Beta Blocker Use in Cocaine-Induced Chest Pain

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.

Labetalol | Propranolol

Dose | 0.25 mg/kg IV OR 100-200 mg PO | 60 – 120 mg PO daily or

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 and warnings | May mask hypoglycemia | CYP1A2, CYP2D6, may mask hypoglycemia

Compatibility | Administer at a rate of 10mg/minute | Can administer IV push over 1 minute

Comments | B1, B2, and a1 activity | B1 and B2 activity

Author, year | Design/ sample size | Intervention & Comparison | Outcome | Outcome

Lange et all, 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 (2mg/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 | 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 – Administer intranasal cocaine, followed by IV saline or labetalol (0.25mg/kg) infusion | Labetalol reduced heart rate, blood pressure; no effect on coronary artery cross sectional area | Labetalol reduced heart rate, 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 | 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 | 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 | 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, myocardial infarction of five previous studies | Beta blocker use is not associated with adverse clinical outcomes in patients presenting with acute chest pain related to cocaine use | Beta blocker use is not associated with adverse clinical outcomes in patients presenting with acute chest pain related to cocaine use

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.

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

Pharmacology | Pharmacology | Pharmacology

Labetalol | Propranolol

Dose | 0.25 mg/kg IV OR 100-200 mg PO | 60 – 120 mg PO daily or

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 and warnings | May mask hypoglycemia | CYP1A2, CYP2D6, may mask hypoglycemia

Compatibility | Administer at a rate of 10mg/minute | Can administer IV push over 1 minute

Comments | B1, B2, and a1 activity | B1 and B2 activity

Overview of Evidence | Overview of Evidence | Overview of Evidence

Author, year | Design/ sample size | Intervention & Comparison | Outcome | Outcome

Lange et all, 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 (2mg/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 | 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 – Administer intranasal cocaine, followed by IV saline or labetalol (0.25mg/kg) infusion | Labetalol reduced heart rate, blood pressure; no effect on coronary artery cross sectional area | Labetalol reduced heart rate, 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 | 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 | 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 | 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, myocardial infarction of five previous studies | Beta blocker use is not associated with adverse clinical outcomes in patients presenting with acute chest pain related to cocaine use | Beta blocker use is not associated with adverse clinical outcomes in patients presenting with acute chest pain related to cocaine use