No abstract

The numerous premature deaths, medical complications and socio-economic repercussions of drug and alcohol addiction suggest that improvements in treatment strategies for addictive disorders are warranted. The use of pharmacogenetics to predict response to medication, side effects and appropriate dosages is relatively new in the field of drug addiction. However, increasing our understanding of the genetic factors influencing these processes may improve the treatment of addiction in the future. We examined the available scientific literature on pharmacogenetic advancements in the field of drug addiction with a focus on alcohol and tobacco to provide a summary of genes implicated in the effectiveness of pharmacotherapy for addiction. In addition, we reviewed pharmacogenetic research on cocaine and heroin dependence. Thus far, the most promising results were obtained for polymorphisms in the OPRM1 and CYP2A6 genes, which have been effective in predicting clinical response to naltrexone in alcoholism and nicotine replacement therapy in smoking, respectively. Opinions differ as to whether pharmacogenetic testing should be implemented in the clinic at this time because clinical utility and cost-effectiveness require further investigation. However, the data summarized in this review demonstrate that pharmacogenetic factors play a role in response to addiction pharmacotherapy and have the potential to aid in the personalization of addiction treatments. Such data may lead to improved cessation rates by allowing physicians to select medications for individuals based, at least in part, on genetic factors that predispose to treatment success or failure rather than on a trial and error basis.

Atrial fibrillation (AF) is the most common clinically significant arrhythmia, and it increases stroke risk. A preventive approach to AF is needed because virtually all treatments such as cardioversion, antiarrhythmic drugs, ablation, and anticoagulation are associated with high cost and carry significant risk. A systematic review was performed to identify effective lifestyle-based strategies for reducing primary and secondary AF. A PubMed search was performed using articles up to March 1, 2021. Search terms included atrial fibrillation, atrial flutter, exercise, diet, metabolic syndrome, type 2 diabetes mellitus, obesity, hypertension, stress, tobacco smoking, alcohol, Mediterranean diet, sodium, and omega-3 fatty acids. Additional articles were identified from the bibliographies of retrieved articles. The control of hypertension, ideally with a renin-angiotensin-aldosterone system inhibitor, is effective for preventing primary AF and recurrence. Obstructive sleep apnea is a common cause of AF, and treating it effectively reduces AF episodes. Alcohol increases the risk of AF in a dose-dependent manner, and abstinence reduces risk of recurrence. Sedentary behavior and chronic high-intensity endurance exercise are both risk factors for AF; however, moderate physical activity is associated with lower risk of AF. Recently, sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 agonists have been associated with reduced risk of AF. Among overweight/obese patients, weight loss of ≥10% is associated with reduced AF risk. Lifestyle changes and risk factor modification are highly effective for preventing AF.

The opponent-process theory of motivation postulates that motivational stimuli activate a rewarding process that is followed by an opposed aversive process in a homeostatic control mechanism. Thus, an acute injection of morphine in nondependent animals should evoke an acute rewarding response, followed by a later aversive response. Indeed, the tegmental pedunculopontine nucleus (TPP) mediates the rewarding effects of opiates in previously morphine-naive animals, but not other unconditioned effects of opiates, or learning ability. The aversive opponent process for acute morphine reward was revealed using a place-conditioning paradigm. The conditioned place aversion induced by 16-h spontaneous morphine withdrawal from an acute morphine injection in nondependent rats was abolished by TPP lesions performed prior to drug experience. However, TPP-lesioned rats did show conditioned aversions for an environment paired with the acute administration of the opioid antagonist naloxone, which blocks endogenous opioids. The results show that blocking the rewarding effects of morphine with TPP lesions also blocked the opponent aversive effects of acute morphine withdrawal in nondependent animals. Thus, this spontaneous withdrawal aversion (the opponent process) is induced by the acute rewarding effects of morphine and not by other unconditioned effects of morphine, the pharmacological effects of morphine or endogenous opioids being displaced from opiate receptors.