MEDizzy - Some of the individual antipsychotics are more likely to

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Combined Neurology XIII

Some of the individual antipsychotics are more likely to lead to specific side effects than others. Which of the following medication–side effect combination is least likely to occur?

ExplanationThe second generation of antipsychotics, so-called atypical antipsychotics, includes clozapine, olanzapine, quetiapine, risperidone, ziprasidone, and aripiprazole. These agents do have antagonistic activity at D2 (dopamine) receptors, however, their clinical antipsychotic effect results in large part from antagonism at serotonergic 5-HT2A receptors. Studies to date have not shown overall superior efficacy of the atypical antipsychotics over the typical ones, though atypical antipsychotics may be more effective at treating some of the negative symptoms of schizophrenia. Because they have less antagonism at D2 receptors, they are less likely to cause extrapyramidal side effects (EPS), but certainly can. As a class, the atypical antipsychotics carry with them an increased risk of weight gain, diabetes, and dyslipidemia. Patients being treated with these medications should therefore periodically be assessed for such side effects. Clozapine and olanzapine are most likely to lead to weight gain. Ziprasidone and aripiprazole are less likely to cause weight gain than the others. Some of the typical and atypical antipsychotics including thioridazine, haloperidol, ziprasidone, and quetiapine have negative ionotropic action on the heart and a quinidine-like effect, leading to QT prolongation with the potential for arrhythmias. Aripiprazole is least likely to do so. Other cardiac side effects include myocarditis, which can rarely be seen with clozapine. The atypical antipsychotics also have activity at muscarinic, adrenergic, and histaminergic receptors, and several side effects result from activity at these sites. Clozapine can lead to agranulocytosis in 1% to 2% of patients, and patients being treated with this medication are required to have periodic complete blood counts checked. Clozapine also leads to a dose-dependent increased risk of seizures. Clozapine is least likely of all the atypical antipsychotics to lead to EPS. Because of the side effect profile of clozapine, its use is usually limited to treatment of patients who have failed trials of other typical and atypical antipsychotics. Among the atypical antipsychotics, olanzapine has the highest antimuscarinic activity, and side effects resulting from this include dry mouth, urinary 1109 retention, confusion, and constipation. Clozapine also has significant antimuscarinic activity. Quetiapine has significant antihistaminergic activity, and along with olanzapine, is the most likely to lead to sedation. Dopamine inhibits prolactin release, and treatment with both typical and atypical antipsychotics can lead to hyperprolactinemia and amenorrhea resulting from dopaminergic antagonism in the tuberoinfundibular pathway. Some of the atypical antipsychotics are available in injectable forms, including long-acting depot formulations.