Toxicity, Cocaine ?>

Toxicity, Cocaine

Toxicity, Cocaine
Introduction


Background

Cocaine is derived from Erythroxylon coca, a shrub endemic to the Andes, Mexico, West Indies, and Indonesia. The people of the Andes held the shrub in religious reverence and buried their dead with bags of coca leaves. The stimulant effects of the coca leaves are believed to have played a major role in the advancement of the Inca civilization, providing the Incas with the energy and motivation to realize dramatic architectural and social achievements despite the barren, icy, cold, and oxygen-poor environment they inhabited. The Spanish conquistadors quickly became enamored of the euphoric effects of the plant and introduced the shrub to the Europeans, who developed a fondness for the taste and sensations it generated.

Spanish physicians described the first medicinal use of coca compounds as early as 1596, but the use of cocaine did not become more widespread until 1859, when Albert Niemann isolated the drug. Following the isolation of the drug, pharmacists began to concentrate large amounts of cocaine for use. Cocaine is not just a new Hollywood trend. In 1863, Marielli made cocaine-containing wine, which received widespread praise throughout Europe and was endorsed by the Pope. In the late 1800s, William Stewart Halsted, an American physician, self-experimented with cocaine and, in 1885, discovered nerve-block anesthesia. Halsted fell prey to cocaine addiction, which took 2 years to control. Similarly, Freud self-experimented with cocaine and became very addicted. He praised it as a cure for depression and used it extensively to facilitate psychotherapy.

In 1886, John Stith Pemberton, an Atlanta pharmacist, manufactured cocaine-containing syrup to be mixed with carbonated water and called it Coca-Cola (60mg/8 oz serving). Coca-Cola was sold as a tonic and contained cocaine until 1906, when the government passed the Pure Food and Drug Act, which required that medicines and elixirs list the ingredients on the label. Cocaine addiction became an increasingly important public health threat, and, in 1914, the Harrison Narcotics Act banned the nonprescription use of cocaine products and labeled cocaine as a narcotic because of its addictive properties. By 1920 it became the most feared illicit drug in the United States.

The passage of the Harrison Narcotics Act drove recreational cocaine use underground. In the late 1960s, cocaine use was preempted by amphetamine use. In the 1970s, cocaine use became increasingly popular. In the 1980s, crack (an impure freebase form), a much cheaper and easier-to-use form of cocaine, became the stimulant of choice for people younger than 18 years and for poor people.

Currently, the medicinal use of cocaine is limited to topical anesthesia of the upper respiratory tract and eye because the vasoconstrictive properties of cocaine are desirable during these procedures.

Cocaine (benzoylmethylecgonine) is an ester that belongs to the tropane family of natural alkaloids, which also includes scopolamine and atropine. Cocaine is an extremely powerful reinforcing psychostimulant with highly addictive properties that produces many pharmacological effects in humans and results in a spectrum of clinical presentations.

Pathophysiology

Cocaine is a local anesthetic, and, like other local anesthetics, it blocks the generation and conduction of electrical impulses in excitable tissues such as neurons and cardiac muscle. The primary site of action of cocaine is the cell membrane, where it blocks the voltage-gated fast sodium channels, thereby reducing the permeability of the membrane to sodium. As the effects of cocaine gradually increase, the threshold for excitation also increases, the rise rate of the action potential declines, impulse conduction slows, and the probability of propagation of the action potential decreases. Ultimately, the ability of the tissue to generate an action potential is abolished. In nerve cells, these effects are manifested by anesthesia. In myocardial conduction tissue, these effects are manifested by type I antidysrhythmic-like activity.

Cocaine may also interfere with other membrane channels, particularly the potassium channels, thus decreasing the resting membrane potential.

