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All antipsychotics are metabolized to varying degrees by the hepatic cytochrome P450 (CYP450) isoenzymes 3A4, 2D6, and 1A2. Some have additional non-P450 metabolism, which lowers the risk for drug interactions by providing alternative pathways if major pathways are inhibited.
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Because 3A4 metabolizes the bulk of antipsychotics, inducers and inhibitors of 3A4 are important clinically.
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Smoking increases the metabolism of 1A2-dependent antipsychotics, requiring dose adjustment for olanzapine and clozapine.
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Although antipsychotics are generally safe even with excessive drug serum levels, pimozide, mesoridazine/thioridazine (cardiac toxicity), and clozapine (seizures and hypotension) are exceptions.
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Some drug interactions problems are “hidden” in that they merely increase the statistical risk factors for later morbidity (e.g., for tardive dyskinesia or diabetes).
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Antipsychotic serum drug levels are not useful routinely, but rather in clinical situations in which you want to confirm that a patient is at the extremes of drug levels.
TABLE 16.1. Antipsychotic Metabolic Pathways | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
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