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Anesthetic Drugs Pharmacokinetics and Pharmacodynamics

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Applied Clinical Pharmacokinetics and Pharmacodynamics of Psychopharmacological Agents

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Abstract

Patients undergoing surgery require anesthesia that involves using a variety of medications that promote sedation, pain mitigation, and abate any response to stimulation. Early agents used for sedation induction were thiopental and etomidate. Although ketamine is commonly used in veterinary medicine, this agent is often employed in combination with a benzodiazepine to induce analgesia and sedation. Ketamine is a racemic mixture where the S(+) isomer is two to four times more potent. Midazolam is a water-soluble benzodiazepine where at pH>4, the molecule’s ring structure closes, and it becomes a highly lipophilic agent. Both ketamine and midazolam pharmacokinetics fit into a two-compartment open model and primarily metabolized by CYP3A4. The muscle relaxant agents succinyolcholine, d-tubocurarine, roncuronium, and vencuronium induce muscle paralysis used for anesthesia. Succinylcholine pharamacokinetics has been described as a one-compartment open model whereas the other agents a two- or three-compartment open model. Their pharmacodynamics effects are closely linked with their pharmacokinetic profiles. The short-acting opioids fentanyl, sufentanil, and alfentanil are used in anesthesia for pain management and maintain cardiovascular stability. The pharmacokinetics of these agents are expressed as either a two- or three-compartment open model and mainly metabolized by CYP3A4. Propofol and thiopental display a three-compartment open model. Various factors can alter anesthetic drug disposition and their pharmacodynamic actions.

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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

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  1. Univ. North Texas Sys, Col Pharmacy, Department of Pharmacotherapy, FORT WORTH, Texas, USA

    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. (2016). Anesthetic Drugs Pharmacokinetics and Pharmacodynamics. 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_15

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