Vasoconstriction cocaine abuse

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. 

Intranasal use, a common method of cocaine abuse, can damage the sinonasal tract, causing acute and chronic inflammation, necrosis, and osteocartilaginous erosion (SEDA-17, 36). These conditions occur secondary to the combined effects of direct trauma from instrumentation, vasoconstriction of small blood vessels with resultant ischemic necrosis, and chemical irritation from adulterants. Intranasal cocaine users can develop septal perforation, saddle-nose deformities, and sinonasal structural damage. 

The cause of cocaine-related stroke and transient ischemic attacks has been studied by transcranial Doppler sonography, a continuous measure of cerebral blood flow velocity, to monitor the course of cerebral hemodynamic changes during acute intravenous injection of placebo, and of cocaine 10, 25, and 50 mg in seven cocaine abusers (150). There was a significant increase in mean and systolic velocity (lasting about 2 minutes) with all doses of cocaine but not with placebo. Cocaine produced an immediate brief period of vasoconstriction... 

The form in which cocaine is administered is an important determinant of abuse liability (see Table 6.2). Street cocaine, which takes the form of a white powder, is produced by combining a paste made from coca leaves with a hydrochloric acid solution to form a salt—cocaine hydrochloride. Because it is a salt, street cocaine is water soluble and can be injected or taken intranasally (sniffed or snorted). Intranasal cocaine can produce intense effects, but because it causes constriction of blood vessels in the nose, absorption is slowed. By the way, it is this vasoconstriction that results in inflammation and tissue damage of the mucous membranes of the nose in chronic intranasal users. Overdo.se deaths, psychosis, and dependence are all possible consequences of intranasal cocaine but are less common than with injected cocaine. Because sniffing was the major method of administration on the street until the late 1980s, the hazards of cocaine abuse were underestimated. 

Adverse effects include increased risk of seizures, myocardial infarction, rhabdomyolysis, renal failure, and stroke. Other life-threatening adverse effects include hyperthermia, hypertension, vasoconstriction, tachycardia, cardiac ischemia, and paranoia. Prolonged cocaine abuse has been shown to cause cardiomyopathy. 

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. 

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 (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. 

Cocaine toxicity has both somatic and psychiatric manifestations. Somatic effects include myocardial depression, malignant dysrhythmias, stroke, and sudden death, partially due to cocaine-related myocardial sodium channel blockade and coronary and cerebral vasoconstriction. Such life-threatening conditions occur mainly when cocaine is combined with other abused drugs. Psychiatric effects can mimic the positive and negative symptoms of schizophrenia. 

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