratory depression in children under 2 years old
Sulfonamides	Kernicterus (neonates)
Tetracyclines	Staining of developing teeth

Patient Safety Notes:

• Pediatric patients may have paradoxical reactions to some drugs (e.g., methylphenidate causes excitability in adults; in children it reduces activity, making it effective for ADHD).
• Due to the risk for Reye syndrome, pediatric patients should not be given aspirin or other drugs containing salicylates (e.g., Pepto-Bismol).

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Pediatric Dosing

Most drugs have not been sufficiently studied in pediatric patients to ensure safety and effectiveness. For drugs without an established pediatric dosage, the dosage can be estimated from adult dosages using body surface area (BSA):

(Child's BSA × Adult dosage) ÷ 1.73 m² = Pediatric dosage

Initial pediatric doses are at best a rough estimate — drug therapy must be adjusted based on therapeutic response and plasma drug concentrations. Pediatric patients must be monitored closely for therapeutic and adverse responses. Nurses should question any medication dosage adjustment different from the recommended dose, and should always double-check pediatric dosage calculations with a colleague.

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Promoting Adherence

Understanding pediatric age classifications facilitates assessment, management, and promotion of adherence through family-centered care and developmentally appropriate patient-specific education.

Infants

• Maintain safe and secure positioning (holding, rocking, cuddling, soothing) and perform administration safely and quickly.
• Allow self-comforting measures (pacifier, sucking on fingers).
• Use a calibrated dropper or oral syringe; give small amounts to prevent choking.

Toddlers

• Offer a brief, concrete explanation using simple terms; parents/caregivers must be part of the process.
• Ensure the toddler is held safely and securely during administration.
• Allow the toddler to choose a place or position to take the drug (e.g., sitting on parent's lap).
• If appropriate, disguise the drug's taste with a small amount of flavored drink or food.
• Accept aggressive behavior as healthy within reasonable limits; provide comfort immediately after; use play to help the child process the experience.

Preschoolers

• Offer a brief, concrete explanation at the patient's level with parent/caregiver present.
• Allow some level of choice and control (e.g., injection site, type of flavored drink).
• Provide comfort after the procedure; accept reasonable aggressive behavior and provide age-appropriate outlet through play.
• Allow the parent to provide comfort and understanding.

School-Age Children

• Explain the procedure, allowing for some control; provide comfort measures.
• Explore feelings, fear, and anger using therapeutic play; art and age-appropriate books may help express fears.
• Set age-appropriate behavior limits (e.g., it is okay to cry, but not to bite).
• Use the interaction to provide teaching (e.g., what a seizure is and how medication helps prevent it).

Adolescents

• Prepare the patient in advance, but do not use scare tactics.
• Allow personal space or time alone after the procedure to enhance coping.
• Allow time to discuss feelings; explore perceptions of illness and treatment and correct misconceptions.
• Encourage self-care and participation in procedures as appropriate.

Additional Considerations for Family-Centered Care

• Provide written instructions and demonstration of proper drug administration techniques; request a return demonstration to ensure understanding.
• Ensure the family understands that if the drug is spilled or spit out, they must estimate the amount lost and re-administer (being careful not to overestimate).
• Recommend use of a drug administration chart/calendar to avoid missed doses or double dosing.
• Reinforce the need to complete antibiotics as instructed even if symptoms resolve.

Age-Specific Considerations in Pharmacology — Considerations Within the Older Adult Population

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Classification of Older Adults

Persons over the age of 65 years are referred to as older adults. Older adults are a diverse and unique population with significant differences existing among 65-, 75-, 85-, and 95-year-olds.

Classification	Age
Young-Old	65–74 years
Old	74–84 years
Old-Old	85+ years

Identifying these subgroups provides a more accurate representation of significant physiologic and social changes.

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Pharmacokinetic Changes in the Older Adult

Physiologic changes occur in all body systems with aging and may affect the ADME of drugs. The actual clinical impact varies by individual.

Absorption

• Hydrochloric acid production is decreased → higher gastric pH (less acidic) → may alter absorption of some drugs (e.g., calcium carbonate).
• Decline in smooth muscle tone and motor activity → delayed gastric emptying.
• Blood flow to the GI tract is reduced by 40–50%.
• Absorptive surface area in the GI tract decreases with aging.

Distribution

• In adults over 60, total body water declines by 10–15% vs. younger adults → reduces volume of distribution of water-soluble drugs.
• Fat content increases by up to 45% due to decreased lean body mass → increases volume of distribution for lipophilic drugs (e.g., diazepam).
• Decreased protein production by the liver and reduced protein intake → reduced overall protein-binding sites.

Metabolism

• Production of microsomal enzymes is reduced → potentially altering drug metabolism and increasing risk for toxicity and drug-drug interactions.
• 25% reduction in liver size and up to 40% decline in hepatic blood flow → may alter hepatic metabolism.

Excretion

• Glomerular filtration rate decreased by up to 50% due to decreased blood flow → potential drug accumulation and increased risk for toxicity.
• Number of functioning nephrons is decreased due to glomerulosclerosis.

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Adverse Drug Effects in Older Adults

Older adults are admitted to the emergency department (ED) with ADEs more often than younger adults — they are seven times more likely to be hospitalized secondary to ADEs. Most ED admissions and hospitalizations occur due to reactions to blood thinners, hypoglycemics, seizure medications, cardiovascular drugs, and opioids. Symptoms in older adults are often nonspecific (e.g., dizziness, cognitive impairment), making identification of ADEs difficult.

Factors increasing ADE incidence in older adults:

• Drug toxicity due to altered pharmacokinetics (e.g., decreased kidney function)
• Polypharmacy
• Multiple comorbidities
• Cognitive impairment
• Use of drugs with a narrow therapeutic index (e.g., warfarin)

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Drug Complications Unique to Older Adults

Drugs Requiring Special Considerations in the Older Adult Patient:

Drug	Common Complications
Opioids	Confusion, constipation, urinary retention, nausea, vomiting, respiratory depression, falls
NSAIDs	Edema, nausea, gastric ulceration, bleeding, renal toxicity
Anticoagulants (heparin, warfarin)	Major and minor bleeding episodes, many drug interactions, dietary interactions
Anticholinergics	Blurred vision, dry mouth, constipation, confusion, urinary retention, tachycardia
Antidepressants	Sedation and strong anticholinergic adverse effects
Antihypertensives	Nausea, hypotension, diarrhea, bradycardia, heart failure, impotence
Cardiac glycosides (e.g., digoxin)	Visual disorders, nausea, diarrhea, dysrhythmias, hallucinations, decreased appetite, weight loss
CNS depressants (muscle relaxants, opioids)	Sedation, weakness, dry mouth, confusion, urinary retention, ataxia
Sedatives and hypnotics	Confusion, daytime sedation, ataxia, lethargy, increased risk for falls
Thiazide diuretics	Electrolyte imbalance, rashes, fatigue, leg cramps, dehydration

Conditions Requiring Special Considerations in the Older Adult Patient:

Condition	Drugs Requiring Special Caution
Bladder flow obstruction	Anticholinergics, antihistamines, decongestants, antidepressants
Clotting disorders	NSAIDs, aspirin, antiplatelet drugs
Chronic constipation	Calcium channel blockers, tricyclic antidepressants, anticholinergics
COPD	Long-acting sedatives or hypnotics, narcotics, beta blockers
Heart failure and hypertension	Sodium, decongestants, amphetamines, OTC cold products
Insomnia	Decongestants, bronchodilators, MAO inhibitors
Parkinson disease	Antipsychotics, phenothiazines
Syncope, falls	Sedatives, hypnotics, opioids, CNS depressants, muscle relaxants, antidepressants, antihypertensives

Alert: Older adults may have paradoxical reactions to benzodiazepines — leading to talkativeness, excessive movement, restlessness, and agitation.

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Beers Criteria

There are many medications that should be avoided in older adults due to changes in pharmacokinetics. A panel of experts developed the American Geriatrics Society Beers Criteria for Potentially Inappropriate Medication Use in Older Adults to identify these drugs (available since 1991; most recently updated in 2019). Despite this, 20% of community-dwelling older adults continue to be prescribed drugs that appear on the list.

The key term is "potentially" inappropriate — drugs identified in the Beers Criteria must be interpreted taking into consideration the patient's preferences, values, and needs.

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Polypharmacy

Polypharmacy refers to the use of more drugs than is medically necessary. Researchers use five drugs as the threshold, as this number has been associated with increased incidence of ADEs, geriatric syndromes, and increased mortality.

Factors increasing the incidence of polypharmacy:

• Increasing age
• Multiple comorbidities
• Multiple drugs needed to treat one disease (e.g., diabetes)
• Drug regimen changes
• Multiple specialist health care providers
• Drugs prescribed to treat side effects
• Use of multiple pharmacies
• Self-treatment with over-the-counter drugs
• Nonadherence

Reducing Polypharmacy: Encourage patients to maintain an up-to-date, complete list of all their drugs (prescribed, OTC, supplements, and herbs), including dosages and reason for taking each drug. Older adults should be educated on the name, appearance, therapeutic effects, side effects, and adverse effects/interactions of each drug; when to call their health care provider; and the importance of taking drugs exactly as prescribed and not self-medicating.

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Promoting Adherence in Older Adults

Nearly half of older adults fail to adhere to their prescribed therapeutic regimen.

Factors increasing risk for poor adherence:

• Multiple comorbidities and multiple prescription drugs
• Complicated drug regimens
• Drug packaging that is difficult to open
• Multiple health care providers; changes to the drug regimen
• Cognitive or physical impairment (memory, hearing, visual acuity, color discrimination, manual dexterity)
• Living alone; recent discharge from hospital
• Low literacy; inability to pay for drugs
• Personal conviction that a drug is unnecessary or dosage is too high
• Inadequate patient education; unpleasant side effects

Interventions to Promote Adherence:

• Recommend simplifying the drug regimen (combination drugs or long-acting formulations).
• Recommend appropriate dosage forms (e.g., liquid if patient has difficulty swallowing).
• Ask pharmacist to use large print labels and easy-to-open containers (e.g., for patients with arthritis).
• Suggest using a calendar, diary, or pill counter to track drug administration.
• Ask about affordability; recommend using only one pharmacy.
• Suggest enlisting a friend, relative, or visiting health professional for assistance.
• Monitor for therapeutic responses and side effects; encourage the patient to report if drugs are not working.
• Ensure the older adult is wearing eyeglasses and hearing aids before education begins.
• Speak in a clear, low tone of voice; sit facing the patient and limit distractions.
• Treat with respect; never use elderspeak. Start with the expectation the older adult is able to learn.
• Use return demonstration to verify knowledge acquisition.
• Use large print and dark type against a light background; use a font with serifs.
• Review all drugs at each patient visit; ask the patient to bring all drugs to each appointment.
• Instruct the patient to keep a list of all drugs and bring it to all health appointments; advise keeping a copy in their wallet or purse.

Section 15 — Anesthetic Therapy: General Principles, Pharmacokinetics, and Pharmacodynamics of Anesthesia

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Page 1 — Overview of Anesthetics

Anesthetics are classified as either general or local.

• General anesthetics depress the central nervous system (CNS), resulting in pain alleviation and loss of consciousness.
• Local anesthetics act on a specific area/site where the drug is administered and block pain at the site.

This topic covers a comparison of the different types of anesthesia, followed by the pharmacokinetics and pharmacodynamics of the prototype anesthetic, lidocaine.

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Page 2 — General Anesthetics

General anesthetics are divided into two groups: (1) inhalation anesthetics and (2) intravenous (IV) anesthetics.

Inhalation Anesthetics

Inhalation anesthetics (gas or volatile liquids administered as gas) rapidly diffuse into the arterial vascular system and cross the blood-brain barrier to produce amnesia, skeletal muscle relaxation, and hypnosis. Certain gases (notably nitrous oxide) are absorbed quickly, have rapid action, and are eliminated rapidly. Inhalation anesthetics typically provide smooth induction with a recovery of consciousness ranging from a few minutes to 1 hour. They are usually combined with other drugs for surgical procedures (balanced anesthesia).

Drugs used as inhalation anesthetics: halothane, enflurane, isoflurane, desflurane, sevoflurane.

IV Anesthetics

IV anesthetics may be used for general anesthesia or for the induction stage of anesthesia. For outpatient surgery of short duration, IV anesthetic may be preferred. Currently used agents: propofol, droperidol, etomidate, and ketamine hydrochloride (for total intravenous anesthetic — TIVA). IV anesthetics have rapid onsets and short durations of action.

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Page 3 — Balanced Anesthesia

Balanced anesthesia is a combination of drugs frequently used to achieve what inhalation anesthetics alone cannot. Drugs are combined to ensure that induction is smooth and rapid and that analgesia and muscle relaxation are adequate.

The agents most commonly used for balanced anesthesia include:

• Propofol and a short-acting barbiturate for the induction of anesthesia
• A neuromuscular blocking agent for muscle relaxation
• An opioid and nitrous oxide for analgesia

The primary benefit: combining drugs enables full general anesthesia at lower (safer) doses of the inhalation anesthetic than would be required if inhalation anesthetic were used alone.

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Page 4 — Spinal Anesthesia

Spinal anesthesia requires that a local anesthetic be injected into the subarachnoid space below the first lumbar space (L1) in adults and the third lumbar space (L3) in children. The spread of the anesthetic — regulated by the density of anesthetic used and position of the patient — determines the level of anesthesia achieved.

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Page 5 — Types of Local Anesthesia Administration

Local anesthetics can be applied topically or injected to provide anesthesia to a limited area. They are useful in dental procedures, suturing skin lacerations, short-term (minor) surgery, blocking nerve impulses (nerve block) below a spinal anesthetic insertion, and diagnostic procedures such as lumbar puncture and thoracentesis. Local anesthetics may also perform regional blocks (brachial plexus, axillary, femoral, sciatic nerves) for analgesia for upper or lower extremity surgery.

Infiltration Anesthesia

Involves injection of a local anesthetic directly into areas surrounding the operative site. Combining the anesthetic with a vasoconstrictive agent (e.g., epinephrine) keeps anesthesia localized, prolongs effect by slowing absorption and elimination. Tourniquets can also provide the same effect. Examples: lidocaine, bupivacaine.

Nerve Block Anesthesia

Accomplished with injection of a local anesthetic at the site where a nerve or nerves innervate a specific area. The injection occurs at a distance from the actual operative site. Nerve blocks allow anesthesia to a specific body area without impacting the patient's level of consciousness (LOC).

• Lidocaine, mepivacaine — for short procedures
• Bupivacaine — for extended procedures

Different injection sites in the spinal column for distinct nerve blocks:

• Spinal block: Injection into the subarachnoid space
• Epidural block: Injection into the epidural space posterior to the spinal cord
• Saddle block: Injection into the lower end of the spinal column, producing anesthesia to the perineal area

Topical Anesthesia

Topical (surface) anesthetics decrease the sensitivity of nerve endings in the affected area. Available in solution, liquid spray, ointment, cream, gel, and powder forms. Limited to mucous membranes, broken or unbroken skin surfaces, and burns. Examples: lidocaine, tetracaine, cocaine.

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Page 6 — Pharmacokinetics of Lidocaine

Lidocaine is the prototype of the amide-type agents. Used as both a topical and injectable local anesthetic agent. It is a moderate-acting anesthetic used for nerve blocks as well as infiltration, epidural, and spinal anesthesia.

Understanding pharmacokinetics is critical because absorption and metabolism directly impact drug effects. The balance between rate of absorption and rate of metabolism is important:

• If metabolism > absorption → systemic effects remain low
• If absorption > metabolism → blood levels may become toxic

Parameter	Details
Absorption	Locally administered lidocaine can have systemic effects if absorbed into the bloodstream, especially when absorption rate exceeds metabolism/excretion rate. Topical bioavailability = only 3%. Absorption increases when applied to an open area, injected into capillary network, or heat is applied to the area.
Distribution	Widely distributed; Protein binding: 60%–80%
Metabolism	Metabolized in liver
Excretion	Primarily in urine; minimally removed by hemodialysis

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Page 7 — Pharmacodynamics of Lidocaine

Lidocaine has different outcomes depending on the area and type of administration. The nurse should be aware of the pharmacodynamics of each method.

Mechanism of Action

Lidocaine causes temporary loss of motor, sensory, and autonomic nervous system function. It acts by blocking sodium channels in the axonal membrane to stop axonal conduction.

Therapeutic Uses

Anesthesia:

• Local anesthetic
• Nerve block for dental/surgical procedures and childbirth
• Topical anesthetic:
  • For local skin disorders (minor burns, insect bites, prickly heat, skin manifestations of chickenpox, abrasions)
  • For mucous membranes (local anesthesia of oral, nasal, laryngeal mucous membranes; local anesthesia of respiratory and urinary tracts; relief of pruritus, hemorrhoids, pruritus vulvae)
  • For IV insertion in the pediatric population

Chronic Pain Relief:

• Dermal patches used for chronic pain in postherpetic neuralgia and allodynia (painful hypersensitivity)
• Off-label use: IV infusion for chronic pain syndrome

Treatment of Dysrhythmias:

• Treats ventricular dysrhythmias: premature ventricular contractions (PVCs), ventricular tachycardia, ventricular fibrillation
• Mode of action: decreases automaticity; increases electrical threshold of ventricle

Pharmacodynamic Profile

Parameter	Details
Onset	Varies by location and indication; ranges from 2–4 minutes as a local anesthetic to 15–30 minutes as an epidural block
Peak	2–5 minutes
Duration	Varies by location; 1–4 hours; longer when combined with a vasoconstrictor such as epinephrine
Half-life	1–2 hours

Section 16 — Anesthetic Therapy: Nursing Process Related to Anesthetic Therapy

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Page 1 — Pre-Administration Assessment for Lidocaine

Before administration of lidocaine, the nurse must perform a baseline assessment of the patient:

• Question the patient for hypersensitivity to lidocaine, specifically amide anesthetics.
• Obtain baseline blood pressure (BP), pulse (P), respiratory rate (RR), electrocardiogram (ECG), and serum electrolytes.
• Obtain a drug and health history, noting drugs that affect the cardiopulmonary systems.
• If a patient states a past history of dysrhythmias, a thorough health history must be completed before administration.

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Page 2 — Contraindications with Lidocaine

Contraindicated in patients with a history of:

• Adams-Stokes syndrome
• Wolff-Parkinson-White syndrome
• Supraventricular arrhythmias
• Sinoatrial (SA), atrioventricular (AV), or intraventricular heart block
• Hypersensitivity to amide-type local anesthetics

Note: If a patient has a functioning pacemaker for treatment of heart block, lidocaine may be used.

Use cautiously in patients with:

• Hepatic disease
• History of malignant hyperthermia
• Shock
• Heart failure
• Marked hypoxia
• Hypovolemia
• Severe respiratory depression
• Older adult population

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Page 3 — Interactions with Lidocaine

Category	Interaction
Drug	Class 1 antiarrhythmics may increase cardiac effects
Herbal	St. John's wort may decrease concentration
Food	None known
Laboratory Values	IM lidocaine may increase creatinine-kinase (CK) level (used to diagnose acute myocardial infarction [MI])

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Page 4 — Dosage and Administration of Lidocaine

The nurse should be prepared to monitor the patient following administration. The patient's room should be set up with necessary emergency equipment for immediate use if required.

Topical Administration

• Topical lidocaine is available as a liquid, ointment, or patch.
• Apply a thin layer using a cotton-tip applicator or gloved finger.
• Do not apply to broken or open skin areas — this may increase systemic absorption and adverse effects.
• Apply to affected areas as needed.

Injectable Administration

Preparation of the Patient:

• Address the patient's vital signs before injection.
• Prep the patient's skin by clipping hair (as needed) and cleansing the injection site.
• Position the patient appropriately and explain the procedure.
• Some patients (especially children and confused/uncooperative adults) may require gentle restraint of the area to be injected.

Dosage and Administration:

• Local anesthetic dosage varies with procedure, degree of anesthesia, vascularity, and duration.
• Injection of local anesthetics requires specific training related to appropriate technique and management of potential side effects.
• Administration is typically performed by advanced-practice health care providers (e.g., dentists, nurse practitioners, physician assistants, and nurse anesthetists).

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Page 5 — Side Effects and Adverse Effects of Lidocaine

The nurse should be aware of any side effects and/or adverse drug effects. Side effects and adverse effects vary from patient to patient and depend on the anesthetic agent. Not every patient will experience them.

Side Effects

• Pain at injection site
• Burning, stinging, and tenderness at application
• Rare and with high doses: drowsiness, dizziness, disorientation, lightheadedness, tremors, apprehension, euphoria
• Sensations of heat, cold, numbness
• Blurred or double vision
• Tinnitus
• Nausea

Adverse Effects

Serious adverse reactions are uncommon, but high doses (any route) can cause:

• Cardiovascular depression, bradycardia, hypotension, arrhythmias, heart block, cardiovascular collapse, cardiac arrest
• Malignant hyperthermia
• CNS toxicity (particularly with regional anesthesia): tremors, drowsiness, seizures
• Vomiting
• Respiratory depression

Systemic Absorption

Application of sizable doses to large areas and/or broken skin increases risk for systemic absorption and adverse effects. Toxicity impacts the CNS and cardiac status:

• CNS toxicity: Initial period of excitement, with or without seizures; followed by CNS and respiratory depression
• Cardiac toxicity: Bradycardia, heart blocks, or cardiac arrest
• Methemoglobinemia (evidenced by cyanosis): Has occurred following topical application for teething discomfort and laryngeal anesthetic spray

Hypersensitivity Reactions

Hypersensitivity reactions to lidocaine are rare. The most common is contact dermatitis (immediate or delayed 2–3 days after administration). More severe reactions (urticaria, bronchospasm, anaphylaxis) have been reported but are more likely with ester-type local anesthetics (e.g., cocaine or procaine) — this is why amide-type anesthetics like lidocaine are preferred for local anesthesia.

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Page 6 — Interventions and Evaluation for Lidocaine

Interventions

• Monitor patient's postoperative state of sensorium; report if patient remains excessively nonresponsive or confused.
• Drowsiness should be considered a warning sign of high serum levels of lidocaine.
• Monitor vital signs following spinal and local anesthesia — hypotension and respiratory depression may result.
• Monitor for cardiac dysrhythmias.
• If used for spinal anesthesia: observe urine output and report deficit of hourly or 8-hour urine output.
• Monitor for headache if used for spinal anesthesia.

Evaluation

• Evaluate the patient's response to the anesthetics.
• Continue to monitor the patient for adverse reactions.

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Page 7 — Patient Teaching for Lidocaine

General Teaching

• Explain to patients preoperative preparation and what to expect postoperatively, including frequent assessment of vital signs and LOC.
• Educate patients that CNS effects are generally dose-related and of short duration. Tell patients to report any side effects.
• Local anesthesia: Inform patients that due to loss of feeling/sensation, protective measures may be needed until anesthetic wears off (e.g., no ambulation; special positions for some regional anesthesia).
• Oral mucous membrane anesthesia: Inform patients to not eat, drink, or chew gum for 1 hour after application (swallowing may be impaired, increasing risk for aspiration; numbness of tongue and buccal mucosa may lead to bite trauma).

Side Effects Teaching

• Teach patients they may experience occasional pain at IM injection site.
• Inform patients that burning, stinging, and tenderness at the application site may occur with topical lidocaine.
• Inform patients that rare side effects generally only occur at high doses.
• Teach patients to immediately notify the health care provider if they experience any of the following: drowsiness, dizziness, disorientation, lightheadedness, tremors, apprehension, euphoria, sensations of heat/cold/numbness, blurred or double vision, tinnitus, nausea.

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Page 8 — Case Study

Patient: Ms. Vega is receiving an epidural with lidocaine. She is having her first baby.

Baseline vital signs: BP 130/80, P 88, R 16, Temp 98.9°F, O₂ saturation 99% on room air.

Assessment findings: Decreased sensory and motor function of bilateral lower extremities. Patient states: "I feel so sleepy, and I feel like I can't get a full breath."

Reassessed vital signs: BP 118/60, P 64, R 10, Temp 98.9°F, O₂ saturation 92% on room air.

(Clinical case illustrating signs of lidocaine systemic absorption/adverse effects — hypotension, bradycardia, respiratory depression — following epidural administration.)

Section 17 — CNS Depressant and Skeletal Muscle Relaxant Therapy: Pharmacokinetics and Pharmacodynamics of CNS Depressant and Skeletal Muscle Relaxant Drugs

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Page 1 — Overview of CNS Depressants

CNS depressant drugs slow brain activity and reduce functional activity to varying degrees depending on the drug and the amount taken. Broad classifications of CNS depressants include: sedative-hypnotics, general anesthetics, analgesics, opioids and nonopioid analgesics, anticonvulsants, antipsychotics, and antidepressants.

This lesson focuses on CNS depressants used for moderate sedation. Examples include:

• Diazepam
• Lorazepam
• Midazolam ← prototype drug of study

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Page 2 — Pharmacokinetics and Pharmacodynamics of Midazolam

Midazolam is the most frequently used drug for moderate sedation. It is a short-acting benzodiazepine commonly used for preoperative sedation, procedural sedation, and severe agitation.

Pharmacokinetics

Parameter	Details
Absorption	Oral: rapidly absorbed from the GI tract
Distribution	95%–98% protein bound
Metabolism	In the liver and gut by CYP3A4 pathway; only 40%–50% reaches circulation due to first-pass metabolism
Excretion	In urine

Mechanism of Action

The exact mechanism of action is unknown. Research suggests midazolam works by stimulating the gamma-aminobutyric acid (GABA) or adjacent receptors. GABA is an inhibitory neurotransmitter in the brain that blocks CNS stimulation — it can produce sedation, relax skeletal muscles, and induce sleep, anesthesia, and amnesia.

Pharmacodynamic Profile

Parameter	Details
Onset	IV: 1–5 min; PO: 10–20 min; IM: 5–10 min
Peak plasma concentration	IV: 5–7 min; IM: 20–60 min
Duration	IV: 30–60 min; IM: 2–6 hr
Half-life	1.8–6.4 hr after IV administration

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Page 3 — Overview of Skeletal Muscle Relaxants

Muscle relaxants are medications used to relieve muscular spasms and the pain associated with these spasms. The actual mechanism of action is not entirely known. Muscle relaxants are believed to depress neuronal action in the spinal cord or brain and may augment neuronal inhibition in skeletal muscles. Centrally acting muscle relaxants are prescribed in cases of spasticity to repress hyperactive reflexes, and for muscle spasms resistant to anti-inflammatory medications, physical therapy, or other treatment modalities.

Spasticity

Skeletal muscle spasticity is a form of muscular hyperactivity causing painful contractions and limited mobility. It can result from increased muscle tone (increased CNS stimulation from cerebral neurons) or lack of inhibition in the spinal cord/skeletal muscles. Centrally acting muscle relaxants act on spinal muscles.

Drugs for spasticity: baclofen, dantrolene, tizanidine. Diazepam (a benzodiazepine) has also been used successfully.

