Cocaine cardiovascular

Fischman MW, Schuster CR, Resnekov L, et al Cardiovascular and subjecrive effecrs of inrravenous cocaine adminisrration in humans. Arch Gen Psychiarry 33 983— 989, 1976... 

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. 

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

Parker, R.B., Perry, G.Y., Horan, L.G. and Flowers, N.C. (1999) Comparative effects of sodium bicarbonate and sodium chloride on reversing cocaine-induced changes in the electrocardiogram. Journal of Cardiovascular Pharmacology, 34, 864-869. 

Autonomic Cocaine has stong sympathomimetic effects due to inhibition of norepinephrine reuptake, and perhaps central mechanisms as well. Effects include those typical of sympathetic autonomic activation. Cardiovascular and cerebrovascular effects are prominent. 

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. 

AntheneUi RM, Despres IP (2004) Effects of Rimonabant in the reduction of major cardiovascular risk factors. Results from the STRATUS-US trial (smoking cessation in smokers motivated to quit), American College of Cardiology 53rd Annual Scientific Session, New Orleans, LA Arroyo M, Markou A, Robbins TW, Everitt B1 (1999) Acquisition, maintenance and reinstatement of intravenous cocaine self-administration under a second-order schedule of reinforcement in rats effects of conditioned cues and continuous acces to cocaine. Psychopharmacology 140 331-344... 

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. 

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. 

Fischman, Marian W., Charles R. Schuster, Javaid Javaid, Yoshio Hatano, and John Davis. 1985. "Acute Tolerance Development to the Cardiovascular and Subjective Effects of Cocaine." Journal of Pharmacology and Experimental Therapeutics 235 677-82. 

Vescovi PP. Cardiovascular and hormonal responses to hyperthermic stress in cocaine addicts after a long period of abstinence. Addict Biol 2000 5 91-5. 

Cocaine is also frequently combined with marijuana. Called a diablito or turbo, a cigar is filled with marijuana and crack and then smoked. This increases the risk to the cardiovascular system as both drugs speed up the heart and increase blood pressure. 

Cardiovascular toxicity is also frequently encountered in poisoning. Hypotension may be due to depression of cardiac contractility hypovolemia resulting from vomiting, diarrhea, or fluid sequestration peripheral vascular collapse due to blockade of -adrenoceptor-mediated vascular tone or cardiac arrhythmias. Hypothermia or hyperthermia due to exposure as well as the temperature-dysregulating effects of many drugs can also produce hypotension. Lethal arrhythmias such as ventricular tachycardia and fibrillation can occur with overdoses of many cardioactive drugs such as ephedrine, amphetamines, cocaine, tricyclic antidepressants, digitalis, and theophylline. 

The most serious toxic effects of cocaine involve changes in the cardiovascular system. These include cardiac arrhythmias, myocardial ischaemia and infarction, and cerebrovascular spasm, all of which can be largely explained by the facilitation of the action of catecholamines on the cardiovascular system. Another explanation of the cardiotoxicity of cocaine lies in the direct vasoconstrictive properties of its major metabolite, norcocaine. It seems likely... 

Similar effects have been reported after abuse of the amphetamines which, in addition, may be associated with increasing stereotyped behaviour and a full psychotic episode (auditory, visual and tactile hallucinations often unassociated with cardiovascular symptoms) which may be difficult to differentiate from paranoid schizophrenia. This is the basis for using amphetamine as a model for schizophrenia, in both animals and human volunteers. The central effects of high doses of cocaine and the amphetamines may be suppressed by the administration of neuroleptics. 

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. 

Cocaine also blocks the reuptake of norepinephrine in the PNS the combination of central and peripheral actions leads to a high probability of toxicity. The cardiovascular system is particularly sensitive to the actions of cocaine, and cardiac arrhythmias, marked increases in blood pressure, cerebral hemorrhage, myocardial ischemia, and outright heart failure are not uncommon with cocaine use. Even young, otherwise healthy individuals with normal coronary and cerebral arteries have died suddenly after cocaine use from cerebral hemorrhage or ventricular fibrillation. There have been several deaths of famous athletes attributed to cocaine cardiotoxicity. These cardiotoxic effects may be related to increased intracellular calcium levels and involve both cardiac and vascular actions of the drug. 

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