Cocaine Toxicity PDF

Cocaine Toxicity 1  Cocaine is a naturally occurring alkaloid with unique local anesthetic and sympathomimetic activity, which served as the prototype for the synthesis of local anesthetics. Cocaine is contained in the leaves of Erythroxylum coca...

Cocaine Toxicity 1  Cocaine is a naturally occurring alkaloid with unique local anesthetic and sympathomimetic activity, which served as the prototype for the synthesis of local anesthetics. Cocaine is contained in the leaves of Erythroxylum coca 2  Cocaine (“crack” or “rock”)is usually abused by either chewing coca leaves, smoking coca paste, or “snorting” cocaine hydrochloride) most popular form of cocaine intake (. Occasionally, cocaine hydrochloride is injected intravenously. 3  Street cocaine is often impure. The content of pure cocaine ranges from 10 to 50 percent (most commonly 15 to 20 percent). Cocaine, which is available on the street, is often adulterated with one or more of the following compounds: talc, lactose, sucrose, glucose, mannitol, inositol, caffeine, procaine, phencyclidine, lignocaine, strychnine, amphetaimne, or heroin (“speed ball”). 4  Neurotransmitter Effects Cocaine blocks the reuptake of biogenic amines. Specifically, these effects on serotonin and the catecholamine( dopamine, norepinephrine, and epinephrine). The CNS stimulant effects of cocaine are mediated through inhibition of dopamine reuptake. The dopamine-reuptake transporter controls the levels of dopamine in the synapse by rapidly carrying the neurotransmitter back into nerve terminals after its release 5  Cocaine, which binds strongly to the dopamine-reuptake transporter, is a classic blocker of such reuptake after normal neuronal activity. Because of this blocking effect, dopamine remains at high concentrations in the synapse and continues to affect adjacent neurons producing the characteristic cocaine “high”. 6  Cocaine also increases the concentrations of the excitatory amino acids ( aspartate and glutamate). These excitatory amino acids increase the extracellular concentrations of dopamine. Excitatory amino acid antagonists attenuate the effects of cocaine induced convulsions and death. 7  Dopamine2 (D2) receptor agonists show cocaine craving, while dopamine1 (D1) agonists diminish such craving. Cocaine also inhibits reuptake of noradrenaline and serotonin. 8  Concerning Peripheral nerves, cocaine direct blockade of fast sodium channels, so it stabilize the axonal membrane, producing a local anesthetic effect. Cocaine is the only local anesthetic that interferes with the uptake of neurotransmitter by the nerve terminals and simultaneously functions as a vasoconstrictor. 9  Cardiovascular Effects Initial effect of cocaine on the CVS is bradycardia, secondary to stimulation of vagal nuclei. However, the bradycardia is too transient to be clinically evident, and tachycardia becomes the prominent effect resulting from central sympathetic stimulation. 10  The cardio-stimulatory effect of cocaine is due to 1. sensitization to adrenaline and noradrenaline. 2. preventing neuronal reuptake of these catecholamine 3. increased release of noradrenaline from adrenergic nerve terminals 11  The sympathomimetic effects of cocaine lead to 1. increase myocardial oxygen demand 2. Increase alpha-adrenergic mediated coronary vasoconstriction which limited coronary artery blood flow. 3. Cocaine inhibits endogenous fibrinolysis 4. increases thrombogenicity which lead to enhances platelet aggregation. 12  Clinical Features Acute Poisoning: A. Hyperthermia. This results from: 1. Augmentation of heat production due to increased psychomotor activity. 2. Diminish of heat dissipation due to vasoconstriction. 3. Direct pyrogenic effect due to action on thermoregulatory centers in the hypothalamus. 4. Stimulation of calorigenic activity of liver. 13  Body temperature often reach to 42.2 to 44.4°C, and does not respond to conventional antipyretics. It is often associated with rhabdomyolysis, seizures, and renal failure. 14  B- CNS effects Headache, Anxiety, agitation. Hyperactivity, restlessness, non-intentional Tremor, hyperreflexia and Convulsions (Generalized tonic-clonic, partial motor have been reported), and pseudo-hallucinations (eg, cocaine bugs). 15 C. Ophthalmologic effects: 1. Mydriasis and/or loss of eyebrow and eyelash hair from smoking crack cocaine may occur. 2. Corneal abrasions/ulcerations due to particulate matter in smoke (“crack eye”). 