Muscle Spasms

Muscle spasms may be attributed to traumatic injuries or chronic debilitating diseases (e.g., multiple sclerosis [MS], cerebrovascular accident [CVA], cerebral palsy, or head/spinal cord injuries). Several muscle relaxants decrease pain associated with muscle spasms and increase range of motion. Many have a sedative effect and should not be taken with other CNS depressants (e.g., alcohol, narcotics, barbiturates).

Drugs for muscle spasms: carisoprodol, chlorzoxazone, cyclobenzaprine, metaxalone, methocarbamol, orphenadrine citrate (all centrally acting). Many of these (except cyclobenzaprine) may lead to drug dependence. Common side effects: vertigo and drowsiness.

Cyclobenzaprine is the prototype drug of study for this class.

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Page 4 — Pharmacokinetics and Pharmacodynamics of Cyclobenzaprine

Cyclobenzaprine is the most commonly used centrally acting skeletal muscle relaxant and is often prescribed to reduce spasms caused by musculoskeletal injuries. It is not effective against muscle spasms caused by CNS disorders.

Pharmacokinetics

Parameter	Details
Absorption	PO, rapidly absorbed in GI tract; only 40%–50% reaches circulation due to first-pass metabolism
Distribution	93% protein bound
Metabolism	In liver
Excretion	In urine

Pharmacodynamics

The exact mechanism of action is unknown, but cyclobenzaprine is believed to block nerve impulses at the brainstem level.

Parameter	Details
Onset	1 hr
Peak	3–8 hr
Duration	12–24 hr
Half-life	8–37 hr

Section 18 — CNS Depressant and Skeletal Muscle Relaxant Therapy: Nursing Process Related to CNS Depressant and Skeletal Muscle Relaxant Therapy

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Page 1 — Pre-Administration Assessment for Midazolam and Cyclobenzaprine

Before administration of CNS depressants or centrally acting muscle relaxants, the nurse should assess the patient to prevent adverse reactions. Harm can be an unintended consequence of treatment or result from ineffective patient screening.

General (Both Drugs)

• Perform a medical history including a thorough drug history and identification of any allergies.
• Determine current use of any drugs and herbal supplements to help avoid drug interactions.
• Obtain baseline vital signs, particularly blood pressure in both sitting and supine positions.

Midazolam-Specific

• Determine any contraindications before administering.
• Assess the mental status of the patient.
• Determine whether the patient has a history of blood dyscrasias or hepatic disease.
• Determine whether the patient is pregnant or breastfeeding.

Cyclobenzaprine-Specific

• Obtain patient's health history to identify the cause of muscle spasms — cyclobenzaprine is only effective for muscle spasms of local origin.
• Obtain liver function studies and a complete blood count (CBC).

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Page 2 — Contraindications and Interactions with Midazolam

Contraindications

• Acute narrow-angle glaucoma
• Concurrent use of a potent CYP3A4 inhibitor

Cautious use with: renal/hepatic/pulmonary impairment, impaired gag reflex, heart failure, treated open-angle glaucoma, obesity, concurrent CNS depressants, alcohol dependency, older adults, and debilitated patients.

Drug Interactions

Category	Interaction
Drugs	Concurrent use with other CNS depressants (lorazepam, morphine, zolpidem) may increase CNS effects, respiratory depression, and hypotensive effects. Concurrent use with a CYP3A4 inhibitor (erythromycin, ketoconazole, ritonavir) may increase concentration/sedative effects.
Herbs	Gotu kola, kava kava, St. John's wort, and valerian may increase CNS depression. St. John's wort may also decrease concentration.
Food	Grapefruit juice products increase oral absorption and systemic availability.

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Page 3 — Dosage and Administration of Midazolam

Midazolam is available in IV, IM, and oral formulations. Dosing for adults by indicated use:

Preoperative Sedation and Amnesia Induction

• IM: 0.07–0.08 mg/kg, 30 min to 1 hr before general anesthesia
• IV (Induction of anesthesia):

  • 55 yr: 200–350 mcg/kg over 30 sec; limit to 250 mcg/kg if not premedicated, or 150 mcg/kg if premedicated

  • <55 yr: 200–350 mcg/kg over 20–30 sec; if not premedicated, may repeat by giving 20% of original dose; if premedicated, reduce by 50 mcg/kg

Continuous Induction for Mechanical Ventilation

• Adult: IV 0.01–0.05 mg/kg over several minutes; repeat q10–15 min intervals until adequate sedation, then 0.02–0.10 mg/kg/hr maintenance; adjust as needed.

Alcohol Withdrawal Off-label (Unlabeled)

• Adult: IV 1–5 mg q1–2hr for mild to moderate symptoms
• Continuous IV infusion: 1–20 mg q1–2hr for delirium tremens

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Page 4 — Side Effects and Adverse Effects of Midazolam

Side effects include:

• CNS: Retrograde amnesia, euphoria, confusion, headache, slurred speech, paresthesia, tremors, weakness
• CV: Hypotension, tachycardia
• EENT: Blurred vision, nystagmus, diplopia, loss of balance
• GI: Nausea, vomiting, increased salivation
• INTEG: Urticaria, pain, pruritus at injection site, rash
• RESP: Coughing, dyspnea

Adverse effects include:

• CV: Cardiac arrest
• RESP: Apnea, bronchospasms, laryngospasm, respiratory depression

⚠ Black Box Warning: Midazolam may cause severe respiratory depression, respiratory arrest, and apnea. Initial doses in older adults should be conservative. Do not administer by rapid IV injection in neonates as it may cause severe hypotension or seizures.

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Page 5 — Contraindications with Cyclobenzaprine

Cyclobenzaprine use is contraindicated in:

• Patients with cardiovascular disorders (e.g., acute MI, AV block, bradycardia, bundle-branch block, cardiac arrhythmia, hypokalemia, HTN, QT prolongation on ECG, or heart failure), hyperthyroidism, hepatic impairment, narrow-angle glaucoma, or myasthenia gravis
• Patients taking monoamine oxidase inhibitors (MAOIs)
• Children and individuals with spinal cord injuries, cerebral palsy, or paralytic ileus

Use cautiously in: seizure disorders, glaucoma, prostatic hypertrophy, urinary retention, hepatic disease, breastfeeding patients, patients who drive or operate machinery, patients who concurrently ingest alcohol or other CNS depressants, older adults, and patients with regular sunlight/UV exposure.

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Page 6 — Interactions with Cyclobenzaprine

Concomitant use with other sedative drugs or herbal supplements can result in increased CNS depression. Extreme caution should be used to avoid accidental overdose; discontinue concomitant use or decrease dosage of either drug.

Category	Interaction
Drugs	Alcohol, barbiturates, tricyclic antidepressants, sedative-hypnotics, and other CNS depressants increase sedation. SSRIs, SNRIs, tricyclics, triptans, fentanyl, buspirone, and tramadol may lead to serotonin syndrome. Class IA/III antidysrhythmics and other QT-prolonging products may prolong QT interval.
Herbs	Kava, chamomile, hops, valerian, gotu kola, SAMe, and St. John's wort may interact.
Food	No known interactions.

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Page 7 — Dosage and Administration of Cyclobenzaprine

Cyclobenzaprine is available in oral formulations as immediate-release tablets and extended-release capsules.

Adults and Adolescents ≥15 years (Immediate Release)

• 5 mg three times per day
• May increase to 10 mg three times per day if needed

Adults (Extended Release)

• 15–30 mg daily
• Maximum dose: 30 mg/day for 3 weeks
• With hepatic disease: maximum dose is 5 mg daily; titrate slowly

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Page 8 — Side Effects and Adverse Effects of Cyclobenzaprine

Main side effects include:

• CNS: Feelings of euphoria, lightheadedness, headache, slurred speech, dizziness, drowsiness, fatigue, confusion, and muscle weakness. Many are transient and will subside over time.
• GI/GU: Weight gain, dry mouth, diarrhea, constipation, GI upset, sexual difficulties in males
• CV: Tachycardia, hypotension

Severe adverse reactions: angioedema, myocardial infarction, seizures, and ileus.

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Page 9 — Interventions for Midazolam and Cyclobenzaprine

General (Both Drugs):

• Record vital signs before administration; report any abnormal results.
• Observe the patient for any CNS side effects or CNS depression (e.g., dizziness, hypotension, decreased respirations).
• Assist with ambulation if necessary to prevent falls.

Midazolam-Specific:

• When administering IV midazolam, monitor vital signs continuously; have emergency equipment and oxygen available.
• The patient may experience anterograde amnesia and may require frequent re-orientation.
• Provide assistance with ambulation until the drowsy period ends.

Cyclobenzaprine-Specific:

• Administer cyclobenzaprine with food or milk if GI upset occurs.

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Page 10 — Patient Teaching for Midazolam and Cyclobenzaprine

Midazolam

• Teach the patient what to expect when receiving this medication.
• Inform patient they may experience retrograde amnesia.
• Teach the patient not to get up without assistance — may experience weakness and lightheadedness.
• Advise not to drive or operate heavy machinery until the medication has worn off.
• If used for surgery or a procedure, the patient must have someone to drive them to their residence.

Cyclobenzaprine: General Teaching

• Teach that the muscle relaxant should not be abruptly stopped — should be tapered over 1 week to avoid rebound muscle spasms.
• Advise not to drive, operate heavy machinery, or make important legally-binding decisions while taking muscle relaxants (sedative effects may cause drowsiness).
• Inform patient that most muscle relaxants for acute spasms are taken for no longer than a few weeks.
• Teach patient to avoid combining with alcohol and CNS depressants.
• Advise patient to avoid OTC medications (e.g., cough preparations, antihistamines) unless directed by health care provider.
• Advise that these drugs must be used cautiously in pregnant women and nursing mothers.

Cyclobenzaprine: Side Effects

• Encourage patient to report side effects: nausea, vomiting, dizziness, fainting, headache, and diplopia.
• Take muscle relaxants with food to avoid GI upset.
• Sugarless gum or sips of water may relieve dry mouth.

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Page 11 — Evaluation for Midazolam and Cyclobenzaprine

Midazolam

• Evaluate level of sedation after administration.
• Monitor vital signs, respiratory rate, and oxygen saturation during administration.
• Monitor level of consciousness during and after administration.

Cyclobenzaprine

• Evaluate effectiveness using a pain scale to determine whether muscular pain and/or spasms have diminished.
• Be alert to both verbal and nonverbal indications of pain and/or pain relief.
• Evaluate the patient for: decreased stiffness and swelling, increased joint mobility, reduced joint tenderness, and improved grip strength.

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Page 12 — Case Study

Patient: Ms. Wilson, 22-year-old female, presents to pain clinic with:

• Stiffness in neck, limited cervical range of motion
• Shooting pains down right arm with numbness and tingling in index finger of right hand
• Duration: approximately 3 weeks
• Physical therapy twice weekly without relief

Orders:

• Cyclobenzaprine 5 mg PO tid prn for muscle spasms
• Ibuprofen 600 mg PO tid
• MRI of the cervical spine ordered
• Follow-up scheduled after MRI

(Clinical case demonstrating cyclobenzaprine use for musculoskeletal-origin neck and cervical spine muscle spasms in a young adult.)

Notes: Overview of Central Nervous System Stimulants

Course: Central Nervous System Stimulant Therapy / Pharmacokinetics and Pharmacodynamics of CNS Stimulant Drugs

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Page 1: Overview of Central Nervous System Stimulants

The spinal cord and brain are parts of the CNS, which controls bodily functions. Approved uses for CNS stimulants are limited to the reversal of respiratory distress and the treatment of ADHD in children. Anorexiants are used for weight loss.

Major Classes of CNS Stimulants:

Class	Action	Examples
Amphetamines/amphetamine-like drugs	Stimulate the cerebral cortex of the brain	Prototype: Methylphenidate; Others: Atomoxetine, modafinil
Anorexiants	Stimulate the satiety centers in the brain causing appetite suppression	Prototype: Phentermine; Others: Benzphetamine, methamphetamine, diethylpropion
Analeptics and caffeine	Act on the brainstem and medulla to stimulate respiration	Prototype: Doxapram; Other: Caffeine

⚡ Best Practice Pearls:

• Anorexiants and amphetamines are the most commonly abused CNS stimulants.
• Dependence or tolerance can develop, requiring larger doses over time for the same effect.
• These medications should only be used short-term (no longer than 12 weeks).
• Withdrawal and depression can result if the drug is stopped suddenly after the dose has been gradually increased.

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Page 2: Pharmacokinetics of Methylphenidate

The most commonly prescribed drug for ADHD is methylphenidate, an amphetamine-like drug. It is typically given orally but can also be prescribed as a transdermal patch worn for 9 hours, which provides slow release and a steady plasma concentration over time.

Property	Details
Absorption	Slowly absorbed through the GI tract (oral) and skin (transdermal)
Distribution	10%–33% protein bound
Metabolism	Metabolized in the liver
Excretion	90% excreted unchanged in urine

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Page 3: Pharmacodynamics of Methylphenidate

Actions of amphetamines involve both norepinephrine and dopamine in both the central and sympathetic nervous systems.

Mechanism of Action: Amphetamines stimulate the release of norepinephrine and dopamine from the brain and sympathetic nervous system (peripheral nerve terminals) and inhibit the reuptake of these transmitters.

Therapeutic Uses: Methylphenidate helps correct ADHD by decreasing hyperactivity and improving attention span. It may also be prescribed for narcolepsy. Amphetamine-like drugs are considered generally safer and more effective than amphetamines for treating ADHD. When methylphenidate does not work, amphetamine, dextroamphetamine, or methamphetamine may be prescribed for narcolepsy or ADHD.

Pharmacodynamic Profile:

Property	Details
Onset (PO)	0.5–1 hour
Peak plasma concentration	Regular release: 1.9 hours; Extended release: 4.7 hours; Transdermal: 9 hours (initial); decreases with continued use
Duration of action	Regular release: 3–6 hours; Extended release: 8 hours
Half-life	1.3–7.7 hours

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Page 4: Pharmacokinetics of Phentermine

Phentermine is used as an appetite suppressor for weight loss under a health care provider's supervision.

Property	Details
Absorption	Well absorbed from the GI tract
Distribution	Protein binding ~16%
Metabolism	Metabolized by the liver
Excretion	In the urine, mostly unchanged

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Page 5: Pharmacodynamics of Phentermine

The pharmacodynamics of anorexiants help the nurse understand where in the body drugs have their actions, the time frame of those actions, and the reasons for administration.

Mechanism of Action: Anorexiants suppress the appetite by stimulating the limbic and hypothalamic regions of the brain.

Therapeutic Uses: Phentermine helps with weight loss by decreasing hunger and making the individual feel full for a longer period of time. Must be used under the supervision of a health care provider. A patient should not take the drug longer than 12 weeks. Although anorexiants do not have the same serious side effects as amphetamines, a nutritious diet, behavior modifications, and exercise should be encouraged instead of appetite suppressant use.

Pharmacodynamic Profile:

Property	Details
Onset	1–2 hours
Peak	3–4 hours
Duration	Unknown
Half-life	19–25 hours

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Page 6: Overview of Analeptics

Analeptics affect the brainstem and spinal cord. The primary therapeutic effect is respiratory stimulation.

Xanthines (methylxanthines) are an analeptic subgroup containing theophylline and caffeine. Large doses of caffeine stimulate respiration and can stimulate the CNS depending on the dose. Newborns may be given caffeine or theophylline to increase respiration if respiratory distress occurs. Theophylline can also be used to promote bronchiole relaxation.

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Page 7: Pharmacokinetics of Doxapram

Doxapram is an analeptic used for postanesthesia respiratory depression.

Property	Details
Absorption	Administered intravenously (IV)
Distribution	Throughout the body
Metabolism	Metabolized by the liver
Excretion	Metabolites excreted in the urine

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Page 8: Pharmacodynamics of Doxapram

Doxapram stimulates an increase in the patient's tidal volume and a small increase in respiratory rate. This effect is mediated via the cardiac carotid chemoreceptors.

Property	Details
Onset (IV)	20–40 seconds
Peak plasma concentration	1–2 minutes
Duration of action	5–12 minutes
Half-life	4–12 hours

Notes: Nursing Process Related to Central Nervous System Stimulant Therapy

Course: Central Nervous System Stimulant Therapy

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Page 1: Pre-Administration Assessment for CNS Stimulants

Before CNS stimulant administration, the nurse must perform a detailed patient assessment, document concurrent drug use and preexisting conditions, and obtain baseline vital signs for future comparison. Patients with cardiac disease need close monitoring because CNS stimulants may reverse the effects of antihypertensives.

Methylphenidate:

• Evaluate for history of heart disease, hypertension, hyperthyroidism, parkinsonism, or glaucoma (usually contraindicated).
• Assess mental status (mood, affect, aggressiveness).
• Evaluate pediatric patient's baseline height, weight, and growth pattern (methylphenidate may cause weight loss).
• Monitor CBC, differential WBCs, and platelets before and during therapy.

Phentermine:

• Determine if patient has a history of drug abuse; allergy to sympathomimetic amines; is taking/has taken an MAOI in the past 14 days; has cardiovascular disease, hyperthyroidism, or glaucoma; or is pregnant — these are contraindications.
• Obtain weight, waist, and hip circumference for future comparisons.

Doxapram:

• Assess for seizure disorders, cardiovascular disorders, severe hypertension, pulmonary embolism, pneumothorax, and acute bronchial asthma (contraindications).
• Take and document vital signs, particularly respirations.

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Page 2: Contraindications and Interactions with Methylphenidate

Methylphenidate should not be given until the patient's history has been reviewed for contraindications and drug interactions.

Contraindications: Hyperthyroidism, anxiety, Tourette syndrome, glaucoma, psychosis, mental depression, or hereditary fructose intolerance.

Use with Caution in: Children younger than 6 years old; pregnant women; patients requiring radiographic contrast administration; patients with psychosis, depression, substance abuse, myocardial infarction, alcoholism, bipolar disorder, dysrhythmias, or seizures.

Drug Interactions:

• Sympathomimetics (e.g., pseudoephedrine) or psychostimulants (e.g., caffeine) → increased stimulatory effects (irritability, nervousness, tremors, insomnia).
• Methylphenidate may reduce the effectiveness of antihypertensives.
• Concurrent use with MAOIs → hypertensive crisis.
• Methylphenidate decreases metabolism and increases serum levels of oral anticoagulants, barbiturates, antiseizure medications, and tricyclic antidepressants.

Food Interactions: Foods with caffeine increase methylphenidate effects. Nuts, guarana, horsetail, yerba mate, and yohimbe increase CNS stimulation.

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Page 3: Dosing and Administration of Methylphenidate

Food affects absorption rate — methylphenidate should be given 30 to 45 minutes before meals.

For Treatment of ADHD:

• Children over 6: PO: 5–10 mg before breakfast and lunch; increase by 5–10 mg weekly; max 60 mg/day. PO sustained-release: 18 mg/day; max 2 mg/kg/day.
• Adults: PO: 20–30 mg/day in divided doses before breakfast and lunch; max 60 mg/day. PO sustained-release: 18–36 mg once daily; max 72 mg/day.

For Treatment of Narcolepsy:

• Adults: PO: 10–60 mg/day in 2–3 divided doses 30 minutes before meals.

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Page 4: Side Effects and Adverse Effects of Methylphenidate

	Side Effects	Adverse Effects
CNS	Anxiety, insomnia, dizziness, hyperactivity, talkativeness	Seizures, psychotic episodes, malignant neuroleptic syndrome
GI	Anorexia, abdominal pain
CV		Tachycardia, hypertension, palpitations, chest pain
ENDO		Transient weight loss in children, growth suppression
HEMA		Leukopenia, anemia
MISC		Rhabdomyolysis

Life-Threatening Adverse Effects: Exfoliative dermatitis, stroke, thrombocytopenia, angioedema, and hepatotoxicity.

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Page 5: Contraindications and Interactions with Phentermine

Contraindications: History of drug abuse; allergy to sympathomimetic amines; taking/taken an MAOI in the past 14 days; cardiovascular disease; hyperthyroidism; glaucoma; pregnancy or plans to become pregnant. Use with caution in patients with thyroid disease.

Interactions:

• Drugs that increase phentermine's effect: caffeine, amphetamines, and CNS stimulants.
• Alcohol decreases the effect of phentermine.

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Page 6: Dosing, Administration, Side Effects, and Adverse Effects of Phentermine

Dosing: Carefully monitored by the prescribing health care provider.

• PO: 8 mg given three times per day, 30 minutes before meals.
• PO: 15–37.5 mg daily 1–2 hours after breakfast.

Side Effects and Adverse Effects:

Body System	Side Effects	Adverse Effects
CNS	Dizziness, fatigue, irritability, headache	Suicidal ideation, paresthesia
CV	Palpitations	Tachycardia, hypertension
INTEG	Flushing
GI/GU	Constipation, diarrhea, abdominal pain, nausea, decreased libido	Impotence
EENT	Dry mouth, unpleasant taste	Facial swelling

Life-Threatening: Pulmonary hypertension, myocardial infarction, cardiac failure.

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Page 7: Contraindications and Interactions with Doxapram

Contraindications: Seizure disorders, cardiovascular disorders, severe hypertension, pulmonary embolism, pneumothorax, and acute bronchial asthma.

Use with Caution in: Patients with bronchial asthma, cardiac tachydysrhythmias, cerebral edema or increased intracranial pressure, hyperthyroidism, or pheochromocytoma.

Interactions:

• Anesthetics (cyclopropane, enflurane, halothane) must be discontinued 10 minutes before administration of doxapram.
• Use caution with MAOIs and sympathomimetic drugs — can increase vasoconstrictive effects.
• Neuromuscular-blocking drug residual effects may be masked; monitor carefully.
• Alcohol should not be used while taking doxapram.

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Page 8: Dosing, Administration, Side Effects, and Adverse Effects of Doxapram

Dosing and Administration (for postanesthesia respiratory stimulation):

• Adults: 0.5–1 mg/kg body weight as a single IV injection (not to exceed 1.5 mg/kg), or several injections every 5 minutes, not to exceed 2 mg/kg total.

Side Effects:

Body System	Side Effects
CNS	Headache, dizziness, confusion
CV	Tachycardia
INTEG	Flushing, sweating, pruritus
GI/GU	Nausea, vomiting, diarrhea, spontaneous urination, urinary retention
RESP	Dyspnea, cough

Adverse Effects: Laryngospasms.

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Page 9: Interventions for CNS Stimulants

General Nursing Interventions (all CNS stimulants):

• Monitor vital signs and report irregularities.
• Advise patients to taper down the dose before discontinuing (do not stop abruptly).
• Monitor for side effects: insomnia, restlessness, nervousness, tremors, irritability.
• Report adverse effects of tachycardia and elevated blood pressure to the HCP.

Methylphenidate-specific: Evaluate height, weight, and growth of children throughout therapy. Monitor for withdrawal symptoms (nausea, vomiting, headache, irritability) upon discontinuation.

Phentermine-specific: Encourage taking drug before breakfast (not at night) to decrease insomnia. Evaluate weight and body measurements throughout therapy. Monitor for suicidal ideation and paresthesia.

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Page 10: Patient Teaching for Methylphenidate

Because this drug is often prescribed to children, parents/caregivers must be included.

General Teaching:

• Use sugarless gum to relieve dry mouth.
• Record weight twice a week; report any weight loss.
• Avoid driving/hazardous equipment if tremors, nervousness, or increased heart rate occur.
• Do not abruptly discontinue; taper dose to avoid withdrawal symptoms.
• Read OTC product labels — many contain caffeine (high caffeine levels could be fatal).
• Nursing mothers should avoid all CNS stimulants (excreted in breast milk; may cause hyperactivity in infants).
• Seek counseling for children with ADHD; drug therapy alone is not appropriate. Notify school nurse of drug therapy regimen.
• Long-term use may lead to drug abuse; keep medication secure and do not share.
• Advise regular blood draws during therapy.

Side Effects Teaching: Teach about serious side effects (tachycardia, palpitations); monitor children for onset of Tourette syndrome; do not take medication after 6 p.m. to avoid insomnia.

Diet: Take drug before meals. Avoid alcohol. Avoid caffeine-containing foods and drinks. Provide nutritious breakfasts (drug may have anorexic effects).

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Page 11: Patient Teaching for Phentermine

General Teaching:

• Contact HCP if suicidal ideations occur.
• Use sugarless gum or water for dry mouth.
• Avoid activities requiring mental alertness until drug effects are known.
• Do not abruptly discontinue; taper dose.
• Read OTC labels — many contain caffeine (not recommended with this medication).
• Long-term use may lead to drug abuse; keep secure and do not share.
• Avoid antihistamines, caffeine, or any CNS stimulant medications.

Side Effects Teaching: Report serious adverse effects (tachycardia, suicidal ideation); do not take after 6 p.m. to avoid insomnia.

Diet: Take drug before meals. Avoid alcohol. Avoid foods/drinks containing caffeine or any stimulants.

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Page 12: Patient Teaching for Doxapram

All teaching should include the patient and family. (Doxapram is only used in the emergency department.)

General Teaching:

• Inform patient and family about the drug and why it was administered.
• Explain that frequent monitoring of vital signs, reflexes, and arterial blood gases will be done before giving and every 30 minutes afterwards until stable.
• Assure patient and family that the nurse is closely monitoring for potential side effects.

Side Effects to Monitor: Dizziness, confusion, dyspnea, cough, spontaneous urination, urinary retention, and laryngospasms.

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Page 13: Evaluation for CNS Stimulants

Methylphenidate: Evaluate therapy effectiveness as evidenced by improved attention span and reduced hyperactivity. Evaluate for presence/subsidence of adverse effects. Evaluate patient's knowledge level about therapy.

Phentermine: Evaluate effectiveness as evidenced by weight loss and decrease in body fat. Evaluate for side effects/adverse reactions. Evaluate if the patient is taking the medication as prescribed.

Doxapram: Evaluate effectiveness as evidenced by increased PaO2, tidal volume, and respiratory rate. Evaluate for side effects/adverse reactions.

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Page 14: Case Study

Christine, a 13-year-old female, is diagnosed with ADHD after 14 months of inability to focus on school assignments and dance practice. She is prescribed methylphenidate 5 mg twice daily for 2 weeks. If she shows signs of improvement, the dose will be increased to 10 mg twice daily.

Notes: Overview of Antiseizure Drugs

Course: Anticonvulsant Therapy / Pharmacokinetics and Pharmacodynamics of Anticonvulsant Drugs

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Page 1: Overview of Antiseizure Drugs

Antiseizure drugs stabilize nerve cell membranes and suppress abnormal electric impulses in the cerebral cortex. They prevent seizures but do not eliminate the cause or provide a cure. Antiseizure drugs are classified as CNS depressants. Phenytoin is the prototype drug for this lesson.

Classification — Types of antiseizure drugs:

• Hydantoins (phenytoin)
• Long-acting barbiturates (phenobarbital, mephobarbital, primidone)
• Succinimides (ethosuximide)
• Benzodiazepines (diazepam, clonazepam)
• Carbamazepine
• Valproate (valproic acid)

Mechanisms of Action (3 ways):

1. Hydantoins, carbamazepine, valproic acid — Suppress sodium influx by binding to the sodium channel when inactivated, prolonging inactivation and preventing neuron firing.
2. Valproic acid, succinimides — Suppress calcium influx, preventing the electric current generated by calcium ions to the T-type calcium channel.
3. Benzodiazepines, barbiturates, valproic acid — Increase the action of GABA (gamma-aminobutyric acid), which inhibits neurotransmitters throughout the brain.

