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This column is the first of a 3-part series illustrating the importance of medical knowledge, including clinical pharmacology, in a forensic context. This first case involved an 18-year-old high school student who suffered an anoxic brain injury and remained in a state of permanent decorticate posture, unresponsive except for grunts and primitive movements until he died several years later. Our investigation began by ruling out plausible causes that were suggested by the defense in the malpractice suit. Once those possibilities were eliminated, the focus was on what accounted for the damage to the patient using general medical knowledge and clinical pharmacology. The 4 Ds of forensic psychiatry (duty, damages, dereliction, and direct cause) are the 4 elements that the plaintiff is required to prove in civil court to prevail in a malpractice suit and are applied to this case with a special focus on dereliction and direct cause. This catastrophic outcome was due to 3 factors. First, the patient had physiologically significant dehydration to the point that he had developed a reflex tachycardia to maintain his blood pressure. Second, the patient had been switched from extended to immediate-release quetiapine, resulting in a doubling of the peak concentration of the drug, which produced higher occupancy of alpha-1 adrenergic, histamine-1, and dopamine-2 receptors, causing a further drop in his blood pressure as well as increased sedation and impairment of his gag reflex. These effects occurred quickly because of the faster absorption of the IR formulation of the drug. Third, the patient had gone to sleep in a reclining chair so that his brain was above his heart and his lower extremities were below his heart, resulting in an increased "steal" of cardiac output going to his brain. These 3 factors together led the patient to aspirate and suffer a hypoxic brain injury after an episode of vomitus. This column explains the process by which the cause of this sad outcome was determined, how it was related to a dereliction of duty to the patient, and how other proposed causes were ruled out., Competing Interests: Over his 45-year career, S.H.P. has worked with over 145 pharmaceutical and biotech companies in the United States and throughout the world. Over the past year, he has received grants/research support from or has served as a consultant on the advisory board or on the speaker’s bureau for Alkermes, BioXcel, and Janssen. All clinical trial and study contracts were with and payments made to the Kansas University Medical Center Research Institute, a research institute affiliated with Kansas University School of Medicine-Wichita. The remaining author declares no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Anoxia in the mammalian brain leads to hyper-excitability and cell death; however, this cascade of events does not occur in the anoxia-tolerant brain of the western painted turtle, Chrysemys picta belli. The painted turtle has become an important anoxia-tolerant model to study brain, heart, and liver function in the absence of oxygen, but being anoxia-tolerant likely means that decapitation alone is not a suitable method of euthanasia. Many anesthetics have long-term effects on ion channels and are not appropriate for same day experimentation. Using whole-cell electrophysiological techniques, we examine the effects of the anesthetic, Alfaxalone, on pyramidal cell action potential amplitude, threshold, rise and decay time, width, frequency, whole cell conductance, and evoked GABAA receptors currents to determine if any of these characteristics are altered with the use of Alfaxalone for animal sedation. We find that Alfaxalone has no long-term impact on action potential parameters or whole-cell conductance. When acutely applied to naïve tissue, Alfaxalone did lengthen GABAA receptor current decay rates by 1.5-fold. Following whole-animal sedation with Alfaxalone, evoked whole cell GABAA receptor current decay rates displayed an increasing trend with 1 and 2 hours after brain sheet preparation, but showed no significant change after a 3-hour washout period. Therefore, we conclude that Alfaxalone is a suitable anesthetic for same day use in electrophysiological studies in western painted turtle brain tissue., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Suganthan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)