Cocaine hydrochloride topical solution contains 4% cocaine and the following inactive ingredients: citric acid, D and C Yellow No. 10, FD and C Green No. 3, sodium benzoate, and water. It is not FDA-approved but allowed for only the following indications: topical anesthesia of the mucous membranes of the oral, laryngeal, and nasal cavities. Its vasoconstrictive properties also make it useful for the temporary treatment of epistaxis before cauterization or packing, which is considered an off-label use. Based on a recent systematic review, cocaine is the most commonly used agent by ENT physicians in preparation for diagnostic and therapeutic nasal procedures. Cocaine is otherwise an illegal drug of abuse and is listed on DEA Schedule II because of its 1) high potential for abuse; 2) accepted medical use in treatment in the United States or a currently accepted medical use with severe restrictions; 3) abuse may lead to severe psychological or physical dependence.
Cocaine pharmacodynamics involve multiple complex mechanisms, although its half-life is short (~ 1 hour). Topical cocaine has an anesthetic effect similar to local anesthetics (such as lidocaine) from sodium channel blockade and interference with action potential propagation. This Vaughn-Williams class IC effect also increases the risk of conduction disturbance and tachyarrhythmias. Cocaine binds and blocks monoamine (dopamine, norepinephrine, epinephrine, and serotonin) re-uptake transporters with equal affinity. Monoamines accumulate in the synaptic cleft resulting in enhanced and prolonged sympathetic effects. The principal action of cocaine on mucosa is anesthesia and vasoconstriction, however significant systemic absorption may occur. This may adversely affect the cardiovascular system, whereupon alpha- and beta 1-adrenoceptor stimulation results 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. Epicardial coronary arteries are especially vulnerable to these effects, leading to decreased myocardial oxygen supply. Cocaine-induced platelet activation and thrombus formation is another unique mechanism of action, caused by alpha-adrenergic- and adenosine diphosphate-mediated increase in platelet aggregation. This may benefit patients by enhancing hemostasis of mucosal hemorrhage. Plasminogen activator inhibitor is also increased following cocaine use, thereby promoting thrombosis. Adding to its complex toxicity, cocaine targets muscarinic acetylcholine, N-methyl-D-aspartate (NMDA), sigma, and kappa-opioid receptors.
Cocaine is absorbed from mucous membranes and the gastrointestinal mucosa if swallowed. Cocaine is degraded by plasma esterases, with a half-life of approximately one hour.
CNS reactions may be excitatory then depressant. In its mild form, the patient may display anxiety, restlessness, and excitement. Full-body tonic-clonic seizures may result from moderate to severe CNS stimulation. This is often followed by CNS depression, with death resulting from respiratory failure and/or asphyxiation if concomitant emesis is present. Other clinical findings may include hyperreflexia, headache, mydriasis, and abdominal pain. Cocaine-induced central sympathetic stimulation and direct cardiac effects may lead to tachycardia, hypertension, and coronary or cerebral artery vasoconstriction leading to myocardial infarction and stroke. As a potent vasoconstrictor, cocaine may result in hyperthermia from impaired heat loss. Cocaine is not meant for ophthalmic use. If it is accidentally introduced into the eye, corneal damage may occur.
Cocaine is contraindicated in patients with a history of allergy or hypersensitivity to the drug or to the components of the topical solution. Elderly patients and/or patients with a history of hypertension or cardiovascular disease should not receive the drug. It is a Category C drug in pregnancy. It is also not known whether cocaine can cause fetal harm and should be given to a pregnant woman only if needed.
Patients receiving topical cocaine should have cardiac monitoring in case of dysrhythmia, and frequent vital signs are taken to check for cocaine-induced hypertension and tachycardia. The lowest dosage that results in effective anesthesia should be used to avoid high plasma levels from mucosal absorption and potential adverse effects. The fatal dose of cocaine has been estimated to be 1.2 g, but severe adverse effects have been reported from doses as low as 20 mg. The single-use vial contains four mL of a 40 mg/mL solution, thus 160 mg in total. There is also a multi-use vial containing 10 mL of 4% cocaine. As mucosal absorption is variable, the possibility of receiving the entire amount of cocaine is low, especially when delivered by cotton pledgets or gauze.
Treatment recommendations of acute cocaine toxicity are based on an extensive systematic review from 2016. Cardiovascular toxicity and agitation are best treated first-line with benzodiazepines to decrease CNS sympathetic outflow. 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.
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. 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.
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 of 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. Of the 1,744 total patients identified in the systematic review, only 7 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 may actually be the from effects of cocaine alone, with or without beta-blockers.