Acute Systemic Effects of Cocaine in Man: A Controlled Study by Intranasal and Intravenous Routes

Resnick, Richard B.; Kestenbaum, Richard S.; Schwartz, Lee K.

doi:10.1126/science.841307

Cited by 249 publications

(79 citation statements)

References 5 publications

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“…For heart rate, the main effect of dose (40 mg, 20 mg, and placebo) was significant (F(2,39) ϭ 37.7, p Ͻ .0001), and the contrasts between placebo and 20 mg (F(1,26) ϭ 41.8, p Ͻ .0001), and between placebo and 40 mg (F(1,26) ϭ 73.7, p Ͻ .0001) were significant, although that between 20 mg and 40 mg (F(1,26) ϭ 4.7, p Ͻ .05) was not. This degree of tachycardia was consistent with previous results (Fischman et al 1976;Resnick et al 1977).…”

Section: Resultssupporting

confidence: 93%

“…cocaine on heart rate and the time course (i.e., tachycardia peaking approximately 10 min after injection) are congruent with earlier studies (Fischman et al 1976;Resnick et al 1977). The higher dose of cocaine (40 mg) in the current study produced significant subjective effects in the positron emission tomography portion of this study (London et al 1990) with which there was some overlap among subjects.…”

Section: Discussionsupporting

confidence: 90%

“…These findings, and evidence that cocaine decreased cardiovascular complexity, contradict the prevailing assumption that the mechanism by which cocaine produces tachycardia is sympathetic (beta-adrenergic Cocaine is a widely abused drug with pronounced subjective and cardiovascular effects (Fischman et al 1976;Johanson and Fischman 1989). Early human research on cocaine (Fischman et al 1976;Resnick et al 1977) revealed dose-dependent positive chronotropic effects on the heart, reaching a mean increase in heart rate of 38 bpm in response to 32 mg i.v. cocaine.…”

Section: We Assessed the Effects Of IV Cocaine On Parasympathetic Amentioning

confidence: 99%

“…Early human research on cocaine (Fischman et al 1976;Resnick et al 1977) revealed dose-dependent positive chronotropic effects on the heart, reaching a mean increase in heart rate of 38 bpm in response to 32 mg i.v. cocaine.…”

mentioning

confidence: 99%

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Intravenous Cocaine Decreases Cardiac Vagal Tone, Vagal Index (Derived in Lorenz Space), and Heart Period Complexity (Approximate Entropy) in Cocaine Abusers

Newlin

Wong

Stapleton

et al. 2000

Neuropsychopharmacology

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We assessed the effects of i.v. cocaine on parasympathetic and sympathetic nervous system activity, and on the complexity vs. regularity of changes in heart rate over time. Fourteen otherwise healthy men with histories of i.v. cocaine abuse received bolus injections of cocaine (20 mg or 40 mg) and placebo (saline) on different days.Cardiovascular measures derived from the electrocardiogram, including heart rate, Porges' vagal tone (respiratory sinus arrhythmia), the 0.10 Hz rhythm, Toichi's vagal index, Toichi's sympathetic index, and approximate entropy (ApEn), were measured continuously. As predicted, cocaine produced tachycardia, accompanied by pronounced decreases in response to 40 mg cocaine in two different vagal tone indexes that precisely mirrored the increases in heart rate. The measure of sympathetic (and vagal) neural influences on the heart (0.10 Hz wave) also decreased in response to cocaine. Converging evidence from Toichi's vagal index supported the conclusion that the tachycardia from cocaine was due to withdrawal of cardiac vagal tone. These findings, and evidence that cocaine decreased cardiovascular complexity, contradict the prevailing assumption that the mechanism by which cocaine produces tachycardia is sympathetic (beta-adrenergic Cocaine is a widely abused drug with pronounced subjective and cardiovascular effects (Fischman et al. 1976;Johanson and Fischman 1989). Early human research on cocaine (Fischman et al. 1976;Resnick et al. 1977) revealed dose-dependent positive chronotropic effects on the heart, reaching a mean increase in heart rate of 38 bpm in response to 32 mg i.v. cocaine. Effects on the cardiovascular system can be remarkable in some subjects. Increases in heart rate have been reported to occur in response to doses as low as 13 mg i.v. cocaine; these increases ranged from 15 to 46 bpm (Ambre et al. 1988). The magnitude of these effects has led to the conclusion that cardiotoxicity from cocaine may be a major factor in death due to cocaine overdose (Billman 1990).The cardiotoxicity of cocaine has directed interest toward the autonomic mechanism by which the drug produces cardiovascular arousal. It has been assumed (Billman 1990;Ritchie and Greene 1990) that the cardiovascular response to cocaine is due primarily to activation of sympathetic autonomic mechanisms. This view stems in part from evidence that cocaine directly blocks reuptake of catecholamines in the periphery (Ritchie and Greene 1990 that propranolol (a beta-adrenergic blocker) and phentolamine (an alpha-adrenergic blocker) may partially reverse cardiovascular arousal in cocaine overdose (Rappolt et al. 1977). However, controlled studies at moderate dosages of cocaine in humans would be needed to confirm these observations. Furthermore, there is conflicting evidence in animal research concerning the role of the sympathetic nervous system in the response to cocaine in the intact organism. Recent findings indicate that central administration of cocaine actually decreases peripheral sympathetic neural activity in c...

