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Betablocker and cocaine.pptx
- 1. Beta Blocker use in Cocaine induced chest pain Mohammed Yaseen
- 2. Epidemiology • SAMHSA (2017) >40.6 million people >age of 12 had at least one lifetime use of cocaine and 9.6 million individuals had at least one lifetime use of crack. • In 2018, Cocaine-related ED visits were 12.9 visits per 10,000 population; (p < 0.001) • Cocaine-related visits had the highest utilization of diagnostic testing, especially cardiovascular testing (e.g., cardiac biomarkers and monitoring) • Cocaine- and opioid-related visits more often resulted in admission (cocaine: 16%, psychostimulant 9%, opioid 16%; p < 0.001) Suen, L.W., Davy-Mendez, T., LeSaint, K.T. et al. Emergency department visits and trends related to cocaine, psychostimulants, and opioids in the United States, 2008–2018. BMC Emerg Med 22, 19 (2022). https://doi.org/10.1186/s12873-022-00573-0
- 3. Pathophysiology • Cocaine blocks the reuptake of NE & DA at the presynaptic adrenergic terminals Increased CA at the postsynaptic receptor = powerful sympathomimetic agent • ↑BP, HR, O2 demand • Coronary Vasoconstriction? • CAD, ACS or other CV risk factors development of myocardial ischemia and/or MI NE: Norepinephrine; DA: Dopamine; Catecholamines: CA
- 4. Additional pathologies: • Aortic Dissection • frequent cause of dissection in younger persons those with untreated/poorly controlled hypertension • Myocarditis • common autopsy finding among subjects dying from cocaine abuse • Arrythmia • occur in cocaine-using patients with MI • effects of cocaine on sodium channels Hsue PY, Salinas CL, Bolger AF, Benowitz NL, Waters DD. Acute aortic dissection related to crack cocaine. Circulation. 2002 Apr 2;105(13):1592-5. doi: 10.1161/01.cir.0000012524.44897.3a. PMID: 11927528. Virmani R, Robinowitz M, Smialek JE, Smyth DF. Cardiovascular effects of cocaine: an autopsy study of 40 patients. Am Heart J. 1988 May;115(5):1068-76. doi: 10.1016/0002-8703(88)90078-6. PMID: 3364339.
- 5. Current Guidelines • Tx: • Asa • Nitroglycerin & CCB’s • Benzodiazepines • Why not Beta-blockers? • Traditional Dogma: β-blockers are contraindicated in the setting of cocaine- associated chest pain. • Previous studies suggest that β-blockers may exacerbate coronary vasospasm and the toxic effects of cocaine by creating “unopposed” α-adrenergic stimulation. • Long Term care: • Concerns for repeated cocaine use in an outpatient setting
- 6. Physiology • Presynaptic: • ⍺2– feed back inhibition • Post-Synaptic • ⍺1 smooth muscle contraction and vasoconstriction of microvasculature and large epicardial vessels • β1 increases heart rate, conduction, and contractility • β2 smooth muscle relaxation • A balance between these adrenergic receptors results in regulation of vascular tone.
- 7. β-Blockers & “Unopposed” ⍺-stimulation • Proposed Mechanism (Ramoska and Sacchetti, 1985): • Use of β-blocker increased CA in NMJ • Increased CA from cocaine blockade of NE reuptake at Pre-synaptic terminal • Favors NE and EPI stimulating alpha adrenergic receptors • Increased systemic and coronary vascular resistance Possible myocardial ischemia or infaction NE: Norepinephrine; EPI: Epinephrine; Catecholamines: CA; NMJ: Neuromuscular junction
- 8. Evidence against use… • Lange 1990 • Investigators injected propranolol directly into the coronary arteries of 10 subjects who received cocaine, which resulted in slightly worsening coronary vasoconstriction and reduced coronary blood flow, despite no change in arterial pressure or rate-pressure product. In half the subjects (four having coronary artery disease) with coronary vasoconstriction following intranasal cocaine administration, propranolol further constricted coronary arteries more than 10%. There was only one adverse event, when a subject experienced complete coronary artery occlusion and ST-elevation that resolved with nitroglycerin.
