Pharmacokinetic and Pharmacodynamic Studies in Anesthetics

• Main Authors: Wen-YingChou, 周文英
• Other Authors: Chen-Hsi Chou
• Format: Others
• Language: en_US
• Published: 2019
• Online Access: http://ndltd.ncl.edu.tw/handle/6yh5na

博士 === 國立成功大學 === 臨床藥學與藥物科技研究所 === 107 === Objective: Pharmacokinetics is described as “what the body does to the drug” (drug concentration) and pharmacodynamics is described as “what the drug does to the body” (response). For anesthetics, taking into account premedication, perioperative antibiotics, intravenous agents used for induction or maintenance, inhalational anesthetics, opioids, muscle relaxants, reverse for neuromuscular transmission and postoperative analgesics, so many kinds of drugs are given. Because the concentration of anesthetics would indicate the depth of anesthesia, anesthesiologists should deliberately understand the mechanisms and avoid the adverse effects and interactions of these drugs to achieve the desired concentration for a safe practice of anesthesiology. Methods: All of the patients of the study, aged 25-65, were recruited from the Chang Gung Memorial hospital, Kaohsiung branch or the National Cheng Kung University Hospital. In the first part, pharmacokinetic, we measured the inspiratory and expiratory (end-tidal) concentration of inhaled anesthetic (sevoflurane) for patients with different body mass index (BMI) during surgery and investigated the possible associations between the genders and the mu-1 opioid receptor polymorphism A118G. In the secondary part, pharmacodynamics, to observe the response, we measured the changes of the 7-componets in Pittsburgh Sleep Quality Index scores for the first postoperative night after anesthesia; we also investigated the optimal dose of patient controlled analgesia (PCA) to get a balance between the adverse effects and analgesia from morphine. Results: In the first part, the different BMIs could affect the wash-in and wash-out curves of sevoflurane for a short term surgery but might not a major factor associated with the recovery profiles. Female patients of homozygous G118G of OPRMI required more morphine from PCA device for post-operative pain control after total knee replacements in comparison with patients of AA and AG genotypes but no significant difference in morphine consumption among these genotypes for male patients. In the secondary part, for female outpatients undergoing minor gynecologic surgery after propofol anesthesia, their postoperative PSQI scores improved, five components (sleep duration, sleep disturbance, sleep latency, sleep quality, and use of sleep medications) became better but not another two components (efficiency and daytime dysfunction). For postoperative sleep disorder, compared with the sevoflurane group, our findings indicated that propofol and sevoflurane have different impacts on postoperative PSQI scores for these ASA I-II female patients undergoing minor gynecologic surgery in the first night. For female receiving PCA with intravenous opioid following gynecological surgery, beyond 30 mg morphine in the postoperative 24 hours, we could replace opioid with non-opioid analgesic to help reducing morphine consumption and get a balance between analgesia and adverse effects. Conclusion: For an anesthesiologist, it is a responsibility to understand the basis for alteration in the pharmacokinetics and pharmacodynamics of any anesthetic used to avoid unintentional supra-therapeutic or sub-therapeutic concentration for anesthesia, the strategically employment in pharmacokinetics and pharmacodynamics to achieve the optimal depth of anesthesia is needed to secure the patient against the harm and to lessen the adverse effects from anesthetics and analgesics.