Cocaine differs from other local anesthetics in that it also binds to monoamine transporters and blocks the reuptake of catecholamines and dopamine into the presynaptic nerve terminals. This results in a high degree of adrenergic and dopamine activity with a widespread toxicity. Alpha-adrenergic stimulation, which is largely due to norepinephrine, induces hypertension, whereas beta-receptor stimulation, which is largely due to epinephrine, commonly results in tachycardia (beta-1 effect) and hypotension (beta-2 vasodilation). Other factors, such as the generation of CNS-excitatory amino acids (glutamate and aspartate), may play a role in CNS hyperactivity and cardiovascular pathology.

In the central ventral nuclei of the limbic system and the basal forebrain, the effect of cocaine on dopamine and serotonin reuptake generates the sensation of pleasure and presumably reinforces the use and addiction of cocaine.

Repeated drug abuse produces enduring changes in brain circuits that subserve incentive motivation and stimulus-response learning, this is suggested by the relapsing to addiction in 80-90% of regular cocaine abusers even after prolonged periods of abstinence.

Cocaine is rapidly and well absorbed from all mucous membranes, including oropharyngeal, nasopharyngeal, pulmonary, gastrointestinal, and genitourinary mucosae. The onset of action, peak effects, duration of action, and the plasma half-life of cocaine depend on the dose and the route of administration. When used intravenously, the onset of action of cocaine is immediate and the peak effect occurs 3-5 minutes after the bolus. The effect lasts for 20-30 minutes after injection, and the half-life is 40-60 minutes. Smoking crack has a similar time of onset and peak effect as an intravenous injection.

With insufflation, the onset of action occurs 1-3 minutes after use and peaks 20-30 minutes later. The effect lasts 45-90 minutes, and the half-life is 60-90 minutes. Inhalation of cocaine results in immediate effects that peak 1-5 minutes after inhalation and last for 20 minutes after inhalation. The half-life is 40-60 minutes. Oral use of cocaine results in an onset of effects 10 minutes after use. The effects peak 60 minutes after use and last for 60-90 minutes.

Cocaine is metabolized mainly by the liver via a number of pathways and by plasma cholinesterases. More than 10 metabolites have been discovered; many retain some of the activity of the parent compound, such as vasoconstriction, proconvulsant activity, and sodium channel blockade, thereby increasing the toxicity of cocaine. The presence of alcohol results in an additional metabolite called cocaethylene, which is more toxic than either of the parent compounds and has been associated with an increased mortality in patients intoxicated with cocaine.

The best-described cocaine metabolites include norcocaine, benzoylecgonine (BE), ecgonine, and ecgonine methylester (EME). EME is the least toxic of the cocaine metabolites because it does not have vasoconstrictive properties and does not block the sodium channels. EME is generated by deesterification of cocaine by the liver and plasma pseudocholinesterases and accounts for 30-50% of cocaine metabolism. Nonenzymatic hydrolysis, which generates benzoylecgonine, accounts for 40% of cocaine metabolism. Demethylation, which generates norcocaine, accounts for the remainder of the metabolism of cocaine. Norcocaine is the most toxic of the metabolites because it has many of the same effects as cocaine and, perhaps, a stronger vasoconstrictive effect than the parent compound.

The activity of plasma cholinesterases determines the relative concentration of cocaine metabolites. Reduced plasma-cholinesterase activity shifts the metabolism of cocaine toward the pathways that produce toxic metabolites. Factors or drugs that decrease the activity of pseudocholinesterases include extremes of age, the presence of atypical cholinesterase, organophosphates (found in insecticides, anti–myasthenia gravis agents, and some eye drops), and carbamates (found in insecticides).

Patients who have these drugs in their systems or who have these characteristics have an increase in the incidence of ischemic chest pain, convulsions, and cardiac arrest. Extremes of plasma cholinesterase levels manipulation have been reported in some individuals by injecting insecticides in order to prolong their high. Similarly, factors that increase hepatic N- demethylation, such as pregnancy and progesterone ingestion, increase cocaine toxicity because more toxic metabolites are formed.

Street cocaine may be accidentally contaminated during the preparation process or may be intentionally adulterated by a number of compounds in order to dilute the amount of cocaine used and to increase profits. Commonly used cocaine adulterants include any of the local anesthetics, phenytoin, sugars, amphetamines, phencyclidine, quinine, talc, and others.

