Pharmacology of Antipsychotic Drugs

Summary Points on Antipsychotic Drugs:

Classification of Antipsychotics: Typical (D2 blockers) and Atypical (acting via other mechanisms)

Actions of Typical Antipsychotics:

  • Blocking D2 receptors with differing potency
  • Sedative effects are more common in low-potency drugs
  • Extrapyramidal symptoms more common in high-potency drugs
  • Low anticholinergic and autonomic side effects in high-potency drugs
  • Lower seizure threshold and potential to precipitate convulsions in epileptic patients
  • Potent antiemetic drugs, except for thioridazine
  • Significant α blocking and anticholinergic properties in low-potency drugs
  • Can increase prolactin release resulting in galactorrhoea and amenorrhea

Actions of Atypical Antipsychotics:

  • Antagonistic actions at 5-HT2 and alpha receptors
  • May or may not possess D2 blocking activity
  • Less likely to cause extrapyramidal symptoms
  • Weight gain, hyperlipidemia, and new-onset diabetes mellitus are common side effects, except for ziprasidone and aripiprazole.

Individual Drugs:

  • Thioridazine:
    • Low incidence of extrapyramidal symptoms
    • Interferes with male sexual function
    • Can cause cardiac arrhythmia and retinal damage
  • Trifluperazine, fluphenazine and haloperidol:
    • High potency drugs
    • Marked extrapyramidal symptoms
  • Penfluridol:
    • Longest acting antipsychotic drug
  • Pimozide:
    • Selectively blocks D2 receptors
    • Carries risk of arrhythmias due to QT prolongation
  • Clozapine:
    • Atypical antipsychotic drug
    • Weak D2 blocking action
    • Suppresses positive and negative symptoms of schizophrenia
    • Risk of seizures and agranulocytosis
    • Powerful anticholinergic effects
    • Least risk of extrapyramidal symptoms
  • Risperidone:
    • Blocks 5-HT2, a adrenergic and D2 receptors
    • More potent D2 blocker than clozapine
    • Can cause extrapyramidal symptoms at high dose
    • Risk of hyperprolactinemia
  • Olanzapine:
    • Similar mode of action as risperidone
    • Potent anticholinergic drug
    • Can cause seizures and weight gain
    • Associated with higher risk of stroke and death in elderly patients
  • Ziprasidone:
    • Causes QT prolongation
    • No association with weight gain, hyperlipidemia or diabetes
  • Quetiapine:
    • Can cause cataract formation
    • Shortest half-life
  • Aripiprazole:
    • Acts as a partial agonist at 5-HT1A and D2 receptors
    • Antagonist at 5-HT2A receptors
    • Known as dopamine-serotonin stabilizer
    • Long half-life
    • Approved for treatment of irritability associated with autistic disorders in children
  • Asenapine:
    • Used sublingually for schizophrenia and acute mania
  • Iloperidone:
    • Less risk of extrapyramidal adverse effects
    • Can cause orthostatic hypotension and prolong QT interval
  • Brexipiprazole and cariprazine:
    • New drugs approved for schizophrenia
  • Pimavanserin:
    • New atypical antipsychotic drug
    • Indicated for oral treatment of hallucinations and delusions associated with Parkinson’s disease.

Adverse Effects:

  • Sedation: maximum with chlorpromazine, minimum with ziprasidone and aripiprazole
  • Weight gain: all except haloperidol; less with ziprasidone
  • Aggravation of seizures: more with clozapine, olanzapine, and chlorpromazine; less with risperidone and quetiapine
  • Postural hypotension and inhibition of ejaculation: α-blocking property
  • Retinal degeneration: thioridazine
  • Agranulocytosis: clozapine
  • Cataract formation: quetiapine
  • Cholestatic jaundice: chlorpromazine
  • Anticholinergic effects: dry mouth, blurred vision, constipation, urinary retention; maximum with thioridazine
  • Hyperprolactinemia, amenorrhea, and galactorrhea: due to D2 blockade in the pituitary
  • Extrapyramidal Symptoms (EPS): acute muscular dystonia, Parkinsonism, akathisia, malignant neuroleptic syndrome, tardive dyskinesia

Other Uses:

  • Acute mania and bipolar disorder
  • Severe depression with psychotic features
  • Alcoholic hallucinosis
  • Gilles de la Tourette’s syndrome and Huntington’s disease

Key Points:

  1. Haloperidol and fluphenazine are potent typical antipsychotics, while risperidone is the most potent atypical antipsychotic.
  2. Clozapine, quetiapine, and aripiprazole have a negligible risk of extrapyramidal adverse effects.
  3. Chlorpromazine, thioridazine, and clozapine have the strongest anticholinergic activity.
  4. Fluphenazine (enanthate and decanoate) and haloperidol (decanoate) are long-acting injectable forms of typical antipsychotics, while risperidone and paliperidone are available in long-acting injectable form as atypical antipsychotics.
  5. Haloperidol is the most commonly used antipsychotic by intravenous route.
  6. Ziprasidone, aripiprazole, asenapine, and iloperidone have a negligible risk of causing metabolic adverse effects such as weight gain, hyperlipidemia, and new-onset diabetes mellitus.
  7. Asenapine, paliperidone, and ziprasidone have the greatest potential to prolong the QT interval.

Disclaimer: This article is for informational purposes only and should not be taken as medical advice. Always consult with a healthcare professional before making any decisions related to medication or treatment.

Disclaimer: This article is for informational purposes only and does not constitute medical advice. Always seek the advice of a healthcare provider with any questions regarding a medical condition.

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