Cocaine is a stimulant and euphoriant that is used by ingestion, snorting, and injection. Clinical manifestations of toxicity include hypertension, arrhythmias, myocardial infarction, aortic dissection, stroke, intestinal ischemia, seizures, and hyperthermia. Diagnosis is by history and physical examination, with ECG to monitor for complications. Toxicity is managed with supportive care, including intravenous benzodiazepines for agitation, hypertension, and seizures and with cooling techniques for hyperthermia. Withdrawal manifests primarily as depression, difficulty concentrating, and somnolence (cocaine washout syndrome).
Cocaine is usually used episodically by recreational users; however, use may also be chronic. Use among adolescents has declined slightly since 2011 (1). In the United States, cocaine has usually been about 45 to 60% pure, but it is increasingly adulterated with fentanyl (2).
Street names for cocaine include Coke, Blow, Crack, and Candy.
General reference
1. Centers for Disease Control and Prevention (CDC): Trends in the prevalence of marijuana, cocaine, and other illegal drug use national YRBS: 1991–2019. Accessed October 3, 2022.
2. Wagner KD, Fiuty P, Page K, et al. Prevalence of fentanyl in methamphetamine and cocaine samples collected by community-based drug checking services. Drug Alcohol Depend. 2023;252:110985. doi:10.1016/j.drugalcdep.2023.110985
Pathophysiology of Cocaine Use
Cocaine enhances norepinephrine, dopamine, and serotonin activity in the central and peripheral nervous systems by blocking the reuptake of biogenic amines. Increased dopaminergic transmission may explain cocaine's euphoriant effects and the reinforcement that contributes to abuse and dependence. Increased noradrenergic activity accounts for its sympathomimetic effects (tachycardia, hypertension, mydriasis, diaphoresis, vasoconstriction, and hyperthermia). Although not structurally related to amphetamine, cocaine has similar clinical effects.
Cocaine also blocks sodium channels, accounting for its local anesthetic and cardiac dysrhythmogenic properties. Cocaine causes vasoconstriction and thus can affect almost any organ. Myocardial infarction, cerebral ischemia and hemorrhage, aortic dissection, intestinal ischemia, and renal ischemia are possible sequelae.
In the most common route of use of cocaine in the United States, the drug is volatilized and inhaled, but it may also be insufflated ("snorted") or injected intravenously. For inhalation, the powdered hydrochloride salt is converted into a more volatile form, usually by adding sodium bicarbonate, water, and heat. The resultant precipitate (crackcocaine) is volatilized by heating and inhaled. The quick onset and intensity of the high caused by crack cocaine rivals that associated with IV use.
The pharmacokinetics of cocaine depends on mode of use, approximate timing of onset of effect, peak effect, and duration by mode are:
Intravenous (IV) or smoking: Onset, immediate; peak effect, 3 to 5 minutes; duration, 15 to 20 minutes
Intranasal (snorting): Onset, 3 to 5 minutes; peak effect, 20 to 30 minutes; duration, 45 to 90 minutes
Oral: Onset, 10 minutes; peak effect, 60 minutes; duration, 90 minutes
Because cocaine is such a short-acting drug, a common behavior of heavy users is to inject it or smoke it repeatedly every 10 to 15 minutes.
The concurrent use of cocaine and alcohol produces cocaethylene and methanol, which has stimulant properties and has a longer duration of effects than cocaine or its other metabolites. Cocaethylene is produced in the liver by liver carboxyesterase 1.
Symptoms and Signs of Cocaine Toxicity
The effects of use of cocaine are hyperstimulation, alertness, euphoria, a sense of increased energy, and feelings of competence and power, similar to amphetamines.
The signs of acute toxicity are similar to that of amphetamine toxicity, with the additional features of myocardial ischemia and coronary artery vasospasm. People who inject cocaine are subject to the typical infectious complications of injection drug use. Binges, often over several days, lead to an exhaustion syndrome or "washout" syndrome, involving intense fatigue and need for sleep.
