Pediatric Cocaine Abuse 

Approximately 4% of adolescents have abused or were dependent on illicit drugs, according to the 2008 National Survey on Drug Use and Health.^[1] The 1998 National Household Survey on Drug Abuse revealed that 0.8% of US children aged 12-17 years had used cocaine in the previous month.^[2] In June 2000, the Centers for Disease Control and Prevention (CDC) reported that 4% of 15,349 students in grades 9-12 reported cocaine use at least once in the prior month.^[3] In 1991, 1.9% of students reported cocaine use at least once in the previous month.

Most recently, the 2004 National Survey on Drug Use and Health (NSDUH), formerly called the National Household Survey on Drug Abuse, focused on 3 major age groups, including the 12- to 17-year-old age group.^[4] The drug use information gathered was pertinent to civilians (nonmilitary) and residents of households and noninstitutional group housing facilities. Military personnel, residents of institutionalized group housing centers (eg, jails, hospitals), and homeless individuals not in shelters were not included. The 2004 NSDUH reported that 2.4% of the 12- to 17-year-old age group used cocaine at some point in their life, 1.6% used cocaine within the past year, and 0.5% used cocaine within the past month. Prevalence of cocaine use in this age group was similar to the use of ecstasy and inhalants but was notably less than cigarettes, alcohol, or marijuana.

The National Institute on Drug Abuse (NIDA) estimates that 10% of people who begin to use cocaine graduate to heavy use.^[5] Adolescent drug use typically develops out of curiosity about available substances. Use begins in a social environment with drugs that are legal for adults and available to minors (eg, alcohol, cigarettes). Children and adolescents rarely experiment with an illicit drug such as cocaine prior to trying alcohol and cigarettes.

Academic and psychosocial impairments are particularly important in pediatric substance abuse. Role impairment at home, school, work, close relationships, and in social life are clues to either a psychiatric disorder, substance abuse, or both. The most common psychiatric conditions associated with substance abuse disorders are mood and anxiety disorders, attention deficit hyperactivity disorder, and antisocial personality disorders. Persons with a major depressive episode were more likely than those without a major depressive episode to abuse or have dependence on illicit drugs. In 2004, 22% of those surveyed in the 12- to 17-year-old age group received treatment or counseling within the past year for emotional or behavioral problems.^[4] This number underestimates the actual percentage of youths with depression and other psychiatric illness.

A family history of substance abuse may be a risk factor for early cocaine use and for rapid dependence on cocaine. The following discussion on pediatric cocaine abuse almost exclusively applies to adolescents. However, accidental ingestion of cocaine, passive inhalation of crack cocaine smoke, and transmission through breast milk have been reported as means of cocaine exposure in infants.^{[6, 7]}

Cocaine is obtained from the leaves of the Erythroxylon coca and other Erythroxylon trees indigenous to Bolivia, Peru, Indonesia, and the West Indies. For centuries, Amerindian workers who traveled in mountainous South American countries have chewed coca leaves, a practice they believe improves their stamina and suppresses hunger.

Deliberate extraction of cocaine from coca leaves began in the second half of the 19th century. Several uses of cocaine were marketed and advocated. Sigmund Freud wrote of cocaine's potential to treat asthma, syphilis, and wasting diseases. Halstead used cocaine's anesthetic effects to perform nerve blocks. Curiously, both these prominent advocates of the medicinal values of cocaine became addicted to the substance.

Cocaine ingestion increased with use of several preparations, including beverages such as early 20th century Coca Cola. Recreational and fashionable use brought increasing reports of cocaine-related morbidities and several fatalities. The Harrison Narcotics Act of 1914 made unprescribed use of cocaine illegal. Elaborate levels of cocaine production, smuggling, and distribution have challenged efforts to diminish supply. Despite extensive drug control policies, cocaine's popularity surged in the 1970s and 1980s. The high potency and relatively cheap cost of crack cocaine created another US cocaine epidemic.

By the late 1970s, modifications in cocaine processing led to the development of freebase and crack cocaine. Cocaine (C₁₇ H₂₁ NO₄), when treated with hydrochloric acid, becomes a water-soluble hydrochloride salt, which can be absorbed through the nasal mucosa and can be taken intravenously (IV).

Freebase is formed when aqueous hydrochloride salt is added to ammonia to form a base, which then is dissolved in ether. The ether then evaporates. Residual ether is flammable and can pose a danger when heated.

Crack cocaine is formed when the aqueous hydrochloride salt is mixed with baking soda and then heated. The soft mass that forms is left to harden into a rock or slab of crack cocaine. This form of cocaine is the cheapest and most potent. Smoked crack is rapidly absorbed by the pulmonary vasculature and reaches the brain's circulation in 6-8 seconds. Other drugs (eg, alcohol, nicotine, heroin) frequently are used either in parallel or as a direct mixture with cocaine.

