Pharmacodynamics

Pharmacodynamics refers to the mechanisms and effects of a medication within the body. Or more simply, it's what medications do to the body and how they do it.

Now, medications bind to receptors, which are specialized proteins found inside the cell or on its surface or, to cause a change in the cell's activity that ultimately creates a physiological effect.

When a medication binds a receptor and mimics the body's own chemical messengers, like hormones and neurotransmitters, to produce a desired response, it's called an agonist. So, an agonist is like a key that fits into a lock, causing it to open. There are also medications that are partial agonists. Like agonists, they fit into the lock, but not as well, so they produce a weaker response. Lastly, there are antagonists, which bind to a receptor and block it so it can't be bound to and activated by other medications or the body's own chemical messengers. So, it's like a key that can't turn the lock, and may even get stuck in the lock.

Now, after a medication binds to a receptor, there are additional factors that determine how the body will respond, including the dose of the medication, its efficacy, and its potency. So, let's draw a graph, to show the relationship between the dose, on the x axis, and the response on the y axis. What we get is an S-shaped curve, called the dose-response curve, which has three phases. At first, in phase 1, the curve is more or less flat; that's because the dose of the medication is too low, so not enough receptors bind to the medication to cause a significant response.

As the dose increases, in phase 2, more receptors are occupied by the medication until just enough is present in the body to produce an effect. This is called the minimum effective concentration, or MEC. As the dose continues to increase, so does the response; but eventually, in phase 3, we reach a point where all the receptors are occupied, and the curve starts to flatten out. This is where the maximal efficacy of the medication is achieved, and at this point, increasing the dose will not produce a stronger effect. Lastly, is the medication's potency, which determines the amount of medication needed to elicit an effect; so medications with a high potency can produce an effect at a lower dose, while medications with a low potency produce an effect at a higher dose.

Okay, let's switch gears and look at how we measure the safety of medications. To do this, we can compare the dose that's effective in 50% of the population for a particular medication, referred to as the effective dose or ED50, with the dose that toxic side effects occur in 50 percent of the population, called the toxic dose TD50. Now, the ED50 to TD50 ratio is the therapeutic index, or TI, which is a measure of a medication's safety. So, the closer this ratio is to 1, the greater the danger of toxicity. In other words, medications with a large or wide therapeutic index are safer, since their toxic dose is much higher than their effective dose. On the flip side, medications with a small or narrow therapeutic index are more dangerous, since their toxic and effective doses are close to each other.

For example, if a medication's ED50 is 10 and the TD50 is 100, the therapeutic index would be 10, which means the medication is relatively safe. In contrast, if a medication's ED50 is 10 and the TD50 is 30, the therapeutic index is 3, which means the medication is much less safe. Examples of medications with a narrow therapeutic index are lithium, which is a mood stabilizer; warfarin, an anticoagulant; digoxin, a cardiac medication; and theophylline, a bronchodilator. For any medication, but especially for medications like these, the dose must fall within the therapeutic range, which is between the minimum effective concentration and the toxic level.

Now, once a medication is administered, it requires some time to reach its minimum effective concentration and start producing a response in the body. This is known as the onset. If a rapid onset is needed, a bolus or a loading dose, meaning a large, initial dose of the medication is given first. Then, the time required for a medication to reach its maximum effectiveness or concentration in the body is known as the peak. The peak is an indication of how fast the medication is absorbed from the site of administration. For example, a medication given orally, usually peaks within 2 to 3 hours, whereas a medication administered IV can peak in 30 to 60 minutes. Finally, the duration is the length of time that the medication's concentration is enough to result in a therapeutic effect, which is an indication of how fast a medication is distributed and eliminated from the body.

Okay, now let's talk about how to use pharmacodynamic principles to promote safe medication administration. First, keep in mind how medications interact with receptors throughout the body, and how these interactions can manifest as side effects in addition to the desired therapeutic effect. So, if your patient is prescribed a cholinergic agonist like bethanechol for urinary retention, you'll monitor for the effects of cholinergic receptor activation around the body. You will expect the therapeutic response of increased bladder emptying, and you'll also watch for side effects like a decreased heart rate, decreased blood pressure, and abdominal cramping.

Also, you will need to be familiar with the onset, peak, and duration of action of the medications you administer. For example, if your patient is diagnosed with diabetes mellitus and is prescribed a rapid-acting insulin like insulin aspart, you'll recall that the onset of action is 5 to 15 minutes. So, in order to avoid hypoglycemia, you'll ensure your patient's breakfast tray is already in their room before you administer the medication, so your patient can eat right afterwards. Finally, you'll need to be aware of any prescribed medications that have a narrow therapeutic index, and monitor your patient closely for signs of toxicity. For example, you will often need to review the trough level, or the lowest plasma level, of aminoglycosides like gentamicin before you administer the next dose, to avoid neurotoxic and nephrotoxic effects.

Alright, as a quick recap… Pharmacodynamics refers to what medications do to the body and how they do it. Medications bind to cellular receptors to create a physiological effect, and can act as an agonist, partial agonist, or antagonist. A dose-response curve illustrates the relationship between the dose of a medication and the body's response. The safety of medications is measured by the therapeutic index. Medications with a wide therapeutic index are safer than medications with a narrow therapeutic. The onset, peak, and duration of action describe the time-related elements of a medication's effectiveness. Nursing considerations related to pharmacodynamics include safe medication administration by reviewing the pharmacodynamic properties of the medication, and monitoring the patient's response to the medication.