Drug class: Local Anesthetics
ATC class: S01HA01
VA class: NT300
CAS number: 53-21-4

Medically reviewed by Drugs.com on Dec 23, 2024. Written by ASHP.

Introduction

Cocaine, a naturally occurring alkaloid, is a local anesthetic.

Uses for Cocaine

Cocaine hydrochloride is used topically to produce local anesthesia of accessible mucous membranes of the oral, laryngeal, and nasal cavities.

Cocaine hydrochloride has also been applied topically to the eye to produce local anesthesia^{† [off-label]}, but because of its corneal toxicity and indirect adrenergic effects, cocaine has generally been replaced by proparacaine and tetracaine for use in ophthalmology. However, because of its effects on the corneal epithelium, cocaine may be useful for facilitating debridement or removal of the surface epithelium (e.g., in the treatment of dendritic ulcers), and because of its indirect adrenergic effects, the drug may also be useful in the differential diagnosis of a miotic pupil^{† [off-label]} (e.g., Horner’s syndrome, Raeder’s syndrome).

Cocaine Dosage and Administration

Reconstitution and Administration

Topical solutions of cocaine hydrochloride are applied to the mucous membranes of the oral, laryngeal, and nasal cavities. The drug may be administered by means of cotton applicators or packs, instilled into a cavity, or as a spray. Cocaine hydrochloride topical solutions should not be administered parenterally or applied to the eye.

Extemporaneously prepared solutions of cocaine hydrochloride have also been applied topically to the eye^{† [off-label]}. Because of its corneal and systemic toxicity, cocaine should only be applied to the eye by clinicians familiar with the risks associated with ophthalmic application of the drug and only for short periods of time.

Dosage

Dosage of cocaine hydrochloride depends on the area to be anesthetized, tissue vascularity, technique of anesthesia, and individual patient tolerance. The lowest dosage necessary to produce adequate anesthesia should be used. Dosage should be reduced in geriatric, debilitated, or acutely ill patients and in children.

For local anesthesia of the mucous membranes of the oral, laryngeal, and nasal cavities, cocaine hydrochloride solutions of 1–10% are employed. To minimize the risk of increasing the incidence and severity of adverse effects, one manufacturer recommends that concentrations greater than 4% be avoided. Generally, the maximum single dose should not exceed 1 mg/kg.

For use as a local anesthetic in ophthalmology^{† [off-label]}, cocaine hydrochloride solutions of 1–4% have been used; the solutions require extemporaneous preparation.

Cautions for Cocaine

Adverse Effects

Adverse effects of cocaine hydrochloride following topical application to mucous membranes usually result from rapid and excessive absorption of the drug. Adverse effects are generally systemic in nature and involve the CNS and/or cardiovascular systems.

Adverse CNS effects of cocaine are excitatory and/or depressant and may be characterized by nervousness, restlessness, excitement, or a feeling of well-being and euphoria (or sometimes dysphoria). Hallucinations (visual, tactile, olfactory, auditory, gustatory) may also occur. Tremors and eventually tonic-clonic seizures may occur (see Acute Toxicity); CNS stimulation may also result in vomiting. Tachypnea may also occur.

Small doses of systemically administered cocaine may slow the heart because of central vagal stimulation, but after moderate doses, the heart rate is increased probably by cocaine-induced central and peripheral effects on the sympathetic nervous system. Blood pressure is increased, and hypertension may result. Large IV doses of the drug have caused immediate death from cardiac failure because of a direct toxic effect on cardiac muscle.

Topical application of cocaine to the eye has caused sloughing of the corneal epithelium with clouding, pitting, and occasionally ulceration of the cornea.

Precautions and Contraindications

Because cocaine hydrochloride is readily absorbed from mucous membranes and can cause severe adverse effects, the drug should be used with caution and careful attention should be given to dosage and administration technique. Resuscitative equipment and drugs for the treatment of severe reactions should be immediately available whenever the drug is used.

Repeated topical application of cocaine can result in psychic dependence and tolerance; the drug is often abused by parenteral or intranasal administration or by inhalation (smoking) because of its CNS stimulating effects. Prolonged intranasal use of cocaine can cause ischemic mucosal damage or perforation of the septum.

The addition of epinephrine to cocaine preparations is unnecessary and may increase the likelihood of cardiac arrhythmias, ventricular fibrillation, and hypertensive episodes. Moistening of cocaine hydrochloride powder with epinephrine solutions to produce “cocaine mud” for application to the nasal mucosa is dangerous and is not recommended. Since cocaine potentiates the effects of catecholamines, the drug should be used with extreme caution, if at all, in patients with hypertension, severe cardiovascular disease, or thyrotoxicosis and in patients receiving drugs (e.g., monoamine oxidase inhibitors) that also potentiate catecholamines.