The concomitant use of other drugs poses additional risks for the person using cocaine. As noted above, the combination of cocaine with alcohol (some studies report up to 70% of cocaine consumers) produces cocaethylene (ethylbenzoylecgonine), which has more potent proconvulsant and cardiotoxic properties than cocaine itself, coupled with a longer half-life. Heroin is also commonly used with cocaine as a “speedball” in an effort to combine a cocaine high (initial phase) with a heroin high (latter phase) of intoxication. Furthermore, nicotine dependence is reported in up to 88% of patients who use cocaine, thus adding to cocaine cardiovascular risk factors.

Physiologic and psychologic tolerance to cocaine emerges between the first and second dose. In other words, the psychologic high and the physiologic body response (eg, pulse, blood pressure) do not increase with additional doses of cocaine once the initial effect is reached.

Cardiovascular effects

Cocaine causes vasoconstriction by preventing the reuptake of catecholamines in the central nervous system and stimulating the release of norepinephrine from adrenergic nerve terminals. These effects result in increased myocardial oxygen demand and coronary artery spasm. This causes roughly a 10% decrease in the caliber of large epicardial vessels and may progress to myocardial infarction, especially in territories of diminished coronary reserve and narrowed arteries. This effect is of increased importance in the chronic user because the repeated use of cocaine results in accelerated coronary atherosclerosis and increased platelet aggregation. With chronic use, dopamine stores in peripheral nerve terminals are depleted. When this store depletion is coupled with cardiovascular sensitivity to catecholamines, a variant anginalike syndrome with ST elevations may develop during cocaine withdrawal.

The chronic use of cocaine is also associated with multiple foci of myocarditis, fibrosis, contraction band necrosis, sarcoplasmic vacuolization, myofibrillar loss, hypertrophy with inefficient oxygen use, and alterations in the genetic material of the myocytes.

Dysrhythmias are the most common cause of death in patients who are acutely intoxicated. The type of arrhythmia that develops depends on numerous factors, but overall cocaine reduces the ventricular fibrillation threshold. Bradycardia may be secondary to stimulation of vagal nuclei of the brain, myocardial infarction, and acidosis. Tachycardia may be secondary to the ability of cocaine to stimulate central and peripheral sympathetic systems, hypoxia, acidosis, and other factors. The quinidine-like effects of cocaine result in a number of intraventricular conduction abnormalities, including widening of the electrocardiographic wave (QRS) and QTc, as well as negative inotropic and chronotropic effects.

A Brugada pattern (right bundle branch block with ST elevation in leads V1, V2, V3) has been reported as associated with cocaine use and appears to occur due to modulation or unmasking of the sodium channels.

Aortic dissection is a known complication of cocaine use and is presumably due to the increases in shear forces on the vascular wall produced by the drug.

Acidemia, which is a common complication of acute toxicity, may also cause conduction delays and depress myocardial contractility.

Neurological effects

Cocaine blocks the reuptake of catecholamines in the brain and stimulates areas that are catecholamine dependent. In the cortex, this blocking leads to increased vigilance, and, with higher doses, cocaine use results in anxiety, psychoses, and excited delirium. Catecholamine release in the CNS also increases motor activity, which may be manifested by abnormal involuntary movements and convulsions, resulting in acidosis, rhabdomyolysis, and hyperthermia.

Similar to alcohol abuse, once seizures develop, a kindling effect occurs and patients develop more severe seizures at smaller doses of cocaine. The vasoconstrictive properties of cocaine may also result in widespread cerebral vasoconstriction and cause ischemia and necrosis of brain tissue. Chronic cocaine use decreases dopamine receptor density in the brain.

In the hypothalamus, this results in abnormalities in temperature control, and, in the nigrostriatal system, it results in a number of extrapyramidal reactions such as bradykinesis, akinesis, akathisia, pseudoparkinsonism, and catalepsy. Furthermore, the effects of cocaine on the dopaminergic system may play a role in the development of asymptomatic rhabdomyolysis observed with chronic cocaine use.