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Page 2: Pharmacokinetics of Phenytoin

Phenytoin is a hydantoin discovered in 1938 — the first anticonvulsant used to treat seizures and still the most commonly used drug for controlling seizures.

Property	Details
Absorption	Slowly absorbed from the small intestine
Distribution	Highly protein bound (90%–95%); a decrease in serum protein or albumin can increase the free phenytoin serum level
Metabolism	Metabolized to inactive metabolites
Excretion	Inactive metabolites excreted in urine

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Page 3: Pharmacodynamics of Phenytoin

Phenytoin and other hydantoins reduce seizures by inhibiting sodium influx, thereby stabilizing cell membranes and reducing repetitive neuronal firing. Oral (PO) phenytoin is most commonly prescribed as a sustained-release (SR) capsule.

Pharmacodynamic Profile:

Property	Details
Onset of Action (PO)	30 minutes to 2 hours
Peak Serum Concentration	1.5–6 hours; 4–12 hours for SR capsules
Steady State of Serum Concentration	7–10 days
Duration of Action	Dependent on the half-life; up to 72 hours
Half-Life	~24 hours for small-to-average dose; can range from 7–42 hours

Section 4 Notes: Nursing Process Related to Anticonvulsant Therapy

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Page 1 — Pre-Assessment Administration of Phenytoin

Before starting a patient on anticonvulsant therapy, complete the following assessments:

• Review history of seizure disorder (intensity, frequency, duration, loss of consciousness).
• Obtain a health history including current drugs and herbs the patient uses. Report and document any probable drug-drug or herb-drug interactions.
• Assess the patient's knowledge regarding medication regimen.
• Perform complete blood count (CBC) before beginning therapy and periodically during therapy.
• Check urinary output to determine whether adequate (>1500 mL/d).
• Determine laboratory values related to renal and liver function.
  • If both blood urea nitrogen (BUN) and creatinine levels are elevated, a renal disorder should be suspected.
  • Elevated serum liver enzymes (alkaline phosphatase, alanine aminotransferase, gamma-glutamyl transferase, 59-nucleotidase) indicate a hepatic disorder.

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Page 2 — Contraindications with Phenytoin

Phenytoin is teratogenic and should only be used as a last resort for seizure control during pregnancy.

Contraindications:

• Hypersensitivity to hydantoins
• Concurrent use of delavirdine
• Intravenous (IV) (additional): Second- and third-degree AV block, sinoatrial block, sinus bradycardia, Adams-Stokes syndrome

Cautions:

• Porphyria
• Renal/hepatic impairment
• Those at increased risk for suicidal behavior/thoughts
• Older adult/debilitated patients
• Low serum albumin
• Underlying cardiac disease
• Hypothyroidism
• Patients of Asian descent

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Page 3 — Interactions with Phenytoin

Phenytoin has a high incidence of interaction with other substances. The nurse should complete and document a thorough health history to screen and monitor for interactions.

Drug/Substance	Possible Interaction
Alcohol, other CNS depressants	Increased CNS depression
Amiodarone, cimetidine, disulfiram, fluoxetine, isoniazid, sulfonamides	Decreased metabolism of phenytoin → increased drug levels and risk for toxicity
Calcium-containing antacids	Decreased absorption of phenytoin
Glucocorticoids, anticoagulants, oral contraceptives	Decreased effects of these drugs
Lidocaine, propranolol	Increased cardiac depressant effects
Valproic acid	Decreased metabolism → increased concentration of phenytoin
Xanthines	Increased metabolism → decreased effects of xanthines
Herb: Evening primrose	Decreased seizure threshold
Herb: Gotu kola, kava, St. John's wort, valerian	Increased CNS depression
Food	None known
Laboratory values	Increased serum glucose, GGT, alkaline phosphates

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Page 4 — Dosage and Administration of Phenytoin

Phenytoin administration requires detailed monitoring.

Dosage: Status Epilepticus

Population	Loading Dose	Maintenance Dose
Adults/Older Adults	IV: 15–20 mg/kg	IV/PO: 100 mg q6–8 hrs; Range: 300–600 mg/day
Infants/Children	IV: 15–20 mg/kg	IV/PO: 5 mg/kg/day in 2–3 divided doses; Range: 4–8 mg/kg; max 300 mg/day
Neonates	IV: 10 mg/kg	IV/PO: 5 mg/kg/day in 2 divided doses; Range: 4–8 mg/kg/day

Dosage: Seizure Control

• Adults/Older Adults/Children: Loading dose PO: 15–20 mg/kg in 3 divided doses, 2–4 hours apart; Maintenance same as for status epilepticus
• No dosage adjustment for renal/hepatic impairment

Administration: IV

• Reconstitution: May give undiluted or dilute with 0.9% NaCl to a concentration of ≥5 mg/mL
• Rate: Adults: 50 mg over 1 min; Older adults with cardiovascular conditions: 20 mg/min; Neonates: ≤1–3 mg/kg/min
• Severe hypotension or cardiovascular collapse can occur if rate exceeds 50 mg/min in adults
• IV toxicity: CNS depression and cardiovascular collapse
• Because phenytoin must be given slowly, a benzodiazepine (e.g., lorazepam) is typically given concurrently with the loading dose for quicker onset
• ⚠️ Safe Practice Alert: Give by IV push or IV piggyback. IV push is very painful (chemical irritation of vein due to alkalinity). Flush vein with sterile saline solution through the same IV needle and catheter after each IV push.

Administration: PO

• Give with food if GI distress occurs
• Tablets may be chewed
• Shake oral suspension well before using
• Separate administration of phenytoin from antacids or tube feeding by 2 hours

Incompatibilities: IV

• Because IV phenytoin is incompatible with numerous drugs, always give only with saline
• Examples of IV incompatibilities: diltiazem, dobutamine, enalapril, heparin, hydromorphone, insulin, lidocaine, morphine, nitroglycerin, norepinephrine, potassium chloride, propofol

Storage

• Precipitate may form if parenteral form is refrigerated (dissolves at room temperature)
• Slight yellow discoloration does not affect potency; do NOT use if solution is cloudy or precipitate forms
• Discard if not used within 4 hours of preparation

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Page 5 — Side Effects and Adverse Effects of Phenytoin

Monitor closely, especially if patient is receiving phenytoin for the first time.

Key adverse effects:

• Abrupt withdrawal may precipitate status epilepticus
• Blood dyscrasias, lymphadenopathy, and osteomalacia (due to interference with vitamin D metabolism)
• Toxic level (≥25 mcg/mL): ataxia, nystagmus, diplopia → as level increases → extreme lethargy → coma

Body System	Side Effects	Adverse Effects
CNS	Drowsiness, lethargy, insomnia, confusion, slurred speech, irritability, headache, muscle twitching	Suicidal tendencies
CV	—	Cardiac arrest, ventricular fibrillation, bradycardia
HEMA	—	Agranulocytosis, leukopenia, aplastic anemia, thrombocytopenia, megaloblastic anemia
EENT	Gingival hyperplasia	—
GI	Constipation, dizziness, nausea	—
ITEG	Hirsutism, coarsening of facial features	Lupus erythematosus, Stevens-Johnson syndrome, toxic epidermal necrolysis
MISC	Hypersensitivity reaction (fever, rash, lymphadenopathy)	—

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Page 6 — Patient Teaching for Phenytoin

When caring for a patient on anticonvulsant therapy, provide the following teaching:

• Reinforce the importance of taking medication as directed — stopping abruptly can cause rebound seizures
• Urine may be a harmless pinkish red or reddish brown
• Maintain good oral hygiene and use a soft toothbrush to prevent gum irritation and bleeding
• Report symptoms of sore throat, fever, bruising, and nosebleeds — may indicate a blood dyscrasia
• Inform the health care provider of adverse reactions such as gingivitis, nystagmus, slurred speech, rash, and dizziness (Stevens-Johnson syndrome begins with a rash)
• Patients with diabetes: monitor serum glucose more closely — phenytoin may inhibit insulin release, increasing glucose levels
• Avoid alcohol (CNS depressant)
• Blood levels will need to be monitored regularly — phenytoin can reach toxic levels in the blood

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Page 7 — Evaluation for Phenytoin

While caring for patients taking antiseizure medication:

• Monitor closely for symptoms of seizure activity
• Monitor for signs/symptoms of depression, suicidal tendencies, and unusual behavior
• Monitor CBC with differential, renal function, LFT, and BP (with IV use); repeat CBC 2 weeks after therapy initiation and 2 weeks after maintenance dose administration
• Assist with ambulation if drowsiness or lethargy occurs
• Monitor for therapeutic serum level (10–20 mcg/mL); toxic level is >20 mcg/mL
• Evaluate frequently for physical symptoms and follow laboratory values for medication-related changes
• Observe frequently for recurrence of seizure activity
• Assess for clinical improvement (decrease in intensity/frequency of seizures)

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Page 8 — Case Study: Mr. Briggs

Patient: Mr. Briggs, 50-year-old male

Presentation: First-time grand mal seizure → admitted to ICU for monitoring and evaluation

Medical History: Hypertension, smoking, hyperlipidemia

Treatment in ED:

• 4 mg IV lorazepam to stop the seizure
• Loading dose: 700 mg IV phenytoin

Current Vital Signs: HR 100, RR 22, BP 190/100, T 99.1°F, SaO₂ 96% on 2 L oxygen, no pain currently

Status: Postictal (after-seizure) state; wife at bedside

Section 5 Notes: Pharmacokinetics and Pharmacodynamics of Drugs Used in the Management of Specific Neurodegenerative Disorders

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Page 1 — Overview of Parkinson's Disease

Parkinsonism (Parkinson's disease) is a progressive neurologic disorder that affects movement. It is the result of an imbalance of dopamine and acetylcholine. Parkinsonism results when the brain stops producing the neurotransmitter dopamine because of the deterioration of neurons in the substantia nigra. The cause of this neuron degeneration is idiopathic (unknown).

Symptoms of Parkinson's Disease:

• Tremor — a shaky limb or constant movement of hands or fingers
• Bradykinesia — slowed movement
• Rigid muscles — muscle stiffness, limited range of motion, and pain
• Impaired posture and balance — controlled by the extrapyramidal motor system
• Loss of automatic movements — unconscious movements such as blinking and smiling
• Speech or writing changes — less inflections with speech or difficulty writing

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Page 2 — Classification of Drugs for Parkinson's Disease

Therapeutic goal: Improve the patient's ability to carry out activities of daily living (ADLs). Prototype drug: Carbidopa-levodopa (a dopaminergic).

Drug Class	Mechanism of Action	Examples
Dopaminergics	Affect dopamine content of the brain. Levodopa is converted into dopamine by nerve cells in the brain. Combined with carbidopa, more levodopa reaches the brain and a lower dose is required.	Carbidopa-levodopa
Dopamine Agonists	Act directly on dopamine receptors of nerve cells in the brain by stimulating them. Exact mechanism not fully understood.	Amantadine, bromocriptine, pramipexole, ropinirole HCl
MAO-B Inhibitors (Monoamine oxidase B)	Inhibit monoamine oxidase (enzyme that breaks down dopamine) → dopamine is available for reabsorption by neurons	Selegiline HCl, rasagiline
COMT Inhibitors (Catechol-o-methyl transferase)	Block COMT (enzyme that breaks down dopamine) → prolongs effect of levodopa; higher brain concentration allows lower levodopa dose	Entacapone, tolcapone
Anticholinergics / Antiparkinsonian agents	Inhibit or reduce activity of acetylcholine. ACh is balanced by dopamine; becomes excessive when dopamine is depleted, contributing to motor symptoms.	Trihexyphenidyl, benztropine, biperiden

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Page 3 — Pharmacokinetics of Carbidopa-Levodopa

Levodopa is rapidly broken down into dopamine in the intestines and peripheral tissues. Most is converted peripherally, leaving only 2% of levodopa to be transported to the brain. This increases to 10% when carbidopa is administered (prevents decarboxylation of peripheral levodopa). Because more is available to the brain, a lower dose is required for therapeutic effect.

Parameter	Details
Absorption	PO: Well-absorbed
Distribution	PB: Carbidopa: 36%; Levodopa: Unknown
Metabolism	Metabolized in the periphery by decarboxylase enzymes and COMT
Excretion	In urine as metabolites

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Page 4 — Pharmacodynamics of Carbidopa-Levodopa

Carbidopa and levodopa are dopaminergics combined for more effective parkinsonism therapy. Carbidopa enhances effects of levodopa by preventing levodopa decarboxylation, resulting in increased availability of levodopa for transport to the brain. More levodopa crosses the blood-brain barrier and is converted into dopamine.

Pharmacodynamic Profile:

Parameter	Details
Onset	Immediate release: 30 min; Extended release: 4–5 hours
Peak	Immediate release: 1–3 hours; Extended release: 2–3 hours
Duration	Unknown
Half-life	1–2 hours

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Page 5 — Overview of Alzheimer's Disease

Alzheimer's disease is a type of dementia, usually presenting after age 65, which is progressive and cannot be cured. Approximately 5% develop symptoms before age 65 (some between ages 30–40 — termed early onset). It causes problems with memory, thinking, and behavior due to loss of neurons.

Physiologic changes thought to cause Alzheimer's disease:

• Acetylcholine deficiency due to cholinergic neuron degeneration
• Neuritic plaques: Apolipoprotein E₄ (apo E₄) binds beta-amyloid within the plaques
• Neuronal injury/death: High levels of beta-amyloid protein contribute to this
• Neurofibrillary tangles

The specific cause is not fully understood. It is believed to involve a combination of environmental, genetic, health, and lifestyle factors.

Drugs for Treatment: Although no cure exists, some medications treat symptoms. Classification: acetylcholinesterase (AChE) inhibitors (also called cholinesterase inhibitors), including rivastigmine, tacrine, and donepezil. Rivastigmine is the prototype drug for this lesson.

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Page 6 — Pharmacokinetics of Rivastigmine

Rivastigmine is available in oral and transdermal doses. When given with food, absorption is enhanced. AChE converts rivastigmine into inactive metabolites (unlike other cholinesterase inhibitors which are converted by liver enzymes). Dose is administered twice daily due to short half-life and is slowly increased. Transdermal administration produces more constant blood levels than oral.

Parameter	Details
Absorption	PO: GI tract (faster on empty stomach)
Distribution	Protein binding: 40%
Metabolism	Metabolized by cholinesterase-mediated hydrolysis
Excretion	Urine

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Page 7 — Pharmacodynamics of Rivastigmine

Rivastigmine and other AChE inhibitors stop the breakdown of acetylcholine, allowing more to be available to the neuron receptors. These drugs are FDA-approved for the treatment of Alzheimer's disease.

Rivastigmine is prescribed for mild to moderate Alzheimer's disease. As an AChE inhibitor, it improves cognitive function through its capability to access the CNS and increase cholinergic transmission. Studies show it improves memory and slows disease progression.

Pharmacodynamic Profile:

Parameter	PO	Transdermal
Onset	Unknown	0.5–1 hour
Peak	1 hour	8–16 hours
Duration	Unknown	24 hours
Half-life	1 hour	1 hour

Section 6 Notes: Nursing Process Related to Drugs Used in the Management of Specific Neurodegenerative Disorders

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Page 1 — Pre-Administration Assessment for Carbidopa-Levodopa

Although Parkinson's disease cannot be cured with carbidopa-levodopa, this drug can help patients improve their ability to perform ADLs. A nursing assessment before administration is important.

Determine Baseline Data:

• Vital signs
• Laboratory tests: CBC, liver function test (LFT), prolactin level, pregnancy test
• Symptoms: Current motor symptoms and any impairment to ADLs

Identify High-Risk Patients:

• Review the patient's medical history for contraindications or conditions requiring caution
• Review the patient's medication history; report possible interactions

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Page 2 — Contraindications and Interactions with Carbidopa-Levodopa

A full medical history of the patient, including current drug therapies, will help determine if levodopa can be used with caution or if a different drug is needed.

Contraindications: Glaucoma, malignant melanoma

Cautions: History of MI, dysrhythmias, asthma, emphysema, renal/hepatic impairment, pulmonary impairment, seizure disorder, peptic ulcer disease, depression

Drug Interactions:

• Anticholinergics and antipsychotics may reduce the effect of levodopa
• Tricyclic antidepressants (TCAs) may cause dyskinesia and hypertension
• Methyldopa may cause psychosis
• MAO inhibitors can result in severe hypertension
• MAO inhibitors may trigger melanoma; monitor skin for changes
• Patients with heart disease, mental disorders, or on MAO-B inhibitor therapy should use with caution

Food: Foods high in protein may reduce levodopa absorption from the intestine

Lab Values: BUN, AST, ALT, ALP, and LDH levels could show an increase

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Page 3 — Dosage and Administration of Carbidopa-Levodopa

Carbidopa-levodopa is available in three different forms and must be titrated carefully for each patient.

Form	Frequency	Max Dose	Initial Dose	Notes
Immediate Release	3–4 times/day	8 tablets (80/800 mg/day)	1 tablet of 10 or 25 mg carbidopa/100 mg levodopa	Maintenance: 25/250 mg
Extended-Release Capsules	2 times/day	1600 mg/day	50 mg carbidopa/200 mg levodopa	—
Enteral Suspension	Over 16 hours	2000 mg/day	—	—

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Page 4 — Side Effects and Adverse Effects of Carbidopa-Levodopa

Body System	Side Effects	Adverse Effects
CNS	Involuntary movements of face, tongue, arms, upper body; depression; anxiety	Involuntary movements, psychosis, depression with suicidal tendencies
CV	Orthostatic hypotension	Palpitations; Life threatening: Cardiac dysrhythmias
HEMA	—	Life threatening: Thrombocytopenia, hemolytic anemia, agranulocytosis
GI	Nausea, vomiting, anorexia, dry mouth, flatulence	Urinary retention

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Page 5 — Interventions and Evaluation for Carbidopa-Levodopa

Interventions:

• Monitor for orthostatic hypotension with initial doses (dizziness and fainting upon changing positions)
• Give with foods low in protein — high-protein diet may inhibit transport of levodopa to the CNS
• Screen for signs/symptoms of parkinsonism: stooped forward posture, shuffling gait, masked facies, resting tremors

Evaluation:

• Assess for reductions in tremor and rigidity
• Assess for improvement in balance, gait, and mobility
• Assess for side effects

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Page 6 — Patient Teaching for Carbidopa-Levodopa

General Teaching:

• If medication is stopped abruptly, an increase in parkinsonism symptoms may occur
• Symptoms may persist for weeks or months before a therapeutic goal is reached
• Extended-release tablets should not be crushed or chewed

Side Effects:

• Discolored urine or dark perspiration may occur
• Report dyskinesia (involuntary muscle movement)
• Side effects may include GI disturbances, orthostatic hypotension, and mental disturbances

Diet:

• If GI problems occur, medication can be taken with food (decreases rate of absorption)
• Patients taking selegiline: eating foods high in tyramine (red wine, yogurt, bananas, aged cheese) can result in hypertensive crisis
• Eat a low-protein diet — protein can interfere with drug reaching the brain, decreasing effectiveness

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Page 7 — Pre-Administration Assessment for Rivastigmine

Before administering rivastigmine, perform a thorough assessment to establish baseline data.

Medical History: noting renal or liver disease, peptic ulcer, COPD, asthma, or urinary obstruction; history of behavioral changes; family coping ability

Symptoms:

• Mental and physical abilities; any impairments in self-care or cognition
• Behavioral disturbances
• Aphasia
• Motor function

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Page 8 — Contraindications and Interactions with Rivastigmine

Rivastigmine can cause serious problems with certain medical histories or when combined with other drugs.

Contraindications: History of reactions to rivastigmine at application site; hypersensitivity to drugs with similar compounds (carbamate derivatives)

Cautions: Liver/renal disease, simultaneous NSAID use, peptic ulcers, urinary obstruction, sick sinus syndrome/bradycardia/supraventricular defects, COPD/asthma, patients under 50 kg (110 lb), seizure disorders, urinary retention

Drug Interactions:

• Effects of theophylline and general anesthetics are increased
• TCAs decrease effects of rivastigmine
• Cimetidine increases effects of rivastigmine
• NSAIDs increase GI effects
• Tobacco increases rivastigmine clearance

Herb: Gingko biloba may increase cholinergic effects

Lab Tests: May result in higher levels of ALT and AST

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Page 9 — Dosage and Administration of Rivastigmine

Rivastigmine can be given orally (tablet) or transdermally (patch).

Oral Dosing:

• Forms: Tablets in 1.5, 3, 4.5, and 6 mg; Solution available in 2 mg/mL
• Initial dose: 1.5-mg tablet or 0.75-mL solution twice daily; Max: 6 mg twice daily
• Administer with food to enhance absorption and reduce GI effects

Transdermal Dosing:

• Single patch applied once daily to chest, upper arm, upper back, or lower back (alternate sites)
• Strengths: 4.6, 9.5, and 13.3 mg/24 hours (max)
• Initial dose: 4.6-mg patch; Maintenance: 9.5-mg patch

⚠️ Patient Safety Alert: Remind the patient to take off the old patch before applying the new one — 50% of the dose may still be in the patch and toxicity could result. If switching from oral to patch therapy, wait until the day after the last oral dose. Initial patch dose of 4.6 mg if oral dose was <6 mg/day, or 9.5 mg if oral dose was 6–12 mg/day.

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Page 10 — Side Effects and Adverse Effects of Rivastigmine

Peripheral cholinergic side effects are more common with rivastigmine than with tacrine and donepezil when given orally.

Body System	Side Effects	Adverse Effects
CNS	Dizziness, headache, insomnia	Life threatening: Suicidal ideation; Seizures
CV	Bradycardia, hypotension with overdose	Life threatening: MI, heart failure
GI/GU	Nausea, vomiting, diarrhea, abdominal pain, anorexia, dyspepsia	Life threatening: Hepatotoxicity; Increased salivation, severe nausea/vomiting with overdose
RESP	—	Life threatening: Respiratory depression with overdose
INTEG	Diaphoresis with overdose	Life threatening: Stevens-Johnson syndrome

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Page 11 — Interventions and Evaluation for Rivastigmine

Interventions	Evaluation
Provide consistent care	Look for any medical or physical improvements which prove the effectiveness of the current drug therapy
Provide ambulation assistance
Assess for side effects common to prolonged use of AChE inhibitors
Check vital signs often for bradycardia or hypotension
Note any changes in behavior, whether better or worse

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Page 12 — Patient Teaching for Rivastigmine

General Teaching:

• Rivastigmine may improve symptoms but will not stop disease progression
• Take medication with meals; swallow whole — do not chew
• Ensure patients/care providers are aware of when medication is due and when the dose should be increased
• Explain safety techniques (keeping paths clear to avoid injury when patient may wander)
• Inform family members that support groups are available (e.g., Alzheimer's Disease and Related Disorders Association)
• Notify family members about specific foods that may help with consumption and tolerance

Side Effects — Report Immediately:

• Common: Nausea, vomiting, diarrhea, anorexia, abdominal pain, weight loss
• Report immediately: Severe nausea/vomiting, increased salivation, diaphoresis, bradycardia, hypotension, respiratory depression, and seizures
• Rise slowly to avoid orthostatic hypotension
• Regular liver tests are important because hepatotoxicity can occur

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Page 13 — Case Study: Mrs. Hill

Patient: Mrs. Hill, 72-year-old woman

Diagnosis: Recently diagnosed with Alzheimer's disease — mild to moderate symptoms

Chief Complaint: Trouble with memory loss

Prescribed Treatment: Daily oral dose of rivastigmine to help with memory loss

Section 7: Pharmacokinetics and Pharmacodynamics of Antidepressant and Mood Stabilizing Drugs

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Page 1 — Overview of Antidepressant Drugs

Antidepressant medications treat major depressive disorder (MDD) — a mood disorder lasting more than 2 weeks, characterized by persistent sadness, despair, loss of energy, withdrawal from social contact, loss of appetite, lack of interest, and insomnia or hypersomnia. There are five categories of antidepressants:

Category	Generation	Indications	Examples	Mechanism of Action
Tricyclic Antidepressants (TCAs)	1st	MDD, neuropathic pain, insomnia, eating disorders	Amitriptyline, imipramine, trimipramine, protriptyline, amoxapine, doxepin	Blocks reuptake of serotonin AND norepinephrine → elevates synaptic concentrations
Selective Serotonin Reuptake Inhibitors (SSRIs)	2nd	MDD, anxiety disorders (OCD), panic attacks, phobias, PTSD, eating disorders, selected drug abuses	Fluoxetine, sertraline (prototype), paroxetine, fluvoxamine, citalopram, escitalopram	Blocks reuptake of serotonin only → elevated synaptic concentrations
Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)	2nd	MDD, GAD, social anxiety disorder	Duloxetine (prototype), venlafaxine, desvenlafaxine	Blocks reuptake of serotonin AND norepinephrine → elevated synaptic concentrations
Atypical Antidepressants	2nd	MDD, reactive depression, anxiety	Bupropion (prototype), mirtazapine	Varies — affects one or two of three neurotransmitters (serotonin, norepinephrine, dopamine)
Monoamine Oxidase Inhibitors (MAOIs)	1st	Atypical depression, Parkinson disease	Isocarboxazid, phenelzine, selegiline, tranylcypromine	Blocks monoamine oxidase → prevents breakdown of monoamine neurotransmitters → enhances availability. Risk: hypertensive crisis triggered by tyramine-rich foods (certain cheeses, red wines, cured/smoked meats or fish)

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Page 2 — Pharmacokinetics of Antidepressants and Mood Stabilizing Drugs

Pharmacokinetics vary depending on drug class.

Drug	Absorption	Distribution	Metabolism	Excretion
Sertraline (SSRI)	Rapidly absorbed in GI tract	Widely distributed	Liver	Urine and feces
Duloxetine (SNRI)	Well absorbed throughout the body	Widely distributed	Extensively in the liver	Urine and feces
Bupropion (atypical antidepressant)	Well absorbed throughout the body	Widely distributed	Extensively in the liver	Urine and feces

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Page 3 — Pharmacodynamics of SSRIs

Prototype drug: Sertraline

Mechanism of Action: SSRIs are based on the theory that depression results from a deficiency in serotonin neurotransmission.

• Selectively block the reuptake of serotonin
• Increase the concentration of serotonin within the synapses and enhance serotonin availability
• Increase activation of postsynaptic serotonin receptors and enhance neurotransmission

Clinical Response Time: Biochemical effect occurs within hours of starting medication; however, the actual clinical response takes about 4 weeks.

Therapeutic Uses:

• Approved: MDD, OCD, panic disorder, phobias, PTSD, PMDD (sertraline), other forms of anxiety including social anxiety disorder (sertraline)
• Off-label: Premenstrual tension, migraine prevention, minimizing aggression in patients with BPD, binge-eating disorder, body dysmorphic disorder, and bulimia nervosa (sertraline)

Pharmacodynamic Profile of Sertraline:

• Onset: usually within a week (therapeutic effect may not be felt until later)
• Peak: 4.5 to 8.4 hours
• Duration: unavailable
• Half-life: 26 hours

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Page 4 — Pharmacodynamics of SNRIs

Prototype drug: Duloxetine

Mechanism of Action: SNRIs inhibit the reuptake of serotonin AND norepinephrine, increasing their availability in the synapse.

