Cocaine

Article Author:
John Richards
Article Editor:
Erik Laurin
Updated:
10/15/2019 8:47:52 AM
PubMed Link:
Cocaine

Indications

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 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.[1] Cocaine is otherwise an illegal drug of abuse listed on DEA Schedule II because of its 1) high potential for misuse; 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.

Mechanism of Action

Cocaine pharmacodynamics involves multiple complex mechanisms, although its half-life is short (approximately 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.[2] Monoamines accumulate in the synaptic cleft resulting in enhanced and prolonged sympathetic effects. The principal action of cocaine on the mucosa is anesthesia and vasoconstriction, however significant systemic absorption may occur; this may adversely affect the cardiovascular system, after which 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 a 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.[3] This action may benefit patients by enhancing the 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.

Administration

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.

Adverse Effects

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. These seizures are 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.[2] As a potent vasoconstrictor, cocaine may result in hyperthermia from impaired heat loss. Cocaine is not for ophthalmic use. If accidentally introduced into the eye, corneal damage may occur.[4]

Contraindications

Cocaine is contraindicated in patients with a history of allergy or hypersensitivity to the drug or 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 was in FDA Category C drug in pregnancy under the old pregnancy rating system. It is also not known whether cocaine can cause fetal harm and should be given to a pregnant woman only if needed.

Monitoring

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 there are reports of severe adverse effects from doses as low as 20 mg.[2] 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.    

Toxicity

Treatment recommendations of acute cocaine toxicity are based on an extensive systematic review from 2016 [5]. Cardiovascular toxicity and agitation are best-treated first-line with benzodiazepines to decrease CNS sympathetic outflow. However, there is a 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 the risk of reflex tachycardia should be recognized. The mixed beta/alpha blocker labetalol is safe and effective for treating concomitant cocaine-induced hypertension and tachycardia, without any “unopposed alpha-stimulation” adverse events recorded. A recent AHA/ACC guideline approves the use of labetalol for cocaine and methamphetamine patients with unstable angina/non-STEMI.[6]

The best treatment for agitated patients is 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.[7] 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 successful for serious ventricular tachydysrhythmia in several case reports.[5] 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 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 [3]. Of the 1744 total patients identified in the systematic review, only seven adverse events were from putative cases of “unopposed alpha-stimulation” due to propranolol (n=3), esmolol (n=3), and metoprolol (n=1).[5] The authors of the original “unopposed alpha-stimulation” articles dating back to the 1980s concluded in a 2017 review that the phenomenon might actually be the from effects of cocaine alone, with or without beta-blockers.[3]

Enhancing Healthcare Team Outcomes

Both the legitimate/clinical use of cocaine as well as toxicity resulting from illicit use requires interprofessional healthcare team coordination.

Cocaine toxicity is managed by a multidisciplinary team that includes the emergency department physician, poison control, internist, cardiologist, and psychiatrist. The management is strictly supportive, with the treatment of symptoms as needed. Some of these patients may require admission to the ICU and monitoring by nurses. If benzodiazepines are used to treat toxicity, a pharmacist should carefully review the patient's medication record and verify benzodiazepine dosing. Before discharge, patients should be referred to a mental health nurse so that they can receive education regarding the detrimental effects of this agent and how to stop further usage.[8][9]

The use of cocaine as an anesthetic agent will require careful consideration by the clinician and should involve the pharmacist for dosing and medication reconciliation. If nursing is administering the drug, they should also coordinate with the clinician and the pharmacist to ensure proper administration and patient safety.

When using cocaine as a therapeutic agent, or when misused by a patient, requires full interprofessional team collaboration and coordination for safe and effective treatment with minimal adverse effects. [Level V]


References

[1] Assessing the safety and efficacy of drugs used in preparing the nose for diagnostic and therapeutic procedures: a systematic review., Saif AM,Farboud A,Delfosse E,Pope L,Adke M,, Clinical otolaryngology : official journal of ENT-UK ; official journal of Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery, 2015 Oct 9     [PubMed PMID: 26452438]
[2] Zimmerman JL, Cocaine intoxication. Critical care clinics. 2012 Oct     [PubMed PMID: 22998988]
[3] Richards JR,Hollander JE,Ramoska EA,Fareed FN,Sand IC,Izquierdo Gómez MM,Lange RA, β-Blockers, Cocaine, and the Unopposed α-Stimulation Phenomenon. Journal of cardiovascular pharmacology and therapeutics. 2017 May     [PubMed PMID: 28399647]
[4] Ghosheh FR,Ehlers JP,Ayres BD,Hammersmith KM,Rapuano CJ,Cohen EJ, Corneal ulcers associated with aerosolized crack cocaine use. Cornea. 2007 Sep     [PubMed PMID: 17721298]
[5] Richards JR,Garber D,Laurin EG,Albertson TE,Derlet RW,Amsterdam EA,Olson KR,Ramoska EA,Lange RA, Treatment of cocaine cardiovascular toxicity: a systematic review. Clinical toxicology (Philadelphia, Pa.). 2016 Jun     [PubMed PMID: 26919414]
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[7] Zun LS, Evidence-Based Review of Pharmacotherapy for Acute Agitation. Part 1: Onset of Efficacy. The Journal of emergency medicine. 2018 Mar     [PubMed PMID: 29361326]
[8] Alonso-Matias L,Reyes-Zamorano E,Gonzalez-Olvera JJ, Cognitive functions of subjects with cocaine and crack dependency disorder during early abstinence. Revista de neurologia. 2019 Apr 1;     [PubMed PMID: 30906976]
[9] Lima DR,Gonçalves PD,Ometto M,Malbergier A,Amaral RA,Dos Santos B,Cavallet M,Chaim-Avancini T,Serpa MH,Ferreira LRK,Duran FLS,Zanetti MV,Nicastri S,Busatto GF,Andrade AG,Cunha PJ, The role of neurocognitive functioning, substance use variables and the DSM-5 severity scale in cocaine relapse: A prospective study. Drug and alcohol dependence. 2019 Feb 16;     [PubMed PMID: 30875646]