complex and consists of nonenzymatic degradation to form benzoylecgonine and metabolism by plasma cholinesterases to form ecgonine methyl ester A small fraction of cocaine is also metabolized through the cytochrome P-450 enzymes to form norcocaine Individuals with congenital deficiencies in plasma cholinesterase are believed to have exaggerated responses to cocaine; cocaine abusers have been known to ingest inhibitors of cholinesterases or P-450 3A4 enzymes (e.g., organophosphate insecticides, cimetidine) to enhance the effect of the cocaine Cocaine metabolites are readily detected in urine for approximately days after exposure Cocaine is absorbed from all sites of application, including GI mucosa Body packing may lead to severe toxicity (seizures and cardiorespiratory collapse) if the container ruptures Probably because of its enhanced lipid solubility, crack crosses the blood–brain barrier rapidly, causing an intense rush of pleasure This habit is highly addictive Clinical Considerations Cocaine’s most dramatic clinical effect is CNS stimulation In humans, this manifests in a feeling of well-being and euphoria, often accompanied by gregariousness, restlessness, excitement, and a sense of clarity However, as the dose is increased, tremors, forced speech, agitation, and even tonic–clonic convulsions may result from excessive stimulation Initially, small doses (1 to 1.5 mg/kg) may slow the heart rate through central vagal stimulation After moderate doses, pulse increases, the result of both central and peripheral adrenergic effects Hypertension may appear abruptly and lead to cerebrovascular accidents Fortunately, hypertension is generally short lived Larger doses of cocaine may cause hypertension that may be followed quickly by cardiovascular collapse, often the result of myocardial ischemia and infarction Myocardial injury ranges from angina pectoris to massive infarction, even in adolescents With chronic cocaine use, a cardiomyopathy may result in depressed cardiac function and death Rhythm disturbances are the most common cause of death after severe cocaine exposure These may consist of ventricular or supraventricular tachyarrhythmias and may be intractable Use of crack has been associated with a number of pulmonary disturbances, including bronchospasm, hemoptysis, pneumothorax, and pneumomediastinum These lesions are believed to result from the barotrauma associated with inhalation of hot, particulate matter, followed by a Valsalva maneuver