Clinical Response Time: Biochemical effect occurs within hours; clinical response takes about 4 weeks.

Therapeutic Uses (Approved): MDD, GAD, social anxiety disorder

Pharmacodynamic Profile of Duloxetine:

• Onset: unavailable
• Peak: 6 hours (empty stomach); up to 10 hours (taken with food)
• Duration: unavailable
• Half-life: 12 hours

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Page 5 — Pharmacodynamics of Atypical Antidepressants

Prototype drug: Bupropion

Mechanism of Action: Atypical antidepressants affect one or two of the three neurotransmitters: serotonin, norepinephrine, dopamine.

Clinical Response Time: Within the first 2 weeks of treatment, some relief will be noted. Full effect may take up to 8 to 14 weeks.

Therapeutic Uses (Approved):

• MDD
• Sleep disorders (mirtazapine, marketed as Remeron)
• Smoking cessation (bupropion, marketed as Zyban)

Pharmacodynamic Profile of Bupropion:

• Onset: 1 to 2 weeks
• Peak: immediate release = 2 hours; 12-hour extended release = 3 hours; 24-hour extended release = 5 hours (all longer if taken with food)
• Duration: 1 to 2 days
• Half-life: 3 to 4 hours (21 hours for the hydrochloride salt)

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Page 6 — Overview of Mood Stabilizer Drugs

Mood stabilizer medications treat bipolar disorder — manifested by alterations in mood and behavior, vacillating between mania and depression.

Examples of mood stabilizers:

• Lithium (prototype drug for this lesson)
• Carbamazepine
• Valproic acid
• Divalproex
• Lamotrigine

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Page 7 — Pharmacokinetics of Lithium

Lithium is one of the most commonly prescribed medications for the stabilization of bipolar affective disorder. Due to its short half-life and high toxicity, it must be administered in divided daily doses (large single daily doses cannot be used, even with slow-release preparations).

Parameter	Details
Absorption	Well absorbed after oral administration
Distribution	Distributed evenly to all tissues and body fluids
Metabolism	Lithium is NOT metabolized
Excretion	Excreted in the urine. Serum sodium levels affect excretion: kidneys process lithium and sodium in the same manner. Decreased sodium → kidneys retain lithium (reduced excretion). Increased sodium → kidneys eliminate lithium (increased excretion).

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Page 8 — Pharmacodynamics of Lithium

The mechanism of action of lithium is unclear, but evidence shows lithium ions alter sodium ion transport in nerve cells, resulting in a change in catecholamine metabolism. Onset of action is fast, but the patient may not experience the desired effect for up to 14 days.

Lithium is only approved for treatment of bipolar disorder and manic episodes.

• Half-life: 18 to 36 hours
• Onset: 5 to 7 days
• Duration: unknown
• Peak: immediate release = 0.5 to 3 hours; extended release = 2 to 6 hours

Section 8: Nursing Process Related to Antidepressant and Mood Stabilizer Drug Therapy

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Page 1 — Pre-Administration Assessment for Antidepressants

Before administering an antidepressant medication, the nurse should assess: patient history of episodes of depression; medication history (current prescribed and OTC medications, alcohol and drug use, herbal preparations and supplements); mental status assessment; suicide risk assessment; baseline vital signs and weight; liver and renal function (urine output >1500 mL/day; BUN, serum creatinine, liver enzymes); bowel pattern; fluid intake; diet.

Special Considerations by Drug Class:

• TCAs may have a sedative action → should be taken at night
• SSRIs should not be started if patient had an MAOI in the previous 14 days
• SNRIs → teach patient to avoid St. John's wort (increased risk for serotonin syndrome and neuroleptic malignant syndrome)
• Atypical antidepressants (e.g., bupropion) → not to be taken with MAOIs, nor within 14 days of stopping an MAOI
• MAOIs → patients must avoid foods rich in tyramine

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Page 2 — Contraindications and Interactions with Sertraline (SSRI)

Contraindications:

• Concurrent use of MAOIs, pimozide, or disulfiram (oral solution only)
• Use within 14 days of stopping MAOI therapy
• Known hypersensitivity to sertraline or inactive ingredients

Extreme Cautions:

• Patients with suicidal thoughts/behaviors (especially pediatric and young adult populations)
• Coadministration with other serotonergic agents (SSRIs, SNRIs, triptans) → serotonin syndrome risk
• Patients using aspirin, NSAIDs, antiplatelet drugs, warfarin, or other anticoagulants → increased bleeding risk
• Patients suspected of having bipolar disorder → activation of mania/hypomania
• Patients with seizure disorders (studies not conducted)
• Patients with angle-closure glaucoma → risk for angle closure attack

Additional Cautions: Pregnancy (third trimester → risk for persistent pulmonary hypertension and neonatal withdrawal); pediatric patients (safety/efficacy not determined except for OCD)

Interactions: Sertraline may increase risk for: bleeding (aspirin, NSAIDs, anticoagulants); serotonin syndrome/neuroleptic malignant syndrome (MAOIs, St. John's wort); QT prolongation and ventricular arrhythmias (pimozide)

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Page 3 — Dosage and Administration of Sertraline

Before administering, nurse reviews indication, dose, route, and drug/food/supplement interactions.

Indication	Starting Dose	Maximum Dose
MDD	50 mg/day	200 mg/day
OCD	50 mg/day	200 mg/day
Panic disorder, PTSD, seasonal affective disorder	25 mg/day	200 mg/day
PMDD (continuous dosing)	50 mg/day	150 mg/day
PMDD (intermittent dosing)	50 mg/day during luteal phase only	100 mg/day during luteal phase only

⚠ Black Box Warning: Antidepressants can increase the risk for suicidal thoughts and behaviors in pediatric and young adult patients. Closely monitor for suicidal thoughts or behaviors.

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Page 4 — Side Effects and Adverse Effects of Sertraline

⚠ Safe Practice Alert: Antidepressants may increase the risk for suicide especially during the early phase of treatment — greatest risk among children, adolescents, and young adults.

Side Effects:

• Sexual dysfunction (erectile dysfunction, ejaculation disorder, decreased libido — underlying cause unknown)
• Weight gain (decreases sensitivity of receptors regulating appetite)
• General: dizziness, fatigue, skin rashes, diarrhea, nausea, excessive sweating

Adverse Effect — Serotonin Syndrome:

• Can occur 2 to 72 hours after starting medication; risk increases with concurrent MAOIs
• Signs/symptoms: alterations in mental status (agitation, confusion, anxiety, hallucinations), altered coordination, myoclonus, tremors, hyperreflexia, excessive sweating, fever
• Can be rapidly fatal: tachycardia, hypertension, hyperthermia, seizures, coma → death
• Minor symptoms may resolve after stopping medication; major symptoms require supportive care/hospitalization

Adverse Effect — Neonatal Effects from Use in Pregnancy:

• Neonatal abstinence syndrome (NAS): irritability, abnormal crying, tremor, respiratory distress, seizures
• Treatment is supportive; generally resolves within a couple of days

Other Adverse Effects: Decreased platelet aggregation → increased bleeding risk

Withdrawal Syndrome: Must taper gradually; symptoms include dizziness, headache, nausea, sensory disturbances, tremor, anxiety, dysphoria (resolve with resumption of medication)

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Page 5 — Contraindications and Interactions with Duloxetine (SNRI)

Contraindications:

• Patients taking linezolid or methylene blue intravenously
• Use within 14 days of stopping MAOI therapy

Interactions: Duloxetine may increase risk for: neuroleptic malignant syndrome, hyperthermia, vital sign instability, and mental status changes (if taken within 14 days of MAOI use); bleeding (anticoagulants, antiplatelet drugs, NSAIDs, salicylates); increased ALT and bilirubin levels (if patient uses alcohol)

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Page 6 — Dosage and Administration of Duloxetine

Indication	Starting Dose	Maximum Dose
Depression	40–60 mg/day in a single dose or 2 divided doses	Can be increased to 120 mg/day (though evidence shows no greater benefit than 60 mg/day)

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Page 7 — Side Effects and Adverse Effects of Duloxetine

Side Effects: Insomnia; visual disturbance (usually resolves at therapeutic level); nausea

Adverse Effects (rare): Serotonin syndrome; neuroleptic malignant syndrome; thrombophlebitis; hepatic failure; Stevens-Johnson syndrome; anaphylaxis

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Page 8 — Contraindications and Drug Interactions with Bupropion (Atypical Antidepressant)

Contraindications:

• Patients with head trauma, stroke, seizures, or intracranial mass
• Use within 14 days of stopping MAOI therapy

Drug Interactions:

• Bupropion toxicity risk increased with ritonavir or cimetidine
• Bupropion may decrease efficacy of: tamoxifen, carbamazepine, phenobarbital, phenytoin

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Page 9 — Dosage and Administration of Bupropion

Indication	Starting Dose	Maximum Dose
Depression (regular formulation)	100 mg bid initially; increase after 3 days to 100 mg tid if needed; max single dose 150 mg	300 mg/day
Depression (extended- or sustained-release)	150 mg in the morning; may increase under HCP guidance if initial dose tolerated	200 mg/day

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Page 10 — Side Effects and Adverse Effects of Bupropion

Side Effects: Headache, dizziness, dysrhythmias, nausea and vomiting, weight loss

Adverse Effects (rare): Seizure; QRS prolongation; Stevens-Johnson syndrome

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Page 11 — Interventions and Evaluation for Antidepressant Drugs

• Monitor vital signs per agency policy; note that some antidepressants can cause orthostatic hypotension; MAOIs → monitor for severe hypertension
• Weigh patient 2–3 times per week in same clothing, same time
• Monitor for suicidal tendencies at all times
• Observe for seizures if patient is taking an anticonvulsant
• Monitor for drug-drug and food-drug interactions
• Monitor for adverse events associated with specific antidepressant prescribed
• Monitor patients taking sertraline or duloxetine for serotonin syndrome
• Monitor patients taking bupropion for QRS prolongation
• Evaluate effectiveness as evidenced by decreasing depression symptoms

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Page 12 — Patient Teaching for Antidepressants

General Teaching:

• Take as prescribed; effects not immediate — may take weeks (nurse personalizes timeframe to drug type)
• Check with HCP before OTC medications or herbal preparations
• Do not abruptly stop — taper gradually under HCP supervision
• No alcohol or other CNS depressants (additive effect)
• Do not drive or operate hazardous machinery until stable medication levels established
• Take with food if GI upset occurs
• Check with HCP if planning to become pregnant

Side Effects by Drug:

• Sertraline/SSRIs: sexual dysfunction, weight gain, rash
• Duloxetine/SNRIs: insomnia, visual disturbances (usually resolve), nausea
• Bupropion: headache, dizziness, dysrhythmias, nausea/vomiting, weight loss
• TCAs: anticholinergic effects (dry mouth, difficulty voiding, constipation), sexual dysfunction, weight gain, cardiovascular disturbances (orthostatic hypotension, dysrhythmias)
• MAOIs: orthostatic hypotension, insomnia, dry mouth, weakness, weight gain

⚠ Alert — MAOI patients: Do NOT take sympathomimetic-like drugs or foods containing tyramine (red wines, cheeses, smoked meats) → may precipitate hypertensive crisis. Symptoms: hypertension, headache, neck stiffness, nausea/vomiting, palpitations.

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Page 13 — Pre-Administration Assessment for Lithium

Obtain Patient History:

• History of bipolar affective disorder (episodes of mania, depression)
• Medication history: current prescribed and OTC medications; note that NSAIDs decrease renal clearance of lithium → accumulation
• Alcohol and drug use; herbal preparation use

Determine Baseline Data:

• Mental status assessment; suicide risk assessment
• Baseline vital signs and ECG
• Baseline labs: CBC with differential, serum electrolytes, renal and hepatic function (BUN, creatinine, liver enzymes), urine output
• Thyroid function tests: T3, T4, TSH
• Neurologic assessment: level of consciousness, gait, reflexes, presence of tremors

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Page 14 — Contraindications with Lithium

Contraindications:

• Hypersensitivity to lithium or components
• For immediate-release formulations: severe cardiovascular or renal disease, severe debilitation, dehydration, sodium depletion, concurrent use with diuretics
• Pregnancy and breastfeeding

Cautions (use with care):

• Cardiovascular disease, dehydration, renal impairment → increased risk for lithium toxicity
• Depression/suicidal ideation → especially risky given lithium's narrow therapeutic index
• Hypothyroidism → can occur with treatment
• Debilitation/older adults → increased risk for lithium toxicity

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Page 15 — Drug Interactions with Lithium

Diuretics: Increase risk for lithium toxicity — increase renal excretion of sodium → decrease excretion of lithium → elevated serum lithium levels

NSAIDs: Increase risk for lithium toxicity — increase renal reabsorption of lithium → elevated serum lithium levels. Exception: aspirin and sulindac do NOT increase lithium levels (good choice for mild analgesia)

Anticholinergic Drugs (antihistamines, phenothiazine antipsychotics, TCAs): Avoid — anticholinergics cause urinary hesitancy while lithium causes polyuria → considerable patient discomfort

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Page 16 — Dosage and Administration of Lithium

Available Preparations: Capsules and standard tablets; slow-release tablets; syrup (8 mEq/5 mL) Take with meals or milk to reduce gastric upset.

Dosing (divided doses):

• Typical: 300 mg taken 3 or 4 times a day for long-term control
• Slow-release tablets: 600 mg twice daily for acute mania
• Dosing is highly individualized based on patient response and serum plasma levels

Therapeutic Plasma Levels:

• Acute therapy (manic episode): 0.8 to 1.4 mEq/L
• Maintenance therapy: 0.4 to 1 mEq/L
• Should not exceed 1.5 mEq/L (toxicity risk)
• At levels above 2.5 mEq/L, death can occur

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Page 17 — Side Effects and Adverse Effects of Lithium

Side Effects:

• GI: nausea, diarrhea, abdominal bloating, anorexia (usually transient)
• CNS: fatigue, muscle weakness, headache, confusion, memory impairment (usually transient)
• Fine hand tremors (worsen with stress, fatigue, caffeine, antidepressants, antipsychotics)
• Polyuria and thirst — lithium interferes with ADH secretion; urine output may exceed 3 L/day
• Goiter — lithium inhibits thyroid hormone secretion → may develop hypothyroidism

Adverse Effects:

• CNS depression
• Heart failure (direct myocardial toxicity)
• Hypercalcemia (with or without hyperparathyroidism)
• Hypothyroidism (particularly in women, usually within 6–18 months of treatment onset)
• Pseudotumor cerebri
• Renal concerns (diminished renal concentrating ability with ongoing therapy)

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Page 18 — Interventions and Evaluation for Lithium

• Obtain lithium levels as ordered — draw blood in the morning (12 hours after evening dose); every 2–3 days during initial therapy; every 3–6 months during maintenance
• Monitor levels to ensure they remain within therapeutic range; notify HCP if outside range
• Ensure annual lab work: CBC with differential, serum electrolytes, renal function tests (creatinine, creatinine clearance, urinalysis), thyroid function tests (T3, T4, TSH)
• Evaluate effectiveness as evidenced by decrease in manic symptoms and enhanced mood stabilization

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Page 19 — Patient Teaching for Mood Stabilizer Drugs (Lithium)

General Teaching:

• Take as prescribed; follow up on ALL appointments including blood draws for therapeutic levels
• Do not stop medication even during periods of stability (manic symptoms will return)
• Effects not immediate — takes 1–2 weeks for clinical response
• Check with HCP before OTC medications or herbal preparations
• Do not drive or operate hazardous machinery until stable levels established
• Maintain adequate fluid intake: 2–3 L/day initially; 1–2 L/day during maintenance; increase in hot weather
• Take lithium with meals to decrease gastric irritation
• Keep a current medication list available at all times

High-Risk Patients:

• Lithium is contraindicated in the first trimester (fetal effects)
• Breastfeeding is contraindicated (toxic levels transmitted in breast milk)

Diet: Avoid caffeine (can exacerbate manic episodes); maintain adequate sodium intake

Signs of Lithium Toxicity (teach patient to report immediately):

• Early: drowsiness, slurred speech, muscle weakness and tremors, loss of appetite, nausea/vomiting, diarrhea
• Late: seizures, confusion, blurred vision, increased urination, severe tremors, unsteady gait

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Page 20 — Case Study: Mr. Chandler

Mr. Chandler is an older adult admitted with vomiting, abdominal pain, diarrhea, blurred vision, and severe tremors. He has a history of bipolar disorder and major depression. Currently taking lithium 300 mg PO q8h and sertraline 50 mg PO daily. His lithium level is 2.5 mEq/L (toxic — above the 1.5 mEq/L limit). His wife reports he started a low-sodium diet 3 months ago to control blood pressure (reduced sodium → kidneys retain lithium → accumulation → toxicity).

Section 9: Pharmacokinetics and Pharmacodynamics of Antipsychotic Drugs

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Page 1 — Overview of Antipsychotic Drugs

Two Categories:

First-Generation Antipsychotics (FGAs) — conventional/typical antipsychotics

• Older category; strong dopamine D₂ antagonists
• High incidence of extrapyramidal side effects (EPS): tardive dyskinesia, rigidity, dystonias
• Mechanism: block postsynaptic dopamine receptors in various parts of the CNS
• Metabolized in liver; excreted in urine and bile
• Include phenothiazines and nonphenothiazines
• Prototype drugs: Fluphenazine and Haloperidol

Second-Generation Antipsychotics (SGAs) — atypical antipsychotics

• Newer category; dopamine D₂ agonists (exception: aripiprazole is a partial D₂ receptor agonist)
• Fewer extrapyramidal side effects than FGAs (only moderate dopamine block)
• Originally used for patients who didn't respond to or tolerate FGAs; now used as first-line therapy
• Clozapine: first atypical antipsychotic (discovered 1960s; available in Europe 1971; US 1990 — delayed due to adverse hematologic reactions)
• Prototype drug: Aripiprazole

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Page 2 — Pharmacokinetics and Pharmacodynamics of Fluphenazine (FGA Prototype)

Overview: High-potency FGA used for psychotic disorders. Thorough patient history important to minimize side effect risk.

Pharmacokinetics:

• Absorption: Rapidly absorbed orally; not affected by food
• Distribution: Protein binding 91%–99%; strongly protein bound → drug may accumulate due to long half-life
• Metabolism: Liver, extensively; crosses blood-brain barrier and placenta
• Excretion: Urine (as metabolites)
• ⚠️ With hepatic dysfunction: dose may need to be decreased; lack of liver metabolism → elevated serum drug level

Pharmacodynamic Profile:

• Onset: HCl — 1 hour; decanoate — 24 to 72 hours
• Peak: HCl oral (PO) — 0.5 hour; IM — 1.5 to 2 hours
• Duration: HCl — 6 to 8 hours; decanoate — 1 to 6 weeks
• Half-life: HCl — 15 hours; decanoate — 7–10 days
• ⚠️ Antacids decrease absorption rate of all phenothiazines — give antacid 1 hour before or 2 hours after an oral phenothiazine

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Page 3 — Pharmacodynamics and Pharmacokinetics of Haloperidol (FGA Prototype)

Overview: One of the oldest FGAs; still commonly used. Available as PO, decanoate injection (IM), and lactate injection (IM). Decanoate form has extremely long duration of action — helpful for nonadherent patients.

Pharmacokinetics:

• Absorption: PO and IM well absorbed; decanoate (IM) slowly absorbed
• Distribution: High concentrations in liver; crosses placenta; protein binding 92%
• Metabolism: Liver, extensively
• Excretion: Kidneys; also excreted in breast milk

Therapeutic Uses: Schizophrenia, Tourette syndrome, psychosis

Pharmacodynamic Profile:

• Onset: PO — erratic; IM — 30 minutes; IM decanoate — 3 to 9 days
• Peak: PO — 2 to 6 hours; IM — 30 to 45 min; IM decanoate — 4 to 11 days
• Duration: PO — 8 to 12 hours; IM — 4 to 8 hours; IM decanoate — 3 weeks
• Half-life: 12 to 36 hours

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Page 4 — Pharmacokinetics and Pharmacodynamics of Aripiprazole (SGA Prototype)

Overview: Commonly used second-generation antipsychotic (SGA).

Pharmacokinetics:

• Metabolized by the liver
• Excreted mostly in urine; small portion in feces

Mechanism of Action:

• Exact mechanism unknown
• Thought to work as a partial agonist at D₂ and 5-HT₁A receptors
• Antagonist activity at 5-HT₂A receptors

Therapeutic Uses: Approved for:

• Schizophrenia
• Bipolar mania
• Major depressive disorder
• Irritability associated with autism spectrum disorder
• Agitation associated with schizophrenia or bipolar mania

Pharmacodynamic Profile:

Route	Parameter	Value
PO	Onset	1 to 3 weeks
PO	Peak	3 to 5 hours
IM (immediate release)	Peak	1 to 3 hours
IM (extended release, deltoid)	Peak	4 days
IM (extended release, gluteal)	Peak	5 to 7 days
	Half-life	74 to 94 hours

Section 10: Nursing Process Related to Antipsychotic Drug Therapy

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Page 1 — Pre-Administration Assessment for Antipsychotic Drugs

Key principle: Document patient behavior before administering antipsychotics — without proper baseline, it is very difficult to assess effectiveness. Some side effects are life-threatening.

Determine Baseline Data:

• Vital signs, weight, overall mental status (mood, orientation, behavior)
• Glucose and lipid levels (ordered by HCP because antipsychotics can cause metabolic syndrome)
• Medical history, current medications, herbal/vitamin supplements (some can accelerate metabolism when combined with aripiprazole)

Identify High-Risk Patients:

• Do NOT give FGAs to: Patients with Parkinson disease, severe hypo/hypertension, breast cancer; narrow-angle glaucoma; severe hepatic/renal disease; cardiovascular disease; brain damage; CNS depression; bone marrow depression
• Fluphenazine → risk for hypotension; coadministration with antihypertensives requires careful monitoring
• History of seizures = high risk; FGAs can lower seizure threshold → anticonvulsant dose adjustment may be needed
• Narcotics and sedative-hypnotics given simultaneously with fluphenazine → risk for additive CNS depression
• Many FGAs can cause severe dysrhythmias; patients with prolonged QT interval are at greater risk for ventricular arrhythmias
• ⚠️ Black Box Warning: Older adult patients with dementia-related psychosis have increased mortality rates — antipsychotic use should be avoided in this population

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Page 2 — Contraindications and Interactions with Fluphenazine and Haloperidol

Both drugs: Cause CNS depression; metabolized by the liver; patients should consult HCP before starting any new medications.

Contraindications with Fluphenazine:

• Absolute: Myelosuppression, coma, severe CNS depression, large doses of hypnotics, hepatic disease, subcortical brain damage
• Cautions: Older adults, seizures, Parkinson disease, severe cardiac disease, renal/hepatic impairment, pneumonia risk, hypotension risk, decreased GI motility, urinary retention, BPH, narrow-angle glaucoma, myasthenia gravis, visual problems

Interactions with Fluphenazine:

• Drug: Alcohol/CNS depressants → ↑ hypotension, CNS/respiratory depression; EPS-causing medications → additive EPS; antihypertensives → worsen hypotension; lithium → ↓ absorption + adverse neurologic effects; MAOIs/TCAs → ↑ anticholinergic/sedative effects; QT-prolonging drugs (erythromycin) → additive QT prolongation
• Herb: Dong quai/St. John's wort → ↑ photosensitivity; Gotu kola/kava/St. John's wort/valerian → ↑ CNS depression
• Lab: May cause false-positive pregnancy/phenylketonuria tests; may cause ECG changes (Q- and T-wave disturbances)

Contraindications with Haloperidol:

• Absolute: Severe toxic CNS depression, coma, hypersensitivity, Parkinson disease, dementia with Lewy bodies, narrow-angle glaucoma, severe hepatic/renal/cardiovascular disease, bone marrow depression, blood dyscrasias, subcortical brain damage
• Cautions: Older adults with dementia-related psychosis

Interactions with Haloperidol:

• Drug: ↑ sedation with alcohol/CNS depressants; ↑ toxicity with anticholinergics, CNS depressants, lithium; ↓ effects with phenobarbital, carbamazepine, caffeine
• Herb: Calculus Bovis Sativus (traditional Chinese medicine) can significantly lower haloperidol dose requirement
• Lab: Can increase serum tricyclic level

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Page 3 — Dosage and Administration of Fluphenazine and Haloperidol

Fluphenazine — Availability:

• Elixir: 2.5 mg/5 mL; Injection (decanoate): 25 mg/mL; Injection solution (HCl): 2.5 mg/mL; Oral concentrate: 5 mg/mL; Tablets: 1 mg, 2.5 mg, 5 mg, 10 mg

Fluphenazine — Administration/Handling:

• ⚠️ Avoid skin contact with solution → contact dermatitis
• Dilute oral concentrate only with water, milk, or juice
• Do NOT dilute with caffeine beverages (coffee, cola), tannics (tea), or pectinates (apple juice) — incompatibility

Fluphenazine — Routes/Dosage:

• PO (adults): 2.5–10 mg/day in divided doses q6–8h; Maintenance: 1–5 mg/day; Maximum: 40 mg/day
• PO (older adults): Initially 1–2.5 mg/day; titrate gradually
• IM (HCl): 1.25 mg single dose; may need 2.5–10 mg/day in divided doses q6–8h
• IM (decanoate): Initially 12.5–25 mg q2–4 weeks; may increase in 12.5-mg increments; Maximum: 100 mg
• No dose adjustment needed for renal/hepatic impairment

Haloperidol — Availability:

• Tablets: 0.5, 1, 2, 5, 10, 20 mg; Lactate SOL: 2 mg/mL; Lactate INJ: 5 mg/mL; Decanoate INJ: 50 mg/mL, 100 mg/mL

Haloperidol — Administration: For doses drawn via ampule: roll ampule in hand to warm before drawing up

Haloperidol — Routes/Dosage:

• Psychosis (tablets): 0.5–5 mg PO bid-tid
• Tourette syndrome (tablets): 0.5–5 mg PO bid-tid
• Agitation, acute (tablets): 0.5–10 mg PO q1–4h
• Lactate psychosis acute: IM/IV 2–10 mg q4–8h; PO 0.5–5 mg bid-tid
• Lactate Tourette: 0.5–5 mg PO bid-tid
• Lactate agitation: 0.5–10 mg PO/IM/IV q1–4h
• Decanoate chronic psychosis: 50–100 mg IM monthly

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Page 4 — Side Effects and Adverse Effects of Fluphenazine and Haloperidol

Side Effects (both drugs):

• Hypotension or hypertension
• Haloperidol additionally: QT prolongation and arrhythmias

Four EPS Categories:

• Akathisia: Inability to sit still, difficulty moving eyes, speaking, or swallowing; muscle spasms; unusual nonpurposeful body movements
• Parkinsonian symptoms: Hypersalivation, mask-like facial expression, shuffling gait, tremors in fingers/hands
• Acute dystonias: Torticollis (neck/muscle spasm), opisthotonos (rigidity of back muscles), oculogyric crisis (rolling back of eyes); may produce diaphoresis and pallor
• Tardive dyskinesia: Tongue protrusion, puffing of cheeks, chewing/puckering of the mouth — occurs rarely, may be irreversible

Additional Side Effects:

• Abrupt withdrawal after long-term therapy → dizziness, gastritis, nausea, vomiting, tremors
• Blood dyscrasias (agranulocytosis, mild leukopenia) → may lower seizure threshold

Adverse Effects (life-threatening):

• More pronounced agranulocytosis
• Torsades de pointes

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Page 5 — Contraindications and Interactions with Aripiprazole

Contraindication: Known hypersensitivity (pruritis, urticaria, or anaphylaxis)

Cautions — Use with caution in patients who:

• Concurrently use CNS depressants (including alcohol)
• Have CNS depression disorders
• Have cardiovascular changes (monitor for orthostatic hypotension, dehydration)
• Have cerebrovascular disease — especially older adults (may induce syncope, TIA, or stroke including fatality)
• Have Parkinson disease (potential exacerbation)
• Have history of seizures or conditions lowering seizure threshold
• Have experienced tardive dyskinesia in the past
• Have metabolic changes
• Operate machinery/vehicles until response established
• Have schizophrenia or bipolar disorder (suicide risk increases as patient begins to feel better)
• Are pregnant (may cause extrapyramidal and/or withdrawal symptoms in newborns exposed in 3rd trimester)
• Are nursing (discuss benefits/risks with HCP)

Interactions:

• Drug: Alcohol → potentiates cognitive/motor effects; CYP3A4 inducers (carbamazepine) → ↓ concentration; CYP3A4 inhibitors (itraconazole, ketoconazole) → ↑ concentration
• Herbal: St. John's wort → ↓ levels; Gotu kola/kava/St. John's wort/valerian → ↑ CNS depression

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Page 6 — Dosage and Administration of Aripiprazole

Availability: Tablets, orally disintegrating tablets, oral solution, IM injection (IM indicated only for agitation with schizophrenia or bipolar mania)

⚠️ Older adults with dementia-related psychosis should NOT take aripiprazole

Indication	Recommended Dose	Maximum Dose
Schizophrenia	10–15 mg/day	30 mg/day
Bipolar mania	15 mg/day	30 mg/day
Major depressive disorder	5–10 mg/day	15 mg/day
Tourette syndrome (<50 kg)	5 mg/day	10 mg/day
Tourette syndrome (>50 kg)	10 mg/day	20 mg/day

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Page 7 — Side Effects and Adverse Effects of Aripiprazole

General: Fewer side effects than FGAs or other SGAs. Vary by age and condition.