Rhabdomyolysis

Rhabdomyolysis may be the result of insufficient energy supply in the setting of the increased demands of psychomotor agitation. Other factors that contribute to the development of rhabdomyolysis include compartment syndrome, hypocalcemia, hypokalemia, hypomagnesemia, hypophosphatemia, and uncontrolled seizures. No correlation exists between muscular symptoms and the development of rhabdomyolysis. No correlation exists between the amount of damaged muscular mass and the extent of renal impairment.
Frequency
United States

In 1997, an estimated 682,000 people (0.3% of the population) frequently used cocaine (more than 51 days of the year); this statistic is similar to that found in 1985.

The estimated number of people occasionally using cocaine (people who used in the past year for fewer than 12 days) was 2.6 million in 1997, which is a large decrease from 1985, when it was 7.1 million.

The estimated number of people using crack was about 604,000 in 1997; this estimate has not changed since 1988.

In 2003 alone, 34.9 million Americans older than 12 years of age reported using cocaine at least once. As of 2005, according to the Office of National Drug Control Policy, more than 3 million people in the United States are considered long-term cocaine users.

Currently, cocaine is reported as the most commonly abused drug in patients presenting to the emergency departments.

International

Cocaine abuse is widespread in the world and is becoming a major public health issue in a number of Canadian and European cities. Data suggest that the prevalence of cocaine use in the world is approximately 13 million people, or 0.23% of the global population. Cocaine use is also increasing in a number of Latin American countries, including the countries that are the main producers of cocaine.
Mortality/Morbidity

According to data from the Drug Abuse Warning Network (DAWN), in 2000, the DAWN survey of medical examiners reported 4043 cocaine-related deaths. Cocaine intoxication is implicated in most fatal injuries in New York City, where it is the leading cause of death among young adults.

Cocaine-related deaths are not dose related, and isolated blood levels do not predict toxicity. Fatalities are multifactorial, and, often times, the cause is difficult to determine. Death from acute cocaine toxicity is a rare event, unless a massive exposure is present (body packers and body stuffers). Otherwise, the cocaine users who are prone to serious illnesses and complications are the chronic users. A list of cocaine-related complications include status epilepticus, ventricular dysrhythmia, myocardial infarction, malignant hyperthermia, aortic dissection, eosinophilic lung disease or “crack lung”, pulmonary edema, alveolar hemorrhage, stroke, central retinal artery occlusion, hepatic necrosis, intestinal ischemia, renal infarction, and rhabdomyolysis.
High mortality rate seems to be associated with rhabdomyolysis, acute renal failure, liver dysfunction, and disseminated intravascular coagulation. An accelerated death has been noted in some patients who develop convulsions within 3-30 minutes of cocaine use. This syndrome is characteristically described in 3 phases. Phase I is characterized by pseudohallucinations (“crawling bugs”), agitation, hyperthermia, and emotional lability. Phase II is characterized by severe hyperthermia, encephalopathy, and seizures associated with ventricular dysrhythmias. Phase III is characterized by coma, fixed dilated pupils, pulmonary edema, and agonal respiration, culminating in death.
The lethal dose of cocaine is undetermined; clinical toxicity seems to be unrelated to measured plasma concentration levels. A concentration that was once considered close to fatal has been found in barely symptomatic patients. Conversely, fatalities have been documented with cocaine levels below threshold to induce measurable alteration in pulse or blood pressure.
Race

Rates of illicit cocaine use vary by ethnicity and race. While most current recreational cocaine users are white and non-Hispanic, the rates of cocaine use were 1.4% for blacks, 0.8% for Hispanic whites, and 0.6% for non-Hispanic whites. Crack is more commonly used by people who are underprivileged.