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Section: Resultssupporting

confidence: 93%

Section: Discussionsupporting

confidence: 90%

Section: We Assessed the Effects Of IV Cocaine On Parasympathetic Amentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Intravenous Cocaine Decreases Cardiac Vagal Tone, Vagal Index (Derived in Lorenz Space), and Heart Period Complexity (Approximate Entropy) in Cocaine Abusers

Newlin

Wong

Stapleton

et al. 2000

Neuropsychopharmacology

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“…8,9 The increase is initially dose dependent, [8][9][10][11] followed by an acute tachyphylaxis in which HR and blood pressure plateau, even with increasingly larger quantities of cocaine and increasing serum cocaine concentrations. 9,11 Animal models have demonstrated that cocaine decreases the reuptake of norepinephrine and dopamine, thereby increasing its plasma concentration and causing increased sympathetic stimulation, 12,13 but one human study questions this.…”

Section: Systemic Cardiovascular Hemodynamicsmentioning

confidence: 99%

Rethinking Cocaine-Associated Chest Pain and Acute Coronary Syndromes

Finkel

Marhefka

2011

Mayo Clinic Proceedings

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Every year more than 500,000 patients present to the emergency department with cocaine-associated complications, most commonly chest pain. Many of these patients undergo extensive work-up and treatment. Much of the evidence regarding cocaine's cardiovascular effects, as well as the current management of cocaine-associated chest pain and acute coronary syndromes, is anecdotally derived and based on studies written more than 2 decades ago that involved only a few patients. Newer studies have brought into question many of the commonly held theories and practices regarding the etiology, diagnosis, and treatment of this common clinical scenario. However, there continues to be a paucity of prospective, randomized trials addressing this topic as it relates to clinical outcomes. We searched PubMed for Englishlanguage articles from 1960 to 2011 using the keywords cocaine, chest pain, coronary arteries, myocardial infarction, emergency department, cardiac biomarkers, electrocardiogram, coronary computed tomography, observation unit, β-blockers, benzodiazepines, nitroglycerin, calcium channel blockers, phentolamine, and cardiomyopathy; including various combinations of these terms. We reviewed the abstracts to confirm relevance, and then full articles were extracted. References from extracted articles were also reviewed for relevant articles. In this review, we critically evaluate the limited historical evidence underlying the current teachings on cocaine's cardiovascular effects and management of cocaine-associated chest pain. We aim to update the reader on more recent, albeit small, studies on the emergency department evaluation and clinical and pharmacologic management of cocaine-associated chest pain. Finally, we summarize recent guidelines and review an algorithm based on the current best evidence. Proc. 2011;86(12):1198-1207 ACS = acute coronary syndrome; AHA = American Heart Association; CCB = calcium channel blockers; CCP = cocaine-associated chest pain; DBP = diastolic blood pressure; ECG = electrocardiography; ED = emergency department; HR = heart rate; MAP = mean arterial pressure; MI = myocardial infarction; PCI = percutaneous coronary intervention; SBP = systolic blood pressure; STEMI = ST-segment elevation myocardial infarction; TIMI = Thrombolysis in Myocardial Infarction E very year millions of Americans abuse cocaine, many of whom present to the emergency department (ED) with cocaine-related complications, most commonly chest pain. Unfortunately, much of the current thinking on cocaine and its cardiovascular effects is either anecdotally derived or based on small studies conducted more than 2 decades ago. Recently, newer studies have brought into question many of the commonly held theories and practices regarding the etiology, diagnosis, and management of cocaine-associated chest pain (CCP) and suspected myocardial ischemia. Mayo ClinWe searched PubMed for English-language articles from 1960 to 2011 using the keywords cocaine, chest pain, coronary arteries, myocardial infarction, emergency department, card...

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