Cardiovascular effects cocaine

Cocaine differs from the other local anesthetics with respect to its cardiovascular effects. Cocaine s blockade of norepinephrine reuptake results in vasoconstriction and hypertension, as well as cardiac arrhythmias. The vasoconstriction produced by cocaine can lead to local ischemia and, in chronic abusers who use the nasal route, ulceration of the mucous membrane and damage to the nasal septum have been reported. The vasoconstrictor properties of cocaine can be used clinically to decrease bleeding from mucosal damage or surgical trauma in the nasopharyneal region. 

Cardiovascular effects of cocaine An autopsy study of 40 patients. Am Heart J 115 1068-1076, 1988. 

Vascular effects Cocaine causes increases in blood pressure and heart rate, which fall to normal levels between doses (Foltin et al. 1995). Tachyphylaxis develops to the cardiovascular effects, even within a single session. Concurrent use of ethanol, cannabis, and cocaine causes even greater cardiovascular effects than those of each drug alone. Interactions can also occur with antidepressant drugs like desipramine. 

Foltin RW, Fischman MW, Levin FR. (1995). Cardiovascular effects of cocaine in humans laboratory studies. Drug Alcohol Depend. 37(3) 193-210. 

Evans SM, Cone EJ, Henningfleld JE (1996) Arterial and venous cocaine plasma concentrations in humans relationship to route of administration, cardiovascular effects and subjective effects. J Pharmacol Exp Ther 279 1345-1356... 

Pozner CN, Levine M Zane R (2005). The cardiovascular effects of cocaine. Journal of Emergency Medicine, 29, 173-8... 

The cardiovascular effects of local anesthetics result in part from direct effects of these drugs on the cardiac and smooth muscle membranes and from indirect effects on the autonomic nervous system. As described in Chapter 14, local anesthetics block cardiac sodium channels and thus depress abnormal cardiac pacemaker activity, excitability, and conduction. At extremely high concentrations, local anesthetics can also block calcium channels. With the notable exception of cocaine, local anesthetics also depress myocardial contractility and produce direct arteriolar dilation, leading to systemic hypotension. Cardiovascular collapse is rare, but has been reported after large doses of bupivacaine and ropivacaine have been inadvertently administered into the intravascular space. 

This only develops to some of the effects of cocaine, for example the euphoric "rush" following intravenous administration and some of the cardiovascular effects, but the degree of tolerance is limited. However, most long-term users do require increasing amounts of the drug to produce the same subjective effects to those experienced initially when taking the drug. 

Cardiovascular effects include tachycardia, hypertension, and increased cardiac irritability large intravenous doses can cause cardiac failure. Cardiac dysrhythmias have been ascribed to a direct toxic effect of cocaine and a secondary sensitization of ventricular tissue to catecholamines (17), along with slowed cardiac conduction secondary to local anesthetic effects. Myocardial infarction has increased as a complication of cocaine abuse (7,8). Dilated cardiomyopathies, with subsequent recurrent myocardial infarction, have been associated with long-term use of cocaine, raising the possibility of chronic effects on the heart (18). Many victims have evidence of pre-existing fixed coronary artery disease precipitated by cocaine (SEDA-9, 35) (19-21). However, myocardial infarction has been noted even in young intranasal users with no evidence of coronary disease (22), defined by autopsy or angiography (23,24). If applied to mucous membranes, cocaine causes local vasoconstriction, and, with chronic use, necrosis. 

Fischman MW, Schuster CR, Hatano Y. A comparison of the subjective and cardiovascular effects of cocaine and hdocaine in humans. Pharmacol Biochem Behav 1983 18(l) 123-7. 

Rush, Roll, Higgins, 1998). The combination of cocaine (or amphetamine) and heroin (or other opiate) is called a speedbair and is particularly popular among heroin addicts. Morphine and cocaine combinations have been studied in the laboratory, and as with alcohol, morphine appeared to enhance the pleasurable effects of cocaine but also increased the cardiovascular effects. Combinations of cocaine and heroin have sometimes been blamed for drug overdose deaths (as in the deaths of comedian John Belushi and actor River Phoenix), and the synergistic effects on blood pressure and heart rate may be a factor (Foltin Fischman, 1992 Rush et al., 1998). 

Newton, T. F., De La Garza, R., Kalechstein, A. D., 8c Nestor, L. (2005). Cocaine and methamphetamine produce different patterns of subjective and cardiovascular effects. Pharmacology, Biochemistry and Behavior, 82, 90-97. 

Chiriboga CA, Bateman DA, and Brust JCM (1993) Neurologic findings in neonates with intrauterine cocaine exposure. Pediatric Neurology 9 115-119. Goldfrank LI and Hoffman KS (1991) The cardiovascular effects of cocaine. Annals of Emergency Medicine 20 165-175. Harvey JA (2004) Cocaine effects on the developing brain current status. Neuroscience and Biobehavioral Reviews 27(8) 751-764. 

Ethanol is frequently consumed with other recreational drugs. Cocaine abuse has resulted in an increase of catastrophic cardiovascular events such as myocardial infarction, ventricular arrhythmias, angina pectoris, and sudden death. Many of those so affected also consume ethanol prior to cocaine use. The drug combination of ethanol first followed by cocaine use has been shown to generate synergistic cardiovascular effects in humans and animalsJ24-27 The findings are believed to be due to the inhibition effect of ethanol on cocaine metabolism. 281... 

The CNS and cardiovascular effects of cocaine exhibit acute tolerance, with its effects more pronounced when the concentration of cocaine in blood is increasing than when it is at a similar but decreasing concentration.Thus a clock-... 

B. Cardiovascular effects of high doses of cocaine, presumably related to blockade of cardiac-cell sodium channels, include depression of conduction and... 

Alcohol increases cocaine levels and the active metabolite coca-ethylene. Subjective effects such as euphoria are enhanced and some of the CNS-depressant effects of alcohol, such as sedation, are attenuated by cocaine. The combination may be potentially more toxic, with increased cardiovascular effects particularly heart rate. The use of alcohol with cocaine may increase violent behaviour. 

Cocaine-related torsade de pointes occurred in a patient taking methadone. Ventricular arrhythmias and increased cardiovascular effects have been reported when other patients taking methadone were given cocaine. The cardiovascular effects of cocaine and morphine appear to be similar to those seen with cocaine alone. 

In contrast, a study in 9 healthy subjects found that although the combination of morphine and cocaine produced significant cardiovascular and subjective effects, for the most part, the cardiovascular effects were similar to those produced by cocaine alone. Neither cocaine nor morphine altered the plasma levels of the other drug. ... 

Chemical Structures. Figure 1 shows the chemical structures for 14 phenylethylamine compounds. Nine of these compounds are used clinically as anorectics (ii-amphetamine, phentermine, diethylpropion, phenmetrazine, phendimetrazine, clotermine, chlorphentermine, benzphetamine, and fenfluramine). Four of these compounds are not approved for clinical use and are reported to have hallucinogenic properties (MDA, PMA, DOM, and DOET). The final compound ( /-ephedrine) is used clinically for bronchial muscle relaxation, cardiovascular, and mydriatic effects. Figure 2 shows the chemical structure for MDMA, the methyl analog of MDA. MDMA is not approved for clinical use and has been reported to produce both LSD-like and cocaine-like effects. 

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