Toxicology – Cocaine

Core Concept

Cocaine is a potent sympathomimetic stimulant, local anesthetic, and vasoconstrictor. Severe toxicity results from a combination of excessive catecholaminergic activity and direct cardiac ion-channel blockade. The classic acute syndrome is agitation, diaphoresis, mydriasis, tachycardia, hypertension, hyperthermia, and seizures, with severe cases progressing to myocardial ischemia, ventricular dysrhythmias, stroke, rhabdomyolysis, shock, or death.

A useful toxicologic sequence is:

Cocaine → monoamine reuptake blockade → sympathetic excess → hypertension/tachycardia/agitation/hyperthermia

while at sufficiently high concentrations:

Cocaine → cardiac Na⁺-channel blockade → QRS widening + impaired contractility → ventricular dysrhythmia/cardiovascular collapse

The immediate management priorities are rapid control of agitation and seizures with benzodiazepines, aggressive treatment of hyperthermia, cardiovascular monitoring, and recognition of cocaine-associated myocardial ischemia and sodium-channel cardiotoxicity. There is no specific antidote.

Current Medical Cocaine

Cocaine remains a legitimate prescription medication despite its widespread illicit use. Current U.S. products include 4% cocaine hydrochloride nasal solutions, including NUMBRINO and GOPRELTO, which are Schedule II controlled substances used to produce local anesthesia of nasal mucous membranes during diagnostic procedures or surgery.

Current NUMBRINO labeling recommends approximately 40–160 mg applied intranasally by pledgets, with a maximum total dose of 3 mg/kg cocaine hydrochloride for a procedure. The approved solution contains 40 mg/mL. These formulations are for topical intranasal use only and should not be injected or applied ophthalmically.

The older use of combinations such as tetracaine-adrenaline-cocaine (TAC) is now largely historical in many settings because alternative topical anesthetics are available and cocaine creates avoidable cardiovascular and abuse-related risks.

Illicit Forms and Routes

Cocaine is derived from leaves of plants in the genus Erythroxylum. Illicit cocaine hydrochloride is commonly insufflated intranasally or injected after dissolution. Crack cocaine is a cocaine base formulation that can be heated and smoked, producing extremely rapid pulmonary absorption and a correspondingly rapid rise in brain cocaine concentrations.

Cocaine may also be taken orally or applied to mucosal surfaces. Particularly dangerous exposures occur in body stuffers, who hurriedly swallow poorly wrapped packets to conceal drugs, and body packers, who intentionally swallow larger numbers of carefully prepared packets for smuggling. Packet rupture can release an enormous dose and produce fulminant poisoning.

Epidemiology

Cocaine remains an important cause of drug-related morbidity and death. Final U.S. mortality data for 2024 showed a cocaine-involved overdose death rate of 6.3 per 100,000 population, down from 8.6 in 2023 but still representing a major public-health burden.

Modern cocaine toxicity also frequently occurs in the context of polysubstance exposure. Opioids, particularly illegally manufactured fentanyl, are commonly involved in stimulant-related deaths. CDC data showed that 78.6% of U.S. cocaine-involved overdose deaths in 2021 also involved an opioid. Consequently, unexpected respiratory depression in a presumed cocaine exposure should immediately raise concern for opioid coexposure, and naloxone should not be withheld while waiting for toxicology results.

Toxic Dose

There is no reliable toxic or lethal dose of cocaine. The older observation that death has followed as little as 25 mg should not be used as a clinical threshold. Individual response varies dramatically according to route, rate of administration, underlying cardiovascular disease, tolerance, adulterants, coingestants, genetic/metabolic factors, and the presence of hyperthermia or acidosis.

Current prescription labeling likewise notes that cocaine toxicity can occur idiosyncratically at relatively low doses. Therapeutic intranasal dosing therefore does not define a “safe” dose for illicit use.

Pathophysiology – Monoamine Reuptake Blockade

The older description that cocaine mainly increases release of norepinephrine is incomplete. Cocaine principally blocks presynaptic reuptake of norepinephrine, dopamine, and serotonin. Accumulation of norepinephrine at peripheral sympathetic synapses drives tachycardia, hypertension, vasoconstriction, diaphoresis, and hyperthermia, while enhanced dopamine signaling contributes to euphoria, reinforcement, agitation, psychosis, and addiction.