Cocaine hydrochloride topical solutions should be used with caution in patients with severely traumatized mucosa and sepsis in the region of intended application. Topical solutions of cocaine hydrochloride intended for use in anesthetizing mucous membranes of the oral, laryngeal, and nasal cavities are not intended for systemic or ophthalmic administration and are contraindicated in patients with known hypersensitivity to the drug.

Pregnancy, Fertility, and Lactation

Pregnancy

Animal reproduction studies have not been performed with cocaine hydrochloride. It is also not known whether the drug can cause fetal harm when administered to pregnant women. Cocaine hydrochloride should be used during pregnancy only when clearly needed.

Fertility

It is not known whether cocaine hydrochloride can affect fertility.

Lactation

It is not known if cocaine is distributed into milk. Because of the potential for serious adverse reactions from cocaine in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.

Acute Toxicity

Severe toxic effects have occurred with cocaine hydrochloride doses as low as 20 mg; the fatal dose is estimated to be approximately 1.2 g.

Cocaine overdosage results mainly in adverse CNS effects. The patient rapidly becomes excited, restless, garrulous, anxious, and confused; reflexes are enhanced. Nausea, vomiting, and abdominal pain often occur. Other signs and symptoms may include headache, rapid pulse, irregular respiration, chills, fever, mydriasis, exophthalmos, and formication (cocaine bugs, Magnan’s symptom). In severe overdosage, delirium, Cheyne-Stokes respiration, seizures, unconsciousness, and death resulting from respiratory arrest may occur.

Treatment of cocaine overdosage consists principally of symptomatic and supportive therapy. Initial treatment should be directed to establishing a patent airway maintaining respiration; assisted pulmonary ventilation may be necessary. If possible, initial treatment should also be directed to limiting further absorption of the drug. If the drug was ingested orally, gastric lavage or induction of emesis and administration of activated charcoal may be beneficial; efforts to remove the drug after 30 minutes of ingestion are probably of no value. If the drug was injected, absorption may be limited by the use of a tourniquet. Seizures may be controlled by IV administration of diazepam or a short-acting barbiturate (e.g., thiopental). IV propranolol may be useful in the management of tachycardia or other cardiac arrhythmias. Blood pressure should be maintained with IV fluids; the use of vasopressors is hazardous.

Pharmacology

Cocaine hydrochloride is a local anesthetic which blocks initiation or conduction of nerve impulses following local application; when applied topically to mucous membranes, the drug also produces intense vasoconstriction. When applied topically to the mucous membranes of the nose or mouth, cocaine reduces the acuity of smell or taste, respectively. Cocaine exerts an indirect adrenergic effect by interfering with the uptake of norepinephrine by adrenergic nerve terminals, and therefore potentiates the effects of catecholamines. The indirect adrenergic effect is apparently the mechanism by which the drug produces vasoconstriction and mydriasis.

Cocaine has CNS stimulating effects. (See Acute Toxicity.) The drug is also markedly pyrogenic, augmenting heat production by stimulating muscular activity and decreasing heat loss through vasoconstriction.

Cocaine Pharmacokinetics

Cocaine hydrochloride is absorbed from all sites of application, including mucous membranes and GI mucosa, and absorption may be enhanced in the presence of inflammation. In recreational cocaine users, the relative bioavailability of the drug, as determined by area under the plasma concentration-time curve (AUC), for a 2-mg/kg intranasal or oral dose of a 10% cocaine solution is the same; however, peak plasma concentrations are reportedly higher and occur sooner following oral administration than after intranasal administration. Following topical application of a 10% solution to the nasal mucosa, peak plasma cocaine concentrations occur within 15–120 minutes. Following topical application of cocaine hydrochloride solutions to mucous membranes, the onset of local anesthesia occurs within about 1 minute, is maximal within about 5 minutes, and may persist for 30 minutes or longer, depending on the dose and concentration used.

The distribution and elimination of cocaine remain to be clearly defined. The drug is hydrolyzed by serum esterases and is partially demethylated in the liver. Cocaine and its metabolites are excreted in urine; probably less than 10% is excreted in urine unchanged. Following topical application to the nasal mucosa as a 10% solution, cocaine reportedly has an average plasma half-life of about 75 minutes.

Chemistry and Stability

Chemistry

Cocaine, a naturally occurring alkaloid found in the leaves of Erythroxylum coca and other species of Erythroxylum, is a local anesthetic agent. Cocaine is commercially available as the hydrochloride salt which occurs as colorless crystals or a white, crystalline powder. Cocaine hydrochloride has a characteristic saline, slightly bitter taste. Cocaine hydrochloride is very soluble in water and freely soluble in alcohol.

Stability

Cocaine hydrochloride crystals and powder should be stored in well-closed, light-resistant containers; topical solutions of the drug should be stored at 15–30°C. Sterilization of the commercially available cocaine hydrochloride topical solution by ethylene oxide or steam autoclaving results in damage to the container and possible loss of drug potency.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Cocaine hydrochloride is subject to control under the Controlled Substances Act of 1970 as a schedule II (C-II) drug.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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