Cocaine powder can be absorbed across any mucous membrane of the body; the nasal route is most common. Snorting or insufflation is usually performed through a strawlike apparatus or from a spoon. Effect onset typically occurs in 3 minutes, peaks in 15 minutes, and lasts 45-90 minutes. The intranasal (IN) route has slower absorption because of cocaine's vasoconstrictive effects on the nasal mucosa. The IV route of self-administered cocaine yields an onset of action in 15 seconds, peaks in 3-5 minutes, and lasts 40-60 minutes.

Cocaine is primarily metabolized by serum cholinesterases. A small portion is metabolized in the liver by carboxylesterase and less than 10% is metabolized by N -methylation in the liver to norcocaine. Pregnancy significantly enhances metabolism. In addition, cocaine diminishes maternal and fetal plasma cholinesterase activity, leading to prolonged presence and effect in pregnant women. Approximately 1-5% of cocaine is not metabolized and is excreted unchanged in the urine. Urinalysis can detect cocaine 3-6 hours after use.

Alcohol used with cocaine increases the drug's bioavailability. In addition, alcohol allows carboxylesterase to transfer an ethyl group to cocaine to form cocaethylene. Cocaethylene, as is true with cocaine, eventually is metabolized to benzoylecgonine. With a half-life of 2.5 hours (compared with cocaine's 40 min), cocaethylene has fewer dysphoric effects than cocaine, but its other toxic effects are more potent.

Chronic nicotine use can damage blood vessels and, just as cocaine, can increase atherosclerotic development or coronary spasm and its consequences.

Cardiac

Cocaine causes a significant release of catecholamines and blocks their presynaptic reuptake. The state of elevated catecholamines leads to tachycardia, hypertension, and increased myocardial oxygen consumption. Enhanced alpha-adrenergic stimulation provokes arterial vasospasm, including the coronary arteries. Cocaine also promotes platelet aggregation, decreases prostacyclin production and release, and increases thromboxane A production.

Local increased levels of platelet-derived serotonin may lead to vasospasm sufficient to provoke distal myocardial ischemia or myocardial infarction (MI).^[8] Chronic cocaine use leads to accelerated atherosclerosis. The dopamine depletion that accompanies chronic cocaine use can lead to coronary vasoconstriction. Thus, cocaine-related myocardial insults could be caused by coronary atherosclerosis, coronary spasm, or both; tachycardia and hypertension may increase myocardial work.

Direct toxic effects on the cardiac muscle include focal myocarditis, fibrosis, and hypertrophy. These histologic changes provide anatomical substrates for dysrhythmias (ie, may be an area of slower conduction and may lead to reentry tachycardia) during a catecholamine surge. Cocaine has quinidinelike effects. Resultant intraventricular conduction delays can lead to cardiac output corrected for heart rate (QTc) prolongation and electrocardiographic wave (QRS) complex widening. Large cocaine doses can induce a state of negative inotropy that may lead to bradycardia and even death.

Neurologic

Chronic depletion of dopamine from long-term cocaine use can impair functioning of the extrapyramidal motor system; consequences include dystonic reactions, bradykinesias, and parkinsonian movements. Cocaine use increases the risk of dystonic reactions when used with medications that antagonize nigrostriatal dopamine function (eg, neuroleptics).

Cocaine lowers the seizure threshold. Most patients with subarachnoid and intracerebral hemorrhages after cocaine use have underlying vascular abnormalities that rupture as a result of cocaine's acute hypertensive effect. Hemorrhagic and ischemic strokes may develop as a result of atherosclerosis and acute and chronic hypertensive states. Vasospasm and increased platelet aggregation may also play a role in CNS infarctions.

Cocaine also blocks sodium channels, thus lessening the membrane potential and the action potential while lengthening the duration of the action potential. This action causes local anesthetic effects. Cocaine, in the form of tetracaine, adrenalin, and cocaine (TAC), continues to be used in medicine, primarily for its topical anesthetic effects in laceration repair. Cocaine is used widely as a local anesthetic in ear, nose, and throat (ENT) and ophthalmologic procedures.

Pulmonary

Wider use of crack cocaine has increased the incidence of pulmonary hemorrhage, pneumonitis, pneumomediastinum, pneumothorax, asthma, and pulmonary edema. Barotrauma and immunologic reactions to cocaine adulterants and foreign bodies are responsible for most pulmonary effects.

GI

Cocaine-induced vasospasm can cause intestinal or splenic ischemia following all routes of cocaine use. Of particular note are "body packers" and "body stuffers." Cocaine body packers ingest usually well-sealed packages of cocaine to avoid detection as they smuggle the drugs across borders. Body stuffers, in contrast, attempt to avoid detection during an impending arrest by hastily ingesting poorly constructed packets of drug.

Renal

Cocaine can cause renal failure by rhabdomyolysis or direct renal infarction. Hyperthermia, seizures, or prolonged unconsciousness can lead to rhabdomyolysis.

Obstetrical

Cocaine use has well-known negative effects on pregnancy, including an increased risk of preterm labor, abruptio placentae, spontaneous abortions, and intrauterine growth retardation.^{[9, 10]} Newborns can be born addicted to cocaine and go through withdrawal within 48 hours of birth. The following effects may also occur:

• Increased spotting or vaginal bleeding
• Precipitous labor
• Placental insufficiency
• Premature rupture of membranes
• Stillbirth
• Intrauterine fetal demise
• Breech presentation
• Low birth weight

Psychiatric

What makes cocaine so addictive? The drug causes a significant release of catecholamines and blocks their presynaptic reuptake. Catecholamine excess causes a physiologically and behaviorally excited state.