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Sex

Rates of illicit drug use vary by gender. As is the case with other drugs, cocaine use among men is almost twice that of women. In terms of emergency department visits, men accounted for 61% and women accounted for 30% of cocaine-related emergency department visits
Age

The rate of current cocaine use is generally highest among people aged 18-25 years, followed by people aged 12-17 years, and people aged 26-34 years (0.9%). The rates of cocaine use in adults older than 35 years dropped to 0.5%. In terms of emergency department visits, the highest peak was found in patients older than 35 years (43% of cases). Forty-one percent of cases involved patients aged 26-34 years, followed by 15% and 1.4% for patients aged 18-25 years and 6-17 years, respectively.
Clinical
History

In general, the clinical presentation of cocaine intoxication is that of a sympathomimetic toxidrome. Virtually any organ system may be affected, and patients may present with a myriad of conditions and symptoms. The lethal effects of cocaine relate to its stimulation of the CNS and the cardiovascular systems. Stimulation of the CNS results in symptoms such as excited delirium, combativeness, hyperactivity, paranoia, violence, involuntary movements, convulsions, severe hyperthermia, intracerebral hemorrhage, and ischemic stroke. Stimulation of the cardiovascular system results in dysrhythmias, myocardial ischemia and infarction, congestive heart failure, hypertensive crisis, and aortic dissection. Other conditions associated with cocaine toxicity include rhabdomyolysis, retinal artery occlusion, renal failure, and infarction of any organ system of the body.