The overall cardiovascular result is particularly dangerous because cocaine simultaneously increases myocardial oxygen demand through tachycardia, hypertension, and increased contractility while decreasing oxygen supply through coronary vasoconstriction. It also promotes platelet activation and thrombosis, allowing myocardial infarction to occur even in young people without conventional atherosclerotic disease.

Sodium-Channel Blockade

Cocaine is also an ester-type local anesthetic. It reversibly blocks voltage-gated sodium channels, preventing normal action-potential conduction. This explains both its therapeutic local anesthetic action and an important component of severe cardiotoxicity.

In massive poisoning, particularly after rapidly absorbed large doses or rupture of an internal packet, sodium-channel blockade may produce QRS widening, impaired myocardial contractility, hypotension, ventricular dysrhythmias, and cardiac arrest. The 2024 ASAM/AAAP stimulant guideline specifically recognizes cocaine-induced QRS widening as a sodium-channel-blocking complication requiring sodium bicarbonate therapy.

Potassium Channels and QT

Cocaine can also interfere with cardiac potassium currents and prolong ventricular repolarization. Current prescription pharmacology demonstrates concentration-dependent QTc prolongation, although the effect at approved 4% topical dosing is generally modest.

Thus severe cocaine poisoning can produce both QRS widening from sodium-channel blockade and QT prolongation from repolarization abnormalities, and management should be guided by the actual ECG pattern.

Cocaine Plus Alcohol – Cocaethylene

When cocaine and ethanol are present simultaneously, hepatic metabolism produces the active metabolite:

Cocaethylene

Cocaethylene has psychoactive and cardiovascular effects and generally persists longer than cocaine itself. Human data suggest that combined cocaine and alcohol exposure carries greater cardiovascular risk than cocaine alone, including increased cardiac-arrest and sudden-death risk.

Therefore a history of alcohol use should always be obtained in cocaine intoxication. A patient may remain at cardiovascular risk longer than expected from cocaine alone.

Clinical Features – Sympathomimetic Toxidrome

Typical acute findings include agitation, anxiety, restlessness, paranoia, mydriasis, diaphoresis, tachycardia, hypertension, and hyperthermia. Tremor, hyperreflexia, increased motor activity, and repetitive stereotyped behavior may occur.

Severe toxicity can progress rapidly to delirium, seizures, extreme hyperthermia, profound metabolic acidosis, ventricular dysrhythmia, hypotension, coma, or cardiac arrest. Severe hyperthermia is particularly ominous because it accelerates rhabdomyolysis, acidosis, hepatic injury, coagulopathy, renal failure, and multiorgan dysfunction.

Neuropsychiatric Effects

Cocaine can cause anxiety, panic, severe agitation, insomnia, paranoia, hallucinations, mania-like behavior, and stimulant-induced psychosis. Tactile hallucinations such as formication may occur during heavy or prolonged use.

Benzodiazepines remain first-line pharmacologic treatment for stimulant-induced agitation. Modern guidance no longer supports the older absolute prohibition against antipsychotics. Antipsychotics may be used when prominent stimulant-associated psychosis or refractory agitation persists, although agent-specific risks such as QT prolongation, seizure threshold, and thermoregulation must be considered.

Neurologic Complications

Seizures are a major manifestation of severe cocaine toxicity and may be followed by lactic acidosis, hyperthermia, rhabdomyolysis, and cerebral injury. Cocaine can also cause ischemic stroke, intracranial hemorrhage, subarachnoid hemorrhage, and hypertensive encephalopathy.

A focal neurologic deficit, persistent altered consciousness, severe headache, or atypical presentation should not simply be attributed to intoxication. Neuroimaging should be performed when stroke or intracranial hemorrhage is clinically suspected.

