Pathophysiology
Clinical meaning
Advanced psychopharmacology requires integration of pharmacokinetic (absorption, distribution, metabolism, excretion) and pharmacodynamic (receptor binding, dose-response, tolerance) principles for complex psychiatric prescribing. Hepatic metabolism through cytochrome P450 enzymes is central: CYP2D6 metabolizes most antipsychotics, many antidepressants (fluoxetine, paroxetine are inhibitors), and opioids; CYP3A4 metabolizes benzodiazepines (except lorazepam, oxazepam, temazepam โ LOT mnemonic โ which undergo glucuronidation), carbamazepine, and quetiapine; CYP1A2 metabolizes clozapine and olanzapine (smoking induces CYP1A2 โ smokers need higher doses; smoking cessation requires dose reduction to avoid toxicity); CYP2C19 metabolizes citalopram, escitalopram, and diazepam. Pharmacogenomic testing identifies poor metabolizers (elevated drug levels, toxicity risk) and ultra-rapid metabolizers (subtherapeutic levels, treatment failure). Drug interactions include pharmacokinetic (enzyme induction/inhibition affecting drug levels) and pharmacodynamic (additive/synergistic effects โ serotonin syndrome from combined serotonergic agents, QTc prolongation from multiple QT-prolonging drugs, additive sedation from combined CNS depressants). The NP manages polypharmacy by rationalizing prescribing: one drug per target symptom cluster, avoiding duplicative mechanisms, cross-tapering when switching medications, and monitoring therapeutic drug levels when available (lithium, valproic acid, clozapine, carbamazepine).