History
Acute effects
Acute effects of cocaine use include the following:
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Decreased food intake
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Increased activity
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Effusiveness
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Diminished fatigue
Long-term use
Long-term use of cocaine interferes with sleep, can lower seizure threshold, and lead to palatal perforation.
Overdose of cocaine
Signs of a cocaine overdose include the following:
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Convulsions
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Hyperthermia
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Coma
Neuropsychiatric complications
Psychiatric disturbances include depression, suicidal ideation, paranoia, kleptomania, violent antisocial behavior, catatonia, and auditory or visual hallucinations. Cocaine use may lead to impulsivity, resulting in sexually risky behavior and increasing the risk of becoming infected with HIV.
Headache is a relatively frequent symptom (3.5%) in cocaine users. Headaches occur in 11% of cocaine paste smokers.
Convulsions
Convulsions occur in about 1-40% of cocaine users. [11] Convulsions caused by cocaine can be generalized or partial, simple or complex. The majority of seizures are single, generalized, induced by intravenous or crack cocaine, and not associated with any lasting neurological deficits. Most focal, multiple, or induced seizures caused by nasal insufflation of cocaine are associated with an acute intracerebral complication or concurrent use of other drugs.
All routes of administration are associated with seizures, and seizures can be induced in some persons by small quantities of cocaine. Once intoxication has passed, these individuals do not require long-term anticonvulsant therapy.
Although most cocaine-induced seizures are benign and self-limiting, seizures may be due to other more severe complications, such as infarction and intracranial hemorrhage.
Renal failure
Cocaine can cause acute renal failure resulting from rhabdomyolysis or vasospasm.
Physical
A dose-dependent increase in heart rate and blood pressure can occur.
Complications
Neuropsychiatric complications
Neuropsychiatric complications occur in about 40% of cocaine users. Psychiatric disturbances include depression, suicidal ideation, paranoia, kleptomania, violent antisocial behavior, intimate partner violence, catatonia, and auditory or visual hallucinations. Hallucinations occurring with cocaine intoxication can be simple or complex, affecting various sensory categories (eg, visual, auditory, cutaneous, visceral, cenesthesic), and may be associated with delusions of persecution.
A moderate proportion of addicts develop panic attacks, which are different from primary panic attacks in that cocaine users frequently have psychosensory symptoms, infrequent agoraphobia, hypersensitivity to caffeine, untoward responses to antidepressants, partial improvement with alprazolam, and marked recovery with clonazepam or carbamazepine.
Cocaine panic attacks can be explained in terms of limbic-neuronal hyperexcitability.
Suspicious and paranoid attitudes can easily be aroused experimentally by cocaine use. The paranoid symptoms are more severe and develop more rapidly with continuous use of cocaine.
Convulsions
Convulsions occur in about 3% of cocaine users. Convulsions caused by cocaine can be generalized or partial, simple or complex. The majority of seizures are single, generalized, induced by intravenous or crack cocaine, and not associated with any lasting neurological deficits. Most focal, multiple, or induced seizures caused by nasal insufflation of cocaine are associated with an acute intracerebral complication or concurrent use of other drugs.
The mechanism of seizures associated with cocaine intoxication has not been fully elucidated. Recent reports emphasize on the interaction of cocaine with GABAergic and glutamatergic systems. [12]
Seizures are one of the few complications of cocaine use in which a direct relationship with dose has been shown.
All routes of administration are associated with seizures, and seizures can be induced in some persons by small quantities of cocaine. Once intoxication has passed, these individuals do not require long-term anticonvulsant therapy.
Although most cocaine-induced seizures are benign and self-limiting, seizures may be due to other more severe complications, such as infarction and intracranial hemorrhage.
Cerebrovascular disorders
Cerebrovascular disorders may be secondary to arterial or venous etiology. Arterial complications include either ischemic or hemorrhagic strokes.
Hemorrhagic manifestations may be intraparenchymal or subarachnoid hemorrhage. Hemorrhage occurs about twice as frequently as ischemia. When neurological signs are present, imaging studies show findings associated with neurological abnormalities in nearly 80% of cases.
Ischemic manifestations of cocaine are postulated to be secondary to vasospasm or vasculitis or due to the procoagulant effect of the drug, which enhances platelet aggregation by depletion of arachidonic acid and thromboxane.
With intravenous use of cocaine, ischemic stroke may be cardioembolic–a complication of endocarditis. Complications include anterior spinal artery syndrome, lateral bulbar syndrome, and transient ischemic attacks.
Rarely, inhalation of cocaine also can lead to subarachnoid hemorrhage. An extensive infarct of the middle cerebral artery can occur after smoking free-base cocaine or cocaine paste.
Hemorrhages can be subcortical, pontine, or subarachnoid and may be associated with malformations, tumors, or aneurysms.
Cocaine-induced stroke in patients with underlying vascular malformations is thought to be due to the transient elevation of blood pressure that occurs after cocaine ingestion.
Hemorrhage may occur within seconds of cocaine use or may lag cocaine use by as long as 12 hours. In many cases, however, it occurs within a few minutes. This corresponds well with the known transient period of increased systolic blood pressure seen in these patients.
Although most cocaine-induced strokes occur in patients younger than 50 years, age and hypertension are regarded as risk factors for cocaine-induced stroke. Alkaloid cocaine probably is associated more commonly with ischemic and hemorrhagic accidents than other forms of cocaine. Impurities of street cocaine, such as talc or sugar, may embolize to the brain after intravenous injection.
