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Antipsychotics

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Book cover Applied Clinical Pharmacokinetics and Pharmacodynamics of Psychopharmacological Agents

Abstract

Antipsychotic medications have been used for the treatment of patients with schizophrenia, schizoaffective, bipolar disorders, and other psychotic conditions. Antipsychotics administration can occur by various routes that includes oral, sublingual, intramuscular, and inhalation. Long-acting depot antipsychotics offer the clinician an additional option for chronic disease management. Most antipsychotics are metabolized by the hepatic CYP enzymes except ziprasidone and paliperidone. Antipsychotics are either substrates or inhibitors of P-glycoprotein. A “therapeutic” plasma concentration range has been recommended for antipsychotics except for asenapine, iloperidone, and lurasidone due to their recent entrance into clinical practice. Each antipsychotic agent possesses a different pharmacodynamic profile with receptor binding that accounts for their varying therapeutic effects regarding daily doses and their different adverse event characteristics. The antipsychotic doses are at the lower therapeutic range that achieves a dopamine receptor subtype 2 (D2) blockade of 65–85 % as measured by the PET technology. Yet, routine daily practice exceeds these low doses based upon the patient’s clinical response and tolerability indicating the limitations of linking pharmacokinetic and pharmacodynamic models with complex psychiatric diseases such as schizophrenia. Other pharmacodynamic effects include QT/QTc prolongation, prolactin changes, anticholinergic, sedation, and cardiovascular actions. Population pharmacokinetic analysis has been extended to antipsychotics, yielding some interesting findings regarding pharmacokinetic and pharmacodynamic models.

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  1. Department of Pharmacotherapy, University of North Texas System College of Pharmacy (UNTSCP) and University of North Texas Health Science Center (UNTHSC), Fort Worth, TX, USA

    Michael W. Jann PharmD

  2. Department of Pharmacy Practice, College of Pharmacy, Mercer University, Atlanta, GA, USA

    W. Klugh Kennedy PharmD

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    Michael W. Jann

  2. Department of Pharmacotherapy, Univ. North Texas Sys, Col Pharm, FORT WORTH, Texas, USA

    Scott R. Penzak

  3. Department of Pharmacotherapy, Univ. North Texas Sys, Col Pharm., FORT WORTH, Texas, USA

    Lawrence J. Cohen

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Jann, M.W., Kennedy, W.K. (2016). Antipsychotics. In: Jann, M., Penzak, S., Cohen, L. (eds) Applied Clinical Pharmacokinetics and Pharmacodynamics of Psychopharmacological Agents. Adis, Cham. https://doi.org/10.1007/978-3-319-27883-4_7

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