Age	Condition	Side Effects
Adult	Schizophrenia	Akathisia
Adult	Bipolar mania (monotherapy)	Akathisia, sedation, restlessness, tremor, extrapyramidal disorder
Adult	Bipolar mania (adjunctive with lithium/valproate)	Akathisia, insomnia, extrapyramidal disorder
Adult	Major depressive disorder (adjunct)	Akathisia, restlessness, insomnia, constipation, fatigue, blurred vision
Adult	Agitation (schizophrenia/bipolar)	Nausea
Pediatric (13–17)	Schizophrenia	Extrapyramidal disorder, somnolence, tremor
Pediatric (10–17)	Bipolar mania	Somnolence, extrapyramidal disorder, fatigue, nausea, akathisia, blurred vision, salivary hypersecretion, dizziness
Pediatric (6–17)	Autistic disorder	Sedation, fatigue, vomiting, somnolence, tremor, pyrexia, drooling, decreased appetite, salivary hypersecretion, extrapyramidal disorder, lethargy
Pediatric (6–17)	Tourette syndrome	Sedation, somnolence, nausea, headache, nasopharyngitis, fatigue, increased appetite

• If stomach irritation: administer with food
• Adverse effect: Not recommended for older patients with dementia-related psychosis — markedly increased risk for mortality

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Page 8 — Interventions and Evaluation for Antipsychotic Drugs

• Ascertain ability to cope with ADLs
• Determine whether side effects or adverse reactions have occurred; notify HCP
• Monitor BP for hypo/hypertension and other cardiac side effects
• Monitor CBC for blood dyscrasias
• Monitor weight, blood pressure, and pulse at every appointment → risk for metabolic syndrome
• Monitor for fine tongue movement and other motor movements → early sign of tardive dyskinesia
• Monitor for acute dystonias: torticollis, opisthotonos, oculogyric crisis (may produce diaphoresis/pallor)
• Monitor for parkinsonian symptoms: hypersalivation, mask-like expression, shuffling gait, finger/hand tremors
• Monitor for tardive dyskinesia: tongue protrusion, cheek puffing, chewing/puckering (rarely occurs, may be irreversible)
• Supervise suicide-risk patients closely — as energy level improves, suicide risk increases
• Assess for therapeutic response: interest in surroundings, improved self-care, increased concentration, relaxed facial expression

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Page 9 — Patient Teaching for Fluphenazine and Haloperidol

General Teaching:

• Full therapeutic effect may take several weeks
• Urine may darken when taking fluphenazine or haloperidol decanoate
• Do NOT abruptly discontinue long-term therapy
• Avoid tasks requiring alertness/motor skills until response established; drowsiness subsides with continued therapy
• Avoid skin contact with fluphenazine solution (contact dermatitis)
• Dilute oral concentrate only with water, milk, or juice — NOT with caffeine beverages, tannics (tea), or pectinates (apple juice)
• Sucking on sugarless hard candy can alleviate dry mouth

Side Effects to Report Immediately:

• Cardiovascular: Monitor BP at home; report hypo/hypertension
• Akathisia: Inability to sit still, difficulty moving eyes/speaking/swallowing, muscle spasms, unusual body movements
• Parkinsonian: Hypersalivation, mask-like expression, shuffling gait, finger/hand tremors
• Acute dystonias: Torticollis, opisthotonos, oculogyric crisis (may produce diaphoresis/pallor)
• Tardive dyskinesia: Tongue protrusion, cheek puffing, chewing/puckering (may be irreversible)

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Page 10 — Patient Teaching for Aripiprazole

• Avoid alcohol while taking aripiprazole
• Avoid tasks requiring alertness/motor skills until drug response established
• Report worsening depression, suicidal ideation, unusual behavior changes, extrapyramidal effects
• Orally disintegrating tablets: Remove from packaging and place directly on tongue; do NOT break or split; can be taken without liquid

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Page 11 — Patient Teaching for Aripiprazole: Side Effects

• Inform patients they may experience weight gain; allow time to discuss body image; report to HCP → may adjust dose, add metformin, or discontinue
• Headaches or insomnia → notify HCP for medications or lifestyle changes
• Nausea may occur; report intractable vomiting (risk of dehydration/electrolyte disturbance)
• Report any safety-risk symptoms immediately

Side effect frequency:

• Frequent (5–11%): Weight gain, headache, insomnia, vomiting
• Occasional (3–4%): Lightheadedness, nausea, akathisia, drowsiness
• Rare (≤2%): Blurred vision, constipation, asthenia (loss of strength/energy), anxiety, fever, rash, cough, rhinitis, orthostatic hypotension

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Page 12 — Case Study: Mr. Crood

Patient: Mr. Crood, 27-year-old male, inpatient psychiatric admission

Diagnosis: Schizophrenia

Presenting symptoms:

• Stopped medications because "they make me feel bad"
• Oriented to person and place; confused about date and events leading to admission
• Vital signs: BP 120/78, P 80, R 18, T 97.8°F
• Disheveled appearance, impulsive behavior

History: Previously prescribed fluphenazine (unable to state when he stopped)

Current Plan: Admitted for titration and dosing of a new antipsychotic regimen. Family notified and present with patient's permission for medication discussions and teaching.

Section 11: Pharmacokinetics and Pharmacodynamics of Sedative-Hypnotic Drugs

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Page 1 — Overview of Sedative-Hypnotic Drugs

Overview: Sedative-hypnotic drugs treat anxiety and insomnia. They cause CNS depression. A single drug may be both an anxiolytic and a hypnotic depending on dose and reason for use. This lesson focuses on benzodiazepines and benzodiazepine-like drugs.

Four Major Groups:

1. Benzodiazepines

• Historically first-choice for anxiety; now used more for situational/short-term management due to high dependence risk
• Depress neuronal function at multiple CNS sites; effects range from sedating to hypnotic to stupor-inducing
• Reduce anxiety via effects on the limbic system
• Can be used as sedative-hypnotics or anxiolytics; doses depend on intended use
• Examples: diazepam, lorazepam, alprazolam
• Prototype: Diazepam

2. Benzodiazepine-Like Drugs (nonbenzodiazepines)

• Used specifically to treat insomnia (NOT indicated for anxiety)
• Work as agonists at benzodiazepine receptor sites on the GABA receptor–chloride channel complex
• Eszopiclone and zolpidem: approved for short- and long-term use; zolpidem taken long-term by many patients with no adverse effects
• Zaleplon: shorter-term therapy
• Examples: zolpidem, zaleplon, eszopiclone
• Prototype: Zolpidem

3. Barbiturates

• Historically used for insomnia or sedation induction
• NOT commonly used today due to low therapeutic index and habit-forming tendencies
• Available in ultra-short-acting, short-acting, intermediate-acting, and long-acting formulations
• Example: Secobarbital

4. Melatonin Receptor Agonists

• Melatonin: hormone produced by the pineal gland; naturally rises in the evening, stays elevated at night, drops in the morning
• Some patients use melatonin supplement or a melatonin receptor agonist (binds to and activates the melatonin receptor)
• Example: Ramelteon — used primarily to assist with sleep onset (not sleep maintenance)

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Page 2 — Pharmacokinetics and Pharmacodynamics of Diazepam (Benzodiazepine Prototype)

(Image: Schematic of GABA receptor–chloride channel complex showing binding sites for benzodiazepines and barbiturates)

Pharmacokinetics:

• Absorption: Well absorbed from the GI tract
• Distribution: 98% protein bound; widely distributed
• Metabolism: Liver
• Excretion: Urine
• Note: Hemodialysis has little effect on removal of benzodiazepines

Mechanism of Action:

• Diazepam and other benzodiazepines depress all levels of the CNS by enhancing the action of GABA (major inhibitory neurotransmitter in the brain)
• Also used to treat seizure disorders, muscle spasms, alcohol withdrawal, and to induce general anesthesia

⚠️ Drug Alert: Benzodiazepines may be more effective than other general CNS depressants. High potential for abuse, tolerance, and dependence — use with caution.

Therapeutic Uses:

• Short-term relief of anxiety
• Acute alcohol withdrawal
• Treatment of seizures (IV for termination of status epilepticus)
• Control of seizure activity in refractory epilepsy (rectal gel only, for patients on stable regimens)
• Skeletal muscle relaxation
• Sedation for patients on mechanical ventilation
• Relief of acute musculoskeletal conditions
• Off-label: Panic disorder; spasticity in children with cerebral palsy

Pharmacodynamic Profile:

Route	Onset	Peak	Half-life	Duration
IV	Immediate	8 minutes	20–50 hours	15–60 minutes
PO	30 minutes	1–2 hours	20–60 hours	12–24 hours

⚠️ Half-life of benzodiazepines (including diazepam) can be longer in older adults or in patients with liver dysfunction

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Page 3 — Pharmacokinetics of Zolpidem (Benzodiazepine-Like Drug Prototype)

Overview: Commonly prescribed sedative-hypnotic; approved for short- or long-term insomnia treatment. Available in an oral spray formulation called Zolpimist (bioequivalent to tablets).

Pharmacokinetics:

• Absorption: Usually administered orally; rapidly absorbed from GI tract
• Distribution: 92.5% protein bound
• Metabolism: Liver
• Excretion: Kidneys
• Note: Hemodialysis does not remove zolpidem

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Page 4 — Pharmacodynamics of Zolpidem

Key characteristics:

• Rapid onset of action; helps patients fall asleep
• Extended-release formulation helpful for patients who have difficulty staying asleep throughout the night
• Binds to benzodiazepine receptor sites on the GABA receptor–chloride channel complex (same as benzodiazepines, but structurally different)
• Effects: prolongs sleep duration, decreases awakenings, reduces sleep latency
• Does not reduce time in REM sleep
• Patients rarely experience rebound insomnia when stopping zolpidem
• Binds only to benzodiazepine 1 subtype of benzodiazepine receptors → therefore lacks anxiolytic, anticonvulsant, and muscle relaxant actions

Pharmacodynamic Profile:

Route	Onset	Peak	Half-Life	Duration
PO	30 minutes	1.6 hours (brain levels remain low)	1.4–4.5 hours (may be longer with liver impairment)	6–8 hours

Section 12: Nursing Process Related to Sedative-Hypnotic Drug Therapy

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Page 1 — Pre-Administration Assessment for Benzodiazepine and Benzodiazepine-Like Drugs

• Assess characteristics of the sleep disturbance and its length; document prolonged latency, frequent awakenings, or early morning wakefulness
• Assess for contributing factors: psychiatric illness, medical condition, caffeine use, stimulant use, poor sleep habits, major life stressors
• Assess BP, pulse, respiratory rate, and oxygen saturation before administration
• Check autonomic response (cold/clammy hands, diaphoresis)
• Check motor response (agitation, trembling, tension)
• Perform pain assessment; assess mobility including stiffness and swelling
• Assess history of seizure disorder (length, intensity, frequency, duration, level of consciousness); observe frequently for recurrence; initiate seizure precautions

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Page 2 — Contraindications and Interactions of Benzodiazepines

Contraindications:

• Acute narrow-angle glaucoma
• Respiratory depression
• Hepatic insufficiency
• Sleep apnea
• Myasthenia gravis
• Pregnancy and breastfeeding
• Children younger than 6 months of age

Cautions:

• Depression; history of drug or alcohol abuse; renal/hepatic impairment; respiratory disease; impaired gag reflex; concurrent use of CNS depressants, psychoactive drugs, or strong CYP3A4 inhibitors/inducers; suicidal ideation

Interactions:

• Drug: Alcohol/CNS depressants → ↑ CNS depression; CYP3A4 inducers (carbamazepine, rifampin) → ↓ benzodiazepine concentration; CYP3A4 inhibitors (itraconazole, ketoconazole) → ↑ concentration
• Herb: Gotu kola/kava kava → ↑ respiratory depression; St. John's wort → ↓ concentration; valerian → ↑ CNS depression
• Food: ⚠️ Grapefruit products → ↑ concentration/effects — do NOT take benzodiazepines with grapefruit juice or products

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Page 3 — Dosage and Administration of Benzodiazepines (Diazepam)

Available routes: PO, IM, IV, and rectal gel

Dosage:

• PO (adults): 2–10 mg, 2–4 times/day
• IV/IM (adults): 2–10 mg; may repeat in 3–4 hours if needed

IV Administration:

• Administer by IV push using port closest to the vein; use large veins (reduce thrombosis/phlebitis risk)
• ⚠️ Administering IV too rapidly → hypotension and respiratory depression
• Rate must not exceed 5 mg/min for adults or 1–2 mg/min for children
• Monitor respirations q5–15 min for 2 hours
• Store at room temperature

IM Administration: Inject deeply into a large muscle to decrease pain

PO Administration:

• Administer with or without food
• Oral concentrate may be diluted with water, juice (NOT grapefruit), or carbonated beverages, or mixed in applesauce/pudding
• Tablets may be crushed

Rectal Gel:

• Insert rectal tip and gently push plunger over 3 seconds
• Remove tip after 3 additional seconds
• Hold buttocks together for 3 seconds after plunger removal

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Page 4 — Side Effects and Adverse Effects of Benzodiazepines

General: Well tolerated; serious adverse reactions rare. Schedule IV drugs — potential for abuse.

Side Effects (can become adverse effects depending on circumstances):

• Drowsiness, lightheadedness, lack of coordination, difficulty concentrating, blurred vision, vertigo, weakness
• Sedation may interfere with waking activities
• Anterograde amnesia — particularly with triazolam (Halcion); assess for forgetfulness

Adverse Effects:

• Complex sleep-related behaviors (more prominent when combined with alcohol/CNS depressants): preparing/eating meals, making phone calls, sexual activity, answering email/internet use, sleep driving → if reported, taper dosing slowly to minimize withdrawal
• Respiratory depression — particularly when combined with other CNS depressants
• Nausea, vomiting, epigastric distress, diarrhea
• Rarely: allergic reactions, neutropenia, jaundice

Paradoxical Effects (opposite of intended):

• Insomnia, excitation, euphoria, heightened anxiety, rage → discontinue benzodiazepine if these occur

Use in Pregnancy:

• Associated with increased risk of congenital malformations: cleft lip, cardiac deformities, inguinal hernias
• Estazolam, flurazepam, temazepam, and triazolam have been associated with fetal risk/abnormalities
• HCP and patient must weigh risks vs. benefits

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Page 5 — Interventions and Evaluation for Benzodiazepines

• Monitor heart rate, respiratory rate, BP, and mental status during administration
• Observe for paradoxical effects
• Conduct ongoing assessment of gas exchange and oxygen saturation

Therapeutic response indicators:

• Decrease in intensity/frequency of seizures
• Calm facial expression
• Decreased restlessness
• Decreased intensity of skeletal muscle pain
• Therapeutic serum level (check agency-specific values)

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Page 6 — Contraindications and Interactions of Benzodiazepine-Like Drugs (Zolpidem)

Contraindications:

• Allergy to benzodiazepines
• Known hypersensitivity to zolpidem or any inactive ingredients
• Respiratory depression

Cautions:

• Hepatic impairment; mild-moderate COPD; mild-moderate sleep apnea; depression; suicidal ideation; abnormal thinking/behavioral changes; complex behaviors; pregnancy/breastfeeding; CNS depression; children, older adults, and debilitated individuals

Interactions:

• Drug: Alcohol; CNS depressants
• Herb: Gotu kola/kava kava → ↑ respiratory depression; valerian → ↑ CNS depression; St. John's wort → ↓ concentration/effect

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Page 7 — Dosage and Administration of Zolpidem

Available formulations:

• Immediate-release tablets (5 mg, 10 mg) — Ambien: usual dose 5 or 10 mg; women start at 5 mg, men start at 10 mg
• Extended-release tablets (6.25 mg, 12.5 mg) — Ambien CR: usual dose 12.5 mg
• Oral spray (5 mg) — Zolpimist: usual dose 5 or 10 mg
• Sublingual tablets — Edluar (5 mg, 10 mg): usual dose 5 or 10 mg

Administration:

• For faster sleep onset → administer without food
• Do NOT break, crush, dissolve, or divide Ambien CR tablets; give whole
• Edluar sublingual: place under tongue, allow to dissolve; do NOT swallow or give with water
• Zolpimist: spray directly into mouth over tongue

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Page 8 — Side Effects and Adverse Effects of Benzodiazepine-Like Drugs (Zolpidem)

Side Effects:

• Minimal side effects
• Unless high doses taken for prolonged periods, zolpidem is not associated with tolerance, abuse, or dependence
• Do NOT combine with alcohol or other CNS depressants
• Abrupt stopping after long-term use → side effects of weakness, diaphoresis, vomiting, tremor, facial flushing

Adverse Effects:

• Complex sleep-related behaviors: driving without recollection, making/eating food, unremembered sexual activity, internet activity → report to HCP immediately
• Overdose: ataxia, bradycardia, diplopia, severe drowsiness, difficulty breathing, nausea, vomiting, possible coma

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Page 9 — Interventions and Evaluation of Benzodiazepine-Like Drugs (Zolpidem)

• Before administration: assess BP, pulse, respirations, mental status, and sleep patterns
• Encourage good sleep hygiene: low lighting, quiet environment, predictable bedtime routine
• Discourage use of electronic devices or TV at least 30 minutes before sleep
• Assess for signs of respiratory depression (slow, irregular breathing); monitor vital signs
• Monitor for confusion; injury may result with first-time use — ensure call light is within reach
• Consider side rails, bed alarms, or alarm mattresses for older adults
• Monitor for residual sedation, lightheadedness, dizziness, and confusion
• Assess for presence of complex sleep-related behaviors
• Evaluate sleep patterns to determine effectiveness

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Page 10 — Patient Teaching for Benzodiazepines

General Teaching:

• Avoid alcohol and caffeine while taking benzodiazepines
• Avoid driving and activities requiring mental alertness/motor coordination
• Take with food if stomach upset occurs
• Swallow sustained-release formulas whole — do NOT crush or chew
• Consult HCP before changing dose or stopping; do NOT abruptly discontinue
• Practice good sleep hygiene; discuss how sleep patterns should normalize once the precipitating stressor is removed

Side Effects:

• Residual CNS depression can cause wake-time sedation — avoid driving
• May develop complex sleep-related behaviors — report to HCP
• Paradoxical reactions (rage, excitement, heightened anxiety) — notify HCP
• Possible drug-dependency insomnia during/after withdrawal — avoid abrupt discontinuation
• ⚠️ Pregnancy risk for fetus — avoid pregnancy; avoid breastfeeding while taking benzodiazepines

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Page 11 — Patient Teaching for Benzodiazepine-Like Drugs (Zolpidem)

General Teaching:

• Do NOT abruptly discontinue after long-term use
• High dosages increase risk for tolerance and dependence
• Ambien CR tablets should be swallowed whole (do not crush, chew, or break)
• Avoid alcohol and caffeine

Side Effects Teaching:

• Benzodiazepine-like drugs can cause decreased alertness
• Possible side effects: headache, dizziness, nausea, diarrhea, muscle pain
• Report complex sleep-related behaviors (driving/sleepwalking, making/eating food, unremembered sexual activity, internet activity) to HCP

Section 13: Pharmacokinetics and Pharmacodynamics of Antianxiety Drugs

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Page 1 — Overview of Antianxiety Drugs

Anxiety disorders are treated with psychotherapy and/or medication — most people respond best to a combination of both.

• First-choice medications for anxiety: SSRIs (covered in the Antidepressant and Mood Stabilizer Drug Therapy lesson)
• Benzodiazepines can also be used if the condition is acute or short term, or if a longer-term disorder is under careful management by the health care provider
  • Work by depressing activity in the limbic system and brainstem
  • Useful in emergency situations — provide quick, short-term relief
• Buspirone — considered an antianxiety medication; significantly different from benzodiazepines in that it is not a CNS depressant

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Page 2 — Pharmacokinetics of Buspirone

Buspirone is a drug in a class of its own, used for short-term treatment of anxiety. If tapering from a benzodiazepine, the provider prescribes an evidence-based weaning process depending on (1) which medication the patient will be transitioned to, or (2) if the drug will be completely discontinued.

PK Parameter	Details
Absorption	Well absorbed from the GI tract; taking with food delays absorption but enhances bioavailability by reducing first-pass metabolism
Distribution	Low and variable bioavailability due to extensive first-pass metabolism
Metabolism	Extensively metabolized in the liver (food effect on first-pass metabolism noted above)
Excretion	In urine, primarily as metabolites

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Page 3 — Pharmacodynamics of Buspirone

Buspirone is used for long-term treatment of generalized anxiety disorder (GAD). It is a preferable alternative to traditional benzodiazepines because it is considered nonaddictive.

Mechanism of Action:

• Mechanism as an anxiolytic is not well understood
• Binds with high affinity to serotonin receptors and, to a lesser degree, dopamine receptors
• Does not depress the CNS

Therapeutic Uses:

• As effective as benzodiazepines in the treatment of anxiety, but with key differences:

	Details
Advantages	No abuse potential (especially appropriate for patients who abuse drugs/alcohol); does NOT intensify effects of CNS depressants (benzodiazepines, alcohol, barbiturates)
Disadvantages	Anxiolytic effects develop slowly (2–3 weeks); NOT suitable for PRN use or when immediate relief is needed

• Can be taken for up to a year with no reduction in benefit (despite short-term label)
• Does not display cross-dependence with benzodiazepines

Pharmacodynamic Profile:

Parameter	Value
Route	PO
Onset	2–3 weeks
Peak	40–60 minutes
Elimination Half-Life	2–3 hours
Duration	Unknown

Section 14: Nursing Process Related to Antianxiety Drug Therapy

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Page 1 — Pre-Administration Assessment for Buspirone

• NEVER administer with an MAOI — assess all current medications to ensure no MAOIs are being taken
• Use with caution in hepatic and renal impairment — check lab values for liver/kidney dysfunction
• Before administration, assess the degree and symptoms of anxiety, including:
  • Motor responses (e.g., agitation, trembling, tension)
  • Autonomic responses (e.g., cold/clammy hands, diaphoresis)

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Page 2 — Contraindications and Interactions with Buspirone

There are few contraindications for buspirone.

Contraindications:

• Only reported contraindication: drug allergy
• Cautions: severe hepatic/renal impairment (not recommended); concurrent use of MAOIs (MAOIs must be discontinued at least 2 weeks before starting buspirone)
• Patients should avoid driving and activities requiring mental alertness and motor coordination until effects are known

Interactions:

Category	Interaction
Drug — CYP3A4 inhibitors (e.g., erythromycin, ketoconazole)	May increase concentration/effect
Drug — CYP3A4 inducers (e.g., rifampin)	May decrease concentration/effect
Drug — Haloperidol	May increase effects if taken concurrently
Drug — MAOIs	May increase effects
Drug — Diltiazem or verapamil	Can increase concentration/effect
Food — Grapefruit products	May increase concentration and risk for toxicity
Lab values	May produce false-positive urine metanephrine/catecholamine assay test

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Page 3 — Dosage and Administration of Buspirone

• Available strengths: 5-, 7.5-, 10-, 15-, and 30-mg tablets
• Initial dosage: 5 to 7.5 mg twice a day (BID)
• Maximum dosage: 60 mg/day (titration at provider's discretion)
• Can be given without regard to food, EXCEPT grapefruit and grapefruit products should be avoided

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Page 4 — Side Effects and Adverse Effects of Buspirone

Buspirone is usually well tolerated with few side effects.

Common side effects:

• Dizziness or lightheadedness
• Drowsiness
• Nausea
• Headache
• Changes in dreams

Adverse effects (rare):

• Little or no risk for suicide associated with buspirone
• Tardive dyskinesia can occur — monitor closely as with any psychiatric drug
• Rare instances of serotonin syndrome and hostility have occurred

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Page 5 — Patient Teaching for Buspirone

The nurse should provide the patient with the following:

• Improvement may be noted in 7 to 10 days, but optimum therapeutic effect generally takes 3 to 4 weeks
• Drowsiness usually disappears during continued therapy
• Dizziness may occur — transition slowly from lying to standing
• Avoid tasks requiring alertness and motor skills until drug response is established
• No alcohol or grapefruit products while taking buspirone
• Severe renal and hepatic impairment can occur if buspirone is taken with an MAOI

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Page 6 — Evaluation for Buspirone

Buspirone therapy is determined to be effective when the patient experiences:

• Decreased anxiety
• Calm facial expression
• Decreased restlessness
• Lessened insomnia
• Improved mental status

Ongoing monitoring:

• For long-term therapy: CBC and hepatic/renal function tests periodically as prescribed
• Assist with ambulation if drowsiness or dizziness occurs

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Page 7 — Case Study: Ms. Gamez

Ms. Gamez is a 35-year-old woman presenting with increasing anxiety and panic attacks that come on suddenly and without warning. She has no medical history, is recently divorced, and reports high stress from job and divorce. The health care provider refers her for psychotherapy and prescribes buspirone 7.5 mg PO BID.

