BSN Tracker

chlorpromazine

Brand: Thorazine

⚠ BBW Beers Criteria Prototype Drug
Drug Class: first-generation antipsychotic (FGA)
Drug Family: antipsychotic
Subclass: low-potency phenothiazine
Organ Systems: cns

Mechanism of Action

Blocks D2 dopamine receptors in the mesolimbic pathway (antipsychotic effect) and tuberoinfundibular pathway (hyperprolactinemia). Wide receptor promiscuity including alpha-1, H1, and muscarinic blockade accounts for its extensive side effect profile. The first antipsychotic drug, developed in 1952.

D2 dopamine receptoralpha-1 adrenergic receptorH1 histamine receptormuscarinic receptors5-HT2A receptor

Indications

  • schizophrenia
  • acute agitation
  • intractable hiccups
  • nausea and vomiting
  • off-label: mania

Contraindications

  • concurrent CNS depressants (relative)
  • bone marrow depression
  • QT prolongation

Adverse Effects

Common

  • sedation (prominent)
  • orthostatic hypotension
  • anticholinergic effects
  • photosensitivity
  • weight gain
  • hyperprolactinemia

Serious

  • extrapyramidal symptoms (EPS)
  • tardive dyskinesia
  • neuroleptic malignant syndrome (NMS)
  • QT prolongation
  • agranulocytosis (rare)

Pharmacokinetics (ADME)

Absorption variable oral bioavailability (~32%); IM absorption more reliable
Distribution highly lipophilic; protein binding ~95-98%; large Vd; accumulates in tissues
Metabolism extensively hepatic via CYP2D6 and CYP1A2; >10 metabolites
Excretion renal and biliary
Half-life 8-35 hours
Onset 30-60 minutes (IM); 30-60 minutes (oral)
Peak 2-4 hours (oral)
Duration 4-6 hours per dose
Protein Binding 95-98%
Vd ~20 L/kg

Drug Interactions

Drug / Agent Mechanism Severity
CNS depressants additive sedation major
antihypertensives additive hypotension via alpha-1 blockade moderate
anticholinergics additive anticholinergic effects moderate
lithium increased neurotoxicity risk moderate

Nursing Considerations

  1. Monitor blood pressure for orthostatic hypotension; low-potency phenothiazines have the highest alpha-1 blockade among antipsychotics — have patient sit before standing.
  2. Assess for extrapyramidal symptoms: akathisia (subjective restlessness), parkinsonian tremor/rigidity, acute dystonia (neck stiffness, tongue protrusion) — report immediately as dystonia responds to diphenhydramine or benztropine.
  3. Protect patient from sunlight; photosensitivity can cause severe burns — apply SPF 30+ sunscreen when outdoors.
  4. Neuroleptic malignant syndrome (NMS) may occur at any time: fever, muscle rigidity, altered consciousness, and autonomic instability — discontinue immediately and treat as emergency.

Clinical Pearls

  • Chlorpromazine's discovery in 1952 revolutionized psychiatry, enabling deinstitutionalization of millions of patients with schizophrenia; it is the 'prototype' of all antipsychotic drugs.
  • Low-potency antipsychotics like chlorpromazine cause more sedation, hypotension, and anticholinergic effects but fewer EPS compared to high-potency drugs like haloperidol — a clinically useful distinction.

Safety Profile

Pregnancy use-with-caution
Lactation avoid
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required

Concordance Terms

Cross-referenced clinical concepts — click any term to see all content where it appears.

Acute Agitation First-generation Antipsychotic (FGA) Intractable Hiccups Nausea And Vomiting Off-label: Mania Schizophrenia
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