Moving on with more AE. Some of the antipsychotics block muscarinic receptors, producing anticholinergic effects. Which ones?
Thioridazine, Chlorpromazine, Clozapine and Olanzapine
- -antimuscarinic effects may be beneficial in relation to extrapyramidal side effects
- -AcH acts in opposition to dopamine in the basal ganglia and it is possible that the lack of extrapyramidal effects with clozapine and thioridazine is due to the high antimuscarinic effects.
Clozapine causes what serious and potentially fatal AE that limits it use?
Agranulocytosis in 1-2% of patients
–patients must have weekly blood counts for the first 6 months of treatment and every 3 weeks thereafter
Moving on to the endocrine and metabolic adverse effects. Blockage of D2 receptors in the pituitary leads to an increase in prolactin secretion. What does this result in?
Women: amenorrhea-galactorrhea syndrome and infertility
Men: Loss of libido, infertility and impotence may result
–atypicals are less likely to produce these effects
Weight gain is another metabolic effect of antipsychotics. What affect does this have on the patient?
Some of the atypical antipsychotic drugs produce more weight gain and increase in lipids than some typical antipsychotic drugs
- -clozapine and olanzapine
- -lead to type 2 DM, HTN, and hyperlipidemia
- -Ziprasidone (atypical) least amount of weight gain
Moving on to cardiac toxicities with antipsychotics. What drugs and what cardiac anomalies are produced?
Thioridazine: QT prolongation and lethal torsade de pointes
Ocular complications are common and important to know. What two drugs cause ocular complications?
Chlorpromazine: deposits in the anterior portions of the eye (cornea and lens)
Thioridazine is the only antipsychotic drug that causes retinal deposits, may seem like retinitis pigmentosa in advanced cases
What are some other Adverse effects of antipsychotics?
- Jaundice: chlorpromazine (mild and disappears)
- Poikilothermia: ability to regulate temperature is impaired
Quick review which antipsychotics cause the most sedation and hypotension?
Moving on to uses of antipsychotics. What are the psychiatric indications?
- Schizoprenia: primary indication
- -atypicals are more effective in treating negative symptoms
- Bipolar disorder: atypicals
- Tourette’s Disorder: suppress tics
- Alzheimers: control of disturbed behavior
- Treatment Resistant Major Depression: adjuncts to antidepressant agents
- Autistic: manage irritability
- NOT indicated for treatment of withdrawal symptoms
What are some non-psychiatric indications for antipsychotics?
Nausea and Vomiting: most older antipsychotics
–dopamine receptor blockage, both centrally (chemoreceptor trigger zone in medulla) and peripherally (receptors in stomach)
Prochlorperazine: sole use is antiemetics
Droperidol is used in combo with fentanyl in neuroleptanesthesia
What is the drug of choice in regards to antipsychotics?
Atypical drugs are preferred due to benefit for negative symptoms and cognition, diminished risk of EPRs, and tardive dyskinesia.
Risperidone: most prescribed
Clozapine: reserved for refractory patients
Finally what are the effects of antipsychotics in pregnancy?
Antipsychotic drugs are pregnancy category C
Only Clozapine is category B