Cardiovascular Challenges in Toxicology

The diagnoses and subsequent treatment of poisoned patients manifesting cardiovascular compromise challenges the most experienced emergency physician. Numerous drugs and chemicals cause cardiac and vascular disorders. Despite widely varying indications for therapeutic use, many agents share a common cardiovascular pharmacologic effect if taken in overdose. Standard advanced cardiac life support protocol care of these patients may not apply and may even result in harm if followed Epidemiology Emergency physicians routinely evaluate and manage poisoned patients. In 2003, more than 2.3 million human exposure cases were reported to poison centers throughout the United States [1]. Of those cases, more than 500,000 (22%) were treated at health care facilities, with most of those cases evaluated in the emergency department. Cardiovascular drugs were listed as the seventh most frequently encountered human exposure in adults (40,896 cases) and the fifth leading cause of poisoning deaths. When taken in overdose, numerous other products can also produce cardiovascular toxic effects. Emergency physicians should consider the cardiac complications of specific agents at the time they are evaluating poisoned patients. Cardiac physiology To understand the cardiac complications of various agents, physicians must have a clear understanding of basic myocardial cell function. Th

Clinical review: Aggressive management and extracorporeal support for drug-induced cardiotoxicity

Poisoning may induce failure in multiple organs, leading to death. Supportive treatments and supplementation of failing organs are usually efficient. In contrast, the usefulness of cardiopulmonary bypass in drug-induced shock remains a matter of debate. The majority of deaths results from poisoning with membrane stabilising agents and calcium channel blockers. There is a need for more aggressive treatment in patients not responding to conventional treatments. The development of new antidotes is limited. In contrast, experimental studies support the hypothesis that cardiopulmonary bypass is life-saving. A review of the literature shows that cardiopulmonary bypass of the poisoned heart is feasible. The largest experience has resulted from the use of peripheral cardiopulmonary bypass. However, a literature review does not allow any conclusions regarding the efficiency and indications for this invasive method. Indeed, the majority of reports are single cases, with only one series of seven patients. Appealing results suggest that further studies are needed. Determination of prognostic factors predictive of refractoriness to conventional treatment for cardiotoxic poisonings is mandatory. These prognostic factors are specific for a toxicant or a class of toxicants. Knowledge of them will result in clarification of the indications for cardiopulmonary bypass in poisonings

Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection

Although the pathogenesis of human immunodeficiency virus (HIV) infection and the general virologic and immunologic principles underlying the use of antiretroviral therapy are similar for all HIV-infected persons, there are unique considerations needed for HIV-infected infants, children, and adolescents, including; A acquisition of infection through perinatal exposure for many infected children, In utero, intrapartum, and/or postpartum neonatal exposure to zidovudine (ZDV) and other antiretroviral medications in most perinatally infected children, Requirement for use of HIV virologic tests to diagnose perinatal HIV infection in infants under age 15 to 18 months old, Age-specific differences in immunologic markers (i.e., CD4+ T cell count), Changes in pharmacokinetic parameters with age caused by the continuing development and maturation of organ systems involved in drug metabolism and clearance, Differences in the clinical and virologic manifestations of perinatal HIV infection secondary to the occurrence of primary infection in growing, immunologically immature persons, and Special considerations associated with adherence to antiretroviral treatment for infants, children and adolescents. This report addresses the pediatric-specific issues associated with antiretroviral treatment and provides guidelines to health care providers caring for infected infants, children, and adolescents. It is recognized that guidelines for antiretroviral use in pediatric patients are rapidly evolving. The Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children will review new data on an ongoing basis and provide regular updates to the guidelines

Drug-induced Fatal Arrhythmias: Acquired long QT and Brugada Syndromes

Since the early 1990s, the concept of primary “inherited” arrhythmia syndromes or ion channelopathies has evolved rapidly as a result of revolutionary progresses made in molecular genetics. Alterations in genes coding for membrane proteins such as ion channels or their associated proteins responsible for the generation of cardiac action potentials (AP) have been shown to cause specific malfunctions which eventually lead to cardiac arrhythmias. These arrhythmic disorders include congenital long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, short QT syndrome, progressive cardiac conduction disease, etc. Among these, long QT and Brugada syndromes are the most extensively studied, and drugs cause a phenocopy of these two diseases. To date, more than 10 different genes have been reported to be responsible for each syndrome. More recently, it was recognized that long QT syndrome can be latent, even in the presence of an unequivocally pathogenic mutation (silent mutation carrier). Co-existence of other pathological conditions in these silent mutation carriers may trigger a malignant form of ventricular arrhythmia, the so called torsade de pointes (TdP) that is most commonly brought about by drugs. In analogy to the drug-induced long QT syndrome, Brugada type 1 ECG can also be induced or unmasked by a wide variety of drugs and pathological conditions; so physicians may encounter patients with a latent form of Brugada syndrome. Of particular note, Brugada syndrome is frequently associated with atrial fibrillation whose therapeutic agents such as Vaughan Williams class IC drugs can unmask the dormant and asymptomatic Brugada syndrome. This review describes two types of drug-induced arrhythmias: the long QT and Brugada syndromes