Cardiovascular Toxicity

Cocaine can produce a broad range of cardiovascular complications, including myocardial ischemia, acute myocardial infarction, coronary vasospasm, thrombosis, myocarditis, acute cardiomyopathy, malignant dysrhythmias, aortic dissection, and sudden cardiac death. These complications reflect the combined effects of catecholamine excess, coronary vasoconstriction, thrombosis, sodium- and potassium-channel blockade, oxidative injury, and increased myocardial oxygen demand.

Chronic use can also contribute to left ventricular hypertrophy, dilated cardiomyopathy, accelerated coronary disease, and heart failure.

Cocaine-Associated Chest Pain

Any patient with cocaine-associated chest pain should be evaluated for acute coronary syndrome, regardless of age. Initial evaluation should include ECG and serial cardiac troponin measurements when clinically indicated. Other life-threatening cocaine-associated diagnoses such as aortic dissection, pneumothorax, pneumomediastinum, myocarditis, pulmonary embolism, and esophageal rupture should be considered according to the presentation.

Modern stimulant guidelines recommend simultaneously treating the underlying hyperadrenergic state with a GABAergic agent such as a benzodiazepine while evaluating persistent chest pain according to standard ACS pathways.

Pulmonary Complications

Smoking crack cocaine can cause cough, bronchospasm, pneumothorax, pneumomediastinum, alveolar hemorrhage, pulmonary edema, and an inflammatory lung injury sometimes termed “crack lung.” Patients may develop hypoxemia, hemoptysis, diffuse infiltrates, and respiratory distress.

Chest radiography is appropriate when respiratory symptoms, hypoxemia, significant chest pain, or suspected pneumothorax/pneumomediastinum is present. CT may be required when serious thoracic pathology remains suspected despite a nondiagnostic radiograph.

Gastrointestinal and Mesenteric Ischemia

Profound splanchnic vasoconstriction can cause mesenteric ischemia and bowel infarction, even in young patients without vascular disease. Severe or persistent abdominal pain after cocaine exposure should therefore not automatically be attributed to benign gastrointestinal upset.

Possible manifestations include severe abdominal pain, vomiting, gastrointestinal bleeding, bowel necrosis, perforation, and peritonitis. Lactate and CT angiographic imaging may be appropriate when intestinal ischemia is suspected.

Renal and Musculoskeletal Toxicity

Rhabdomyolysis can result from agitation, prolonged exertion, seizures, hyperthermia, ischemia, or prolonged immobilization. Complications include hyperkalemia, metabolic acidosis, acute kidney injury, and compartment syndrome.

Patients with severe agitation, hyperthermia, seizures, or substantial muscle pain should have CK, potassium, creatinine, and urinalysis monitored. Management focuses on controlling the driving agitation/hyperthermia and providing appropriate IV crystalloid. Routine urinary alkalinization is not required. The current ASAM/AAAP guideline emphasizes fluids and treatment of agitation and hyperthermia rather than routine urine alkalinization.

Hepatic and Hematologic Effects

Severe hyperthermic cocaine poisoning may cause acute hepatocellular injury or hepatic necrosis. Disseminated intravascular coagulation and thrombocytopenia may occur as part of catastrophic hyperthermia and multiorgan failure rather than as routine manifestations of cocaine exposure.

CBC, coagulation testing, liver enzymes, CK, renal function, lactate, and blood gas analysis are appropriate in critically ill or markedly hyperthermic patients.

Adulterants

Illicit cocaine frequently contains pharmacologically active adulterants. Levamisole has historically been associated with cocaine and can cause neutropenia/agranulocytosis, retiform purpura, vasculitis-like skin lesions, and other immune complications.

A more immediately lethal modern concern is polysubstance exposure to fentanyl or other opioids. Respiratory depression, apnea, profound miosis, or unexpectedly reduced consciousness in a presumed cocaine exposure should prompt opioid management, including naloxone when indicated.

Diagnosis

Cocaine poisoning is primarily a clinical diagnosis. The typical combination of agitation, diaphoresis, mydriasis, hypertension, tachycardia, hyperthermia, and compatible exposure strongly supports stimulant toxicity.

