Effects of non-prescribed drugs on the heart

EFFECTS OF NON-PRESCRIBED DRUGS ON THE HEART

Cocaine is associated with multiple cardiovascular complications including chest pain, myocardial ischemia/infarction, arrhythmias, aortic dissection, and stroke [1]. Felker et al., reported cocaine use as a rare cause of cardiomyopathy, with 10 cases found among 1278 cases of dilated cardiomyopathy at Johns Hopkins Hospital [2]. Cocaine blocks reuptake of dopamine and neuroepinephrine at the post synaptic receptor, resulting in increased sympathetic activation. The mechanisms underlying cocaine cardiomyopathy are not fully understood, but are thought to include sympathomimetic effects, increased calcium flux, enhanced oxidative stress, and promotion of intra-coronary thrombus formation.

The clinical characteristics of cocaine cardiomyopathy are similar to other forms of dilated cardiomyopathy. Cocaine cardiomyopathy should strongly be considered in young (less than 50 years of age) males presenting with signs of adrenergic excess and heart failure or left ventricular dysfunction. Cocaine cardiomyopathy presents suddenly without a long prodrome. The electrocardiogram tends to show sinus tachycardia with frequent arrhythmias, including atrial fibrillation and ventricular tachycardia [2]. Echocardiogram demonstrates increased left ventricular mass and dysfunction. Urine testing for cocaine and its metabolite, benzoylecgonine, should be performed. The management of cocaine cardiomyopathy is similar to other forms of dilated cardiomyopathy, except beta-blockers should be avoided initially, and benzodiazepine should be given to blunt adrenergic excess. Beta-blockers can be added later in the compliant patient who follows up and abstains. Left ventricular function can improve dramatically with abstinence from cocaine, like alcohol. Unfortunately, the rate of recidivism is high and left ventricular dysfunction and symptomatic heart failure often recurs.

Anabolic Steroid-Induced Cardiomyopathy. Anabolic/androgenic steroids mimic the effects of male steroids testosterone and dihydrotestosterone. Increased cellular protein synthesis, results in buildup of tissue (anabolism), especially in muscles. One survey found that two thirds of elite US powerlifters self-reported use of anabolic steroids to enhance performance [3]. Anabolic steroids share with endogenous steroids influences on left ventricular hypertrophic response through actions on the androgen receptor. Androgen receptors are ubiquitously expressed, found not only in skeletal muscle cells, but also on cardiac myocytes. Anabolic steroids can cause hypertension, dyslipidemia, and impaired fasting glucose [3]. Anabolic steroids can cause alterations in heart structure, including left ventricular hypertrophy and dilation, and impaired contraction and relaxation [4]. Potential sequelae include hypertension, arrhythmias, heart failure, myocardial infarction, and sudden death. Side effects are dose-dependent. In a recent postmortem series of 34 anabolic steroid abusers aged 20 to 45 years, twelve showed cardiac pathology including hypertrophy, myocardial and endocardial fibrosis, cardiac steatosis, myocardial coagulation necrosis, and coronary atheroma [5]. Prolonged anabolic steroid use leads to dose-dependent reversible myocardial hypertrophy, decreased inotropic capacity of the myocardium, and irreversibly reduced compliance of the left ventricle.

Amphetamine-Induced Cardiomyopathy. Crean and Pohl published an interesting case report of a 30-year-old female admitted to the hospital complaining of four month history of ankle swelling, increased abdominal extension, and a three-day history of shortness of breath [6]. She admitted to four years of daily amphetamine use. She initially used amphetamines to stay thin but this became a habit. Chest x-ray showed cardiomegaly, pulmonary edema, and pleural effusion. Electrocardiogram showed sinus tachycardia with left atrial enlargement and left ventricular hypertrophy with repolarization abnormality. Echocardiogram demonstrated dilated left ventricle and atrium with a left ventricular ejection fraction a 26%. After seven days of abstention and treatment, left ventricular dilation and ejection fraction showed significant improvement.

Amphetamines are related to natural occurring biogenic amines (dopamine, serotonin, catecholamines) by their phenylethylamine structure. The mechanism of the dilated cardiomyopathy is unclear, but may be adrenegically driven tachycardia-induced cardiomyopathy or recurrent hypertensive crises or tachycardia leading to left ventricular failure. Abstinence and standard dilated cardiomyopathy therapy lead to functional improvement.

Ma Huang (Ephedra)-Induced Cardiomyopathy. The dietary supplement ephedra, also known as ma huang, contains two alkaloids, ephedrine and its enantiomer, pseudoephedrine. Ma Huang has been associated with stroke, myocardial infarction, sudden death, and cardiomyopathy [7]. Samenuk et al., found at autopsy in seven ma huang-related cases of sudden death, three cardiomyopathies (ages 23 to 37 years old) [7]. Ma huang increases catecholamines at synaptic areas in the brain and heart and directly stimulates alpha and beta-adrenergic receptors. Thus, ma huang can increase heart rate, blood pressure, cardiac output and peripheral resistance. Coronary artery spasm and proarrhythmic effects can account for acute events and death. Prolonged catecholamine excess with long-term ma huang use is one likely underlying mechanism for cardiomyopathy.

• 3,    4- Methylenedioxymethamphetamine (MDMA), commonly known as ecstasy, can cause myocardial infarction, arrhythmias and cardiomyopathy. Animal studies have shown that repeated administration of MDMA and/or its metabolites causes eccentric left ventricular dilation and diastolic dysfunction as well as contractile dysfunction in myocytes [8]. Shenouda and colleagues demonstrated MDMA-induced myocarditis with inflammatory infiltrates and areas of necrosis. MDMA is metabolized to catechols that can undergo redox

cycling, producing reactive oxygen and nitrogen species [9]. This suggests that potential mechanisms of MDMA-induced cardiomyopathy are related to oxidative stress, as well as catecholaminergic stimulation.

Refrences:

• 1.    Maraj S, Figueredo VM, Lynn Morris D: Cocaine and the heart. Clin Cardiol; 33(5): 264-9.

• 2.    Felker GM, Hu W, Hare JM, Hruban RH, Baughman KL, Kasper EK: The spectrum of dilated cardiomyopathy. The Johns Hopkins experience with 1,278 patients. Medicine (Baltimore) 1999; 78(4): 270-83.

• 3.    Curry LA, Wagman DF: Qualitative description of the prevalence and use of anabolic androgenic steroids by United States powerlifters. Percept Mot Skills 1999; 88(1): 224-33.

• 4.    De Piccoli B, Giada F, Benettin A, Sartori F, Piccolo E: Anabolic steroid use in body builders: an echocardiographic study of left ventricle morphology and function. Int J Sports Med 1991; 12(4): 408-12.

• 5.    Ahlgrim C, Guglin M: Anabolics and cardiomyopathy in a bodybuilder: case report and literature review. J Card Fail 2009; 15(6): 496-500.

• 6.    Thilbin I, Kristiansson, M, & Rajs, J: Anabolic androgenic steroids and behavioral patterns among violent offenders. J Forensic Psych 1997; 8: 299-310.

• 7.    Samenuk D, Link MS, Homoud MK, et al.: Adverse cardiovascular events temporally associated with ma huang, an herbal source of ephedrine. Mayo Clin Proc 2002; 77(1): 12-6.

• 8.    Haller CA, Benowitz NL: Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med 2000; 343(25): 1833-8.

• 9.    Заднипряный И.В., Третьякова О.С., Сатаева Т.П. Особенности развития митохондриальной дисфункции при гипоксических состояниях // International scientific review. – 2016. – № 2 (12). – С. 249-251.