26 - Depot atypicals

Depot atypicals

© SPMM Course  Lipid storage and brain retention are significant; depot forms of haloperidol or fluphenazine may persist for 1 to 3 months.  Thioridazine has an active metabolite mesoridazine, and loxapine produces 7hydroxyloxapine.  Typical antipsychotics are mainly substrates of CYP1A or CYP2D6, or both and can inhibit 2D6.  Chlorpromazine has highly variable absorption rate (around 37% bioavailability) for different persons and has nearly 100s of metabolites.  Antacids can decrease absorption of phenothiazines; this leads to reduced plasma concentration and therapeutic effect of phenothiazines Interactions: Enzyme inducers Carbamazepine, phenytoin, ethambutol, barbiturates - reduce antipsychotic levels. Clearance inhibitors SSRIs, TCAs, cimetidine, erythromycin, ciprofloxacin, and ketoconazole can inhibit metabolism – increase antipsychotic levels. Depot atypicals Depot drug Preparation Kinetics Flupenthixol decanoate Esterified in coconut oil Peak levels 3–7 days post IM. Apparent half-life of 17 days Fluphenazine decanoate Esterified in sesame oil Peak levels are 24h post-IM. The apparent half-life of 7-14 days. Smoking reduces levels Haloperidol decanoate Esterified in sesame oil Peak levels 7 days post IM. The apparent half-life of 3 weeks. Smoking reduces levels Perphenazine decanoate Esterified in sesame oil Peak levels 1-7 days post IM. Apparent half-life of 2 weeks Pipotiazine palmitate Esterified in coconut oil Peak levels 1-2 weeks post IM. Apparent half-life of 2 weeks Zuclopenthixol decanoate Esterified in coconut oil. Contrast this depot from zuclopenthixol acetate preparation used for rapid tranquillisation Peak levels 1 week post IM. The apparent half-life of 7-20 days.