A patient with acute cocaine toxicity may present with severe anxiety, panic, agitation, aggression, sleeplessness, hallucinations, paranoid delusions, impaired judgment, tremors, seizures, and/or delirium.
On physical examination, mydriasis and diaphoresis are apparent, and heart rate and blood pressure are increased. Without treatment patients may develop rhabdomyolysis, coagulopathy, kidney failure, and seizures. Some people may be more sensitive to cocaine because of a genetic polymorphism that decreases the activity of serum cholinesterase, an enzyme that inactivates cocaine in the serum.
Cocaine may cause chest pain from myocardial ischemia, coronary vasospasm, dysrhythmias, aortic dissection, or respiratory tract injury, all of which can be lethal without treatment. Electrophysiologically, cocaine blocks cardiac sodium channels, leading to a widened QRS and increased risk of ventricular tachycardia. The sudden inhalation and exhalation against a closed glottis may lead to a pneumothorax or pneumomediastinum acutely. People who inhale or smoke cocaine, particularly if it is adulterated with contaminants, may develop a hypersensitivity pneumonitis, previously termed "crack lung,". It may progress to respiratory failure. Vasospasm in the pulmonary vasculature may mimic a pulmonary embolism. Pulmonary infarction may develop if the spasm is severe.
Diagnosis of Cocaine Toxicity
History and physical examination
Sometimes urine or serum drug testing
Diagnosis of cocaine intoxication is usually made clinically based the patient reporting use and the presence of characteristic symptoms and signs.
The basic laboratory evaluation of a patient with suspected use of a xenobiotic is typically performed, including: complete metabolic profile; serum acetaminophen (paracetamol), salicylate, and ethanol concentrations; serum lactate and blood gas; urinalysis; and urine toxicology screen. The cocaine metabolite, benzoylecgonine, is part of most routine urine drug screening tests, forming a reliable confirmatory test for exposure to cocaine. In the setting of diagnosis of acute cocaine toxicity, serum drug levels are usually not required for diagnosis and are not typically measured.
Cocaine-related chest pain is evaluated in the same manner as for any patient with potential myocardial ischemia (serial ECG, serum cardiac markers and chest radiograph) or aortic dissection (ECG, chest radiograph and chest CT).
Treatment of Cocaine Toxicity
IV benzodiazepines as initial therapy
For severe agitation, a barbiturate or propofol (do not use phenothiazines)
For cardiovascular effects unresponsive to benzodiazepines, IV nitrates, nicardipine, or alpha-adrenergic antagonists (do not use beta blockers)
For hyperthermia, external cooling methods (eg, ice bath, evaporative cooling)
Preventing absorption
Cocaine is removed from the site of administration if possible. For intranasal use, the nares may be irrigated with isotonic fluid or sterile water to remove any remaining cocaine powder.
In cases of body stuffing or body packing, patients may need gastrointestinal decontamination or surgical removal.
Mitigating toxicity or overdose
Treatment of mild cocaine intoxication is generally unnecessary because the drug is extremely short-acting.
For more severe or persistent toxicity, defined as hemodynamic instability and/or evidence of ongoing end-organ damage, or behavior that is imminently dangerous to the patient or those around them, benzodiazepines are the preferred initial treatment and the dose titrated to effect. Lorazepam 2 to 3 mg IV every 10 to 20 minutes titrated to effect may be used. If after the initial dose signs and symptoms of toxicity resolve, then no further medication may be needed. If there is only partial improvement, give another bolus at the same initial dose in 10 to 20 minutes. If there is minimal improvement or no improvement, then the initial dose may be doubled. After three escalating doses, a benzodiazepine infusion may be administered at a rate of 0.06 mg/kg/hr, on average 4 mg/hr. Midazolam or diazepam may also be used with the same dosing strategy but starting with 5 mg instead of 2 mg.
