Catecholamines cocaine abuse

Cocaine acts similarly to amphetamine with regard to its ability to enhance the effects of the catecholamines and serotonin at the synapse. The actions of cocaine on the brain lead to increased alertness, reduced hunger, increased physical and mental endurance, increased motor activity, and an intensification of most normal pleasures. This last feature may explain why so many claim that cocaine enhances emotional and sexual feelings. Cocaine abusers usually co-administer other drugs that are brain depressants (e.g., alcohol, heroin, or marijuana) to decrease the unpleasant hyperstimulant aspects of cocaine. 

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. 

Cocaine is a central nervous system stimulant that inhibits the peripheral re-uptake of catecholamines, leading to increased sympathomimetic activity [115]. Its abuse is associated with a variety of medical problems. These include acute myocardial infarction, cardiac arrhythmias, cerebrovascular accidents, hyperpyrexia and stimulated sympathetic activity, seizures and coma, obstetrical complications, intestinal ischemia, and a variety of psychiatric complications [114-117]. The most prominent renal complication of cocaine abuse is acute renal failure associated with rhabdomy-olysis. 

Reith M., Kramer H., Sershen H., Lajtha A. Cocaine completely inhibits catecholamine uptake into brain synaptic vesicles. Res. Commun. Subst. Abuse. 10 205, 1989. 

The sympathomimetic drugs are discussed in Chapter 10. In brief, the most commonly abused of these drugs, such as cocaine, work primarily as indirect agonists of the catecholamine neurotransmitter systems via inhibitory actions upon the transmitter reuptake system. Considerable evidence supports a role for dopamine in mediating the rewarding effects of cocaine. There is also evidence that blockade of serotonin uptake may contribute to cocaine s actions. 

Studies of sudden death in novice as well as experienced drug abusers found that cocaine causes vasoconstriction of the coronary arteries which seems to result from an enhancement of Ca2+ influx across myocardial membranes. However, remember that this class of drug affects other neurotransmitter systems. Cocaine inhbiits reuptake of NE and 5-HT as well as binds to the DA transporter. It increases catecholamine receptor sensitivity but does not seem to directly influence enkephalinergic receptors. In addition it also affects neurotransmission the H, Ach and phenylethylamine pathways. Activation of DA, NE or 5-HT neurons independently does not produce the euphoria associated with cocaine misuse. Euphoria seems to be related to simultaneous inteeraction between catecholamine and serotoninergic systems. 

The natural substance cocaine was already beeing employed for local anesthesia in ophthalmological surgery in 1884 (Vandam, 1987). However, the clinical use of cocaine is limited because of its abuse potential, its intense vasoconstriction and eventual arrhythmias due to its reuptake-inhibition of catecholamines, and instability upon sterilization. The chemical search for synthetic substitutes started in 1892 and gave rise to several compounds without abuse potential and with improved onset and duration of action, tolerability and stability of the preparation. 

Cocaine [50-36-2] - [ALKALOIDS] (Vol 1) - [ALKALOIDS] (Vol 1) -and catecholamines [EPINEPHRINE AND NOREPINEPHRINE] (Vol 9) -forensic testing for [FORENSIC CHEMISTRY] (Vol 11) -substance abuse of [PSYCHOPHARMACOLOGICAL AGENTS] (Vol 20)... 

Cocaine (alkaloid) is used medicinally solely as a surface anaesthetic (for abuse toxicity, see p. 192) usually as a 4% solution, because adverse effects are both common and dangerous when it is injected. Even as a surface anaesthetic sufficient absorption may take place to cause serious adverse effects and cases continue to be reported only specialists should use it and the dose must be checked and restricted. Cocaine prevents the uptake of catecholamines [adrenaline (epinephrine), noradrenaline (norepinephrine)] into S5nnpathetic nerve endings, thus increasing their concentration at receptor sites, so that cocaine has a built-in vasoconstrictor action, which is why it retains a (declining) place as a... 

Cocaine is a powerful psychomotor stimulant, commonly used as a drug of abuse. Its actions are very like those of the amphetamines. It works by blocking reuptake of catecholamines within the central (and peripheral) nervous systems and is an Indirect sympathomimetic. 

Cocaine (Figure 14-1) is an ester of benzoic acid and methylecgonine. The clinically desired actions of cocaine are the blockade of nerve impulses, as a consequence of its local anesthetic properties, and local vasoconstriction, secondary to inhibition of local norepinephrine reuptake. Toxicity and its potential for abuse have steadily decreased the clinical utility of cocaine. Its high toxicity is due to reduced catecholamine uptake in both the central and peripheral nervous systems. 

Its euphoric properties are due primarily to inhibition of catecholamine uptake, particularly dopamine, in the CNS. Other local anesthetics do not block the uptake of norepinephrine and do not produce the sensitization to catecholamines, vasoconstriction, or mydriasis characteristic of cocaine. Currently, cocaine is used primarily for topical anesthesia of the upper respiratory tract, where its combination of both vasoconstrictor and local anesthetic properties provide anesthesia and shrinking of the mucosa. Because of its abuse potential, cocaine is listed as a schedule II drug by the U.S. Drug Enforcement Agency. 

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