Subarachnoid hemorrhages primarily occur in patients with underlying vascular malformations. Berry aneurysms of the circle of Willis are a common finding; AV malformations or tumors may be seen as well.
Ruptures of multiple mycotic aneurysms and large-vessel thromboses have been described. Venous complications include superior sagittal sinus thrombosis with hemorrhagic venous infarction, ie, dural AV fistula.
Movement disorders
One single cocaine inhalation in patients with Tourette syndrome can worsen the clinical picture considerably, possibly reflecting the intrinsic receptor hypersensitivity to dopaminergic transmission in the CNS.
Opsoclonus and myoclonus also are seen after cocaine inhalation.
Cocaine addicts can develop marked dystonic reactions during the withdrawal phase. These attacks subside quickly with administration of diphenhydramine HCl. The dystonia probably is precipitated by the functional dopamine deficiency in these patients.
Muscular disorders
In regions of the world with warm climates, cocaine-intoxicated patients in emergency rooms may show rhabdomyolysis. These patients have blood CK values exceeding 12,000 U/L. More than one third of these patients develop severe kidney insufficiency with hypotension, hyperpyrexia, disseminated intravascular coagulation, hepatic dysfunction, and CK values greater than 30,000 U/L. Dialysis is indicated in such patients.
The pathogenesis of rhabdomyolysis remains obscure and speculative.
Probably because of dopamine depletion, administration of neuroleptics in agitated long-term cocaine users can worsen the clinical picture and cause development of malignant hyperthermia. These patients should be treated with a dopaminergic agonist (eg, bromocriptine) and not with neuroleptics.
Leukoencephalopathy
While heroin-associated leukoencephalopathy is well recognized, leukoencephalopathy has also been noted with cocaine use. Clinical presentation may vary from cognitive dysfunction to focal neurologic deficits. Imaging may show extensive confluent white matter signal changes best appreciated on FLAIR images of the brain, with no contrast enhancement of lesions and a lack of involvement of brainstem or cerebellum as opposed to heroin-associated leukoencephalopathy. Treatment is mainly supportive; occasionally steroids and CoeQ have been used with equivocal results. [13]
Secondary complications
Cocaine-induced arterial thrombosis may occur in patients with a recent history of cocaine abuse. This presents as acute limb ischemia without an identifiable cardiovascular risk factor. Prompt angiography with operative or endovascular intervention should be performed. [14]
The effects of cocaine on other organ systems may lead to CNS complications.
Cocaine use may lead to myocardial infarction, cardiac arrhythmias, and respiratory arrest; any of these complications could lead to cerebral hypoperfusion or cerebral embolization of blood products.
Systemic complications from levamisole-laced cocaine
Levamisole-laced cocaine has been associated with dermatological, systemic, and hematological manifestations. Dermatological manifestations include painful hemorrhagic bullae over the face, cheeks, and helix, as well as retiform purpura on the lower extremities. Pathologically, a vasculitic and pseudovasculitic picture has been noted. Other systemic manifestations include arthralgias, flulike symptoms, leukopenia, and thrombocytopenia with positive antineutrophil antibody, antineutrophil cytoplasmic antibody, and antiproteinase-3 antibodies. Antihuman elastase antibodies are specific and sensitive for levamisole-associated vasculitis. [15]
Spinal cord involvement
Infarction of the spinal cord due to anterior spinal artery involvement leading to quadriplegia has been reported as a complication following acute cocaine intoxication.
Cardiovascular
Cocaine use is associated with cardiac ischemia, myocarditis, cardiomyopathy, and arrhythmias. Chest pain is a common complication of cocaine use. [16] Reports of acute myocardial infarction vary from 1-31%. [17] Cocaine causes increased myocardial oxygen demand, coronary vasoconstriction, platelet aggregation, and in situ thrombus formation, which can lead to acute myocardial infarction in patients with normal coronary arteries. [18] A study by Chang et al that examined acute coronary syndromes reported no increased likelihood of development of coronary disease in cocaine users. [19]
Skin
Cocaine use is associated with vasculitides, infectious complications, and numerous dermatologic conditions. It has been associated with formication (ie, tactile hallucinations of insects crawling underneath the skin), which leads to delusions of parasitosis.
Pregnancy and newborns
Women using cocaine have higher numbers of spontaneous abortions, premature births, placental abruption, and placenta previa than nonusers. Babies born to these mothers exhibit significant depression in behavior and response to stimuli. Newborn babies may develop cerebral infarcts. Intrauterine fetal growth may be retarded; microcephaly, small-for-date birth weights, convulsions, infarcts, cerebral hemorrhages, hypertonicity, motor restlessness, and absence of saccadic movements on oculovestibular stimuli are more common than in newborns of mothers who do not use the drug.
Congenital malformations are postulated to result from fetal ischemia during the first trimester, and occlusive stroke is a consequence of ischemia during the third trimester.
Respiratory anomalies in newborns are more noticeable during sleep. Severe respiratory difficulty syndromes and failures of the awakening mechanism have been documented. Sonography, CT scan, and MRI revealed cortical infarcts and midline congenital malformations in 15% of infants born to mothers who used cocaine.
Prenatal exposure to cocaine is related to aggressive behavior at age 5 years.