For severe agitation, if sedation is not achieved with benzodiazepines, a barbiturate or propofol may be needed. Occasionally, severely agitated patients must be pharmacologically paralyzed and mechanically ventilated to ameliorate rhabdomyolysis, hyperthermia, and resultant acidosis or multisystem dysfunction. Phenothiazines are not used for sedation because they lower seizure threshold, and their anticholinergic effects can interfere with cooling.
Persistent hypertension that does not respond to benzodiazepines is treated with IV nitrates (eg, nitroprusside), nicardipine, or alpha-adrenergic antagonists (eg, phentolamine).
For patients with chest pain, as noted, beta-blockers are contraindicated in cocaine toxicity, and benzodiazepines are first-line therapy. If coronary vasodilation is required after benzodiazepines, nitrates are given, or phentolamine 1 to 5 mg IV administered slowly may be considered. Beta blockers and type Ia (eg, quinidine, procainamide) and Ic (eg, flecainide, propafenone) antiarrhythmics should be avoided for the treatment of cocaine-induced arrhythmias.
Hyperthermia can be life threatening and should be managed aggressively with sedation plus either an ice bath or evaporative cooling (covering in wet towels an placing in front of a fan) and IV normal saline to maintain intravascular volume and urine flow.
Chronic Use of Cocaine
Complications
Chronic use results in severe toxic effects.
Cardiovascular effects may include myocardial fibrosis, left ventricular hypertrophy, and cardiomyopathy (1).
Rarely, repeated intranasal use causes cocaine-induced midline destructive lesions such as nasal septal perforation due to local ischemia.
Cognitive impairment, including impaired attention and verbal memory, occurs in some heavy users.
Pregnancy
Cocaine use during pregnancy can adversely affect the fetus and is a risk factor for spontaneous abortion and placental abruption.
(For treatment of infants born to cocaine-addicted mothers, see Prenatal Drug Exposure.)
Tolerance and dependence
Dependence is most likely in people who use multiple times a week, use intravenously, or smoke the drug. Those who use less than weekly or take the drug intranasally or orally are at lower risk of becoming dependent.
Discontinuing sustained use requires considerable assistance, and the depression that may result requires close supervision and treatment.
Many outpatient therapies are available, including support and self-help groups and cocaine hotlines. Inpatient treatment is used primarily when it is required for serious physical or mental comorbidities or when outpatient therapy has repeatedly been unsuccessful.
Withdrawal
Withdrawal from heavy cocaine use is characterized by somnolence, difficulty concentrating, increased appetite, and depression. Appetite is increased. Because of cocaine's short half-life, the withdrawal symptoms develop quickly after the last dose in habitual users. Withdrawal symptoms can last for several weeks to months. Many people feel a strong urge to resume use after a period of withdrawal.
Chronic use reference
1. Dominic P, Ahmad J, Awwab H, et al. Stimulant Drugs of Abuse and Cardiac Arrhythmias. Circ Arrhythm Electrophysiol. 2022;15(1):e010273. doi:10.1161/CIRCEP.121.010273
Key Points
Cocaine is a stimulant that enhances norepinephrine, dopamine, and serotonin activity in the central and peripheral nervous systems by blocking the reuptake of biogenic amines.
Clinical manifestations of toxicity includes hypertension, arrhythmias, myocardial infarction, aortic dissection, stroke, intestinal ischemia, seizures, and hyperthermia.
Diagnose with history and physical examination and sometimes urine testing. Evaluate for cardiac arrhythmias with ECG.
Treatment of mild cocaine intoxication is generally unnecessary because the drug has a short duration of effects.
For severe or persistent toxicity, treat with IV benzodiazepines to control central nervous system excitement, hypertension, and tachycardia.
For severe persistent agitation, treat with a barbiturate or propofol, which requires mechanical ventilation.
For cardiovascular effects unresponsive to benzodiazepines, treat with IV nitrates. Do not use or beta blockers.
For hyperthermia, treat with external cooling methods (eg, ice bath).
Drug Information for the Topic
