568 Postgrad Med J: first published as 10.1136/pgmj.2004.028571 on 2 September 2005. Downloaded from REVIEW Cocaine and the heart M Egred, G K Davis ............................................................................................................................... Postgrad Med J 2005;81:568–571. doi: 10.1136/pgmj.2004.028571 Cocaine is the second commonest illicit drug used and the N Genitourinary and obstetric: renal and testi- cular infarction, abruptio placentae, sponta- most frequent cause of drug related deaths. Its use is neous abortion, prematurity, and growth associated with both acute and chronic complications that retardation.9 may involve any system, the most common being the N Neurological: seizures, migraine, cerebral 10 cardiovascular system. Cocaine misuse has a major effect infarction, and intracranial haemorrhage. N Musculoskeletal and dermatological: rhabdo- in young adult drug users with resulting loss of productivity myolysis, skin ischaemia, superficial and deep and undue morbidity with cocaine related cardiac and venous thrombosis, and thrombophlebitis.11 cerebrovascular effects. Many cocaine users have little or In this review we will focus on the cardiovas- no idea of the risks associated with its use. Patients, health cular effects of cocaine. care professionals, and the public should be educated about the dangers and the considerable risks of cocaine PHARMACOLOGY OF COCAINE use. This review concentrates on the cardiovascular effects Cocaine (benzoylmethylecgonine, C17,H21,NO4) is an alkaloid extract from the leaf of the of cocaine and their management. Erythroxylon coca plant, which usually grows in ........................................................................... South America. It is available in two forms: N Hydrochloride salt: prepared by dissolving the alkaloid in hydrochloric acid forming a water ocaine is the second commonest illicit drug soluble powder or granule that decomposes used and the most frequent cause of drug when heated. It can be taken orally, intrana- Crelated deaths. The younger age group of sally, or intravenously. 18–25 are the most common users and it is N Free base: manufactured by processing the estimated that 11% of the population has used it cocaine with ammonia or sodium bicarbonate at some point.1–2 Cocaine may be taken by (baking soda). It is a heat stable form that smoking, nasal inhalation, or injection with melts with temperature allowing it to be varying pharmacokinetics leading to peak blood smoked and it is known as ‘‘crack’’ because concentration ranging from 1 to 90 minutes. Its of the popping sound it makes when heated. http://pmj.bmj.com/ use is associated with both acute and chronic Crack cocaine is considered the most potent complications that may involve any system, the and addictive form. most common being the cardiovascular system.2–4 Complications can also follow any route of Cocaine is absorbed, in both forms, from all administration.5 It is worth noting that pre- body mucus membranes. The peak effect ranges existent vascular disease or other abnormalities from 1 to 90 minutes depending on the route of 6 are not a prerequisite for the development of administration. The half life ranges from 0 min- 5 utes after inhalation or intravenous injection to cocaine related cardiovascular complications. on September 23, 2021 by guest. Protected copyright. Cocaine misuse and its related morbidity are two to three hours after gastrointestinal inges- important and have to be considered on the tion, with duration of action between 15 minutes differential diagnosis of cardiovascular events in by intravenous or inhalation routes to three 5 young adults because of its major effect and the hours by the gastrointestainal route. (table 1). resulting loss of productivity and undue morbid- Cocaine is metabolised to inactive water ity with its related cardiac and cerebrovascular soluble metabolites (benzoylecgonine and ecgo- events. nine methyl ester) by hepatic and plasma Cocaine related complications include cholinesterase and also by non-enzymatic hydro- See end of article for lysis. The elderly population, people with liver authors’ affiliations disease, the fetus, infants, pregnant women, and ....................... N Cardiac: myocardial ischaemia, coronary artery spasm, acute myocardial infarction adults with pseudicholinesterase deficiency have Correspondence to: (MI), atherosclerosis, myocarditis, cardiomyo- lower cholinesterase activity and thus carry an Dr M Egred, increased risk with cocaine. The concomitant use Cardiothoracic Centre, pathy, arrhythmia, hypertension, and endo- Thomas Drive, Liverpool carditis. of cocaine and alcohol, a common practice in young users, has a dangerous and multiplicative L14 3PE, UK; m.egred@ N Vascular: aortic dissection and rupture, vas- ctc.nhs.uk cardiovascular risk. They are metabolised in the culitis.6 liver to cocaethylene, which has been associated Submitted N Gastrointestinal: mesenteric ischaemia or with a 40-fold increase in risk for acute cardiac 7 9 September 2004 infarction, perforation. 