Vasoconstriction cocaine causing

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. 

Correct choice = D. Cocaine causes peripheral vasoconstriction. 

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. 

The ocular effects of cocaine include anesthesia (see Chapter 6), mydriasis, and vasoconstriction. The mydriatic effect of cocaine depends on the presence of a functioning adrenergic innervation. After topical appUcation to the eye, the pupil begins to dilate within 15 to 20 minutes. The maximum effect, which is typically less than 2 mm of dilation, occurs within 40 to 60 minutes, and the pupil may remain dilated for 6 or more hours. The mydriasis is accompanied by vasoconstriction that causes blanching of the conjunctiva. Cocaine is also readily absorbed through the mucous membranes into the systemic circulation. 

Local anesthetics block the sodium channels, are cardiac depressants, and bring about a ventricular conduction defect and block that may progress to cardiac and ventilatory arrest if toxic doses are given. In addition, these agents produce arteriolar dilation. Circulatory failure may be treated with vasopressors such as ephedrine, metaraminol (Aramine), or mephentermine (Wyamine). Artificial respiration and cardiac massage may also become necessary. Among the local anesthetics, only cocaine blocks the uptake of norepinephrine, causes vasoconstriction, and may precipitate cardiac arrhythmias. 

Cocaine, which blocks the uptake of catecholamines, produces dose-dependent effects, initially causing euphoria, vasoconstriction, and tachycardia, and in toxic doses, convulsions, myocardial depression, ventricular fibrillation, medullary depression, and death. Cocaine is able to block nerve conduction and currently is used only for topical anesthesia. 

Cocaine produces vasoconstriction (blanching) probably by sensitizing to sympathetic stimulation. This action is lacking in the other local anesthetics. Procaine has practically no vascular effect alypin, eucaine, and stovaine cause some dilatation. Cocaine decreases capillary hemorrhage procaine, apothesine, and other synthetic anesthetics tend rather to increase bleeding. 

The clinical symptoms of cocaine intake are the following vasoconstriction, dilated and reactive pupils, hyperthermia, arrhythmias, increased blood pressure, dry mouth, increased sweating, tremors, dizziness, muscle spasms, hyperactivity, and insomnia. Cocaine-related deaths are generally caused by cardiac arrest or seizures followed by respiratory arrest [11],... 

Therapeutic uses Cocaine has a local anesthetic action that represents the only current rationale for the therapeutic use of cocaine-, cocaine is applied topically as a local anesthetic during eye, ear, nose, and throat surgery. While the local anesthetic action of cocaine is due to a block of voltage-activated sodium channels, an interaction with potassium channels may contribute to cocaine s ability to cause cardiac arrhythmias. [Note Cocaine is the only local anesthetic that causes vasoconstriction. This effect is responsible for the necrosis and perforation of the nasal septum seen in association with chronic inhalation of cocaine powder.]... 

The authors speculated that cocaine may have caused aortic inflammation by assuming that cocaine-related increased sympathetic tone along with possible cocaine-related aortic inflammation (similar to reported cases of cocaine-related vascular injury) may have led to enhance aggregation of platelets at the inflamed area, which would act as a nidus to form a thrombus. The thrombus resolved with anticoagulation within 13 days and similar results have been reported before (81). The patient had very high creatine kinase activity, suggesting rhabdomyolysis, which could have been caused by intense cocaine-related vasoconstriction. 

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 authors thought that cocaine applied to the glans penis may have been well absorbed through the thinner keratinized squamous epithelium. They attributed the superficial necrosis to intense skin vasoconstriction caused by cocaine. 

Cocaine exhibits several pharmacologic effects. After local application it acts as an anesthetic by blocking the initiation and conduction of nerve impulses. In addition, it has been shown to block neuronal reuptake of norepinephrine, thus potentiating adrenergic activity. Moderate doses increase heart rate and cause vasoconstriction. The most striking systemic effect of cocaine is central nervous system stimulation. 

The authors speculated that cocaine and amfeta-mine-induced catecholamine stimulation of a-adrenocep-tors may cause intense vasoconstriction and thus a reduced blood supply to an ulcer, resulting in a giant ulcer. 

Cocaine can cause acute renal insufficiency (SEDA-21,19) (SEDA-24, 38). Acute renal insufficiency, with malignant hypertension, apparently precipitated by cocaine-induced vasoconstriction, has been described in a 33-year-old woman who had pre-existing scleroderma and normal renal function (154). She was successfully treated with hemodialysis. 

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 Blocks reuptake of NE into sympathetic nerve endings, causing vasoconstriction. CNS effects are via block of reuptake of NE, DA and 5HT. Cocaine also blocks voltage-dependent Na+ channels and is used as a local anesthetic. 

Coadministration of alpha adrenoceptor agonists (e.g., epinephrine) will decrease local anesthetic (LA) absorption into the systemic circulation, prolonging effects and possibly decreasing toxicity. Cocaine is distinctive because it causes vasoconstriction via its blockade of NE reuptake at sympathetic nerve endings. 

Cocaine intrinsically causes vasoconstriction by blocking norepinephrine uptake. 

Cocaine No Minutes to hours To cause vasoconstriction atHl local anesthesia... 

Propranolol reduces the clearance of bupivacaine and so theoretically the toxicity of bupivacaine may be increased. There has been a single report of enhanced bupivacaine cardiotoxicity in a patient also receiving metoproioi and digoxin. The coronary vasoconstriction caused by cocaine is increased by propranolol. Beta blockers may interact with adrenaline (epinephrine)-containing local anaesthetics. 

A study in 30 patients being evaluated for chest pain found that 2 mg/kg of a 10% intranasal solution of cocaine reduced coronary sinus flow hy about 14% and coronary artery diameter by 6 to 9%. The coronary vascular resistance increased by 22%. The addition of propranolol 400 micrograms/minute by intracoronary infusion, (to a total of 2 mg) reduced coronary sinus flow by a further 15% and increased the coronary vascular resistance by 17%. The probable reason is that the cocaine stimulates the alpha-receptors of the coronary blood vessels causing vasoconstriction. When the beta-receptors are blocked by propranolol, the resultant unopposed alpha-adrenergic stimulation may lead to enhanced coronary vasoconstriction (see also Beta blockers + Inotropes and Vasopressors , p.848). The clinical importance of these frndings is uncertain but the authors of the report suggest that beta blockers should be avoided in patients with myocardial ischaemia or infarction associated with the use of cocaine. ... 

---