Section 15: Desired Effects of Commonly Misused Drugs

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Page 1 — Overview

People take drugs and/or consume alcohol mainly to obtain a desired effect — whether treating illness (prescribed use) or seeking other effects (misuse). The three most commonly abused drug classes are amphetamines, opioids, and benzodiazepines.

• In 2017, 19.7 million Americans older than age 12 experienced substance use disorder (SAMHSA, 2018)
• Of that number, 74% (1 in 8 people) also experienced alcohol use disorder
• 38% were engaged in use of illicit drugs (SAMHSA, 2018)

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Page 2 — Desired Effects of Alcohol

Alcohol can be consumed as hard liquor, beer, wine, or spirits. Per the 2016 National Survey on Drug Use and Health, approximately 14.6 million adults aged 18 and older had an alcohol use disorder; an additional 488,000 adolescents (ages 12–18) also met these criteria (SAMHSA, 2017).

Desired effects of alcohol: relaxation, decreasing inhibition, celebrating/having a good time, increasing sociability or self-esteem, or simply enjoying the taste. The Desired Effects of Drinking tool (Miller, 2004) can help nurses work with patients to identify desired effects and healthy alternative ways to achieve those feelings.

Blood Alcohol Concentration (BAC) Effects:

BAC Level	Effects
0.0–0.05% (Mild Impairment)	Mild speech, memory, attention, coordination, and balance impairments; perceived beneficial effects such as relaxation; sleepiness can begin
0.06–0.15% (Increased Impairment)	Perceived beneficial effects give way to increasing intoxication; increased risk of aggression; speech, memory, attention, coordination, balance further impaired; significant impairments in all driving skills; increased risk of injury to self and others; moderate memory impairments
0.16–0.30%	All driving-related skills dangerously impaired; judgment and decisionmaking dangerously impaired; vomiting and signs of alcohol poisoning common; loss of consciousness

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Page 3 — Desired Effects of Stimulants

Stimulants (amphetamines) stimulate the CNS. Legally prescribed for ADHD, short-term obesity treatment, and narcolepsy.

• Nonprescription/misuse: Associated with college students seeking to stay awake without fatigue for academic performance; used in excess can produce euphoria and hallucinations
• Illegal stimulants: Cocaine (powdered), crack cocaine (crystalized rock), methamphetamine ("meth") — all induce euphoria when smoked or injected
• Tolerance builds quickly, leading individuals to seek higher and more frequent doses

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Page 4 — Desired Effects of Benzodiazepines

Benzodiazepines are a type of sedative-hypnotic drug. Common examples: lorazepam, clonazepam, diazepam, alprazolam — all prescribed with caution for patients with anxiety.

• These are CNS depressants and, because of their calming effect, are highly subject to misuse
• Nonbenzodiazepine "Z-drugs" are also often misused: eszopiclone, zaleplon, zolpidem (Brandt & Leong, 2017)
• Desired effect of misuse: calm, sedation, muscle relaxation, absence of anxiety

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Page 5 — Desired Effects of Opioids

Opioids can be legal (prescription) or illegal. Prescription examples: Percocet, Vicodin, Demerol, oxycodone — prescribed for postoperative/postinjury pain.

Key statistics:

• 21%–29% of people legally prescribed opioids misuse them (NIDA, 2019b)
• 8%–12% of those develop an opioid use disorder
• As tolerance/dependence evolve, individuals may turn to heroin (cheaper, illegal) or fentanyl (50–100× more potent than morphine)
• CDC/NCHS estimates 130 people in the U.S. die daily from opioid overdose
• More than 652,000 people have heroin use disorder; 1.7 million have a substance use disorder from opioid pain reliever misuse — the "opioid crisis"
• Desired effect: Pain relief; opioid use triggers release of endorphins, creating short-lived euphoria — this short duration drives repeated use seeking to re-create the feeling

Section 16: Side Effects, Adverse Effects, and Long-Term Consequences of Commonly Misused Drugs

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Page 1 — Side Effects and Adverse Effects of Commonly Misused Drugs

All drugs, whether legal or illegal, carry the risk for side and adverse effects.

Substance	Side Effects	Adverse Effects
Alcohol	Slurring of speech; impairment of gait and coordination; impairment of vision; changes in cognition; lowering of inhibition → poor decision making	Overdose: "Blackouts" (unable to recall time), difficulty breathing, dangerously low body temperature, diminished/absent gag reflex, risk for death if untreated. Long-term: Structural brain changes (loss of gray/white matter), irreversible cognitive impairment, hepatitis, gastritis, malnutrition, increased risk for cancer
Stimulants	Hypertension and increased pulse; increase in respirations; decrease in peripheral blood flow; increase in blood glucose	Dangerously high temperature (high doses); cardiac irregularity/heart failure (high doses); seizures (high doses); psychosis, anger, and paranoia (with repeated misuse)
Benzodiazepines and Z-drugs	Headache, drowsiness, dizziness, lethargy	Respiratory depression (especially when mixed with alcohol or other substances); Z-drugs: complex sleep behaviors (driving while asleep, making/eating food without recollection, suicidality, engaging in unremembered sexual activity)
Opioids	Confusion, difficulty arousing, hypotension, vomiting, constipation	Respiratory depression (especially when mixed with alcohol); immunosuppression (especially with long-acting opioids); death (particularly related to heroin and fentanyl)

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Page 2 — Alcohol Toxicity

Physiologic manifestations of alcohol dependence and acute toxicity can (and often do) overlap. Classic signs include confusion, vomiting, seizures, slow breathing (<8 breaths/min), irregular breathing (gap >10 seconds between breaths), blue-tinged or pale skin, low body temperature (hypothermia), passing out and cannot be awakened.

Physical effects of long-term alcohol dependence (body diagram):

• Brain: Blackouts, fits, acute confusional states, subdural haematoma, degeneration of cerebellum
• Head/Neck: Cancer of mouth/pharynx/larynx; cancer of oesophagus
• Cardiovascular: Hypertension, atrial fibrillation, cardiomyopathy
• Abdominal: Cirrhosis, cancer, hepatitis, fatty liver; gastritis, pancreatitis
• Reproductive: Infertility, impotence, loss of secondary sexual characteristics
• Extremities/Peripheral: Myopathy, peripheral neuropathy, gout
• Other: Nutritional deficiencies, injuries, Cushing's syndrome, anaemia, osteoporosis, Foetal Alcohol Syndrome (failure to thrive, developmental delay, facial abnormalities, cardiac abnormalities)

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Page 3 — Stimulant Toxicity

Chronic cocaine use body effects (diagram):

• Brain: Increased risk of strokes, reduced attention, insatiable hunger, insomnia/hypersomnia, lethargy
• Systemic: Fever, eosinophilia
• Nose: Rhinorrhea (discharge)
• Teeth: Bruxism (abrasion)
• Throat: Soreness, hoarse voice
• Heart: Increased risk of infarction
• Lungs: Hemoptysis, bronchospasm, dyspnea, infiltrates, eosinophilia, chest pain, asthma
• Skin: Pruritus

Classic signs of stimulant toxicity:

• Diaphoresis, hypertension, hyperthermia, tachycardia
• Severe agitation (patient poses danger to self or others)
• Psychosis
• Increased troponin, elevated liver transaminase

Long-term consequences: Seizures, altered mental status, metabolic acidosis, imminent cardiovascular collapse, and death.

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Page 4 — Benzodiazepine Toxicity

Classic signs of benzodiazepine toxicity:

• CNS depression
• Respiratory depression
• Stupor
• Comatose

Long-term consequences: Respiratory depression, coma, or death.

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Page 5 — Opioid Toxicity

Classic signs of opioid toxicity ("opioid triad"):

• Depressed mental status
• Decreased respiratory rate
• Decreased tidal volume
• Decreased bowel sounds
• Miotic (constricted) pupils

Agent-specific additional signs:

• Fentanyl: Associated with acute amnestic syndrome in overdose
• Meperidine: Seizure, serotonin toxicity (in combination with other agents)
• Oxycodone: Possible QT interval prolongation

Long-term consequences: Seizure, coma, hypoxia, or death.

⚠️ Patient Safety: Certain opioids (morphine, methadone, fentanyl) have immunosuppressive properties. Risk varies by patient population and pathogen exposure. Nurses must assess patients taking these drugs for signs and symptoms of immunosuppression (Portenoy, 2019).

Section 17: Pharmacodynamics and Pharmacokinetics of Drugs Used in the Management of Substance Use Disorders

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Page 1 — Overview

Some addictions benefit from targeted medication therapy; others do not:

• Alcohol and opioid addiction: Have FDA-approved medications for withdrawal and abstinence maintenance
• Benzodiazepine and stimulant misuse: No FDA-approved medications specifically designed for withdrawal/abstinence — medications may be prescribed to address symptoms, but no specific FDA drugs exist for these

Medication supports alcohol/opioid addiction treatment in two ways:

1. Facilitating withdrawal from alcohol or opioids
2. Helping maintain abstinence once withdrawal is successfully accomplished

Goals of Treatment:

• Prevention/minimization of future alcohol or opioid consumption after detoxification
• Total abstinence from alcohol or opioid use
• If a person resumes drinking, keeping it to a minimum (associated with reduced alcohol-related morbidity)

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Page 2 — Drugs Approved for Alcohol Abstinence Maintenance and Treatment of Opioid Addiction

Prototype drugs of study: Disulfiram (alcohol abstinence) and Naltrexone (opioid addiction)

FDA-Approved Drugs for Alcohol Abstinence Maintenance:

Drug	How It Works
Disulfiram	Causes unpleasant side effects when alcohol is consumed
Naltrexone	Blocks the pleasurable effects of alcohol and reduces the desire to drink
Acamprosate	Reduces unpleasant feelings (agitation, depression, feelings of foreboding) resulting from alcohol discontinuation/withdrawal

FDA-Approved Drugs for Treatment of Opioid Addiction:

Drug	How It Works
Methadone	Synthetic opioid agonist; eliminates withdrawal symptoms and relieves drug cravings by acting on opioid receptors in the brain
Buprenorphine	Partial opioid antagonist; binds with opioid receptors → decreased pain and increased feelings of well-being
Naltrexone	Blocks the pleasurable effects of opioids and reduces the desire to use them
Suboxone	Combination of buprenorphine and naltrexone
Lofexidine (withdrawal only)	The only FDA-approved drug that mitigates withdrawal symptoms associated with opioid withdrawal

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Page 3 — Pharmacokinetics and Pharmacodynamics of Disulfiram

Disulfiram is an oral (PO) drug indicated only for treatment of alcoholism. It decreases frequency of drinking after relapse, because the patient is familiar with the unpleasant reaction that follows alcohol consumption.

Pharmacokinetics:

Parameter	Details
Absorption	Rapidly absorbed from GI tract; peak plasma concentrations after 8–10 hours (PO)
Distribution	1/5 of a dose may remain in the body for a week or longer
Metabolism	Reduction to diethyldithiocarbamate by glutathione reductase system in erythrocytes
Excretion	Urine (as metabolites); exhaled gas (carbon disulfide)

Mechanism of Action: Irreversible inhibition of aldehyde dehydrogenase (the enzyme that converts acetaldehyde → acetic acid). When alcohol is ingested, acetaldehyde accumulates to toxic levels in the blood → unpleasant and potentially harmful effects.

Therapeutic Effects: The resulting effects act as a deterrent to alcohol ingestion: intense headache, nausea, chest pain, weakness, blurred vision, mental confusion, sweating, choking/breathing difficulty, heart palpitations, anxiety, and emesis. Supervised administration is more effective than independent use. Noncompliance is a risk due to the unpleasant effects; patients with chronic misuse may continue drinking despite the drug (dangerous).

Pharmacodynamic Profile:

Parameter	Value
Onset	12 hours
Peak	8–10 hours after PO dose
Duration	Up to 20% can stay in body for 1–2 weeks after last dose
Half-life	60–120 hours

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Page 4 — Pharmacokinetics and Pharmacodynamics of Naltrexone

Extended-release injectable naltrexone (XR-NTX) approved by FDA in 2006 for alcohol dependence and October 2010 for opioid dependence. Injected intramuscularly once a month.

Pharmacokinetics:

Parameter	Details
Absorption	Well absorbed orally; significant first-pass metabolism; PO bioavailability 5%–40%
Distribution	Low plasma protein-binding (21%)
Metabolism	Extensively metabolized by the liver
Elimination	Via urine (and breast milk)

Mechanism of Action: Opioid antagonist that inhibits the pleasurable effects from drinking alcohol or misusing opioids. Exact mechanism unknown — one hypothesis: blocks release of dopamine expected after inhibition of opioid receptors. Well tolerated overall but can initiate withdrawal symptoms in patients actively misusing opioids.

Therapeutic Effects: Blocks cerebral opioid receptors; blocks effects of morphine, heroin, and other opioids. Patients reported less craving for alcohol, fewer drinking days, fewer drinks per occasion, and reduced severity of alcohol-related problems vs. placebo. XR-NTX (once monthly) is effective for opioid misuse.

Pharmacodynamic Profile (onset by route):

Route	Onset
PO	15–30 minutes
IV	1–2 minutes
IM	2–5 minutes
SQ	2–5 minutes

Note: Peak plasma concentration, elimination half-life, and duration are dose- and route-dependent. More than one administration may be required in emergent treatment.

Section 18: Nursing Process Related to Drugs Used in the Management of Substance Use Disorders

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Page 1 — Pre-Administration Assessment for Disulfiram and Naltrexone

Disulfiram — Key Assessment Points:

• Patients must be highly motivated to abstain from alcohol — disulfiram is self-administered daily
• Strong support systems (family, etc.) improve abstinence and adherence
• Candidates must be chosen carefully — patients likely to relapse or attempt drinking should NOT be considered
• Abstinence from alcohol for at least 24 hours required before starting disulfiram
• If patient abstains 3–5 days without withdrawal symptoms → no medically assisted detox needed

Metrics to verify abstinence:

• Patient reports abstaining (typically sufficient to start acamprosate or naltrexone)
• Family member/caretaker vouches for patient
• Negative urine alcohol test
• Provider documents recent medically assisted withdrawal/detox
• Blood/breath alcohol level is zero (required before starting disulfiram)

Naltrexone — Key Assessment Points:

• Treatment should not start unless patient has been opioid-free for 7–10 days and alcohol-free for 3–5 days
• Obtain a complete medication history with attention to opioid use history
• If opioid dependence suspected → perform a naloxone challenge test (naloxone administered to verify opioid dependence and eligibility for opioid treatment program)
• Assess for hepatitis and other liver diseases

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Page 2 — Contraindications of Disulfiram and Naltrexone

Disulfiram — Contraindicated in:

• Those known or suspected of being unable to abstain from alcohol
• Those with cardiac disease, coronary artery occlusion, or psychosis
• Those who have recently ingested metronidazole, alcohol, or alcohol-containing medications (e.g., OTC cough syrups, cold remedies)

Naltrexone — Contraindicated in:

• Those with a known drug allergy to any component of the medication
• Those with hepatitis or other severe liver dysfunction

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Page 3 — Interactions of Disulfiram

Interaction	Details
St. John's Wort	May cause a reaction similar to that associated with alcohol consumption
Phenytoin and other metabolism-slowing drugs	Disulfiram decreases metabolism rate → increased blood levels → risk for toxicity (e.g., phenytoin intoxication). Obtain baseline phenytoin serum level; monitor serum levels on different days
Oral anticoagulants	May prolong prothrombin time; anticoagulant dose adjustment may be necessary when starting/stopping disulfiram
Isoniazid	May cause unsteady gait or significant mental status changes; discontinue disulfiram immediately if these signs appear

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Page 4 — Drug Interactions of Naltrexone

• No conclusive evidence that naltrexone reacts with drugs other than opioids, but all co-administered drugs warrant caution
• Patients taking naltrexone may not benefit from opioid-containing medicines (cough/cold preparations, antidiarrheal preparations, opioid analgesics)
• Emergency situation (e.g., orthopedic trauma): If opioid analgesia must be given to a patient receiving naltrexone, the required opioid dose may be greater than usual — but higher doses increase risk for respiratory depression

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Page 5 — Dosage and Administration of Disulfiram and Naltrexone

Disulfiram:

• Available in 250- and 500-mg tablets (oral)
• First dose cannot be given until patient has ingested no alcohol or alcohol-containing substance for at least 12 hours
• Initial dose: 500 mg once daily for 1–2 weeks
• Maintenance dose: 125–500 mg/day as a single morning dose
• Treatment may continue for months to years depending on the patient's needs

Naltrexone:

• Available in two formulations:
  • 50-mg tablets (PO, once daily)
  • 380-mg parenteral liquid (IM, once monthly)
• IM naltrexone is preferred when there is concern about compliance with PO medication
• IM is a depot formulation — slow, sustained release over the entire dosing period; administered in health care setting → minimizes noncompliance risk
• Patients who have misused alcohol must be alcohol-free for at least 12 hours before initiating naltrexone

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Page 6 — Side Effects and Adverse Effects of Disulfiram and Naltrexone

Disulfiram:

• Side effects without alcohol: rarely causes undesired effects; initial drowsiness and skin irritation may occur (self-limiting)
• "Mild" acetaldehyde syndrome (from as little as 7 mL alcohol): nausea, copious vomiting, flushing, palpitations, headache, sweating, thirst, chest pain, weakness, blurred vision, hypotension; lasts 30 min to several hours
• Fully developed acetaldehyde syndrome (life-threatening adverse effect): marked respiratory depression, cardiovascular collapse, cardiac dysrhythmias, MI, acute heart failure, convulsions, severe hypotension → shock and death

Naltrexone:

• Side effects at IM injection site: pain, tenderness, induration, swelling, edema, erythema, bruising, pruritus
• Most common adverse effects: nausea and tachycardia (related to reversal of opioid effect)
• Adverse effects — excessive dose → hepatic injury at cellular level
• Severe IM injection site reactions (can cause significant scarring, may require surgical intervention): cellulitis, hematoma, abscess, necrosis

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Page 7 — Patient Teaching: Interventions for Patient Safety

General safety interventions:

• Inform patients about the potential hazards of treatment
• Teach patients to avoid ALL forms of alcohol including alcohol in vinegar, sauces, cough syrups, OTC cold medications, tonics, and topical alcohol (aftershave, colognes, liniments)
• Encourage patients to carry identification to alert emergency personnel to their condition
• Warn against use of alcohol and other depressants concurrently with drug therapy
• Emphasize life-threatening effects while maintaining a balance with importance of compliance

Disulfiram-specific:

• Effects persist for ~2 weeks after last dose — no alcohol during this time
• First dose not until at least 12 hours after last drink
• Tablets may be crushed or mixed with liquid

Naltrexone-specific:

• Explain the IM dosing schedule
• Inform about adverse drug effects with IM administration
• Explain risk for liver damage with high naltrexone dosing

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Page 8 — Patient Teaching: Drug Interactions and Side Effects to Report

Disulfiram — Interactions to report:

• Alcohol-containing medicines (certain HIV protease inhibitors, cough syrups, liquid medicines), metronidazole → increased risk for severe adverse effects
• Anticoagulants, benzodiazepines, isoniazid, phenytoin → side effects may be worsened

Disulfiram — Side effects to watch for and report: Eye pain/tenderness/vision changes, mood/mental changes, numbness/tingling/pain/weakness in hands or feet, darkening of urine, light gray stools, severe stomach pain, yellow eyes/skin, drowsiness, decreased sexual ability (males), headache, metallic/garlic taste in mouth, skin rash, unusual fatigue

Naltrexone — Report signs of liver injury and discontinue if hepatitis develops

Naltrexone — Side effects to report: Blurred vision or eye problems; tachycardia; mood changes, hallucinations, confusion, thoughts of hurting oneself; nausea, stomach pain, low fever, loss of appetite; dark urine, clay-colored stools, jaundice; ear pain/ringing; skin rash/itching; wheezing/respiratory distress; anxiety, nervousness, restlessness, irritability; lightheadedness/fainting; increased thirst; muscle/joint pain; weakness/fatigue; insomnia; decreased sex drive, impotence, or difficulty with orgasm

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Page 9 — Evaluation for Disulfiram and Naltrexone

Effectiveness is measured by:

• Patient adherence to the drug regimen and appropriate administration times
• Patient adherence to refraining from alcohol or opioid misuse
• Patient adherence to refraining from other substances that could interact with drug treatment
• Patient demonstration of avoidance of alcohol or opioids

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Page 10 — Case Study: Renae

Renae is a 27-year-old female who began using prescription opioids after surgery for a broken ankle from a skiing accident. After full physical recovery, her provider discontinued opioid prescriptions; Renae began seeking opioids from friends, coworkers, and found her grandmother's prescription. When she found herself considering stealing the medication, she sought help and was prescribed naltrexone. The nurse will teach Renae about timeliness of administration and side and adverse effects.

Section 19: Pharmacokinetics and Pharmacodynamics of Adrenergic Drugs

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Page 1 — Overview of Adrenergic Drugs

Drugs that stimulate the sympathetic nervous system are called adrenergic agonists, adrenergics, or sympathomimetics — so named because they mimic the actions of sympathetic neurotransmitters norepinephrine and epinephrine.

Adrenergic drugs act on one or more adrenergic receptor sites located in the effector cells of muscles: heart, bronchiole walls, GI tract, urinary bladder, and ciliary muscles of the eyes. The specific action of the drug depends on which type of adrenergic receptor is stimulated.

(Diagram: Parasympathetic and sympathetic nervous systems — parasympathetic uses ACh, nicotinic + muscarinic receptors → smooth muscle, cardiac muscle, glands; sympathetic uses NE, adrenergic receptors [alpha + beta] → heart, blood vessels, skeletal muscle.)

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Page 2 — Major Adrenergic Receptors

There are many adrenergic receptors. The four main types are alpha₁, alpha₂, beta₁, and beta₂. A fifth type — dopaminergic receptors — are located in the renal, mesenteric, coronary, and cerebral arteries; when stimulated, blood vessels dilate and blood flow increases. Only dopamine can activate these receptors.

Receptor	Location	Effect of Stimulation
Alpha₁	Blood vessels, eyes, bladder, prostate	Vasoconstriction of arterioles and venules → ↑ peripheral resistance → ↑ BP; excess stimulation → ↓ blood flow to vital organs
Alpha₂	Postganglionic sympathetic nerve endings	Inhibit NE release → ↓ vasoconstriction → vasodilation → ↓ BP
Beta₁	Heart (primarily), kidneys	↑ myocardial contractility and ↑ heart rate
Beta₂	Lungs, GI tract, liver, uterine muscle	Bronchodilation; ↓ GI tone/motility; glycogenolysis in liver → ↑ blood glucose; relaxation of uterine muscle → ↓ contractions

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Page 3 — Classification of Adrenergic Drugs

Adrenergic agonists fall into two major chemical classes: catecholamines and noncatecholamines. They can also be classified by mechanism of action: direct-acting, indirect-acting, or mixed-acting. Direct-acting adrenergics mainly affect the peripheral nervous system; indirect-acting mainly affect the central nervous system.

• Alpha receptor activation → primarily associated with vasoconstriction
• Beta receptor activation → primarily associated with vasodilation

Feature	Catecholamines	Noncatecholamines
Chemical structure	Contain catechol groups	No catechol groups
Route	Cannot be given orally	May be given orally
Duration of action	Short	Longer
Blood-brain barrier	Do NOT cross	DO cross
Examples	Endogenous: epinephrine, norepinephrine, dopamine; Synthetic: isoproterenol, dobutamine	Phenylephrine, ephedrine, albuterol
Prototype drug	Epinephrine — activates all 4 adrenergic receptor subtypes; broad spectrum sympathomimetic effects	Albuterol — prevention and treatment of bronchospasm

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Page 4 — Pharmacokinetics of Epinephrine

Epinephrine is a catecholamine frequently used in emergency treatment of anaphylaxis (life-threatening allergic response). Routes: SC, IM (vastus lateralis), IV, topical, inhalation, or intracardiac injection. Not given orally due to rapid metabolization.

PK Parameter	Details
Absorption	Parenteral (IM, SQ): well absorbed; Inhalation: minimal absorption
Distribution	Protein binding: unknown
Metabolism	Rapidly metabolized by MAO and COMT before reaching systemic circulation; metabolized in liver and sympathetic nervous tissues
Excretion	Urine

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Page 5 — Pharmacokinetics of Albuterol

Albuterol is primarily used to treat or prevent bronchospasm.

PK Parameter	Details
Absorption	Oral: rapidly absorbed from GI tract; Inhalation: rapidly absorbed from bronchi
Distribution	Low protein binding; Oral: widely distributed; Inhalation: primarily in lungs
Metabolism	Metabolized by the liver
Excretion	Urine

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Page 6 — Pharmacodynamics of Epinephrine

Epinephrine is a potent inotropic and chronotropic drug. It:

• ↑ cardiac output
• ↑ systolic BP (vasoconstriction)
• ↑ heart rate
• Causes bronchodilation
• Can cause renal vasoconstriction → ↓ renal perfusion and urinary output
• High doses → dysrhythmias (cardiac monitoring necessary)

Therapeutic Uses by Receptor:

Receptor Activated	Effect/Use
Alpha₁-mediated vasoconstriction	Delays absorption of local anesthetics; controls superficial bleeding; elevates BP
Beta₁ receptor activation	Corrects AV heart block; restores cardiac function in V-fib, pulseless V-tach, PEA, or asystole; hypotension unresponsive to volume resuscitation; bradycardia/hypotension unresponsive to atropine or pacing
Beta₂ receptor activation in lungs	Promotes bronchodilation
Alpha + beta receptor combination	Treats anaphylactic shock

Pharmacodynamic Profile:

Route	Onset of Action	Peak Plasma Concentration	Duration
SQ	5–10 min	20 min	1–4 hr
IV	<2 min	Rapid	5–30 min
IM	5–10 min	20 min	1–4 hr
Inhaled	3–5 min	20 min	1–3 hr

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Page 7 — Pharmacodynamics of Albuterol

Albuterol causes beta₂-mediated bronchodilation — useful in treatment and prevention of asthma. It is relatively selective for beta₂ receptors, producing far less activation of cardiac beta₁ receptors than isoproterenol → better choice for asthma. However, in large doses, albuterol loses its selectivity and can cause undesired cardiac stimulation.

Pharmacodynamic Profile:

Route	Onset of Action	Peak Plasma Concentration	Duration
Oral	0.5 hr	2–3 hr	4–6 hr
Inhaled	5–15 min	0.5–2 hr	2–6 hr

Section 20: Nursing Process Related to Adrenergic Therapy

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Page 1 — Pre-Administration Assessment for Adrenergic Drugs

The nurse would assess all patients receiving adrenergic medications before administering the first dose. There are contraindications, side effects, and cautions related to these medications. It is also imperative to teach the patient signs and symptoms that could indicate an adverse reaction.

