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.

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