Laboratory testing should be tailored to severity. Mild, rapidly resolving intoxication may require little testing, whereas severe toxicity warrants ECG, glucose, electrolytes, renal function, CK, lactate, acid-base assessment, and additional tests directed by organ injury.

Urine Cocaine Testing

Routine urine drug testing usually detects benzoylecgonine, a cocaine metabolite, rather than active cocaine. A positive test confirms recent exposure but does not establish the timing, route, dose, clinical severity, or whether the patient’s current symptoms are actually caused by cocaine.

Because metabolites can remain detectable after the acute pharmacologic effects have resolved:

Treat the patient, not the urine screen.

Serum cocaine concentrations are not routinely useful for clinical management.

Initial Treatment

The first priorities are airway, breathing, circulation, temperature, glucose, and rapid control of dangerous agitation or seizure activity. Cardiac monitoring and IV access should be established in moderate or severe poisoning.

A quiet environment and verbal de-escalation can help in mild agitation, but medication should not be delayed in patients with severe agitation, delirium, hyperthermia, or imminent risk of injury.

Benzodiazepines

Benzodiazepines are first-line therapy for acute cocaine toxicity.

They treat several components simultaneously by reducing central sympathetic activation and muscle activity. Benefits include improvement in agitation, anxiety, seizures, tachycardia, hypertension, hyperthermia, and catecholamine-mediated myocardial oxygen demand.

Modern ASAM/AAAP guidance recommends GABAergic agents for the stimulant-induced hyperadrenergic state, with benzodiazepines considered first-line. Phenobarbital or propofol can be considered in severe or refractory cases at an appropriate level of care.

Repeated doses may be required. Fear of sedation should not lead to undertreatment of a severely hyperadrenergic patient, although airway and ventilation must be monitored.

Seizures

Cocaine-induced seizures should be treated first with benzodiazepines. Recurrent or refractory seizures may require additional GABAergic therapy such as phenobarbital or, in an intubated patient, propofol.

Phenytoin is generally a poor choice for primary toxin-induced seizures because it does not address the underlying catecholaminergic mechanism and sodium-channel blockade may already be present.

Hyperthermia

Severe cocaine hyperthermia is a medical emergency.

Treatment requires immediate control of agitation and muscle activity together with active external cooling. Antipyretic drugs such as acetaminophen are ineffective because this is not hypothalamic fever.

The ASAM/AAAP guideline notes that severe stimulant hyperthermia, generally above approximately 40.5°C, may require rapid cooling such as cold-water immersion together with pharmacologic sedation and, when necessary, neuromuscular paralysis. Less severe hyperthermia may respond to evaporative cooling with mist and fans.

Do not wait for laboratory abnormalities before aggressively treating extreme hyperthermia.

Hypertension

Cocaine-associated hypertension often improves substantially after adequate benzodiazepine sedation. If severe hypertension persists despite control of agitation, a short-acting, titratable agent should be used.

Current stimulant guidance recommends agents such as phentolamine, sodium nitroprusside, or a dihydropyridine calcium-channel blocker for hypertensive emergency and recommends nitroglycerin when myocardial ischemia is present. Long-acting antihypertensive drugs should be avoided because rapid disappearance of stimulant activity can produce abrupt hypotension.

Cocaine-Associated Myocardial Ischemia

Initial management of cocaine-associated ischemic chest pain should include benzodiazepines and coronary vasodilation, commonly with nitroglycerin when clinically appropriate. Aspirin and other ACS therapies should be used according to the clinical diagnosis and contraindications.

Persistent ST elevation, elevated troponin, or other evidence of ACS should be managed using contemporary cardiology standards, including urgent reperfusion or PCI when indicated. Cocaine use should not be used as a reason to undertreat a true myocardial infarction.

The β-Blocker Controversy

The older teaching that all β-blockers are absolutely contraindicated whenever cocaine is involved is now too simplistic. The concern arose from the possibility that pure β blockade during intense cocaine intoxication could leave α-mediated vasoconstriction relatively unopposed and worsen coronary or systemic vasoconstriction.

