Cocaine Toxicity

Article Author:
John Richards
Article Editor:
Jacqueline Le
Updated:
3/2/2019 5:37:35 PM
PubMed Link:
Cocaine Toxicity

Introduction

Cocaine abuse is a major worldwide health problem. Patients with acute cocaine toxicity presenting to the emergency department (ED) may require urgent treatment for tachycardia, dysrhythmia, hypertension, and coronary vasospasm, leading to pathological sequelae such as acute coronary syndrome, stroke, and death.[1][2][3]

Etiology

The leaves of the coca plant Erythroxylon coca have been used as a stimulant in South America for over 4000 years. Cocaine was first isolated from the leaves in the mid-1800s. It was considered safe and used in toothache drops, nausea pills, energy tonics, and, of course, the original “Coca-Cola” beverage. Since 1961 the International Single Convention on Narcotic Drugs has made recreational use of cocaine a crime internationally. The resurgence of cocaine’s popularity occurred in the 1970s during the disco era, and then in the 1980s, with the advent of crack cocaine. Cocaine is listed as a DEA Schedule II controlled substance because it has a medical use (see StatPearls chapter “Cocaine”), but also has a high potential for abuse.[4]

Epidemiology

Cocaine abuse remains a major public health problem, with an estimated 20 million users worldwide based on the most recent United Nations World Drug Report. The number of frequent cocaine users, which had been declining since 2006 in North America, has experienced a recent increase, with an estimated 1% of the population reporting use. The Drug Enforcement Agency estimated that in 2012 639,000 persons aged 12 or older had used cocaine for the first time within the previous 12 months in the United States (US), averaging approximately 1,800 initiates per day. In the US, cocaine was the most common drug of abuse resulting in hospital treatment, with 505,224 ED visits (40.3% of drug reported visits) in 2011 based on data from the Substance Abuse and Mental Health Services Administration. This translates to a rate of 162 ED visits per 100,000 population.[5][6]

Pathophysiology

Patients were abusing cocaine risk life-threatening consequences, including tachydysrhythmia, severe hypertension, acute coronary syndrome, stroke, acute myocardial and renal failure, seizure, hyperthermia, cocaine-induced rhabdomyolysis, and fetal/maternal morbidity and mortality.[7]

Toxicokinetics

Cocaine can be snorted, swallowed, injected, or smoked. Its pharmacodynamics involve multiple complex mechanisms although its half-life is short (~ 1 hour). This drug binds and blocks monoamine (dopamine, norepinephrine, and serotonin) re-uptake transporters with equal affinity. Monoamines accumulate in the synaptic cleft resulting in enhanced and prolonged sympathetic effects. The principal actions of cocaine on the cardiovascular system are from alpha- and beta-1-adrenoceptor stimulation resulting in increased heart rate, systemic arterial pressure, and myocardial contractility, which are major determinants of myocardial oxygen demand. Cocaine and its metabolites may cause arterial vasoconstriction hours after use.[7] Epicardial coronary arteries are especially vulnerable to these effects, leading to decreased myocardial oxygen supply. Cocaine-induced platelet activation and thrombus formation are another deleterious effects, caused by alpha-adrenergic- and adenosine diphosphate-mediated increase in platelet aggregation. Plasminogen activator inhibitor is also increased following cocaine use, thereby promoting thrombosis. Similar to local anesthetics such as lidocaine, cocaine blocks sodium channels and interferes with action potential propagation. This Vaughn-Williams Class IC effect increases the risk of conduction disturbance and tachyarrhythmias. Adding to its complex toxicity, cocaine targets muscarinic acetylcholine, N-methyl-D-aspartate (NMDA), sigma, and kappa-opioid receptors.[8]

History and Physical

These patients present to the hospital with agitation, chest pain, anxiety, psychosis, and blunt and penetrating traumatic injuries. They are frequently hypertensive and tachycardic. They may be unwilling to disclose their cocaine use, and clinicians must consider a wide spectrum of diagnoses during the initial evaluation, such as withdrawal syndromes, thyrotoxicosis, acute psychosis, sepsis, pheochromocytoma, anticholinergic toxicity, serotonin and neuroleptic malignant syndromes, and intracranial hemorrhage.