Epinephrine: Used for cardiac, bronchial, antiallergic, ophthalmic, and vasopressor effects. Assessment focuses on vital signs, breath sounds, and if prescribed, arterial blood gas levels and ECG findings. Liver and renal function should be monitored.

Albuterol: Assess lung sounds, pulse, BP, color, and character of sputum.

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Page 2 — Contraindications and Interactions with Epinephrine

The nurse must know contraindications for epinephrine before administration because serious reactions can occur.

Contraindications: Cardiac dysrhythmias, pregnancy, narrow-angle glaucoma, cardiogenic shock

Cautions: Angina pectoris, hypertension, prostatic hypertrophy, hyperthyroidism, cerebral arteriosclerosis, pregnancy, diabetes mellitus (hyperglycemia could result)

⚠️ NOTE: There are no absolute contraindications with injectable epinephrine in a life-threatening situation.

Interactions:

• Increased effects: Decongestants, tricyclic antidepressants, MAO inhibitors (MAOIs)
• Antagonized effects: Methyldopa, beta blockers
• Dysrhythmia risk: Digoxin when used with epinephrine
• Increased stimulation: Caffeine, guarana, yerba mate

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Page 3 — Dosage and Administration of Epinephrine

Epinephrine can be administered by various routes for different indications. The nurse must know the correct dosage relevant to the indication and route.

For Anaphylaxis/Hypersensitivity Reaction:

• Adult SQ/IM: 0.2–0.5 mg (0.2–0.5 mL of 1:1000 solution); may repeat q5–15 min (anaphylaxis) or q15–20 min (hypersensitivity). EpiPen provides 0.3 mg dose.
• Adult IV: 0.1–0.25 mg of 1:10,000 solution infused slowly over 5–10 min; may repeat q5–15 min as needed; may follow with 1–4 mcg/min infusion
• Children SQ/IM: 0.01 mg/kg (0.001 mg/kg of 1:1000 solution); may repeat q5–15 min; max 0.3 mg. EpiPen Jr provides 0.15 mg dose.

For Asthma Bronchodilation:

• Adult/Adolescent SQ: 0.3–0.5 mg (0.3–0.5 mL of 1:1000) q20 min × 3 doses if needed
• Nebulizer: Add 0.5 mL to hand bulb nebulizer; 1–3 inhalations up to q3h if needed

For Cardiac Arrest:

• Adult IV: Initially 1 mg; may repeat q3–5 min as needed
• Endotracheal: 2–2.5 mg q3–5 min as needed

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Page 4 — Side Effects and Adverse Effects of Epinephrine

Side Effects	Adverse Effects
CNS: Tremors, anxiety, dizziness, insomnia	CV: Palpitations, tachycardia, hypertension, tissue necrosis at IV site upon infiltration
RESP: Dyspnea	Life-threatening: Ventricular fibrillation, pulmonary edema
CV: Palpitations, tachycardia
GI: Anorexia, nausea, vomiting
MISC: Sweating, dry eyes

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Page 5 — Interventions for Epinephrine

To evaluate patient response, the nurse monitors vital signs, watches for drug-drug interactions (including OTC cold/allergy drugs, caffeine, alcohol, herbs, dietary supplements).

• Monitor changes in BP and HR — epinephrine can cause increases in both due to sympathetic activation
• Titrate dose of epinephrine infusion to maintain BP per prescribed parameters
• Assess lung sounds for rhonchi, wheezing, and rales
• Monitor ABGs if used for respiratory distress
• Monitor ECG for dysrhythmias when IV is administered
• Check urinary output and assess for bladder distention (urinary retention can result from high dose or continuous use of adrenergic agonists)
• In cardiac arrest, adhere to ACLS protocols
• Evaluate for therapeutic effect: improved BP, breathing pattern, and cardiac output

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Page 6 — Patient Teaching for Epinephrine

Patients prescribed epinephrine need to know how to self-administer using an epinephrine autoinjector (e.g., EpiPen) in an emergency. Nurse must advise patient and family on proper administration and allow return demonstrations.

General Teaching:

• Take medication as prescribed
• Have epinephrine autoinjector available at all times; store additional medication in a cool, dark place (refrigeration NOT recommended)
• Seek immediate medical attention after using the autoinjector — anaphylaxis requires emergency care
• Notify provider if autoinjector needed more than once per week

Self-Administration:

• Administer immediately upon initial occurrence of difficulty breathing, wheezing, hoarseness, hives, itching, or swelling of lips/tongue
• Inspect solution for particles or discoloration before administration; do NOT use if solution is pink to brown in color
• Inject IM or SQ — NOT intradermally; apply sufficient pressure to activate and hold in place 5–10 seconds
• Inject into the outer thigh
• Massage injection site for 10 seconds after administration (promotes absorption, reduces vasoconstriction and tissue irritation)

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Page 7 — Patient Teaching for Epinephrine: Side Effects

Frequency	Systemic Effects	Ophthalmic Effects
Frequent	Tachycardia, palpitations, anxiety	Headache, eye irritation, watering of eyes
Occasional	Dizziness, lightheadedness, facial flushing, headache, diaphoresis, increased BP, nausea, trembling, insomnia, vomiting, fatigue	Blurred/decreased vision, eye pain
Rare	Chest discomfort/pain, arrhythmias, bronchospasm, dry mouth/throat	—

Notify HCP immediately if any rare side effects occur.

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Page 8 — Contraindications and Interactions with Albuterol

Contraindications: Hypersensitivity, milk protein hypersensitivity

Cautions: Cardiac dysrhythmias, coronary artery disease, severe cardiac disease, hypertension, hyperthyroidism, diabetes mellitus, renal dysfunction, older adults, heart failure, seizures, MAOI therapy, pregnancy, breastfeeding

Interactions:

• Increased effect: Other sympathomimetics; MAOIs and tricyclic antidepressants
• Antagonized effects: Beta-adrenergic blockers (beta blockers)
• Decreased effects: St. John's Wort
• Increased CNS stimulation: Ephedra and yohimbe

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Page 9 — Dosage and Administration of Albuterol

Adults/Children Older than 12 Years:

• PO: 2–4 mg t.i.d./q.i.d.; max: 32 mg/d in four divided doses
• SR: 4–8 mg q12h
• Inhaler: 1–2 puffs q4–6h PRN
• Nebulizer: 0.5 mL of 0.5% solution in 3 mL of 0.9% NaCl in 5–15 min

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Page 10 — Side Effects and Adverse Effects of Albuterol

Side Effects	Adverse Effects
CNS: Tremors, anxiety, restlessness	CNS: Hallucinations, seizures
CV: Palpitations, tachycardia, angina	CV: Palpitations, tachycardia, hypertension, chest pain, hyperglycemia, hypokalemia
EENT: Dry nose, irritation of nose and throat	MISC: Hyperglycemia, hypokalemia
GI: Heartburn, nausea, vomiting, anorexia	Life-threatening: Cardiac dysrhythmias, bronchospasm
INTEG: Flushing, sweating

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Page 11 — Interventions for Albuterol

• Monitor rate, depth, rhythm, and type of respiration and ABG results
• Monitor changes in HR or rhythm (albuterol can cause tachycardia and other dysrhythmias)
• Monitor serum glucose in patients with diabetes (albuterol can cause elevation)
• Assess serum potassium levels (hypokalemia can increase risk for dysrhythmias)
• Assess lung sounds for wheezing (bronchoconstriction) and rales
• Evaluate for therapeutic effect: decreased respiratory rate and clear breath sounds
• Offer emotional support — patients commonly experience anxiety from difficulty breathing and sympathomimetic response to the drug

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Page 12 — Patient Teaching for Albuterol

Explain use of albuterol to all patients. Ensure patient understands correct method for the prescribed inhaler type; allow time for return demonstration.

• Follow guidelines for proper use of the inhaler
• Increase fluid intake to decrease lung secretion viscosity
• Do NOT take more than 2 inhalations at one time (excessive use may produce paradoxical bronchoconstriction or decrease bronchodilating effect)
• Rinse mouth with water immediately after inhalation to prevent mouth/throat dryness
• Avoid excessive use of caffeine derivatives (chocolate, coffee, tea, cola, cocoa)

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Page 13 — Patient Teaching for Albuterol: Side Effects

Frequency	Side Effects
Frequent (4%–27%)	Headache, restlessness, nervousness, tremors, nausea, dizziness, throat dryness and irritation, pharyngitis, BP changes (including hypertension), heartburn, transient wheezing
Occasional (2%–3%)	Insomnia, asthenia, altered taste; Inhalation-related: dry/irritated mouth or throat, cough, bronchial irritation
Rare	Drowsiness, diarrhea, dry mouth, flushing, diaphoresis, anorexia

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Page 14 — Evaluation of Adrenergic Drug Therapy

Effectiveness is evidenced by clear breath sounds and respiratory rate within normal limits. If side/adverse effects occur, notify the HCP as appropriate. Evaluate patient understanding of patient teaching, drug administration, and management post-discharge. Reinforce any information not understood and provide written instructions. Significant others should also have a clear understanding.

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Page 15 — Case Study: Alyssa

Patient: Alyssa, 12 years old, known peanut allergy. Presents to ED accompanied by parents with hives, swollen eyes, a red rash, difficulty breathing, pulse of 96, BP 112/80. Was at a school party and is assumed to have had peanut contact. No other health problems. (Epinephrine would be the treatment of choice for anaphylaxis in this scenario.)

Section 21: Pharmacokinetics and Pharmacodynamics of Cholinergic Drugs

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Page 1 — Overview of Cholinergic Drugs

Cholinergic medications affect the parasympathetic nervous system (PNS). Acetylcholine (ACH) is the main neurotransmitter responsible for transmission of nerve impulses to effector cells in the PNS. ACH is located at the ganglia and parasympathetic terminal nerve endings. It innervates cholinergic receptors in organs, tissues, and glands. ACH binds with a cholinergic receptor and mediates its actions. There are two types of cholinergic receptors: nicotinic and muscarinic.

Category	Mechanism of Action	Other Names	Prototype & Examples
Cholinergic Agonists	Stimulate the PNS either directly or indirectly. Direct-acting: bind directly to cholinergic receptors, mimicking ACH. Indirect-acting: inhibit acetylcholinesterase (enzyme that breaks down ACH), prolonging action of naturally occurring ACH	Parasympathomimetics	Prototype: Bethanechol; Others: Metoclopramide, Physostigmine
Cholinergic Antagonists	Inhibit the actions of ACH, which inhibits the PNS	Parasympatholytics, Anticholinergics, Cholinergic blocking agents	Prototype: Atropine; Others: Tolterodine tartrate, Scopolamine

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Page 2 — Pharmacokinetics of Bethanechol and Atropine

Bethanechol (prototype cholinergic agonist): available as oral formulation; was also available as parenteral SQ. Atropine (prototype cholinergic antagonist): can be administered oral, IM, SubC, and IV.

PK Parameter	Bethanechol	Atropine
Absorption	Poorly absorbed by GI tract	Absorbed rapidly with oral and IM administration
Distribution	Protein binding: unknown; Crosses blood-brain barrier	Widely distributed; Protein binding 14%–22%; Crosses blood-brain barrier; Crosses placenta; Found in breast milk
Metabolism	Unknown	Metabolized in the liver
Excretion	Most likely excreted in urine	Urine, 30%–50% unchanged

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Page 3 — Pharmacodynamics of Bethanechol

Bethanechol is a direct-acting cholinergic agonist that stimulates muscarinic receptors in the bladder and GI tract.

Mechanism of Action:

• Increases bladder tone and relaxes the bladder sphincter
• Increases GI smooth muscle tone and motility; relaxes GI sphincters

Therapeutic Uses:

• Postoperative nonobstructive urinary retention
• Urinary retention associated with neurogenic bladder

Pharmacodynamic Profile:

• Onset (Oral): 30–90 minutes
• Peak (Oral): ~1 hour
• Duration: 1–6 hours
• Half-life: 2–3 hours

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Page 4 — Pharmacodynamics of Atropine

Atropine is a cholinergic antagonist that blocks the effects of the PNS.

Mechanism of Action:

• Inhibits actions of ACH by occupying muscarinic receptors
• Blocks vagus stimulation → increased heart rate
• Paralyzes the iris sphincter → pupillary dilation (mydriasis)

Therapeutic Uses:

• Decrease salivation and respiratory secretions preoperatively
• Increase heart rate in the presence of bradycardia
• Dilate pupils before an eye exam

Pharmacodynamic Profile:

• Onset (IV): Immediate
• Peak (IV): 1–2 minutes
• Duration: 4–6 hours
• Half-life: 2.5 hours

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Page 5 — Major Responses of Cholinergic Drugs

Key principle: Cholinergic agonists stimulate parasympathetic responses; cholinergic antagonists inhibit PNS responses.

Body Tissue	Effects of Cholinergic Agonists	Effects of Cholinergic Antagonists
CNS	None	Large doses: Drowsiness, disorientation, hallucinations
Cardiovascular	↓ Heart rate; slow AV node conduction; ↓ BP (vasodilation)	Large doses: ↑ HR; Small doses: ↓ HR
Pulmonary	↑ Bronchial constriction; ↑ bronchial secretions	↓ Bronchial constriction; ↓ bronchial secretions
GI	↑ Gastric motility and peristalsis; relax sphincter muscles	↓ Gastric motility and peristalsis
Genitourinary	Contract bladder muscles; relax bladder sphincter	Relax bladder muscles; ↑ constriction of bladder sphincter
Ocular	Constrict pupils (miosis); ↑ accommodation	Dilate pupils (mydriasis); ↓ accommodation
Glandular	↑ Salivation, perspiration, and tears	↓ Salivation, perspiration, and tears
Skeletal muscle	↑ Neuromuscular transmission; maintain muscle strength and tone	↓ Muscle rigidity; ↓ tremors

Section 22: Nursing Process Related to Cholinergic Therapy

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Page 1 — Pre-Administration Assessment for Cholinergic Drugs

Before administering cholinergic drugs (bethanechol and atropine), the nurse conducts a head-to-toe assessment and complete patient history to identify contraindications or possible drug interactions. The nurse pays attention to:

• Medication allergies
• Past medical history
• Current medications — prescribed and over the counter
• Alcohol and drug use
• Herbal preparation use
• Patient's baseline vital signs
• Patient's urine output (should be >1500 mL/d)

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Page 2 — Contraindications and Drug Interactions with Bethanechol

Contraindications:

• CNS: Seizures, parkinsonism
• Cardiac: Bradycardia, coronary artery disease, hypotension
• Respiratory: Asthma, COPD
• GI/GU: GI/GU obstruction, irritable bowel syndrome, peptic ulcer disease, recent GI/GU surgery
• Also contraindicated when integrity of GI or bladder wall is questionable

Drug Interactions:

• Decreased effects: Sympathomimetics, anticholinergics, or opioids
• Increased effects: Other cholinergic agonists (direct or indirect) and anticholinesterase drugs
• Caution: Ganglionic blocking agents (e.g., mecamylamine) — may result in severe hypotension

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Page 3 — Dosage and Administration of Bethanechol

Used for treatment of urinary retention.

Adults: Oral Dosage

• Initial: 5–10 mg; may repeat every hour until voiding or until 50 mg given
• Maintenance: 10–50 mg three or four times a day
• Maximum: 200 mg/day
• Special considerations: Give 1 hour before meals or 2 hours after meals to minimize GI upset (may give with food if GI pain occurs)

Adults: SQ Dosage

• Initial: 2.5 mg; may repeat every 15–30 min until voiding or until 10 mg given
• Maintenance: 5 mg three or four times a day
• Maximum: 40 mg/day
• Special considerations: Observe patient closely for 30 min to 1 hour for adverse effects; have atropine readily available in the event of cholinergic overdose

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Page 4 — Side Effects and Adverse Effects of Bethanechol

Side effects are rare when administered orally.

Body System	Side Effects	Adverse Effects
CNS	Dizziness, headache, malaise	Insomnia, anxiety, seizures
CV	Hypotension, bradycardia, reflex tachycardia	Orthostatic hypotension
EENT	Miosis, increased salivation, lacrimation, blurred vision	Increased diaphoresis, nausea, vomiting
GI/GU	Nausea, diarrhea, belching, vomiting, abdominal cramps, urgency	Abdominal pain
ITEG	Rash, urticaria, increased sweating	Flushing
RESP	Bronchoconstriction	Bronchoconstriction, increased secretion

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Page 5 — Interventions for Bethanechol

• Monitor vital signs and intake and output ratio
• Auscultate breath sounds — rhonchi may indicate increased respiratory secretions; wheezes may indicate bronchospasms
• Assess bowel and bladder patterns (bethanechol contraindicated with intestinal or urinary tract obstruction)
• Monitor serum amylase, lipase, AST, and bilirubin levels
• Provide comfort measures: bathe patient and change linens frequently if diaphoretic
• Monitor for signs of cholinergic overdose: insomnia, anxiety, headache, seizures; increased salivation and diaphoresis; nausea and vomiting; severe abdominal pain; flushed skin and muscle weakness
• Have IV atropine sulfate (0.6–1.2 mg) readily available in the event of cholinergic overdose
• Notify HCP if significant changes occur in HR or BP, or if patient develops dysrhythmias or signs of cholinergic overdose

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Page 6 — Patient Teaching for Bethanechol

• Take medication as prescribed
• Take 1 hour before meals or 2 hours after meals to avoid gastric upset
• Change positions slowly to avoid dizziness
• Ensure bathroom facilities are readily available after taking medication
• Maintain good oral and personal hygiene (increased saliva and sweat promote bacteria growth)
• Contact HCP if side effects occur: extreme dizziness, chest tightness, shortness of breath, blurred vision, diarrhea, belching, irregular heartbeat, vision changes, urinary urgency or frequency
• Contact HCP if signs/symptoms of cholinergic overdose occur: insomnia, anxiety, dizziness when standing, headache, increased sweating and salivating, nausea/vomiting, abdominal pain, muscle weakness, flushed skin, seizures
• Provide patient and caregivers information about adverse effects; use teach-back method and ask open-ended questions to evaluate learning

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Page 7 — Contraindications and Drug Interactions with Atropine

Atropine (cholinergic antagonist): used to treat bradycardia, dilate pupils, and decrease oral and respiratory secretions preoperatively.

Absolute Contraindications: Hypersensitivity to atropine; narrow-angle glaucoma; obstructive GI disorders; pyloric stenosis; ulcerative colitis; benign prostatic hypertrophy; myasthenia gravis; myocardial ischemia; tachycardia

Cautions: Paralytic ileus, severe ulcerative colitis, coronary artery disease, tachydysrhythmia, kidney disorders, hepatic disorders, COPD, heart failure

Drug Interactions:

• Increased effects: Antiparkinsons, antidysrhythmics, phenothiazines, antihistamines, tricyclic antidepressants, amantadine, quinidine
• Decreased effects: Other cholinergic agonists (direct or indirect)
• Caution: Carbidopa or levodopa — atropine may interfere with absorption, decreasing therapeutic effect

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Page 8 — Dosage and Administration of Atropine

Treatment of Bradycardia/Bradydysrhythmias:

• Adults: 0.5–1 mg IV; may repeat q3–5 min as needed; max 2 mg
• Children: 0.01–0.03 mg/kg IV; may repeat in 5 min; max 0.1 mg

Aspiration Prophylaxis-Presurgical (adults or children >20 kg):

• 0.4–0.6 mg SQ/IM/IV/PO; 30–60 minutes before administration of anesthesia

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Page 9 — Side Effects and Adverse Effects of Atropine

	Side Effects	Adverse Effects (associated with overdose)
CNS	Headache, anxiety	Slurred speech, confusion, drowsiness, dizziness, psychosis (agitation, restlessness, rambling speech, visual hallucinations, delusions, paranoid behavior followed by depression)
EENT	Mydriasis, blurred vision, dry mouth, photophobia
INTEG	Dry skin, flushing, decreased sweating	Hot, dry, flushed skin
GI/GU	Nausea, urinary retention, constipation	Absent bowel sounds, nausea, vomiting
RESP		Increased respirations
CV		Palpitations, tachycardia or paradoxical bradycardia, hypertension or hypotension

⚠️ Alert — Life-threatening effects of atropine: Ventricular fibrillation; Stevens-Johnson syndrome (rare); Coma

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Page 10 — Interventions for Atropine

• Monitor vital signs and intake and output
• Monitor ECG if given for bradycardia
• Auscultate abdomen for bowel sounds (decreased/absent bowel sounds may indicate paralytic ileus)
• Palpate abdomen for bladder or abdominal distention
• Assess bowel and bladder habits (constipation and urinary retention are common)
• Encourage patient to: void before taking medication; drink adequate fluids; eat high-fiber foods; ambulate as appropriate
• Provide comfort measures for dry mucous membranes: oral rinses and lubricants (dry mouth); artificial tears (dry eyes); lip balm (dry lips)
• Observe for side and adverse effects: blurred vision, drowsiness, excitement, confusion, urinary hesitancy, decreased sweating
• Notify HCP if significant changes in HR or BP, or if patient develops dysrhythmias

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Page 11 — Patient Teaching for Atropine

General Teaching:

• Take medication as prescribed
• Limit outdoor activity when temperature is hot (avoid hyperthermia)
• Avoid strenuous activity (avoid hyperthermia)
• Void before taking medication to avoid urinary retention
• Do not drive or operate hazardous machinery (drowsiness can occur)
• Maintain good oral hygiene

Managing Side Effects:

• Drink adequate fluids and eat high-fiber foods to avoid constipation
• Use artificial tears to avoid dry eyes
• Chew gum, suck on hard candy, use oral rinses to avoid dry mouth
• Use lip balm to avoid dry lips
• Contact HCP if marked decrease in urine output or urinary retention occurs

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Page 12 — Evaluation for Bethanechol and Atropine

Nurse evaluates effectiveness and whether patient is experiencing side effects.

• Bethanechol: Absence of urinary retention and constipation
• Atropine: Increased heart rate, dry mouth, and anxiety (expected effects)

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Page 13 — Case Study: Mr. Graves

Patient: Mr. Graves — admitted with severe urinary retention due to bladder atony caused by chronic benign prostatic hypertrophy. Had his prostate removed several weeks ago; has been having difficulty voiding since surgery. Was catheterized on admission, then prescribed bethanechol. Nurse is developing a patient education plan for discharge.

Section 23: Pharmacokinetics and Pharmacodynamics of Drugs Impacting the Renin-Angiotensin-Aldosterone System (RAAS)

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Page 1: Overview of the RAAS

The RAAS regulates blood pressure (BP) through vasoconstriction and increases in blood volume via the following sequence:

1. Renin forms angiotensin I
2. ACE converts angiotensin I → angiotensin II
3. Angiotensin II (potent vasoconstrictor) triggers the adrenal cortex to secrete aldosterone
4. Aldosterone enhances excretion of potassium and resorption of sodium and water → increases blood volume → increases BP

(Diagram shows where direct renin inhibitors, ACE inhibitors, ARBs, and aldosterone antagonists act in this pathway)

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Page 2: Overview of ACE Inhibitors and ARBs

Feature	ACE Inhibitors	ARBs
Mechanism	Inhibit ACE enzyme (Ang I → Ang II conversion)	Block Ang II from binding to AT₁ receptors
Effect on aldosterone	Suppress aldosterone → ↑ K⁺ retention, ↑ Na⁺/H₂O excretion	Prevent Ang II from stimulating aldosterone release
Effect on BP	Reduce BP via vasodilation; minimal effect on CO/HR	Prevent vasoconstriction of arterioles/veins; block renal vasoconstriction
Cardiac	—	Can prevent Ang II from altering cardiac structure
Name clue	Suffix -pril (lisinopril, captopril, benazepril, enalapril)	Examples: losartan, valsartan, irbesartan
Prototype	Lisinopril	Valsartan

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Page 3: Pharmacokinetics and Pharmacodynamics of ACE Inhibitors (Prototype: Lisinopril)

Uses: Hypertension, heart failure, diabetic nephropathy, myocardial infarction (MI), prevention of cardiovascular events

Mechanism of Action: Block ACE → prevent Ang I → Ang II conversion → reduce aldosterone release → ↓ Na⁺/H₂O retention, spare K⁺ from excretion

Pharmacokinetics:

• All ACE inhibitors except lisinopril and captopril must convert to their active forms in the small intestine and liver
• Lisinopril is active as given (no prodrug conversion needed)
• All excreted through the kidneys — doses must be reduced in kidney disease

Pharmacodynamic Profile of Lisinopril:

Parameter	Value
Onset	1 hr
Peak	6–8 hr
Duration	24 hr
Half-life	12 hr

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Page 4: Pharmacokinetics and Pharmacodynamics of ARBs (Prototype: Valsartan)

Mechanism of Action: Block Ang II from binding to AT₁ receptors in blood vessels

• Unlike ACE inhibitors (which block production of Ang II), ARBs block the action of Ang II
• Result: vasodilation, reduced Na⁺/H₂O retention, reduced aldosterone stimulation

Pharmacokinetics of Valsartan:

• Most ARBs: well absorbed, extensively metabolized
• Valsartan: protein bound, excreted in urine, feces, and breast milk
• ⚠️ Black Box Warning: Crosses the placenta → can cause fetal death in pregnancy

Pharmacodynamic Profile of Valsartan:

Parameter	Value
Onset	Up to 2 hr
Peak	2–4 hr
Duration	24 hr
Half-life	6 hr

Section 24: Nursing Process Related to Drugs Impacting the Renin-Angiotensin-Aldosterone System

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Page 1: Pre-Administration Assessment for ACE Inhibitors

Purpose: Collect baseline data and identify patients at high risk for serious adverse effects.

Determine Baseline Data:

• Obtain baseline BP
• Obtain baseline serum WBCs with differential — risk for neutropenia (mainly with captopril), which may progress to agranulocytosis (potentially fatal) if undetected
• Obtain baseline lithium level for patients on lithium (risk for lithium toxicity)
• Review diet, medication, and OTC drug histories for recent use of diuretics, potassium supplements, and salt substitutes with potassium (ACE inhibitors ↑ potassium levels)

Identify High-Risk Patients:

• Patients with depleted sodium or blood volume
• Patients with impaired renal function (may require smaller doses)
• Patients taking potassium supplements or recently using potassium-sparing diuretics
• Patients with collagen vascular diseases (systemic lupus erythematosus, scleroderma)
• Pregnant patients — ACE inhibitors not recommended in pregnancy

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Page 2: Pre-Administration Assessment for ARBs

Determine Baseline Data:

• Assess baseline BP and monitor BP throughout therapy

Identify High-Risk Patients:

• Patients with prior angioedema from ACE inhibitors — ARBs should be avoided unless benefits outweigh risk
• Pregnancy: ARBs not recommended
• Patients with renal artery stenosis — ARBs used with extreme caution (interfering with angiotensin II compromises the compensatory mechanism maintaining GFR, potentially causing chronic kidney disease)
• Older patients and those with renal dysfunction have increased sensitivity to ARBs → use cautiously

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Page 3: Contraindications with ACE Inhibitors and ARBs

Drug Class	Cautions	Contraindications
ACE Inhibitors	All except lisinopril must be used with caution in liver failure (lisinopril does not require liver metabolism)	Pregnancy (major fetal harm); history of angioedema (swelling of tongue, lips, pharynx, eyes); high serum potassium; renal artery stenosis
ARBs	Older patients and those with renal dysfunction have increased sensitivity	Pregnancy (major fetal harm); history of angioedema; renal failure

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Page 4: Drug Interactions with ACE Inhibitors

Interactions can lead to hypotension, hyperkalemia, hypoglycemia, and lithium toxicity.