Current ASAM/AAAP guidance still generally prefers vasodilators and calcium-channel blockers for cardiac ischemia during active stimulant intoxication. However, when a β-blocker is considered necessary, it recommends favoring an agent with concurrent α₁ antagonism, such as labetalol or carvedilol. If a pure β-blocker has already been given during acute intoxication, a coronary vasodilator such as nitroglycerin or a calcium-channel blocker can be considered.

Thus, “never give a β-blocker to anyone who uses cocaine” is not modern practice. The greatest caution applies to acute hyperadrenergic intoxication, while longer-term β-blocker use for established cardiac indications should be individualized rather than reflexively withheld.

QRS Widening and Sodium-Channel Toxicity

A widened QRS in severe cocaine poisoning indicates significant fast sodium-channel blockade and is a major warning sign.

Sodium bicarbonate is first-line therapy.

The contemporary ASAM/AAAP guideline strongly recommends sodium bicarbonate when cocaine causes QRS widening or impaired cardiac contractility.

A practical toxicology approach is an IV sodium bicarbonate bolus with repeated dosing guided by improvement in QRS duration, hemodynamics, and acid-base status. Excessive alkalemia, hypernatremia, hypokalemia, and volume loading should be avoided.

If bicarbonate is unavailable, hypertonic sodium may provide sodium loading, although it does not correct acidosis.

Ventricular Dysrhythmias

Treatment depends on the electrical mechanism. Wide-complex ventricular dysrhythmia associated with QRS prolongation should prompt sodium bicarbonate because sodium-channel blockade is likely.

If polymorphic VT occurs in the setting of substantial QT prolongation, manage as torsades with IV magnesium, correction of potassium and magnesium, and defibrillation if unstable or pulseless.

The historical routine use of bretylium is obsolete. Lidocaine may occasionally be considered for refractory ventricular dysrhythmia with toxicology/cardiology guidance, but it is not a substitute for sodium bicarbonate when sodium-channel blockade is present.

In refractory severe cocaine sodium-channel cardiotoxicity or arrest despite standard treatment, the ASAM/AAAP guideline notes that 20% lipid emulsion may be considered as rescue therapy in an acute-care setting, although clinical evidence is limited.

Hypotension and Shock

Hypotension in severe cocaine poisoning can result from myocardial sodium-channel blockade, dysrhythmia, myocardial infarction, hyperthermia, volume depletion, or terminal catecholamine depletion.

Treatment should address the mechanism. Give isotonic crystalloid when hypovolemia is present and correct QRS widening/acidosis promptly. Persistent shock generally warrants a titratable vasopressor such as norepinephrine, with cardiac ultrasound and hemodynamic assessment useful when cardiogenic shock is suspected. The older routine preference for dopamine and Trendelenburg positioning is outdated.

Rhabdomyolysis

Rhabdomyolysis should be treated with appropriate crystalloid resuscitation and serial monitoring of CK, potassium, creatinine, calcium, and urine output. The most important upstream treatments are rapid sedation, seizure control, and correction of hyperthermia.

Routine urinary alkalinization has not been shown to improve outcomes and is not required. Dialysis is reserved for standard renal indications such as refractory hyperkalemia, severe acidosis, volume overload, or uremic complications.

Gastrointestinal Decontamination

Induced vomiting and ipecac have no role. Cocaine can cause sudden seizures and deterioration, making induced emesis particularly dangerous.

Routine gastric lavage is also not indicated. A single dose of activated charcoal may be considered after a substantial recent oral ingestion if the airway is intact or protected and aspiration risk is acceptable. Decontamination must never delay benzodiazepines, cooling, ECG management, or resuscitation.

Body Stuffers

A body stuffer usually swallows a relatively small number of hastily wrapped drug packets to avoid detection. The packaging is often fragile, so leakage or rupture is more likely than in professional body packing.

Because even one poorly wrapped packet can release a major cocaine dose, body stuffers require careful observation for sudden hyperadrenergic toxicity. Imaging may miss small or poorly prepared packets, so a negative abdominal radiograph does not reliably exclude stuffing.

Management is individualized and should involve medical toxicology or a poison center when possible.

