Introduction
Cocaine is one of the most used illicit substances in the US. Cocaine-associated complications, most commonly chest pain, account for roughly 40% of all drug-related emergency department visits.
Cocaine can cause chest pain or acute coronary syndrome (ACS) by increasing myocardial oxygen demand and decreasing oxygen supply through vasoconstriction.
This occurs because cocaine blocks the reuptake of norepinephrine and dopamine, causing an accumulation of catecholamines at the post-synapse, therefore acting as a sympathomimetic agent.
Activates alpha receptors, calcium influx into smooth muscle, and can lead to coronary vasoconstriction
The use of beta blockers in cocaine induced chest pain is controversial. Earlier studies suggested beta blockers usage in this population was harmful due to causing an unopposed alpha stimulation leading to an increase in blood pressure and coronary artery vasoconstriction.
Clinical Detail
The two beta blockers with the most relevant data in this setting are labetalol (combined α/β activity) and propranolol (non-selective β activity). Key pharmacologic features are summarized below.
| Parameter | Labetalol | Propranolol |
|---|---|---|
| Dose | 0.25 mg/kg IV OR 100–200 mg PO | 60–120 mg PO daily or IV/intracoronary |
| Administration | IV | IV/intracoronary |
| PK/PD | Onset: 5 minutes; Half-life: 6–8 hours | Onset: within 5 minutes; Half-life: 3–6 hours |
| Adverse Effects | Orthostatic hypotension, bradycardia, dizziness, fatigue | Hypotension, bradycardia, sleep disorders, dizziness, agitation |
| Drug Interactions & Warnings | May mask hypoglycemia | CYP1A2, CYP2D6; may mask hypoglycemia |
| Compatibility | Administer at a rate of 10 mg/minute | Can administer IV push over 1 minute |
| Comments | β1, β2, and α1 activity | β1 and β2 activity |
Evidence
The controversy over beta blocker use in cocaine-associated chest pain rests on a small, mixed evidence base — early mechanistic studies suggesting harm (unopposed alpha stimulation) versus more recent retrospective and meta-analytic data showing no adverse clinical outcomes. Key studies are summarized below.
| Author, Year | Design / Sample Size | Intervention & Comparison | Outcome |
|---|---|---|---|
| Lange et al, 1990 | Prospective, randomized double-blind controlled trial; 10 participants | Measured heart rate, arterial pressure, coronary sinus blood flow, and epicardial left coronary arterial dimensions. Intranasal saline or cocaine (2 mg/kg) administration followed by intracoronary propranolol administration | Intracoronary propranolol administration caused no change in arterial pressure or rate pressure, but further decreased coronary blood flow and increased coronary vascular resistance |
| Boehrer et al, 1993 | Prospective, controlled; 9 participants | Patients undergoing catheterization for chest pain had heart rate, mean arterial pressure, and coronary arterial area measured. Intranasal cocaine administered, followed by IV saline or labetalol (0.25 mg/kg) infusion | Labetalol reduced heart rate and blood pressure; no effect on coronary artery cross-sectional area |
| Dattilo et al, 2008 | Retrospective; 60 participants | Outcomes included myocardial infarction and in-hospital mortality. Excluded patients on a beta blocker prior to admission. Beta blockers used included metoprolol, atenolol, labetalol, propranolol, carvedilol | Beta blockers associated with decreased incidence of myocardial infarction |
| Rangel et al, 2010 | Retrospective; 151 participants | Evaluated EKG changes, troponin levels, length of stay, vasopressor use, intubation, and death between patients that did and did not receive beta blockers. Beta blockers used included metoprolol, atenolol, labetalol, and carvedilol | Beta-blocker use associated with greater reduction in blood pressure and death |
| Gupta et al, 2014 | Retrospective; 600 participants | Evaluated outcomes of patients experiencing a myocardial infarction that received a beta blocker at any point in time | The majority of cocaine-positive patients with myocardial infarction received beta blockers and showed no difference in hospital mortality |
| Lo et al, 2019 | Review and meta-analysis; 1447 participants | Evaluated all-cause mortality and myocardial infarction across five previous studies | Beta blocker use is not associated with adverse clinical outcomes in patients presenting with acute chest pain related to cocaine use |
Conclusions
ACC/AHA recommends against the use of beta blockers due to the risk of exacerbating coronary artery spasm.
Deaths from cocaine induced MI are relatively low, this driving the further questioning of risk vs benefit of beta blocker administration
Propranolol and esmolol were associated with worsening vasoconstriction and an increase in blood pressure
Other agents such as metoprolol, labetalol have very limited data
Most negative data were observed in animals
Human retrospective data show no harm or potential benefit
More recent retrospective studies suggest that there is no difference in MI incidence or mortality in patients with a positive UDS for cocaine that also received a beta-blocker.
These meta-analyses suggest that beta blocker use was not associated with adverse clinical outcomes, and even a potential benefit in some studies reducing the incidence of MI
From the limited data, a beta blocker with alpha and beta activity such as labetalol may be preferred if needed in these situations.
Although beta blockers may not be as detrimental in cocaine associated chest pain as previously thought, more data is needed to assess if the use of beta blockers provides a true benefit in this patient population.
References
Micromedex [Electronic version].Greenwood Village, CO: Truven Health Analytics. Retrieved January 17, 2021, from http://www.micromedexsolutions.com/
Shin D, Lee ES, Bohra C, Kongpakpaisarn K. In-Hospital and Long-Term Outcomes of Beta-Blocker Treatment in Cocaine Users: A Systematic Review and Meta-analysis. Cardiol Res. 2019;10(1):40-47. doi:10.14740/cr831
Richards JR, Hollander JE, Ramoska EA, et al. β-Blockers, Cocaine, and the Unopposed α-Stimulation Phenomenon. J Cardiovasc Pharmacol Ther. 2017;22(3):239-249. doi:10.1177/1074248416681644
Lange RA, Cigarroa RG, Flores ED, et al. Potentiation of cocaine-induced coronary vasoconstriction by beta-adrenergic blockade. Ann Intern Med. 1990;112(12):897-903. doi:10.7326/0003-4819-112-12-897
Lo KB, Virk HUH, Lakhter V, et al. Clinical Outcomes After Treatment of Cocaine-Induced Chest Pain with Beta-Blockers: A Systematic Review and Meta-Analysis. Am J Med. 2019;132(4):505-509. doi:10.1016/j.amjmed.2018.11.041
Pham D, Addison D, Kayani W, et al. Outcomes of beta blocker use in cocaine-associated chest pain: a meta-analysis. Emerg Med J. 2018;35(9):559-563. doi:10.1136/emermed-2017-207065
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