Antipsychotics

Question 1

Haloperidol (a butyrophenone)

• typical antipsychotic

high potency, high incidence of motor SE, low anticholinergic + antiandrenergic effects,
significant 1st pass metabolism

Answer 1

Mechanism: Blocks 75% of D2 receptors at clinically effective doses – inhibits mesolimbic & mesocortical DA receptors –> antipsychotic efficacy
- Chronic administration inhibits pathways by DA accumulation & depolarization blockade (2-3 weeks)

Use: (+) symptoms

• Delusions
• Hallucinations

Also used for behavioral syndromes accompanied by motor disturbances – Gilles de la Tourette’s

Toxicity:
inhibition of basal ganglia DA receptors: motor SE
inhibitions of tuberoinfundibular DA receptors: inc. prolactin secretion
- Short term use: Parkinson-like motor effects (nigrostriatal block)
- Long term use (mo-yrs): perioral tremor (rabbit face) & permanent tardive dyskinesia
- Hyperprolactinemia (tuberoinfundibular block) leading to menstrual irregularity, galactorrhea
- Low anticholinergic & antiadrenergic effects:
dry mouth, urinary retention (M block);
orthostatic hypotension, reflex tachycardia (α1 block); sedation (hist block)
- Weight gain
- Prolonged QT interval
- Neuroleptic malignant syndrome (rare ANS collapse)

Metabolism: - Lipid soluble

• Significant first pass metabolism
• Pregnancy category C (benefit > risk)

Question 2

Clozapine

• atypical antipsychotic

Answer 2

Mechanism:
Blocks 50% of D2 receptors & 80% of 5-HT2A receptors at clinically effective doses
- Chronic administration inhibits pathways by DA accumulation & depolarization blockade (2-3 weeks)

Use: (+ & -) symptoms

• Delusions
• Hallucinations
• Flattened affect
• Emotional or social withdrawal

Risperidone also used for bipolar disorder

Toxicity: - Agnranulocytosis – requires regular blood testing

• Weight gain w/ insulin resistance & diabetes mellitus
• Hyperlipidemia
• Low incidence of motor side-effects

Interaction: - Lipid soluble

• Significant first pass metabolism
• Pregnancy category B

Question 3

Risperidone

• atypical antipsychotic

Answer 3

Mechanism:
Blocks 50% of D2 receptors & 80% of 5-HT2A receptors at clinically effective doses
- Chronic administration inhibits pathways by DA accumulation & depolarization blockade (2-3 weeks)

Use: (+ & -) symptoms

• Delusions
• Hallucinations
• Flattened affect
• Emotional or social withdrawal

Risperidone also used for bipolar disorder

Toxicity: - Weight gain & diabetes mellitus

• Hyperlipidemia
• Minor extrapyramidal sx & hyperprolactinemia