Body Packers

A body packer intentionally swallows numerous well-prepared packets for smuggling. The immediate risks are intestinal obstruction and catastrophic drug poisoning from packet rupture.

CT is substantially more reliable than plain radiography for packet detection and is now regarded as the most sensitive imaging method when body packing must be assessed. A 2025 systematic review found CT to outperform plain radiography and ultrasound.

Stable, asymptomatic body packers can often be managed conservatively. Whole-bowel irrigation with polyethylene glycol electrolyte solution may be considered to facilitate packet passage, although controlled evidence that WBI improves outcomes is lacking. WBI is contraindicated in obstruction, perforation, ileus, hemodynamic instability, or an unprotected airway.

Evidence of packet rupture with cocaine toxicity or mechanical obstruction requires urgent surgical consultation. A ruptured cocaine packet can release an immediately lethal dose, so systemic treatment and surgical source control may need to occur simultaneously.

Antidote

There is no specific antidote for cocaine.

Treatment is directed at the physiologic consequences of sympathetic excess, hyperthermia, sodium-channel blockade, ischemia, seizures, and organ injury.

However, naloxone should be given when opioid coexposure is possible and respiratory depression is present. The modern illicit drug supply makes cocaine-opioid coexposure clinically important.

Enhanced Elimination

Hemodialysis and hemoperfusion do not meaningfully enhance cocaine elimination because cocaine is rapidly distributed into tissues and extensively metabolized. Current prescription labeling specifically states that dialysis and hemoperfusion are ineffective for cocaine overdose.

Urinary acidification is also ineffective and potentially harmful. There is no role for forced diuresis.

Pregnancy

The old FDA Pregnancy Category X classification is obsolete; FDA no longer uses the pregnancy letter system. Cocaine crosses the placenta and fetal exposure occurs after maternal use. Current pregnancy information does not support a simple statement that cocaine produces one specific pattern of congenital malformations, but exposure is associated with major obstetric risks including placental abruption, impaired fetal growth, preterm birth, and pregnancy loss, with risk influenced by dose, frequency, timing, and associated tobacco, alcohol, or other drug use.

During acute maternal cocaine poisoning, maternal stabilization is the priority. Severe hypertension, hyperthermia, hypoxemia, seizures, and placental abruption can all threaten both mother and fetus.

Breastfeeding

Breastfeeding during active cocaine use is not recommended because cocaine passes into breast milk and can cause serious infant toxicity, including irritability, hypertension, vomiting, respiratory abnormalities, and seizures.

For medically administered topical cocaine, individual product instructions should be followed. Current GOPRELTO labeling advises avoiding breastfeeding and pumping/discarding milk for 48 hours after administration.

Monitoring

Moderate or severe cocaine toxicity requires continuous ECG, blood-pressure, respiratory, and temperature monitoring. Serial neurologic examinations are important, particularly after seizures or severe hypertension.

Chest-pain patients require serial ECG and troponin evaluation according to their risk and clinical findings. Hyperthermic, severely agitated, or convulsing patients require serial CK, renal function, electrolytes, lactate, acid-base assessment, liver tests, and coagulation studies as clinically indicated.

Observation and Disposition

Mild uncomplicated intoxication often resolves over several hours because cocaine itself has a relatively short pharmacologic duration. However, there is no universal fixed observation period because risk depends on the route, dose, formulation, coingestants, ECG findings, chest pain, temperature, organ injury, and whether body stuffing or packing occurred.

Discharge is reasonable only after the patient has returned to baseline mental status, temperature and vital signs are stable, significant ischemia or dysrhythmia has been excluded when relevant, and there is no evolving end-organ injury. Persistent chest pain, neurologic abnormality, hyperthermia, rhabdomyolysis, significant hypertension, QRS/QT abnormality, or major body-packet exposure requires longer monitoring or admission.

Prognosis

Most mild or moderate cocaine intoxication resolves completely with prompt supportive treatment. Poor outcomes are associated particularly with severe hyperthermia, prolonged seizures, major acidosis, sodium-channel cardiotoxicity, myocardial infarction, stroke, aortic catastrophe, rhabdomyolysis, packet rupture, and polysubstance overdose.