Because of the widespread effects of cocaine, the review of history and systems should be detailed and extensive.
In the alert patient with symptoms, obtain a history of present illness, including the type, amount, and route of administration of cocaine; the time of cocaine use; and the circumstances surrounding and following the ingestion of cocaine. Always be aware of the possibility of toxicity or side effects related to cocaine contaminants added for bulk or profit.
Obtain the patient’s prior medical history, including the presence or absence of comorbid conditions, such as coronary artery disease, congestive heart failure, seizure disorder, and liver disease.
Obtain history of prior drug use.
Also obtain history regarding co-ingestions and medications used because they may alter the pharmacokinetics, symptomatology, and outcome of patients with cocaine intoxication.
In a patient with an altered mental status, search for corroborating evidence, eg, empty crack vials and drug paraphernalia.
Emergency Medical Services (EMS) personnel, police, and bystanders may assist in identifying signs and symptoms that immediately precede the present illness and may assist in the diagnosis.
Question the patient’s family regarding the patient’s immediate history of present illness such as the timing of drug use, co-ingestions, and any history of recent trauma. Also question the family regarding the presence of chronic medical conditions; use of other medications, including prescription and nonprescription medications (eg, aspirin); use of alcohol; use of other drugs; and allergies.
Body packers and body stuffers may be asymptomatic when brought in by police.
The body packers, also called mules, pack their gastrointestinal tract with bags of cocaine (or other illicit drugs) in order to smuggle the drug from one country to another.
In contrast, body stuffers hastily insert packages into the mouth, rectum, or vagina in order to conceal the evidence from police at the time of their arrest.
Central nervous system and neuromuscular system
Headache: Cocaine use commonly results in headaches. Cocaine may trigger migraine headaches, but, most importantly, the headache may be secondary to complications of cocaine use such as stroke, subarachnoid hemorrhage, meningitis, brain abscess, and vasculitis. In the presence of trauma, headache may be secondary to a skull fracture and/or epidural or subdural hematoma. Withdrawal from cocaine may also result in headaches that are commonly relieved by the additional administration of cocaine.
Seizures: Cocaine-related seizures are usually due to a hyperadrenergic state and usually occur within 90 minutes of drug use but have been delayed for as long as 12 hours. They usually are single, generalized, tonic-clonic seizures that are self-limited and usually follow the intravenous injection of cocaine or the smoking of crack. These patients recover without neurologic deficits and have negative cranial computed tomography (CT) scan and electroencephalogram. The presence of multiple seizures or status epilepticus may be observed in patients with a history of seizure disorder and patients who concomitantly use other drugs, eg, adulterants such as lidocaine, amphetamines, and quinine. Seizures may also be a manifestation of an underlying central nervous system injury such as a stroke, intracerebral and subarachnoid hemorrhages, and vasculitis.
Abnormal movements: A variety of abnormal movement disorders have been observed with cocaine use. Patients may present with torticollis, trismus, dystonic reactions, and choreiform movements (“crack dancing”). While most of these are benign, abnormal contractions of the vocal cords and larynx result in laryngospasm, which may be severe enough to cause airway obstruction and suffocation.
Nausea and vomiting: Nausea and vomiting are commonly due to stimulation of the vomiting center of the brain and are usually self-limited.
Anxiety: Anxiety and restlessness are common manifestations of cocaine toxicity and are due to the sympathomimetic effect of cocaine on the brain.
Cardiac
Chest pain: Chest pain is the most frequent cocaine-related symptom and constitutes approximately 40% of cocaine-related emergency department visits. The etiology of the chest pain following cocaine use remains largely obscure and poorly understood in most patients, but a number of causes may be evident, including myocardial infarction and aortic dissection; other causes of chest pain can be related to the route of administration, including pneumomediastinum and pneumothorax when sniffed, or septic emboli if the intravenous route is used.1
The incidence of cocaine-associated myocardial infarction has been found to range from 0-31% in retrospective studies of patients who present to the emergency department with chest pain following cocaine use. The Cocaine Associated Chest Pain (COCHPA) trial has been the largest prospective multicenter study. That study determined the incidence to be 6%. The pain is frequently described as substernal pressurelike discomfort and is associated with shortness of breath and diaphoresis. Patients who are affected are usually young males (aged 19-40 y) who smoke cigarettes and repetitively use cocaine. Most commonly, the chest pain occurs within 60-120 minutes after use when blood concentration of cocaine is highest, but the period of cocaine metabolites-ischemia may persist for as long as 2 weeks following use. Atypical presentations of myocardial infarction are also very common in the cocaine-using population.
Respiratory: Shortness of breath, like chest pain, is a frequent symptom that brings patients who use cocaine to the emergency department and may be due to a number of cardiopulmonary processes. Cocaine smoking is associated with acute exacerbations of asthma, bronchiolitis obliterans, cardiogenic and noncardiogenic pulmonary edema, interstitial pneumonitis, pulmonary vascular hypertension, pulmonary hemorrhage, thermal injury to the airway, pneumothorax, and significant impairment of the diffusing capacity of the lung. Shortness of breath may also be due to cocaine-induced laryngospasm. Inhalation of cocaine may result in pneumomediastinum and pneumothorax.
