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Chapter 8: Psychopharmacology
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A 56-year-old man who has a 30-year history of smoking cigarettes is being treated for schizophrenia with clozapine. He is hospitalized for an acute exacerbation of his psychoses; his clozapine therapy is continued. During the third week of his hospital stay, he has a seizure that is thought to be due to clozapine toxicity. The clozapine toxicity in this patient is likely due to
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a. increased GI absorption of clozapine.
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b. decreased renal excretion of clozapine.
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c. a decrease in his blood-brain barrier function.
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d. decreased metabolism of clozapine.
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Answer is d. Changes in smoking status can be especially problematic for clozapine-treated patients and will alter serum levels by 50% or more. Within 2 weeks of smoking discontinuation (eg, hospitalization in nonsmoking environment), the absence of aryl hydrocarbons will cause upregulated CYP1A2 activity to return to baseline levels, with a concomitant rise in serum clozapine concentrations (see Table 8-5).
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