3. Central retinal artery occlusion and bilateral blindness due to diffuse vasospasm. Retinal foreign body granuloma may occur with IV abuse. 16  D-CVS effects: 1. Tachycardia. 2. Systemic arterial hypertension. 3. Coronary artery vasoconstriction with myocardial ischaemia and infarction. 4. Tachyarrhythmia. 5. Chronic dilated cardiomyopathy has been reported. 6. Aortic dissection and rupture. 7. Coronary artery dissection. 8. Sudden cardiac death can occur 17  E-Pulmonary Effects 1. Thermal injuries to the upper airway leading to epiglottitis, laryngeal injury, and mucosal necrosis. 2. Exacerbation of asthma. 3. Non-cardiogenic pulmonary edema. 4. Diffuse alveolar hemorrhage 18  F-Musculoskeletal effects Rhabdomyolysis with hyperthermia, massive elevation of creatine phosphokinase, and acute renal failure: the mechanism of cocaine-associated rhabdomyolysis is postulated that it may result from ischemia due to vasoconstriction, hyperpyrexia, and increased muscle activity from agitation or seizure activity. 19  Diagnostic Testing Cocaine and benzoylecgonine, its principle metabolite, can be detected in blood, urine, saliva, hair, and meconium. Routine drug-of-abuse testing relies on urine testing using a variety of immunologic techniques. 20  Although cocaine is rapidly eliminated within just a few hours of use, benzoylecgonine is easily detected in the urine for 2– 3 days following last use. When more sophisticated testing methodology is applied to chronic users, cocaine metabolites can be identified for several weeks following last use. 21  Urine testing limitations 1. Offers little information to clinicians for managing patients with presumed cocaine toxicity 2. it cannot distinguish recent from remote cocaine use. 3. false-negative testing can result when there is a large quantity of urine in the bladder with very recent cocaine use or when the urine is intentionally diluted by increased fluid intake leading to a urine cocaine concentration below the cut-off value and interpretation of the test as negative. 22  While false-positive tests do occur, they are more common with hair testing than urine or blood because of the increased risk of external contamination. 23  many body packers will have negative urine throughout their hospitalization, a positive urine test is suggestive of the hidden drug but obviously not confirmatory. More importantly, a conversion from a negative study on admission to a positive study not only confirms the substance ingested, but also suggests packet leakage, which could be indications of life-threatening toxicity 24  Routine diagnostic tests such as a bedside rapid reagent glucose, electrolytes, renal function tests, and markers of muscle and cardiac muscle injury are more likely to be useful than urine drug screening. An ECG may show signs of ischemia or infarction, or dysrhythmias that require specific therapy 25  Cardiac markers are therefore always-required adjuncts when considering myocardial ischemia or infarction. Because cocaine use is associated with diffuse muscle injury, assays for troponin are preferred over myoglobin or myocardial band enzymes of creatine phosphokinase (CPK-MB). 26  Management General Supportive Care As in the case of all poisoned patients, the initial emphasis must be on stabilization and control of the patient’s airway , breathing, and circulation 27  If tracheal intubation is required, it is important to recognize that cocaine toxicity may be a relative contraindication to the use of succinylcholine. Specifically, in the setting of rhabdomyolysis, hyperkalemia may be exacerbated by succinylcholine administration, and life-threatening dysrhythmias may result. 28  If hypotension is present, the initial approach should be infusion of intravenous 0.9% sodium chloride solution as many patients are volume depleted as a result of poor oral intake and excessive fluid losses from uncontrolled agitation, diaphoresis, and hyperthermia 29  elevated temperature represents the most critical vital sign abnormality. Determination of the core temperature is an essential element of the initial evaluation, even when patients are severely agitated. When hyperthermia is present, preferably rapid cooling with ice water immersion, or the combined use of mist and fanning, is required to achieve a rapid return to normal core body temperature 30  Pharmacotherapy including antipyretics, drugs that prevent shivering (chlorpromazine or meperidine), and dantrolene are not indicated as they are ineffective and have the potential for adverse drug interactions such as serotonin syndrome (meperidine) or seizures (chloropromazine). 