Evaluation

Depending on the patient's presentation, laboratory testing for suspected cocaine toxicity can include complete blood count, comprehensive chemistry panel, troponin, B-type natriuretic peptide, creatinine kinase, urinalysis, urine toxicology screen, and electrocardiogram. Imaging may also include chest x-ray, abdominal x-ray for suspected body packers or stuffers, and head CT if altered mental status suggests intracranial hemorrhage.[9][10]

Treatment / Management

Based on a large systematic review referenced below, cardiovascular toxicity and agitation are best treated first-line with benzodiazepines to decrease CNS sympathetic outflow.[11] However, there is risk of over-sedation and respiratory depression with escalating and numerous doses of benzodiazepines, which is often necessary. Non-dihydropyridine calcium channels blockers such as diltiazem and verapamil have been shown to reliably reduce hypertension, but not tachycardia. Dihydropyridine agents such as nifedipine should be avoided, as reflex tachycardia may occur. The alpha blocker phentolamine has been recommended but only treats alpha-mediated hypertension and not tachycardia. It is a rarely-used drug, and most clinicians are unfamiliar with its use and limited titratability. Nitroglycerin and nitroprusside are effective at lowering blood pressure, but risk of reflex tachycardia should be recognized. The mixed beta/alpha blocker labetalol has been shown to be safe and effective for treating concomitant cocaine-induced hypertension and tachycardia, without any “unopposed alpha-stimulation” adverse events recorded. The use of labetalol is approved by a recent AHA/ACC guideline for cocaine and methamphetamine patients with unstable angina/non-STEMI.[12]

Agitated patients are best treated with benzodiazepines, but antipsychotics such as haloperidol and olanzapine may also be useful. Combination treatment with benzodiazepines and antipsychotics has been shown to be more efficacious than monotherapy.[13]  Diphenhydramine is often added to enhance sedation and as prophylaxis against dystonia and akathisia. A common example of this is the “B-52” with its combination of haloperidol (5 mg), diphenhydramine (50 mg), and lorazepam (2 mg). Lidocaine and intravenous lipid emulsion have been successfully used for serious ventricular tachydysrhythmia in several case reports. Hyperthermia from cocaine toxicity is best treated with external cooling measures. Tepid water misting with convection cooling from a fan is the easiest and safest method to accomplish this in the field and in all emergency departments.[11]

Complications

  • Thrombophlebitis
  • HIV
  • Cellulitis
  • Hepatitis
  • Endocarditis
  • Pulmonary emboli
  • Aneurysms

Pearls and Other Issues

The phenomenon of “unopposed alpha-stimulation,” in which blood pressure increases or coronary artery vasoconstriction worsens after blockade of beta-2 vasodilation in cocaine-abusing patients, is controversial. This rarely-encountered adverse effect has resulted in some clinicians advocating for an absolute contraindication to the use of all beta-blockers, including specific, non-specific, and mixed. Many clinicians disregard this dogma and administer beta-blockers for cocaine-related chest pain and acute coronary syndrome, especially when there is demand ischemia from uncontrolled tachycardia.[8] Of the 1,744 total patients identified in the systematic review, only seven adverse events were from putative cases of “unopposed alpha-stimulation” due to propranolol (n=3), esmolol (n=3), and metoprolol (n=1). The authors of the original “unopposed alpha-stimulation” articles dating back to the 1980s concluded in a 2017 review that the phenomenon might actually be the from effects of cocaine alone, with or without beta-blockers.[11]

Enhancing Healthcare Team Outcomes

Over the past three decades, the rates of overdose from cocaine have gradually increased. In the US, deaths involving cocaine range from 0.9-1.6 per 100,000 population. Only in the last five years have the rates started to decrease to 0.78 per 100,000 population. People who inject cocaine into the neck veins have been known to develop a pneumothorax, thrombophlebitis, hemothorax, and myositis. In addition, there are reports that intravenous injections can be associated with aneurysms of vessels, resulting in rupture, obstruction and fistula formation. When cocaine is combined with other illicit and prescription drugs, the mortality rates are also high. More important, cocaine and alcohol have been associated with a 16 fold increase in the risk of suicide than either agent alone. Individuals who use cocaine often select a violent method for self-harm. Finally, cocaine use during pregnancy is also associated with adverse perinatal outcomes.[14][15](Level V) 

To date, there is no drug to prevent or cure cocaine addiction. The key is to educate the patient when he or she presents to the emergency department. Patients should be urged to seek drug counseling. Those who intended to commit suicide should be referred to a mental health counselor prior to discharge.


References

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