Psychotropic Pharmacotherapy Associated With QT Prolongation Among Veterans With Posttraumatic Stress Disorder

Simonsen

2020

Basic Clin Pharma Tox

Opioid poisoning is a frequent cause of death in drug addicts and occurs with opioid treatment. Quetiapine is often found in forensic autopsies and may increase the risk of fatal opioid poisoning by enhancing sedation, respiratory depression, hypotension and QT prolongation. We systematically searched for studies of acute toxicity of quetiapine or other antipsychotics combined with morphine or methadone. Case reports describing toxicity of quetiapine combined with morphine or methadone were also included. We retrieved one human study that observed pharmacokinetic interaction between quetiapine and methadone, and 16 other human studies. Fourteen investigated the combination of droperidol and morphine in treatment doses, and some indicated an additive sedative effect. Five animal studies with acepromazine in combination with morphine or methadone were located and indicated an additive effect on sedation and hypotension. Six forensic case reports in which death could have been caused solely by quetiapine, the opioid, or other drugs were found. Thus, acute toxicity of quetiapine combined with morphine or methadone has not been studied. Because of quetiapine's effects on alpha-adrenoceptors, muscarinic and histamine receptors, human ether-ago go channels and methadone kinetics, we suggest further research to clarify if the indicated additive effects of opioids and droperidol or acepromazine are also true for quetiapine.

Section: Pharmacodynamic Interactions Of Antipsychotics and Opioidsmentioning

confidence: 95%

“…Fifty-nine were excluded because quetiapine or droperidol was used in monotherapy, and seven because outcome was assessed more than 24 hours after exposure. [57][58][59][60][61][62][63] Four relevant references were found by looking through reviews ( Figure 1).…”

Section: Retrieved Studiesmentioning

confidence: 99%

Quetiapine and other antipsychotics combined with opioids in legal autopsy cases: A random finding or cause of fatal outcome?

Simonsen

2020

Basic Clin Pharma Tox

“…Antipsychotic and antiepileptic medications have been reported to have a range of cardiac side-effects, including orthostatic hypotension [43], cardiomyopathy [44], QT prolongation [45] and increased risk for SCD [9]. Moreover, antidepressant drugs have been associated with adverse cardiac effects: the selective serotonin reuptake inhibitors (SSRIs) and particularly the tricyclic antidepressants are known to cause prolongation of the heart rate corrected QT interval (QT c ) on an ECG and predispose to ventricular arrhythmias [46,47]. These cardiotoxic effects of psychiatric disorder therapeutics are of particular importance in patients with an underlying CVD.…”

Section: Psychiatric Disorders and Cardiovascular Diseasesmentioning

confidence: 99%

Neurological Disorders and Risk of Arrhythmia

Bernardi

Aromolaran

2020

IJMS

Neurological disorders including depression, anxiety, post-traumatic stress disorder (PTSD), schizophrenia, autism and epilepsy are associated with an increased incidence of cardiovascular disorders and susceptibility to heart failure. The underlying molecular mechanisms that link neurological disorders and adverse cardiac function are poorly understood. Further, a lack of progress is likely due to a paucity of studies that investigate the relationship between neurological disorders and cardiac electrical activity in health and disease. Therefore, there is an important need to understand the spatiotemporal behavior of neurocardiac mechanisms. This can be advanced through the identification and validation of neurological and cardiac signaling pathways that may be adversely regulated. In this review we highlight how dysfunction of the hypothalamic–pituitary–adrenal (HPA) axis, autonomic nervous system (ANS) activity and inflammation, predispose to psychiatric disorders and cardiac dysfunction. Moreover, antipsychotic and antidepressant medications increase the risk for adverse cardiac events, mostly through the block of the human ether-a-go-go-related gene (hERG), which plays a critical role in cardiac repolarization. Therefore, understanding how neurological disorders lead to adverse cardiac ion channel remodeling is likely to have significant implications for the development of effective therapeutic interventions and helps improve the rational development of targeted therapeutics with significant clinical implications.

The Journal of Clinical Pharma

“…In contrast to the medical specialties focusing on LQTS, drug‐induced QT prolongation is relevant to a much wider group of health care professionals involved in therapeutic decisions, for example, physicians in family practice and a wide variety of medical specialties, physician assistants, nurses, and pharmacists and hence this article's focus on this topic. A wide range of drugs and drug classes for many conditions as diverse as liver and kidney disease, chronic obstructive pulmonary disease, psychiatric conditions, and posttraumatic stress disorder have an identified proarrhythmic liability. If prescribed to patients with certain risk factors, they can occasionally precipitate bradyarrhythmias and tachyarrhythmias, including TdP.…”

Section: Normal Cardiac Ion Channel Activity Inherited Long Qt Syndrmentioning

confidence: 99%

How to Prescribe Drugs With an Identified Proarrhythmic Liability

Thind

Rodríguez

Kosari

et al. 2019

This is an article in the Journal of Clinical Pharmacology's Core Entrustable Professional Activities in Clinical Pharmacology series that discusses druginduced proarrhythmia and is offered as a teaching aid for medical students and residents. Drugs from diverse pharmacological classes can lead to multiple types of arrhythmias including the polymorphic ventricular tachycardia torsades de pointes (TdP). Although typically occurring in selflimiting bursts with or without associated symptoms, which can range from mild lightheadedness and palpitations to syncope and seizures, TdP can also occasionally progress to ventricular fibrillation and sudden cardiac death. To provide patients with the optimal therapeutic benefits of potentially proarrhythmic drugs, prescribers are responsible for obtaining a good understanding of the compound's benefit-risk properties and perform a judicious assessment of the patient's clinical characteristics and individual risk factors. Dose adjustments and/or additional monitoring of electrocardiograms and electrolyte balances may be appropriate in some cases. This article explains the pharmacological mechanism of action of drug-induced proarrhythmia associated with compounds that prolong the repolarization period, illustrates how this liability is conveyed in a drug's prescribing information (label), details the clinical characteristics of patients most susceptible to this type of proarrhythmia, and describes interventions that can be made if TdP occurs. Three clinical vignettes are provided at the end of the article to highlight the relevance of the preceding discussions.