Cocaine arrhythmia with

Increased oxygen demand secondary to increased heart rates and blood pressure has been hypothesized to lead to myocardial infarction (especially in patients with fixed coronary disease) and/or ventricular arrhythmias. In patients with no history of cardiac disease, cocaine is thought to induce acute isehemie complications via vasospasm of the coronaries (Ascher et al. 1988). In addition, Virmani et al. (1988) have reported a 20 percent incidence of myocarditis thought to be secondary to accumulated microvascular injuries. 

The answer is b. (Kn.lzu.ng, p 5.38.) Crack is the free-base (nonsalt) form of the alkaloid cocaine. It is called crack because, when heated, it makes a crackling sound. Heating crack enables a person to smoke it the drug is readily absorbed through the lungs and produces an intense euphoric effect in seconds Use has led to seizures and cardiac arrhythmias. Some of cocaine s effects (sympathomimetic) are due to blockade of norepinephrine reuptake into presynaptic terminals it does not block receptors. Flashbacks can occur with use of LSD and mescaline but have not been associated with the use of 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. 

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. 

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. 

Central nervous system toxicity is rarely observed with catecholamines or drugs such as phenylephrine. In moderate doses, amphetamines commonly cause restlessness, tremor, insomnia, and anxiety in high doses, a paranoid state may be induced. Cocaine may precipitate convulsions, cerebral hemorrhage, arrhythmias, or myocardial infarction. Therapy is discussed in Chapter 59 Management of the Poisoned Patient. 

The cardiovascular effects of local anesthetics result partly from direct effects upon the cardiac and smooth muscle membranes and partly from indirect effects upon the autonomic nerves. As described in Chapter 14 Agents Used in Cardiac Arrhythmias, local anesthetics block cardiac sodium channels and thus depress abnormal cardiac pacemaker activity, excitability, and conduction. At very high concentrations, they may also block calcium channels. With the notable exception of cocaine, local anesthetics also depress the strength of cardiac contraction and cause arteriolar dilation, both effects leading to severe hypotension. Cardiovascular collapse and death are rare and usually occur only after large doses of 0.75% bupivacaine. 

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. 

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. 

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.]... 

There have been another 11 cases showing a direct link between QT interval prolongation and oral methadone maintenance treatment at doses of 14-360 micrograms/ day (15) (16). QT interval prolongation can lead to arrhythmias such as torsade de pointes, especially when high doses of methadone are given intravenously and associated with concomitant use of cocaine and/or medications that inhibit the hepatic clearance of methadone (e.g. antidepressants and antihistamines). 

For events in which output of energy is explosive (100 m sprint) stimulants, e.g. amphetamine, bro-mantan, carphendon, cocaine, ephedrine and caffeine (> 12 mg/1 in urine). Death has probably occured in bicycle racing (continuous hard exercise with short periods of sprint) due to h3q>erthermia and cardiac arrhythmia in metabolically stimulated and vaso-constricted subjects exercising maximally under a hot sun. 

Cocaine is a central nervous system stimulant that inhibits the peripheral reuptake of catecholamines, leading to increased sympathomimetic activity [129]. 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 comphcations, intestinal ischemia and a variety of psychiatric complications [128-131]. A number of reports in the mid to late 1980 s described patients who developed rhabdomyolysis while using cocaine [132-134]. Some of these patients experienced acute kidney injury [135-139]. While the exact incidence of acute kidney injury secondary to cocaine rhabdomyolysis is unknown, in one reported series it occurred... 

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... 

Cocaine can have marked effects on the heart and cardiovascular system. Adverse actions may include myocardial ischemia, cardiac arrhythmias, cardiotoxicity, hypertensive effects, cerebrovascular events, and a hyperco-agulable state (24,40). By 1997 more than 250 cases of myocardial infarction related to the recreational use of cocaine had been documented in the literature (41). Although less common, aortic dissection related to use of cocaine-free base ("crackcocaine") has also been documented (42). Seizures also can be associated with cocaine use (43). 

Toxicity 1. Excess NE cardiac arrhythmias, generalized ischemia with possible MI and strokes acute renal and hepatic failures 2. Excess DA major psychosis, cocaine delirium 3. Excess 5HT possible serotonin syndrome 4. All of the above convulsion, hyperpyrexia, and death... 

Cardiac arrhythmias, myocardial infarction, and stroke occur more frequently in cocaine overdose than with other CNS stimulants. 

Overdoses with amphetamines or cocaine have many signs and symptoms in common. However, the ability of cocaine to block the reuptake of norepinephrine at sympathetic nerve terminals results in greater cardiotoxicity. Tachycardia is the rule, with the possibility of an arrhythmia. infarct, or stroke. The answer is (B). 

Stimulants (amphetamines, cocaine, phencyclidine) Agitation, anxiety, seizures. Hypertension, tachycardia, arrhythmias. Mydriasis, vertical and horizontal nystagmus with PCP. Skin wana and sweaty, hyperthermia, increased muscle tone, possible rhabdomyolysis Control seizures, hypertension, and hyperthermia... 

Cocaine has sympathomimetic actions (tachycardia, peripheral vasoconstriction, and hypertension). Combined use with sympathomimetics such as adrenaline increases these effeets, and the risk of life-threatening arrhythmias. This risk may be further inereased if halothane anaesthesia is used (two of the above patients reeeived halothane ). See also Anaesthetics, general + Anaesthetics, local , p.92 and Anaesthetics, general + Ino-tropes and Vasopressors , p.99. 

The use of adrenaline with topical cocaine is controversial. Some consider that the addition of adrenaline is of doubtful value and that the combination should not be used, especially in the form of a concentrated paste. However, others consider the combination to be safe and useful. Whether or not adrenaline is combined with cocaine, the BNF considers that topical cocaine should be used only by those skilled in the precautions needed to minimise absorption and the consequent risk of arrhythmias. Note also that the use of local anaesthetics containing adrenaline should be avoided in patients who abuse cocaine, unless it is certain that they have not used cocaine for at least 24 hours. ... 

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. 

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