Gastrointestinal: Abdominal pain following cocaine use should raise suspicion of ischemic bowel; bowel perforation; and, in the smuggler, bowel obstruction. Abdominal pain may also be caused by hepatic necrosis due to cocaine use, which is similar to the necrosis commonly observed with acetaminophen. Renal infarction may also manifest as abdominal pain.
Skeletal muscle: Cocaine use can lead to rhabdomyolysis, which may be associated with hyperthermia, seizures, or agitation. Rhabdomyolysis associated with cocaine use is usually severe, leading to renal failure and acidosis. Asymptomatic rhabdomyolysis may be observed in patients who chronically use cocaine and may be attributed to the effects of cocaine on the dopaminergic system.
Back pain may be a symptom of rhabdomyolysis, renal infarction, or aortic dissection.
Physical
Vital signs
Pulse: Cocaine affects the pulse rate and the heart rhythm in numerous ways. The initial effect of cocaine on the pulse is a reduction of the rate, presumably because of stimulation of the vagal centers in the medulla. Subsequently, when epinephrine is released from the adrenal gland, tachycardia ensues. This may be offset by the reflex of the carotid body to hypertension, which results in bradycardia. Pulse rates may be altered by any complication of cocaine use, concomitant disease, or co-ingestants. Cocaine use may result in any arrhythmia, benign or malignant, including life-threatening supraventricular and ventricular tachycardias, atrial and ventricular fibrillation, disorders of atrioventricular (AV) nodal conduction, disorders of the His bundle conduction, and abnormalities in the fascicles and myocytes.
Respirations: The initial effect of cocaine on the medulla results in an increase in the respiratory rate. Dyspnea, labored breathing, or irregular breathing may herald demise or may be a sign of developing complications. Massive overdoses may result in shutdown of the medulla and respiratory failure. Respirations may be altered by any complication of cocaine use, concomitant disease, or co-ingestants.
Blood pressure: Hypertension is commonly observed in patients with cocaine intoxication and is due to the persistence of adrenergic activity, namely that of norepinephrine at the neurovascular receptor terminals. The blood pressure may be altered by any complication of cocaine use, concomitant disease, or co-ingestants.
Temperature: Cocaine causes hyperthermia by increasing motor activity, thereby increasing heat production and reducing heat dissipation by constricting vessels.
Central nervous system
Agitation, delirium, coma, convulsions, and focal neurologic findings may all be a sign of neurologic catastrophe. Agitated delirium characterized by severe hyperthermia and associated with incoherence, hyperactivity, agitation, paranoia, and combativeness is a preterminal event commonly followed by cardiac arrest.
Involuntary movements, such as nonintentional tremors, chorea, and dystonic reactions, as well as stereotyped movements, such as scratching, picking, and bruxism, are commonly observed with cocaine use and are referred to as “crack dancing”. Tourette syndrome has also been described with cocaine use.
Head, ears, eyes, nose, and throat
Head: The general examination of the head may reveal evidence of trauma.
Eyes: Examination of pupils reveals dilation, reactivity to light, and nystagmus. Unequal pupils may be secondary to uncal herniation. Funduscopic examination may reveal hemorrhages associated with subarachnoid hemorrhage and disc edema associated with brain edema.
Nose: Cerebrospinal fluid rhinorrhea due to cribriform plate damage secondary to chronic ischemia and necrosis of the nasal septum with chronic intranasal use of cocaine; nasal septum perforation; sinusitis; and epistaxis may be present.
Neck: Examination of the neck may reveal subcutaneous emphysema associated with pneumomediastinum. Barotrauma may result from smoking and snorting when performing a Valsalva maneuver to increase the penetration of the drug to the alveolar spaces. Deviation of the trachea may be secondary to a tension pneumothorax
Lungs: Unequal breath sounds may be secondary to pneumothorax. Bilateral wheezing secondary to asthma, eosinophilic lung disease, and thermal lung injury may be present. Bilateral rales may indicate the presence of pulmonary edema, eosinophilic lung disease, and angiitis obliterans. Unilateral wheezing or rales may be secondary to pulmonary infarction.
Cardiac: Tachycardia, bradycardia, flow murmurs, and the pathologic murmurs may all be encountered with cocaine toxicity due to valvular disease. Typical signs of congestive heart disease can also be the result of cocaine-related cardiomyopathy.
Abdomen: Absent bowel sounds may be noted in cases of mesenteric ischemia, and right upper quadrant tenderness may occur in cases of hepatic necrosis.
Vascular: Differences in pulses between upper and lower extremities and right and left extremities may be noted with vascular dissections. Bruits may be notes in areas of dissection and partial obstructions. Absent pulses may be noted in totally occluded vessels.
Dermatologic: The skin may be pale and diaphoretic due to vasoconstriction. Linear excoriations and ulcers are due to intensive scratching associated with imaginary cocaine bugs. Signs of skin and soft-tissue necrosis may be evident in massive overdoses.
Causes
Cocaine is an addictive psychostimulant with euphoric effects that may be used occasionally by the casual user and frequently by people who are dependent on cocaine. The addictive properties of cocaine are thought to be due to brain dopamine D2-receptor stimulation. Patient dependence depends on a number of different factors, including the following: genetics, social and environmental factors, and preexisting medical and mental conditions.
New research in mice suggests that the extent of some organ damage may be influenced by gender and sex hormones, particularly testosterone.
Poisoning may occur with a single dose of recreational use or after an overdose.
Poisoning may also occur in body stuffers and body packers when one of the ingested packets ruptures or leaks.

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