Cocaine Toxicity

Cocaine is one of the most commonly used recreational drug. It is both a CNS stimulant and a local anaesthetic.Its clinical effects and toxicity are due to sympathetic nervous system stimulation. Cocaine can be used topically, swallowed, or injected IV. 

                          

Cocaine is metabolized by plasma cholinesterase. Therefore, deficiency of this enzyme may predispose affected patients to life-threatening toxicity.  Central effects of cocaine are mediated by enhancement of excitatory amino acids and blockade of presynaptic reuptake of norepinephrine, dopamine, and serotonin. The excess of neurotransmitters at postsynaptic receptor sites leads to sympathetic activation, producing a characteristic toxidrome of mydriasis, tachycardia, hypertension, and diaphoresis, dysrhythmias, seizures, and hyperthermia. 

Like other local anesthetics, cocaine also inhibits conduction of nerve impulses by blocking fast sodium channels in the cell membrane. This can lead to QRS widening and QT-interval prolongation. 

Systemic Effects

Cardiac

• Dysrhythmias (Na/K Channel Blockade - Sinus Tachy, Wide QRS, Prolonged QTc, Rightward Axis, Brugada Pattern, Takotsubo Cardiomyopathy)
• Myocarditis
• Acute coronary syndromes
• Aortic rupture and aortic/coronary artery dissection
• Cocaine-induced chest pain (Coronary Vasospasm, also hastens atherogenesis through increased platelet aggregation, thrombogenesis)

CNS

• Seizures
• Stroke (ischemic and haemorrhages)
• Hypertension
• Spinal cord infarction
• Cerebral vasculitis
• Intracranial abscesses
• Crack dancing - Choreoathetosis and repetitive movements due to dopamine dysregulation. 
• Blindness (central retinal artery occlusion)

Other effects

• Pulmonary haemorrhage
• Pneumonitis, Asthma
• Pulmonary edema
• Acute Lung Injury
• Thermal uvulitis 
• Bowel schema and necrosis
• Splenic infarctions
• Rhabdomyolysis and AKI 
• Renal infarction 

Differential Diagnosis of Sympathomimetic Syndrome

• Anticholinergic Syndrome
• Serotonin Syndrome
• Neuroleptic Malignant Syndrome
• Alcohol Withdrawal
• Sepsis and CNS Infections
• Hypoglycaemia, Metabolic (Electrolyte Issues)
• Thyrotoxicosis
• Pheochromocytoma
• Psychosis
• Heat Stroke 

Management

• Benzodiazepines are the drugs of choice for sedation
• Antipsychotics increase QT prolongation and increase risk of ventricular dysrhythmias

• Treat Cardiac Chest Pain with aspirin and nitroglycerin, CCBs and reperfusion therapy if needed.  
• Use of β-adrenergic antagonists (“β-blockers”) in the management of cocaine-associated myocardial ischemia or infarction is controversial. 

• Sinus tachycardia - Rx with sedation, cooling, and intravenous fluid rehydration 
• Reentrant supra ventricular tachycardia /Fast atrial fibrillation or flutter - Rx with CCBs
• Wide-complex tachycardia - Rx with sodium bicarbonate (do not alkalinize above a pH of 7.55). Although Lidocaine is also a Na Channel blocker, it may be considered for use in refractory arrhythmias.
• Torsades de points - Rx with Magnesium, lidocaine, and overdrive pacing.
• Hypotension/Persistent Arrhythmias - Intravenous lipid emulsion should be considered in this scenario.

• Severe hypertension - Rx with sedation or GTN drip or Phentolamine
• Rhabdomyolysis - IV Fluids

• Seizures - BZD, Phenobarbitone (Do not Rx with phenytoin which may worsen Na Channel Blockade)

References:

1. Zimmerman JL: Cocaine intoxication. Crit Care Clin 28: 517, 2012. 
2. Phillips K, Luk A, Soor GS, Abraham JR, Leong S, Butany J: Cocaine cardiotoxicity: a
3. review of the pathophysiology, pathology, and treatment options. Am J Cardiovasc Drugs 9: 177, 2009. 
4. Lange RA, Cigarroa RG, Yancy CW, et al: Cocaine-induced coronary artery vasocon-striction. N Engl J Med 321: 1557, 1989. 
5. Hollander JE, Hoffman RS: Cocaine-induced myocardial infarction: an analysis and
6. review of the literature. J Emerg Med 10: 169, 1992. 
7. O’Leary ME, Hancox JC: Role of voltage-gated sodium, potassium and calcium channels in the development of cocaine-associated cardiac arrhythmias. Br J Clin Pharmacol 69:427, 2010. 
8. Yap YG, Behr ER, Camm AJ: Drug-induced Brugada syndrome. Europace 11: 989, 2009.
9. Arora S, Alfayoumi F, Srinivasan V: Transient left ventricular apical ballooning after cocaine use: is catecholamine cardiotoxicity the pathologic link? Mayo Clin Proc 81: 829, 2006. 
10. Rangel C, Shu RG, Lazar LD, Vittinghoff E, Hsue PY, Marcus GM: Beta-blockers for chest pain associated with recent cocaine use. Arch Intern Med 170: 874, 2010. 
11. Jakkala-Saibaba R, Morgan PG, Morton GL: Treatment of cocaine overdose with lipid emulsion. Anaesthesia 66: 1168, 2011. 

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     Lakshay Chanana

     

     Speciality Doctor

     Northwick Park Hospital

     Department of Emergency Medicine

     England

     @EMDidactic