After acute stabilization, patients with problematic cocaine use should be offered evidence-based treatment for stimulant use disorder and harm-reduction support. Current ASAM/AAAP guidance emphasizes structured addiction treatment rather than treating the emergency episode as an isolated event.

Important Pitfalls

A major diagnostic pitfall is assuming that every cocaine-positive urine sample explains the patient’s current illness. Benzoylecgonine can remain detectable after acute intoxication has resolved, so alternative diagnoses must still be considered.

Another important error is regarding cocaine only as a sympathomimetic. Severe poisoning also produces direct sodium-channel blockade, and QRS widening requires sodium bicarbonate rather than simply more antihypertensive therapy.

The old absolute statement that haloperidol must never be given is also outdated. Benzodiazepines remain first-line for agitation, but antipsychotics can be used selectively for stimulant-induced psychosis or refractory agitation when their individual risks are considered.

Similarly, the traditional statement that all β-blockers are absolutely forbidden after any cocaine exposure is too broad. During acute hyperadrenergic intoxication, benzodiazepines and vasodilators remain preferred; if β-blockade is required, contemporary stimulant guidance favors an agent with α₁-blocking properties such as labetalol or carvedilol.

Hyperthermia should never be managed as ordinary fever. Sedation plus rapid physical cooling is required, and extreme hyperthermia is an immediate resuscitation priority.

Finally, apparent cocaine intoxication with marked respiratory depression should raise immediate concern for fentanyl or another opioid, and naloxone should be given when indicated rather than assuming cocaine alone explains the presentation.

High-Yield Toxicology Pearls

• Cocaine = sympathomimetic + local anesthetic sodium-channel blocker.
• Main mechanism of stimulation is dopamine/norepinephrine/serotonin reuptake inhibition, not simply increased norepinephrine release.
• Classic syndrome: agitation + diaphoresis + mydriasis + tachycardia + hypertension + hyperthermia.
• Severe toxicity causes seizures, MI, stroke, rhabdomyolysis, QRS widening, ventricular dysrhythmias, and hyperthermic multiorgan failure.
• Benzodiazepines are first-line for agitation, seizures, and the hyperadrenergic state.
• Severe hyperthermia requires immediate active cooling; antipyretics do not work.
• Cocaine chest pain requires evaluation for ACS, aortic dissection, pneumothorax/pneumomediastinum, and other serious causes.
• Ischemia: benzodiazepines + nitroglycerin/vasodilator therapy, then standard ACS care when indicated.
• β-blockers are not an absolute lifelong contraindication; during acute intoxication, alternatives are generally preferred, and labetalol/carvedilol are favored if β-blockade is needed.
• Wide QRS = sodium-channel blockade → sodium bicarbonate.
• QT prolongation/torsades → magnesium, electrolyte correction, and defibrillation when required.
• Bretylium is obsolete.
• Cocaine + alcohol produces cocaethylene, which prolongs toxicity and increases cardiovascular risk.
• Rhabdomyolysis treatment centers on fluids + cooling + control of agitation/seizures, not routine urinary alkalinization.
• Do not induce vomiting.
• Activated charcoal is only for selected recent oral exposures with a safe airway.
• Body stuffer = few poorly wrapped packets → higher leakage risk.
• Body packer = many prepared packets → obstruction or catastrophic rupture risk.
• CT is the most reliable imaging method for suspected body packing.
• WBI may be considered for stable body packers, but evidence of outcome benefit is limited.
• Packet rupture or obstruction requires urgent surgical evaluation.
• No specific antidote exists.
• Naloxone should be given when opioid coexposure is suspected, especially with respiratory depression.
• Hemodialysis and hemoperfusion do not meaningfully remove cocaine.
• Pregnancy letter categories are obsolete; maternal cocaine exposure is strongly associated with placental abruption, preterm birth, and fetal-growth problems.
• Breastfeeding during active cocaine use is not recommended.
• A positive urine cocaine metabolite test proves recent exposure but does not prove current intoxication.