indication

For the introduction of local (topical) anesthesia of accessible mucous membranes of the oral, laryngeal and nasal cavities.

pharmacology

Cocaine is a local anesthetic indicated for the introduction of local (topical) anesthesia of accessible mucous membranes of the oral, laryngeal and nasal cavities.

mechanism of action

Cocaine produces anesthesia by inhibiting excitation of nerve endings or by blocking conduction in peripheral nerves. This is achieved by reversibly binding to and inactivating sodium channels. Sodium influx through these channels is necessary for the depolarization of nerve cell membranes and subsequent propagation of impulses along the course of the nerve. Cocaine is the only local anesthetic with vasoconstrictive properties. This is a result of its blockade of norepinephrine reuptake in the autonomic nervous system. Cocaine binds differentially to the dopamine, serotonin, and norepinephrine transport proteins and directly prevents the re-uptake of dopamine, serotonin, and norepinephrine into pre-synaptic neurons. Its effect on dopamine levels is most responsible for the addictive property of cocaine.

toxicity

Intense agitation, convulsions, hypertension, rhythm disturbance, coronary insufficiency, hyperthermia, rhabdomyolysis, and renal impairment. Oral mouse LD₅₀ = 96 mg/kg

biotransformation

Hepatic. Cocaine is metabolized to benzoylecgonine and ecgonine methyl ester, which are both excreted in the urine. In the presence of alcohol, a further active metabolite, cocaethylene is formed, and is more toxic then cocaine itself.

absorption

Cocaine is absorbed from all sites of application, including mucous membranes and gastrointestinal mucosa. By oral or intra-nasal route, 60 to 80% of cocaine is absorbed.

half life

1 hour

drug interactions

Atomoxetine: CYP2D6 Inhibitors (Strong) such as cocaine may increase the serum concentration of atomoxetine. Initiate atomoxetine at a reduced dose (patients up to 70kg: 0.5mg/kg/day; patients 70kg or more: 40mg/day) in patients receiving a strong CYP2D6 inhibitor. The dose should only be increased to usual doses if symptoms fail to improve after 4 weeks. Patients established on atomoxetine therapy may require dosage reductions and should be monitored for increased levels/adverse effects with initiation/dose increase of a strong CYP2D6 inhibitor.

Disulfiram: Increases the cardiac toxicity of cocaine

Tamoxifen: Cocaine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Concomitant therapy should be avoided.

Tamsulosin: Cocaine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Cocaine is initiated, discontinued, or dose changed.

Telithromycin: Telithromycin may reduce clearance of Cocaine. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Cocaine if Telithromycin is initiated, discontinued or dose changed.

Tetrabenazine: CYP2D6 Inhibitors (Strong) such as cocaine may increase the serum concentration of tetrabenazine. Specifically, concentrations of the active alpha- and beta-dihydrotetrabenazine metabolites may be increased. Patients receiving a strong inhibitor of CYP2D6 together with tetrabenazine should not exceed 50mg of tetrabenazine. Also, patients already taking tetrabenazine prior to starting a strong CYP2D6 inhibitor should have their tetrabenazine dose reduced by 50% upon initiation of the strong CYP2D6 inhibitor.

Tolterodine: Cocaine may decrease the metabolism and clearance of Tolterodine. Monitor for adverse/toxic effects of Tolterodine.

Tramadol: Cocaine may decrease the effect of Tramadol by decreasing active metabolite production.

Trimipramine: The strong CYP2D6 inhibitor, Cocaine, may decrease the metabolism and clearance of Trimipramine, a CYP2D6 substrate.

Venlafaxine: Cocaine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Cocaine is initiated, discontinued, or dose changed.

Voriconazole: Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of cocaine by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of cocaine if voriconazole is initiated, discontinued or dose changed.

Zuclopenthixol: Cocaine, a strong CYP2D6 inhibitor, may increase the serum concentration of zuclopenthixol by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zuclopenthixol if cocaine is initiated, discontinued or dose changed.