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cocaine
Cocaine is well absorbed following contact with the oral, nasal,
gastrointestinal, rectal, and vaginal mucosa; by the pulmonary alveoli
following inhalation; and by intravenous injection. Oral administration
reaches peak concentrations in approximately 60 minutes. Effects from
nasal insufflation begin almost immediately, and peak concentrations
occur within 30–60 minutes. Intravenous and inhalational use of cocaine
produces very rapid distribution of cocaine to both the central nervous
system and the systemic circulation.
Cocaine is rapidly hydrolyzed to its major metabolite, ecgonine methyl
ester (EME). EME, formed by hydrolysis by liver and plasma esterases,
accounts for 30–50 per cent of the parent product. Nonenzymatic
hydrolysis results in the formation of the other major metabolite,
benzoylecgonine, which accounts for approximately 40 per cent of the
parent product. Other minor metabolites (norcocaine, ecgonine, and
cocethylene) constitute the remainder of cocaine’s degradation products.
The activity of plasma cholinesterase determines the relative
concentrations of the various metabolites and quite possibly affects the
degree of toxicity that develops.
The biologic half-life of cocaine is 0.5–1.5 hours. A relatively minor
amount is excreted unchanged in the urine. Benzoylecgonine and EME
are also excreted in the urine , because of a long elimination half-life,
assays typically detect benzoylecgonine for as long as 48–72 hours
following cocaine use.
Pathophysiology
The effects of cocaine are related to its sympathetic nervous system
effects, central nervous system stimulation, and local anesthetic effects.
The initial effect of cocaine on the cardiovascular system is vagotonic,
producing a transient bradycardia; however, the increased sympathetic
stimulation rapidly produces tachycardia and hypertension. In the
peripheral nervous system, cocaine inhibits the reuptake of both
epinephrine and norepinephrine and stimulates the presynaptic release of
norepinephrine. The resulting increased concentration of norepinephrine
at the postsynaptic α and β receptors accounts for the stimulatory effects
of cocaine. In the central nervous system, the mechanism of increased
stimulation has not been as well defined. Enhanced release of
norepinephrine and excitatory amino acids and/or blockade of neuronal
reuptake of dopamine, serotonin, and excitatory amino acids might
account for the observed effects.
The vascular effects of cocaine include arterial vasoconstriction, in situ
thrombus formation, platelet aggregation, and accelerated atherosclerosis
are the principal factors responsible for cocaine-induced ischemia in
many vascular beds. These effects have been best described in the heart.
Cocaine-induced hypertension, tachycardia, and left ventricular
hypertrophy increase myocardial oxygen demand at the same time that
blood flow is diminished by coronary artery vasoconstriction, enhanced
platelet aggregation, in situ thrombus formation, and premature
atherosclerosis. This combination makes cocaine a potent precipitant of
myocardial ischemia. Coronary vasoconstriction is further exacerbated by
β-adrenergic blockade. Most cocaine-using patients are also cigarette
smokers and the combination of cocaine and nicotine has a synergistic
effect on coronary vasoconstriction.
Clinical presentation
Cardiovascular Effects
Acutely, cocaine causes arterial vasoconstriction and enhanced thrombus
formation. Chronic cocaine use can result in accelerated atherosclerosis,
and left ventricular hypertrophy. These effects provoke myocardial
ischemia or infarction. Aortic dissection and rupture occur less commonly
after use of cocaine. Supraventricular and ventricular dysrhythmias may
occur. The negative inotropic effects of cocaine may cause acute
depression of left ventricular function and congestive heart failure.
Chronic cocaine use can result in dilated cardiomyopathy.
Neurologic Effects
Most cocaine-intoxicated patients are anxious or agitated. Bland cerebral
infarcts, hemorrhagic infarcts, and subarachnoid hemorrhages occur.
Seizures may occur secondary to infarction or hemorrhage or in their
absence. Patients who remain extremely lethargic and are difficult to
arouse for up to 24 hours after cocaine use may have the “cocaine
washed-out syndrome.”[ Patients with the cocaine washed-out syndrome
assume normal sleep postures and can occasionally be aroused to full
orientation, in contrast to lethargic patients with subarachnoid
hemorrhage or other intracranial catastrophes.