A similar but more moderate effect on dopamine and serotonin occurs. Elevated dopamine may be the root of positive reinforcement and addiction, according to current hypotheses. Dopamine has been implicated in the incentive motivational effects of food, sex, and several abused drugs.

All commonly abused drugs stimulate the brain's limbic system. The limbic system is a group of well-defined structures that communicate with each other to regulate memory, learning, and emotions. The limbic system networks with the hypothalamus, which coordinates the interaction between many brain structures. The limbic system also communicates with the frontal lobe, which is the central area for perceptions, feelings, and speech. Indeed, the structural center for pleasure perceptions is located in the nucleus accumbens of the limbic system. Localized dopamine elevations support this theory. All psychoactive drugs affect sleep, level of alertness, perceptions, emotions, movement, judgment, and attention.

Use of cocaine, a psychoactive drug, can lead to significant and socially unacceptable behavioral and psychological changes that are destructive to the user or others. Cocaine-associated environments, people, and thoughts become etched into the memory of the cocaine user.

Cocaine's effects are biphasic; the pleasurable "rush" or "high" is temporary and is followed by a "crash" as binding sites release cocaine and dopamine and other neurotransmitters resume reuptake. The user slips into a state of physical exhaustion and diminished alertness and emotion. The symptoms in some individuals may include agitation, anxiety, and psychosis.

Cocaine's dopamine-driven rush serves as a positive reinforcement for repeated cocaine use. With continued use, the nervous system adapts to the drug's effects. Up-regulation of presynaptic binding sites results in less intense pleasure from a given amount of the drug, promoting increased cocaine use.

Intense and unpleasant withdrawal symptoms contribute to eventual dependence on the drug. Psychiatric symptoms are evident in most substance users during intoxicated and withdrawal states. About 60% of cocaine users say they have experienced psychiatric problems related to drug use. Almost 20% of patients report tactile or visual hallucinations. Their most common hallucination is formication, the sensation of bugs crawling on the skin. Persistent or worsening symptoms suggest a comorbid psychiatric disorder that requires treatment.

Frequency

United States

Approximately 50 million Americans have used cocaine at least once. According to preliminary results of the 1997 National Household Survey, approximately 1.5 million Americans currently use cocaine.^[2] In 1985, approximately 3% of the population used cocaine (5.7 million people). In 1992, usage rates declined to 0.7% (1.4 million people) and remained essentially unchanged in 1997. Rates of frequent use, defined as cocaine use on 51 or more days in the past year, remained similar from 1985-1997; 600,000-700,000 Americans described themselves as frequent cocaine users. One quarter of the 12- to 17-year-old age group in the 2004 NSDUH reported that obtaining cocaine or crack was easy.^[4]

International

Cocaine abuse has become an increasingly international public health concern.

Mortality/Morbidity

According to the National Household Survey, one third of deaths after cocaine use were due to drug intoxication; the remaining two thirds were associated with traumatic injuries (eg, homicides, suicides, falls, motor vehicle collisions).^[2] For morbidity information, see Pathophysiology.

Race

The 2004 NSDUH reported current illicit drug in the 12- to 17-year-old age group of 26% among American Indians or Alaskan Natives, 12.2% of those reporting 2 or more races, 11.1% among whites, 10.2% among Hispanics, 9.3% among blacks, and 6% among Asians.^[2] In a study of racial and ethnic variations in substance-related disorders in the US, Wu et al concluded that substance use is widespread among Native American, white, Hispanic, and multiple race/ethnicity adolescents.^[11]

Sex

In 1997, men continued to have a higher rate of current cocaine use (0.9%) than women (0.5%). In the 2004 NSDUH report, the rate of substance abuse or dependence was similar among females and males in the 12- to 17-year-old age group.^[2]

Age

A few other studies have examined cocaine use among teenagers. The NIDA, part of the National Institute of Health (NIH), funds the Monitoring the Future Survey, conducted by the University of Michigan's Institute for Social Research.^[5] Since 1975, this survey has tracked illicit drug use and related attitudes of 12th-grade students; in 1991, students in the eighth and 10th grades were added to the study. For the 1999 study, 49,866 students were surveyed from a representative sample of 422 public and private schools nationwide. This survey noted that lifetime prevalence of cocaine use was 4.7% for students in the eighth grade, 7.7% for students in 10th grade, and 9.8% for students in 12th grade.

According to the NIH, the highest rate of current cocaine use in 1997 was among persons aged 18-25 years (1.2%).^[5] In other age groups, rates were 1% for persons aged 12-17 years, 0.9% for persons aged 26-34 years, and 0.5% for persons aged 35 years and older.

Rates declined from 1996-1997 for adults aged 18-25 years and 26-34 years; rates remained stable for other age groups.