• Diuretics and other antihypertensives: ↑ risk for first-dose hypotension; diuretics usually discontinued 2–3 days before starting ACE inhibitor; multiple antihypertensives may require dose reductions
• Drugs raising potassium levels: Potassium supplements and potassium-sparing diuretics (e.g., spironolactone) usually discontinued before starting ACE inhibitors to reduce hyperkalemia risk
• Lithium: ACE inhibitors promote Na⁺/H₂O excretion → may cause excessive lithium levels; monitor serum lithium frequently
• NSAIDs (aspirin, ibuprofen): Impair the BP-lowering effect of ACE inhibitors — should be avoided

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Page 5: Drug Interactions with ARBs

• Antihypertensive agents (diuretics, sympatholytics, vasodilators, ACE inhibitors, calcium channel blockers): Additive antihypertensive effects → hypotension; doses may need to be reduced when ARBs are added
• Potassium supplements: ARBs can increase risk for hyperkalemia (lower risk than ACE inhibitors); monitor serum potassium levels regularly; some patients may still need K⁺ supplements if at risk for hypokalemia

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Page 6: Dosage and Administration of ACE Inhibitors and ARBs

ACE Inhibitors:

• Available as single-drug or combination formulations (with hydrochlorothiazide or calcium channel blocker)
• Start low, gradually increase based on response
• Enalaprilat is the only ACE inhibitor available for parenteral use; all others are given orally
• Captopril and moexipril: Take at least 1 hour before food; all other ACE inhibitors may be taken with food
• Reduce doses in patients with impaired renal function

Drug	Indication	Dosage
Lisinopril	Hypertension	PO 10 mg initially; 10–40 mg/day

ARBs:

• All ARBs are PO formulations; can be given without regard to food
• Dosages vary by individual drug

Drug	Indication	Dosage
Valsartan	Hypertension	PO 80 or 160 mg/day alone or with other antihypertensives
Valsartan	Heart failure	PO 40 mg twice/day, up to 160 mg twice/day

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Page 7: Side Effects and Adverse Effects of ACE Inhibitors

Side Effects:

• Most common: Persistent, irritated cough ("ACE Cough") caused by accumulation of bradykinin (angiotensin I) — affects ALL ACE inhibitors; resolves when therapy is discontinued
• Other: nausea, vomiting, headache, dizziness, fatigue, taste changes

Serious and Potentially Fatal Adverse Effects:

Adverse Effect	Details
Angioedema	Extreme allergic reaction — swelling of lips, face, tongue, larynx, limbs; may occur with first dose or within first week; African Americans at higher risk
Neutropenia/Agranulocytosis	Primarily associated with captopril; rare
Severe first-dose hypotension	Most common in severe hypertension, history of diuretic use, or depleted sodium/blood volume; treat with lying down + IV saline if needed
Hyperkalemia/Tachycardia	Higher risk in patients on K⁺-sparing diuretics, K⁺ supplements, or K⁺-containing salt substitutes
Other serious effects	Bleeding, chronic kidney disease

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Page 8: Side Effects and Adverse Effects of ARBs

ARBs are generally well tolerated. Unlike ACE inhibitors, ARBs do NOT significantly increase risk for hyperkalemia and have much LOWER risk for chronic cough.

• Side effects: weakness and fatigue, diarrhea, hypoglycemia, dizziness, urinary tract infection, anemia
• Toxic effects: chest pain, hypotension, tachycardia, bradycardia (treat overdose with IV fluids)

Adverse Effects:

Adverse Effect	Details
Angioedema	Less common than with ACE inhibitors; stop immediately if it occurs; do not use again; give epinephrine IM
Fetal Harm	Contraindicated in 2nd and 3rd trimesters; discontinue as soon as pregnancy is detected
Chronic Kidney Disease	Extreme caution in bilateral renal artery stenosis or single-kidney stenosis

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Page 9: Interventions and Evaluation for ACE Inhibitors and ARBs

General Interventions (Both Classes):

• Check BP to determine effectiveness in reaching patient's goal level
• Monitor closely for first-dose hypotension; check BP periodically after initial administration
• Monitor for reduction of heart failure symptoms (dyspnea, edema, jugular vein distention)
• Monitor for neutropenia: baseline WBCs with differential before therapy, then every 2 weeks for first 3 months
• Monitor for symptoms of angioedema

ACE Inhibitor–Specific Interventions:

• Serum WBCs with differential every 2 weeks × first 3 months, then periodically
• Monitor serum potassium for hyperkalemia
• Closely monitor serum lithium in patients on lithium
• Validate avoidance of NSAIDs (drug-drug interaction)
• Validate avoidance of K⁺-containing salt substitutes

ARB-Specific Interventions:

• Monitor for reduced BP (hypertension)
• Monitor for decreased heart failure symptoms (dyspnea, JVD, peripheral edema, cyanosis)
• Patients with diabetic nephropathy: monitor for proteinuria and changes in GFR

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Page 10: Patient Teaching for ACE Inhibitors

General Teaching:

• Take at the same time every day
• All ACE inhibitors may be taken with food except captopril and moexipril (take ≥1 hr before eating)
• Avoid NSAIDs — impair effectiveness
• Notify HCP of any early signs of infection (risk for neutropenia, especially with captopril)
• Frequent blood draws needed to monitor for serious side effects
• Do not stop medication abruptly — coordinate discontinuation with HCP (risk for rebound hypertension)
• Initial dose is low and increased gradually
• Avoid salt substitutes containing potassium (risk for hyperkalemia)

Adverse Effects Teaching:

• Report nonproductive cough, but don't discontinue without medical consultation
• Lie down immediately if dizziness/lightheadedness occurs
• Angioedema can occur up to 1 week after first dose — seek immediate attention for swelling of lips, face, or throat
• Diabetic patients on insulin or oral hypoglycemics may experience hypoglycemia

Precautions:

• Inform HCP/pharmacist of history of angioedema or allergy to ACE inhibitors; also disclose heart disease, kidney disease, lupus, scleroderma, liver impairment
• Do not take ACE inhibitors during pregnancy; women of childbearing age should avoid pregnancy

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Page 11: Patient Teaching for ARBs

• All ARBs are given orally; may take with or without food (often better tolerated with food)
• Women of childbearing age: do not take ARBs while pregnant — high risk for fetal injury in 2nd and 3rd trimesters, lower risk in 1st trimester; notify HCP immediately if pregnancy occurs and ARB will be withdrawn
• Seek immediate medical attention for swelling of tongue or throat (signs of angioedema — potentially fatal)
• Do not alter dose or discontinue ARB without consulting HCP
• Report shortness of breath, dizziness, and unusual fatigue immediately
• Follow self-monitoring BP regimen at scheduled intervals
• ARBs dilate blood vessels → blood pools in lower vessels; take caution when rising/changing positions (orthostatic hypotension risk)

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Page 12: Case Study — Mr. Lowe

Patient: Mr. Lowe, 60-year-old African American man admitted in hypertensive crisis

• Symptoms: headache with flushed face lasting 2 hours
• BP: 180/110 mm Hg
• Current medications: glipizide 5 mg daily (type 2 diabetes), ibuprofen 400 mg q6h prn (osteoarthritis)
• Prescription: lisinopril 10 mg PO

Key nursing considerations: ibuprofen (NSAID) will impair lisinopril's antihypertensive effect; glipizide may cause hypoglycemia with ACE inhibitor; Mr. Lowe (African American) is at higher risk for angioedema — monitor closely with first dose.

Section 25: Pharmacokinetics and Pharmacodynamics of Beta Blocker Drugs

(Prototype: Metoprolol)

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Page 1: Overview of Beta Blockers

Beta-adrenergic antagonists (beta blockers) work by blocking beta receptors in the heart, reducing: heart rate, force of contraction, and impulse conduction through the heart. Uses include angina, hypertension, cardiac dysrhythmias, myocardial infarction, and heart failure. The most commonly prescribed beta blocker is metoprolol (prototype).

Categories of Beta Blockers:

Generation	Type	Mechanism	Examples
First Generation	Nonselective	Block both β₁ and β₂ receptors	Propranolol, sotalol
Second Generation	Cardioselective	Limited blockade of β₁ receptors only	Metoprolol, atenolol
Third Generation	Vasodilating	Create vasodilation + can produce nonselective or cardioselective beta blockade	Carvedilol, labetalol

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Page 2: Pharmacokinetics of Metoprolol

• Solubility: High — penetrates the blood-brain barrier with ease
• Elimination: Primarily by hepatic (liver) metabolism
• Placenta/Breast milk: Crosses the placental barrier (risk to fetus); excreted in breast milk

Parameter	Details
Absorption	Well absorbed from the GI tract
Distribution	Crosses the blood-brain barrier and placenta
Metabolism	In the liver
Excretion	Through the kidneys

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Page 3: Pharmacodynamics of Metoprolol

Mechanism of Action:

• Reduces heart rate, force of contraction, and conduction through the AV node
• Promotes BP reduction via the β₁-blocking effect
• Reduces secretion of renin by the kidney

Therapeutic Uses:

• Primary indication: Hypertension
• Also approved for: angina pectoris, heart failure, myocardial infarction

Pharmacodynamic Profile:

Route	Onset	Peak	Duration
PO	15 min	2–4 hr	10–19 hr
IV	Immediate	20 min	5–8 hr

⚠️ Drug Alert: The Institute for Safe Medication Practices lists IV metoprolol as a "high-alert" medication — increased risk for significant patient harm when used inappropriately.

Section 26: Nursing Process Related to Beta Blocker Therapy

(Prototype: Metoprolol)

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Page 1: Pre-Administration Assessment for Beta Blockers

Purpose: Thorough patient assessment including current medications, baseline vital signs, kidney function, and contraindications (e.g., asthma).

Baseline assessment must include:

• Blood pressure: If BP < 90/60 mm Hg → beta blocker may not be appropriate; contact HCP
• Heart rate: If HR < 60 bpm → beta blocker may not be appropriate; contact HCP
• Liver function: Liver impairment can affect metabolism of some beta blockers
• Blood sugar: If diabetic, assess blood sugar before administration — beta blockers can mask signs of hypoglycemia, making it difficult to treat

💡 Best Practice Pearl: Patients already on a beta blocker will have lower baseline BP and HR as expected drug effects. The health care team must still check BP and HR before each dose to prevent a sudden drop.

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Page 2: Contraindications and Drug Interactions with Beta Blockers

Contraindications:

• Sinus bradycardia or AV heart block greater than first degree — CONTRAINDICATED
• Heart failure — use with great caution (can precipitate heart failure even though used to treat it)
• Diabetes — use with caution (masks hypoglycemia signs)
• History of depression — use with caution
• Taking calcium channel blockers — use with caution
• Bronchial asthma or nonallergic bronchospasm — use with extreme caution
• Pregnancy or breastfeeding — metoprolol should be avoided

⚠️ Black Box Warning: Abrupt discontinuation of metoprolol can precipitate myocardial infarction

Drug Interactions:

Interacting Drug/Class	Effect
Antacids	Decrease absorption of beta blockers → reduced activity
Diuretics and cardiovascular drugs (including calcium channel blockers)	Additive effect → additional hypotension
Insulin and PO hypoglycemic drugs	Metoprolol suppresses symptoms of hypoglycemia → difficult to recognize early
NSAIDs	Decrease effectiveness of beta blockers
Digoxin	Increased risk for bradycardia and heart block

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Page 3: Dosage and Administration of Metoprolol

• Available as immediate-release (Lopressor) and extended-release (Toprol XL)
• Available in PO and IV forms; IV reserved for myocardial infarction
• Dose determined by indication for use

Formulation	Hypertension	Heart Failure
Metoprolol (Lopressor) — Immediate Release	50 mg twice daily or 100 mg/day; may give up to 100–450 mg in divided doses	Extended-release formulation used for heart failure
Metoprolol (Toprol XL) — Extended Release	25–100 mg daily; titrate at weekly intervals; max 400 mg/day	25 mg/day × 2 weeks for Class II HF; 12.5 mg/day for Class III HF

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Page 4: Side Effects and Adverse Effects of Beta Blockers

Side Effects: dizziness, insomnia, depression, fatigue, nightmares, nausea, vomiting, diarrhea, sexual dysfunction

Adverse Effects:

• AV heart block
• Rebound cardiac excitation with abrupt cessation → rebound hypertension, ventricular dysrhythmias, myocardial infarction (rationale for Black Box Warning)
• Bronchospasm
• Bradycardia
• Agranulocytosis
• Heart failure (paradoxically — even though used to treat it)

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Page 5: Interventions and Evaluation for Beta Blockers

• Measure BP and HR before each administration and periodically thereafter; notify HCP if HR < 60 bpm or significant changes occur
• Assess for signs of heart failure: dyspnea (especially on exertion/lying down), peripheral edema, crackles on auscultation, distended neck veins; monitor I&O (increased weight or decreased urine output may indicate heart failure)
• Institute fall precautions for newly prescribed patients — beta blockers cause dizziness and BP reduction (especially risky in older adults); teach position changes slowly
• Therapeutic response for hypertension: noted in 1–2 weeks
• Evaluate effectiveness: decreased BP, absence of side effects
• Ensure patient adheres to drug regimen
• Discuss need for periodic laboratory values while on beta blockers

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Page 6: Patient Teaching for Beta Blockers

• Change positions slowly to reduce dizziness/fall risk; avoid driving until drug response is known
• Notify HCP if dizziness or fatigue becomes excessive
• Never stop abruptly — risk of heart attack; dose must be tapered; refill medication before running out
• If a dose is missed, take the next scheduled dose — do not double dose
• Inform all HCPs and pharmacists about beta blocker therapy — can affect medical tests and may be held before surgical procedures
• Self-monitor BP and HR at scheduled intervals; keep a log
• Diabetic patients: monitor blood sugar carefully — beta blockers mask hypoglycemia presentation
• Be aware of potential side effects: depression, sexual dysfunction, early heart failure signs (swelling, shortness of breath especially when lying down) — report these to HCP

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Page 7: Case Study — Ms. Jones

Patient: Ms. Jones, 55-year-old woman with history of hypertension

• Previous BP: 195/98; Current vitals: Pulse 88, BP 198/96, RR 26, Temp 98.1°F
• No other health issues
• Prescription: Metoprolol to treat hypertension

Key nursing considerations: Educate about no abrupt cessation (Black Box Warning); self-monitor BP/HR; fall precautions; teach expected therapeutic response in 1–2 weeks.

Section 27: Pharmacokinetics and Pharmacodynamics of Calcium Channel Blocker Drugs

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Page 1: Overview of Calcium Channel Blockers

Mechanism: CCBs prevent calcium from entering cells and connecting to receptors → smooth muscle relaxation → coronary artery dilation → ↑ blood flow and oxygen supply to the heart

First-line treatment for: angina, cardiac dysrhythmias, and hypertension

Classification:

Group	Drugs
Nondihydropyridines	Verapamil, Diltiazem
Dihydropyridines	Nifedipine, Amlodipine (and others ending in -pine: felodipine)

💡 Best Practice Pearl: Only two nondihydropyridines — verapamil and diltiazem. All other CCBs are dihydropyridines ending in -pine (nifedipine, amlodipine, felodipine).

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Page 2: Pharmacokinetics of Calcium Channel Blockers

CCBs are highly protein bound but have a short half-life (except amlodipine).

Parameter	Verapamil	Diltiazem	Nifedipine	Amlodipine
Absorption	Well absorbed	Well absorbed	Well absorbed	Well absorbed
Distribution	Protein bound 90%	Protein bound 70–80%; in breast milk	Protein bound	Protein bound; crosses placenta; in breast milk
Metabolism	In the liver	In the liver	In the liver	In the liver
Excretion	In urine	In urine and feces	In urine and feces	In urine

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Page 3: Pharmacodynamics of Calcium Channel Blockers

General MOA: Block calcium from crossing the cell membrane → vasodilation → ↑ blood flow → improved oxygenation of myocardial tissue

Verapamil (Nondihydropyridine)

• MOA: Blocks calcium channels in blood vessels and the heart → coronary smooth muscle relaxation + coronary artery dilation
• Therapeutic Uses: Angina, hypertension, cardiac dysrhythmias
• Pharmacodynamic Profile:

Route	Onset	Peak	Duration	Half-life
PO	Variable	3–4 hr	17–24 hr	3–7 hr
IV	3 min	3–5 min	10–20 min	2–5 hr

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Diltiazem (Nondihydropyridine)

• MOA: Similar to verapamil — blocks calcium channels in heart and blood vessels → coronary smooth muscle relaxation + coronary artery dilation
• Therapeutic Uses: Angina, hypertension, cardiac arrhythmias; commonly used IV for atrial fibrillation and flutter
• Pharmacodynamic Profile:

Route	Onset	Peak	Duration	Half-life
PO	30–60 min	2–3 hr	4–12 hr	3.5–9 hr
IV bolus	Within 3 min	—	1–3 hr (0.5–10 hr after stopping continuous infusion)	—

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Nifedipine (Dihydropyridine)

• MOA: Blocks calcium channels in vascular smooth muscle → vasodilation; minimal blockade in the heart
• Therapeutic Uses: Angina and hypertension; NOT used for dysrhythmias (minimal cardiac calcium blockage)
• Pharmacodynamic Profile:

Route	Onset	Peak	Duration	Half-life
PO	20 min	1–2 hr	8 hr	2–5 hr
IV	1 min	45 min	—	—

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Amlodipine (Dihydropyridine)

• MOA: Selective calcium blockade in blood vessels → relaxation of coronary vascular smooth muscle
• Therapeutic Uses: Angina and hypertension
• Pharmacodynamic Profile: Long half-life → effective with once-daily dosing

Onset	Peak	Duration	Half-life
24–48 hr	6–12 hr	24 hr	30–50 hr

Section 28 Notes: Nursing Process Related to Calcium Channel Blocker Therapy

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Page 1 — Pre-Administration Assessment for Calcium Channel Blockers

CCBs are used to treat several cardiac conditions. Nurses are responsible for obtaining baseline assessment information, identifying high-risk patients, and conducting ongoing assessments specific to CCBs.

Determine Baseline Data

• Obtain baseline blood pressure and heart rate for patients prescribed CCBs.
• Assess liver and kidney function.

Identify High-Risk Patients

• Patients with low blood pressure, those with second- and third-degree AV block, and those with sick sinus syndrome (in the absence of pacing) should NOT be given CCBs.
• Patients with heart failure, renal disease, and liver disease require special caution.
• Patients receiving digoxin and beta blockers also require special consideration and monitoring (especially with the use of verapamil and diltiazem).

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Page 2 — Contraindications with Calcium Channel Blockers

CCBs are contraindicated with:

• Known drug allergy
• Acute myocardial infarction (MI)
• AV heart block (second- and third-degree) and sick sinus syndrome (unless the patient has a pacemaker)
• Liver failure (verapamil and diltiazem specifically — exclusive liver metabolism)
• Hypotension (verapamil and diltiazem rapidly decrease blood pressure)

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Page 3 — Drug Interactions with Calcium Channel Blockers

Because CCBs are often used in conjunction with other drugs for hypertension, angina, and cardiac dysrhythmias, nurses must be aware of interactions.

Interacting Drug/Food	Interaction/Effect
Digoxin	Verapamil or diltiazem + digoxin → partial or complete AV block; monitor for slowed HR and skipped beats; digoxin dose may need to be reduced (CCBs raise digoxin blood levels)
Beta Blockers	Verapamil or diltiazem + beta blockers → increased chance of bradycardia, AV block, and heart failure; monitor HR; IV verapamil and beta blockers should be administered several hours apart
Adrenergic Blockers	Adrenergic blockers increase adverse effects of verapamil and diltiazem; beta blockers may be combined with nifedipine to prevent reflex tachycardia
Grapefruit Juice	Toxicity can result if verapamil or diltiazem are taken with grapefruit juice; grapefruit juice affects absorption and raises blood levels of verapamil and diltiazem

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Page 4 — Dosage and Administration: Nondihydropyridines

Verapamil: Available in immediate-release, timed-release, and extended-release PO formulations; also available IV for dysrhythmias. Timed-release and sustained-release formulations: only approved for hypertension — do NOT crush or chew.

Diltiazem: Available in PO, extended-release PO, sustained-release PO, and IV formulations. Given IV as bolus and/or continuous infusion for atrial fibrillation, flutter, or paroxysmal supraventricular tachycardia.

Drug	Forms/Dosage	Indication
Verapamil	PO 80 mg TID, may titrate upward; Extended-release: PO 120–240 mg/day as single dose	Hypertension
Diltiazem	PO 30 mg TID; Extended-release: PO 120–240 mg/day; Sustained-release: PO 60 mg BID	Hypertension

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Page 5 — Dosage and Administration: Dihydropyridines

Nifedipine: Available PO in immediate-release, sustained-release, and extended-release formulations. Sustained- and extended-release tablets should be swallowed whole — do NOT crush or chew.

Amlodipine: Available as PO drug administered daily due to long half-life.

Drug	Dosage	Indication
Nifedipine	PO extended-release 30–60 mg/day; can be titrated up; maximum depends on formulation	Hypertension
Amlodipine	PO 2.5–5 mg/day initially; max 10 mg/day	Hypertension

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Page 6 — Side Effects and Adverse Effects of Calcium Channel Blockers

All CCBs (general): Headache, flushing, dizziness (due to arterial dilation); lower extremity edema; chronic rash mimicking eczema in older adults.

Nondihydropyridines (Verapamil & Diltiazem):

• Verapamil: usually well tolerated; most common side effect is constipation; adverse effects include bradycardia and cardiac conduction blockages; contraindicated in sick sinus syndrome or 2nd/3rd-degree heart block
• Diltiazem: similar side/adverse effects as verapamil; constipation less common than with verapamil

Dihydropyridines (Nifedipine & Amlodipine):

• Nifedipine: very potent CCB → hypotension more likely; side effects include flushing, dizziness, headache, peripheral edema, gingival hyperplasia, rash in older adults; adverse effect: reflex tachycardia (heart rate increases in response to vasodilation — can be prevented by combining nifedipine with a beta blocker)
• Amlodipine: most common side effects are peripheral and facial edema; other side effects similar to all CCBs (flushing, dizziness, headache, rash in older adult)

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Page 7 — Interventions and Evaluation for Calcium Channel Blockers

• Assess baseline heart rate and blood pressure; anticipate BP will decrease with therapy.
• If hypotension or bradycardia occurs → may need to hold medication and notify the HCP.
• In older adult patients, nifedipine and amlodipine can cause rash that mimics eczema → assess skin for new onset rash.
• Monitor carefully for development of edema (peripheral edema can occur; can be reduced by combining a diuretic with CCB therapy if necessary).
• Evaluate therapeutic effect: BP should be monitored routinely with the expectation to reduce systolic/diastolic pressure to below 130/80 mm Hg.

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Page 8 — Patient Teaching for Calcium Channel Blockers

General Teaching:

• Always take CCBs as prescribed
• Consult HCP before stopping — sudden cessation can cause rebound hypertension and heart muscle damage
• Measure weight daily
• Change positions slowly (syncope/dizziness/lightheadedness may occur)
• Swallow sustained-release formulations whole — do NOT crush or chew
• Increase fluid and fiber in diet (constipation is common with verapamil)
• Avoid grapefruit and grapefruit juice (can lead to drug toxicity, affects metabolism of nifedipine)

Self-Monitoring:

• Teach signs/symptoms of edema; notify HCP if swelling in ankles/feet
• Notify HCP of cardiac effects: shortness of breath, weight gain, slower-than-normal heart rate
• Teach how to assess heart rate
• Teach importance of checking blood pressure and maintaining accurate BP record
• Patients taking CCBs for angina: keep record of angina attacks (when, severity, circumstances); notify HCP if attacks increase
• Alcohol can affect how CCBs work and can cause severe side effects — avoid alcohol

Side Effects:

• Teach patients that side effects of CCBs are due to vasodilation
• Headache, dizziness, and peripheral edema are common side effects

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Page 9 — Case Study: Ms. James

Patient: Ms. James, 70-year-old female, admitted to medical-surgical unit recovering from a total hip replacement. Recently changed diet to lose weight per HCP recommendation.

Presentation: Since being on the unit, BP measurements ranging from 158/84 to 184/100 mm Hg. Denies pain. No prior history of blood pressure problems.

Prescription: Amlodipine 5 mg PO once daily (prescribed by primary HCP after nurse consultation).

Section 29 Notes: Pharmacokinetics and Pharmacodynamics of Centrally Acting Alpha₂ Adrenergic Agonist Drugs

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Page 1 — Overview of Centrally Acting Alpha₂ Adrenergic Agonists

Background:

• Indirect-acting adrenergic agents prevent the activation of peripheral adrenergic receptors.
• Two groups of indirect-acting adrenergic agents: (1) centrally acting alpha₂ agonists and (2) adrenergic neuron-blocking agents.
• Centrally acting alpha₂ agonists work within the CNS to decrease the outflow of impulses along the sympathetic neurons.

Mechanism:

• Alpha₂ receptors are found along nerve synapses in the CNS.
• Alpha₂ adrenergic agonists work by decreasing the release of norepinephrine within these synapses.
• This action creates vasodilation → decreases blood pressure.

Drugs in this class:

• Three centrally acting alpha₂ agonists: clonidine, methyldopa, and guanfacine
• Prototype drug for this lesson: Clonidine

(Diagram: Site and method of action of various antihypertensive drugs — shows how central-acting adrenergic antagonists act at the hypothalamus/vasomotor center; also shows relationship to CCBs, ACE inhibitors, ARBs, diuretics, beta blockers, adrenergic blockers, and direct arterial vasodilators — from JNC 7)

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Page 2 — Pharmacokinetics of Clonidine

Clonidine is very lipid soluble → rapid absorption after oral dosing; widely distributed throughout the body; eliminated by hepatic metabolism and renal excretion.

Absorption	Well absorbed both orally and transdermally
Distribution	Widely distributed; crosses blood-brain barrier
Metabolism	In the liver
Excretion	Through the kidneys

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Page 3 — Pharmacodynamics of Clonidine

Mechanism of Action:

• Clonidine reduces sympathetic outflow to the blood vessels and the heart.
• Effects are primarily to the heart and vascular system.
• Suppresses sympathetic nerves to the heart → bradycardia and decreased cardiac output.
• Suppresses sympathetic regulation of blood vessels → vasodilation.
• Both actions result in a decrease in blood pressure.
• Orthostatic hypotension is minimal with clonidine — BP is reduced whether patient is supine or standing.

Therapeutic Uses:

• Primary use: treatment of severe hypertension
• Other uses: severe pain management; treatment of ADHD (attention-deficit/hyperactivity disorder)

Pharmacodynamic Profile:

	Oral Clonidine	Transdermal Clonidine
Onset	30 min to 1 hr	3 days
Peak	2–4 hr	Unknown
Duration	8–12 hr	1 week
Half-Life	6–12 hr	20 hr (after patch removal)