31  central role of benzodiazepines. The goal is to use parenteral therapy with a drug that has a rapid onset and a rapid peak of action, making titration easy. Using this rationale, midazolam and diazepam are preferable to lorazepam, because significant delay to peak effect for lorazepam often results in over sedation when it is dosed rapidly or in prolonged agitation when the appropriate dosing interval is used 32  if using diazepam, the starting dose might be 5–10 mg, which can be repeated every 3–5 minutes and increased if necessary. Large doses of benzodiazepines may be necessary (on the order of 1 mg/kg of diazepam). 33  The use of phenothiazines or butyrophenones is contraindicated. Why?? 1. these drugs enhance toxicity (seizures) 2. Increase lethality 3. interference with heat dissipation 4. exacerbation of tachycardia 5. prolongation of the QT interval 6. induction of torsade de pointes and precipitation of dystonic reactions. 34  hypertension and tachycardia usually respond to sedation and volume recovery. In the uncommon event that hypertension and/or tachycardia persists, the use of a β- adrenergic antagonist or a mixed α- and β-adrenergic antagonist is contraindicated. 35  A direct-acting vasodilator like nitroglycerin, nitroprusside or possibly nicardipine or a α-adrenergic antagonist (such as phentolamine) may be considered. 36  Specific Management End-organ manifestations of vasospasm that do not resolve with sedation, cooling, and volume resuscitation should be treated with vasodilatory agents (such as phentolamine) Phentolamine can be dosed intravenously in increments of 1– 2.5 mg, and repeated as necessary until symptoms resolve or systemic hypotension develops. 37  Acute Coronary Syndrome In approach that is similar to the treatment of coronary artery disease (CAD) is indicated, although there are certain notable exceptions 38  American Heart Association guidelines and a number of reviews. 1. High-flow oxygen therapy 2. Aspirin is safe in patients with cocaine-associated 3. morphine is likely to be effective as it relieves cocaine-induced vasoconstriction. Morphine also offers the same theoretical benefits of preload reduction and reduction of catecholamine release in response to pain that is thought to be responsible for its usefulness in patients with CAD. 4. Nitroglycerin is clearly beneficial as it reduces cocaine-associated coronary constriction of both normal and diseased vessels and relieves chest pain and associated symptoms. 5. benzodiazepines are at least as effective or superior to nitroglycerin. 39  Over the last decade, the benefits of β-adrenergic antagonism have been demonstrated in patients with CAD. In contrast, β-adrenergic antagonism increases lethality in cocaine-toxic animals and in humans, exacerbates cocaine- induced coronary vasoconstriction, and produces severe paradoxical hypertension 40  If tachycardia does not respond to accepted therapies above, then diltiazem can be administered and titrated to effect 41  There are no data on the use of either unfractionated or low- molecular- weight heparins, glycoprotein IIb/IIIa inhibitors, or clopidogrel. The recent guidelines recommend the administration of unfractionated heparin or low-molecular-weight heparin in patients with cocaine- associated MI. 42  Cocaine abuse is well-known for its propensity to cause sudden death not only due to its deleterious effects on health (cerebrovascular accidents, myocardial infarction, malignant hyperthermia, renal failure), but also due to its capacity to provoke the user to commit acts of aggression and violence. 43  Body packer Syndrome Sudden death due to massive overdose can occur in either a body packer or a body stuffer, if one or more of the ingested packages burst within the gastrointestinal tract. 44  Treatment: 1. Emesis, lavage, charcoal, as applicable. 2. Cathartic/whole bowel irrigation to flush the packages out of the intestines. 3. Symptomatic patients should be considered a medical emergency, and be evaluated for surgical removal of the packets. 4. Asymptomatic patients should be monitored in an intensive care unit until the cocaine packs have been eliminated. This must be confirmed by follow-up plain radiography and barium swallows. 5. Bowel obstruction in asymptomatic patients may necessitate surgery. Endoscopic removal has been successful in some cases. 45