- 9. Additional Evidence • Sand 1991 • Esmolol reliably decreased HR but had an inconsistent effect on BP • Cohort 7 patients: 1 Tx failure and 3 AE’s • Fareed 2007 • Cocaine-induced ACS whose chest pain resolved with NTG, but tachycardia persisted despite diazepam treatment • Metoprolol, IV Chest pain, Systolic BP: 50 mmHG; HR: 120 bpm; Patient expired • Gomez 2009 • A patient with ST-elevation ACS after cocaine use who then developed ventricular fibrillation • Tx: Electrical defibrillation. • IV propranolol for diaphoresis, tachycardia, and hypertension • Chest pain • higher elevation of the inferior ST segments • New reciprocal anterior ST-depression
- 10. Evidence for use… • Lo et al, 2018 • Beta-blocker use is not associated with adverse clinical outcomes in patients presenting with acute chest pain related to cocaine use • Meta analysis of Five Studies and 1447 patients
- 11. Conclusion • More research is needed • Animal vs Human trials • Mechanism isn’t fully understood • Should we continue to pursue this controversial topic if alternate guidelines already exist?
Editor's Notes
- The unopposed α-stimulation phenomenon is based on 2 small prospective studies, 1 case series, and 3 case reports.6 In 1985, Ramoska and Sacchetti reported the first case of unopposed α-stimulation in an agitated, cocaine-toxic patient.24 After receiving propranolol, the patient’s blood pressure increased from 170/118 to 180/140 mm Hg, but heart rate decreased from 112 to 104 beats per minute (bpm). Despite this increase in blood pressure, no adverse event or outcome occurred. The patient’s agitation resolved, and he left against medical advice. If a non-selective beta-blocker, such as propranolol, is used that has both beta-1 and beta-2 effects, this balance is disrupted in favor of alpha-1 and vasoconstriction is favored. Another explanation is beta-1 blockade results in decreased heart rate and increased end diastolic pressure and cardiac fiber length, with resultant increase in BP and ventricular contraction from the Frank-Starling Law.
- In 1991, Sand and colleagues published a cohort of 7 patients with cocaine toxicity treated with esmolol, a short-acting selective β1-blocker.27 Esmolol reliably decreased heart rate but had an inconsistent effect on blood pressure. There was 1 treatment failure with esmolol for control of hypertension, for which the dihydropyridine calcium channel blocker nifedipine was then successfully used. There were 3 adverse events. In 1 patient, esmolol caused a 15% rise in systolic blood pressure and 50% rise in diastolic blood pressure, which was then successfully treated with labetalol. Esmolol caused hypotension in another patient that required reversal with the α1-adrenoceptor agonist phenylephrine. The third patient had resolution of symptoms of cocaine cardiovascular toxicity with esmolol but subsequently developed vomiting and lethargy and was intubated. Fareed and associates published a case report describing a patient with cocaine-induced ACS whose chest pain resolved with nitroglycerin, but tachycardia (115 bpm) persisted despite diazepam treatment.28 Two doses of IV metoprolol, a lipophilic β1-specific blocker, were given. Ten minutes later, the patient developed chest pain, became unresponsive with systolic blood pressure 50 mm Hg and heart rate 120 bpm, and expired. In 2009, Izquierdo Gómez and colleagues reported a patient with ST-elevation ACS after cocaine use who then developed ventricular fibrillation.29 He was successfully treated with electrical defibrillation, after which IV propranolol was administered for diaphoresis, tachycardia, and hypertension. Following this, the patient had another episode of chest pain, with higher elevation of the inferior ST segments and new reciprocal anterior ST-depression. Coronary angiography demonstrated a 60% stenosis in the mid-left circumflex artery, and he was later discharged.