Leveraging Knowledge of Clozapine's Pharmacodynamics and Pharmacokinetics to Improve Outcomes-View Presentation

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Video Summary

The webinar, led by Dr. Robert Kotez, focuses on enhancing outcomes by understanding clozapine's pharmacodynamics and pharmacokinetics. Clozapine is pivotal for treatment-resistant schizophrenia (TRS), administered after two unsuccessful antipsychotic trials. Despite being the only FDA-approved medication for TRS, only about 5% of eligible U.S. patients receive clozapine. The discussion emphasizes clozapine's narrow therapeutic index, underlying both its benefits and complex side effects, such as neutropenia, myocarditis, cardiometabolic issues, sedation, tachycardia, and constipation.<br /><br />Dr. Kotez highlights therapeutic drug monitoring's role in ensuring effective dosing, utilizing clozapine/norclozapine ratios, and identifying metabolic irregularities. Factors affecting clozapine levels include smoking cessation, caffeine consumption, and possible drug interactions, like those with CYP1A2 inhibitors.<br /><br />Side effects management strategies are discussed, including using beta-blockers for tachycardia and various treatments for clozapine-induced sedation and constipation. Additionally, the webinar covers clozapine's unique efficacy in reducing symptoms of TRS, potential suicidal behavior, and aggression due to its complex receptor binding involving dopamine and serotonin receptors.<br /><br />The session concludes with audience queries on topics like concurrent use of clozapine with other medications, its impact on pregnancy, and long-term monitoring strategies. The overriding message promotes clozapine's significant potential benefits against its challenging side effects, urging careful management and patient-informed decision-making to optimize therapeutic outcomes.

Keywords

clozapine

treatment-resistant schizophrenia

pharmacodynamics

pharmacokinetics

therapeutic drug monitoring

side effects management

CYP1A2 inhibitors

neutropenia

myocarditis

receptor binding