A REVIEW ON PHARMACO KINETIC DRUG INTERACTIONS OF STATINS

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are generally well tolerated as monotherapy. Statins are associated with two important adverse effects, asymptomatic elevation in liver enzymes and myopathy. Myopathy is most likely to occur when statins are administered with other drugs. Statins are substrates of multiple drug transporters (including OAT- -P1B1, BCRP and MDR1) and several cytochrome P450 (CYP) enzymes (including CYP3A4, CYP2C8, CYP2C19, and CYP2C9). Possible adverse effects of statins can occur due to interactions in concomitant use of drugs that substantially inhibit or induce their methabolic pathway. This review aim is to summarize the most important interactions of statins

Drug-drug interactions in the treatment for alcohol use disorders: A comprehensive review

Abstract Drug interactions are one of the most common causes of side effects in polypharmacy. Alcoholics are a category of patients at high risk of pharmacological interactions, due to the presence of comorbidities, the concomitant intake of several medications and the pharmacokinetic and pharmacodynamic interferences of ethanol. However, the data available on this issue are limited. These reasons often frighten clinicians when prescribing appropriate pharmacological therapies for alcohol use disorder (AUD), where less than 15% of patients receive an appropriate treatment in the most severe forms. The data available in literature regarding the relevant drug–drug interactions of the medications currently approved in United States and in some European countries for the treatment of AUD (benzodiazepines, acamprosate, baclofen, disulfiram, nalmefene, naltrexone and sodium oxybate) are reviewed here. The class of benzodiazepines and disulfiram are involved in numerous pharmacological interactions, while they are not conspicuous for acamprosate. The other drugs are relatively safe for pharmacological interactions, excluding the opioid withdrawal syndrome caused by the combination of nalmefene or naltrexone with an opiate medication. The information obtained is designed to help clinicians in understanding and managing the pharmacological interactions in AUDs, especially in patients under multi-drug treatment, in order to reduce the risk of a negative interaction and to improve the treatment outcomes

Toxicology in Emergency Medicine

Poisoning is a serious worldwide public health problem. Based on WHO data in 2012, almost 190,000 people died worldwide and the number of deaths due to poisoning in 2008 exceeded the number of deaths due to motor vehicular crashes; also, poisoning death rate nearly tripled worldwide. Number of patients presenting to the emergency departments with overdose, had been increased both intentionally and accidentally. All the previous facts make Toxicology an important field in emergency medicine. Management of intoxicated patients has a unique approach because of the challenge in diagnosis and treatment of overdose cases. This chapter is focusing on general approaches for intoxicated patients and initial management and on how the history and physical examinations could help physicians to have what drug have been abused as well as review the mechanism of action, physical finding and treatment of the most common drugs-causing toxicity in addition to the drugs with high mortality morbidity rates

Pharmacokinetic Aspects of Statins

Statins are the most used therapeutic group in the treatment of hypercholesterolemia and reduce the risk of cardiovascular events and mortality. Long prescription periods and their pharmacokinetic characteristics increase the possibility of interactions, especially at the metabolism level. Simvastatin, lovastatin, and atorvastatin are metabolized by CYP3A4 isoenzymes, so they will have more significant interactions than fluvastatin, pitavastatin, and rosuvastatin that require CYP2C9. The main interactions are with macrolides, azole antifungals, antiretrovirals, platelet antiaggregants, anticoagulants, oral antidiabetics, calcium channel blockers, immunosuppressants, and other hypolipidemic agents, among others. A review of all medications that are taken by patients treated with statins should be performed at each medical consultation and during all healthcare transitions

HIV infection in the elderly

In the US, an estimated 1 million people are infected with HIV, although one-third of this population are unaware of their diagnosis. While HIV infection is commonly thought to affect younger adults, there are an increasing number of patients over 50 years of age living with the condition. UNAIDS and WHO estimate that of the 40 million people living with HIV/AIDS in the world, approximately 2.8 million are 50 years and older. With the introduction of highly active antiretroviral therapy (HAART) in the mid-1990s, survival following HIV diagnosis has risen dramatically and HIV infection has evolved from an acute disease process to being managed as a chronic medical condition. As treated HIV-infected patients live longer and the number of new HIV diagnoses in older patients rise, clinicians need to be aware of these trends and become familiar with the management of HIV infection in the older patient. This article is intended for the general clinician, including geriatricians, and will review epidemiologic data and HIV treatment as well as provide a discussion on medical management issues affecting the older HIV-infected patient