12 Accepted events and 25-fold increase in sudden death. 28 December 2004 N Pulmonary: pulmonary oedema, pulmonary Cocaine water soluble metabolites are excreted ....................... infarction, and haemoptysis.8 in the urine,13 which remains positive for cocaine www.postgradmedj.com Cocaineandtheheart 569 Postgrad Med J: first published as 10.1136/pgmj.2004.028571 on 2 September 2005. Downloaded from metabolite up to 72 hours, providing an indicator of recent these patients would have experienced chest pain pre- cocaine use.14 15 Norcocaine is formed by an N-demethylation viously.24 Interestingly, the anterior wall is involved in most reaction, and represents less than 5% of the total quantity of cases (77%) of cocaine induced MI.31 Chest pain and ECG cocaine metabolites. It may mediate delayed effects of changes are very common in cocaine users even in the cocaine via enterohepatic recirculation.16 Cocaine use can absence of myocardial ischaemia and MI31 and only 6% of also be detected by hair analysis, which is a sensitive marker cocaine induced chest pain are attributable to MI.25 and provides information about cocaine use in the preceding The risk of MI is increased up to 24 times over baseline in weeks or months, depending on the length of the hair the first 60 minutes after cocaine use. In one series, 1% of analysed.9 Interestingly, the prevalence of cocaine use is three patients who had an acute MI, had used cocaine within the to five times more than in standard surveys and interview previous year. Of this group, about 25% used cocaine within with patients, when hair analysis was used.17 18 60 minutes before the infarct.29 Young patients presenting with chest pain and suspected MECHANISM OF ACTION acute coronary syndrome should be questioned about cocaine Cocaine acts as a powerful sympathomimetic agent. It blocks use. the presynaptic reuptake of norepinephrine and dopamine Cocaine induced MI can be difficult to diagnose accurately, producing high level of these neurotransmitters at the as the ECG is difficult to interpret in young patients, with the postsynaptic receptors.2 Cocaine also may increase the release high incidence of early repolarisation and left ventricular of catecholamines from central and peripheral stores.19 It can hypertrophy. On the other hand, MI can occur with normal act as a local anaesthetic by blocking the initiation and ECG or with only non-specific findings. Up to 84% of patients transmission of electrical signals, as it inhibits membrane with cocaine induced chest pain may have an abnormal ECG permeability to sodium during depolarisation.20 The arryth- and up to 43% of cocaine misusers without MI may have ST mogenic potential of cocaine has led to the decline in its use segment elevation in two or more ECG leads that may even in ear, nose, eye, and throat surgery.21 meet the thrombolysis criteria.25 32 33 The reported ECG Cocaine produces a dose dependent increase in blood sensitivity for detecting cocaine induced MI is 36% with a pressure and heart rate, which, in recreational doses, usually 90 % specificity.25 remains within the physiological range.21 The sympathomi- Serum creatine kinase is not a reliable indicator of metic actions of cocaine, at cellular level, are mediated by myocardial injury and is increased in almost half of cocaine stimulation of the a and b adrenergic receptors. Cocaine also users without MI. This is thought to be attributable to interacts with the muscarinic receptors,22 and inhibits the rhabdomyolysis. In contrast, cardiac troponins are more reuptake of dopamine and seretonin by nerve endings. sensitive and specific for myocardial injury and should be used for the diagnosis of MI.33–36 CARDIOVASCULAR EFFECTS OF COCAINE USE Complications after cocaine induced MI, fortunately, have The most common symptom in cocaine users is chest pain,4 a low incidence, possibly because of the young age of most and the most common cardiac disorders is ischaemia and patients, and occur mostly within 12 hours of presentation. acute coronary syndrome, which can occur with all routes of Ventricular arrhythmias occur in 4% to 17%, congestive heart cocaine intake.23 24 Other cardiac problems include myocardi- failure in 5% to 7%, and death in less than 2%. However, tis, cardiomyopathy, and arrhythmias. continuous cocaine use and recurrent chest pain are common, with occasional recurrent non-fatal MI or death.37 38 COCAINE RELATED CHEST PAIN AND MYOCARDIAL INFARCTION