Vascular Ischemia
In addition to cardiovascular and cerebrovascular ischemia, ischemia of
the mesenteric, renal, pulmonary, and ophthalmic arteries can occur.
Rhabdomyolysis
Skeletal muscle injury may result in rhabdomyolysis. Most patients
present without signs and symptoms of muscle injury, and the diagnosis
of rhabdomyolysis is made by demonstration of myoglobinuria and/or
measurement of serum creatine kinase. Patients with severe
rhabdomyolysis may have lactic acidosis and life-threatening
hyperkalemia.
Body Packers
Patients with continued toxicity despite treatment may be body packers.
Most body packers will be asymptomatic unless leakage occurs. Recent
travel or transportation of the patient from an airport should raise
suspicion of body packing. Symptomatic patients should be considered a
major medical emergency and must be evaluated for surgical removal of
the packets.
Obstetric and Neonatal Effects
Obstetric complications secondary to cocaine use include premature labor
as a result of increased uterine contractility as well as abruption placenta.
Symptoms of neonatal cocaine withdrawal usually begin within 24–48
hours of birth. Withdrawal results in infants with jitteriness, irritability,
poor eye contact, and vigorous sucking. In utero cocaine exposure may
also result in infants with a small head circumference and low birth
weight. Rapid diagnosis and treatment of neonatal withdrawal are
imperative because of the risk of seizures and cardiovascular collapse.
The physician should be thorough and exclude alternative diagnoses such
as sepsis, hypoglycemia, and electrolyte abnormalities. The use of drug
screens is unreliable for assessing neonatal withdrawal because the drug
may have been metabolized and excreted prior to birth. Benzodiazepines
and phenobarbital are effective agents for the treatment of stimulant
withdrawal.
Treatment
 If the patient is agitated, sedation with benzodiazepines is needed.
 Hyperthermic patients should be cooled with restricted activity;
iced water baths or tepid water with fans may be used, depending
on the severity of the hyperthermia and clinical status of the
patient. Cooling blankets are not adequate for severe hyperthermia,
and antipyretics are not effective.
 Hypotensive patients should receive intravenous fluids. If pressor
support is necessary, norepinephrine should be used. Hypertension
and sinus tachycardia are generally transient and do not require
specific treatment in most cases. When treatment is necessary for
mild to moderate hypertension, benzodiazepines can be used. For
malignant or refractory hypertension, IV nitroglycerin,
nitroprusside, or phentolamine can be used. Beta-adrenergic
blockade has not been demonstrated to be useful, and may
exacerbate hypertension and myocardial ischemia by facilitating
unopposed α-adrenergic stimulation.
 Supraventricular tachycardia, in hemodynamically stable patients,
can be treated with benzodiazepines followed by either calciumchannel antagonists or adenosine. Hemodynamically unstable
patients should be cardioverted. Ventricular dysrhythmias may be
managed with benzodiazepines to decrease central sympathetic
stimulation and with sodium bicarbonate or lidocaine as
antidysrhythmic agents.[
 Ischemic chest pain should be treated with benzodiazepines,
aspirin, and sublingual nitroglycerin. Refractory pain can be treated
with either morphine sulfate or intravenous nitroglycerin, Patients
who do not respond to this regimen can be treated with
phentolamine or verapamil. Patients with unstable angina should
receive heparin according to standard protocols. Beta-adrenergic
antagonists and mixed alpha-beta antagonists should not be used in
patients with cocaine-induced myocardial ischemia because they
increase coronary artery vasoconstriction and decrease myocardial
blood flow. Pulmonary edema should be treated with diuretics,
morphine, and nitroglycerin according to standard protocols.
 Seizures are usually brief and transient. If necessary, seizures can
be managed with benzodiazepines. If high doses do not control the
seizures, phenobarbital should be used.
 Seizures are usually brief and transient. If necessary, seizures can
be managed with benzodiazepines. If high doses do not control the
seizures, phenobarbital should be used.
 Asymptomatic body packers should receive activated charcoal to
limit cocaine absorption and whole bowel irrigation to decrease
gastrointestinal transit time.