Alicia B. Minns and Richard F. Clark

Perspective

The use and abuse of psychoactive substances are not unique to our country or century. People used hallucinogenic plants to achieve altered states of consciousness in prehistoric times, and psychoactive substances have been used in all eras and cultures. As Osler remarked, “The desire to take medicine is, perhaps, the great feature which distinguishes man from other animals.”¹ The human cost of substance abuse is high, and deaths secondary to the use of psychoactive substances are common. In the United States, illicit drug use results in thousands of deaths each year (Box 186-1).²

A major barrier to appropriate recognition and treatment of substance abuse is the lack of a precise definition. The American Psychiatric Association defines it as a maladaptive pattern of drug use associated with some manifest harm to the user or others.³ Physicians have a difficult time recognizing such abuse when up to 44% of emergency department (ED) patients report underlying chronic pain syndromes.⁴ Chronic pain may not manifest the typical overt sympathetic changes or physical findings of acute pain.⁵ Therefore, emergency physicians constantly walk a tightrope between undertreating legitimate pain and inappropriately rewarding substance abusers with controlled medications.

Epidemiology

A variety of stereotypes come to mind in compiling the profile of a substance abuser. These stereotypes pose dangerous traps for the clinician. Physicians are likely to ignore the possibility of drug intoxication in the well-dressed businessman or in those at the extremes of age. Yet children may ingest psychoactive substances they find in homes where drugs are used.

Abuse of prescription and over-the-counter (OTC) drugs by adolescents is on the rise. According to the 2005 Partnership for a Drug-Free America’s 18th annual self-administered study of 7300 teenagers in grades 7 to 12, one in five (19%, or 4.5 million) report abusing prescription medications and one in ten (10%, or 2.4 million) report abusing cough medications to “get high.” This use is on par with or higher than the abuse of illegal drugs such as ecstasy and cocaine.⁶ Dextromethorphan abuse has become epidemic in the last decade. Increasing numbers of teens are ingesting dextromethorphan-containing OTC products such as Coricidin HBP Cough & Cold tablets,⁷ known on the streets as triple C, red devils, red C, red box, or skittles. Other dextromethorphan compounds include cough medicines, such as NyQuil and Robitussin DM, that provide the sought-after high known as the robo-buzz. Adolescents may also abuse medication used to treat obsessive-compulsive disorder and attention-deficit/hyperactivity disorder. Methylphenidate and related compounds have been a particular concern. Tablets can be abused orally, or they can be crushed and the powder injected or snorted. Despite its abuse potential, experts disagree about the extent to which methylphenidate is diverted from therapeutic use to abuse in preteens and adolescents.⁸ In addition, some parents deliberately give psychoactive substances to their children to calm or to abuse them.

The emergence of “legal highs” has become a concerning trend. Numerous synthetic and naturally derived psychoactive substances are easy to obtain from Internet websites, “head shops,” and local suppliers. One such example is known as bath salts. These products are available in small quantities, with packaging that usually includes the disclaimer “not for consumption” to avoid regulation.⁹ Bath salts contain synthetic cathinones, which are pharmacologically similar to methamphetamine and MDMA (ecstasy) and produce similar clinical effects.¹⁰ A variety of adverse effects have been reported from cathinone derivatives, including tachycardia, hypertension, agitation, hyponatremia, hallucinations, paranoia, and suicide.^9–11 The legal status of bath salts is rapidly changing. The U.S. Department of Justice Drug Enforcement Administration has temporarily placed three of the synthetic stimulants under Schedule I of the Controlled Substances Act; however, numerous other synthetic cathinones have been found in these products.⁹

The elderly also abuse substances, and geriatric patients may suffer new-onset psychosis as a result of sympathomimetic abuse or drug withdrawal. Drug use is frequent among pregnant women, resulting in both maternal and fetal morbidity. A study of an inner-city population reported that 19% of women had a positive urine toxicology screen for at least one of seven substances at the time of admission for delivery.¹² Manifestations of abuse may be acute, as in abruptio placentae or premature birth, or insidious, producing growth restriction and birth defects. Drug problems are more prevalent among the disadvantaged minority and lower socioeconomic groups. As a result, these groups are disproportionately affected by drug-related problems, such as incarceration, acquired immunodeficiency syndrome, and tuberculosis.

The Drug Alert Warning Network (DAWN) collects data from hospital EDs and medical examiners that include drug-related visits or deaths. The data consist of patients who abuse illegal drugs or use legal substances for a nonmedical purpose. According to DAWN, the drugs of misuse or abuse most commonly involved in deaths are cocaine, opioids, antidepressants, benzodiazepines, stimulants, and club drugs.¹³

For 2005, DAWN estimated that 816,696 ED visits involved an illicit drug; cocaine was involved in 448,481, marijuana in 242,200, heroin in 164,572, and stimulants (including amphetamines and methamphetamine) in 138,950 ED visits. Other illicit drugs (phencyclidine [PCP], ecstasy, and γ-hydroxybutyric acid [GHB]) were much less frequent.¹⁴ Despite efforts to control nonmedical use of prescription drugs in the United States, the estimated number of ED visits for nonmedical use of opioid analgesics increased 111% during 2004-2008 (from 144,600 to 305,900 visits) and increased 29% during 2007-2008. The highest numbers of these ED visits were recorded for oxycodone, hydrocodone, and methadone, all of which showed statistically significant increases during the 5-year period. The estimated number of ED visits involving nonmedical use of benzodiazepines increased 89% during 2004-2008 (from 143,500 to 271,700 visits) and 24% during 2007-2008. In 2008, the number of ED visits involving nonmedical use of prescription or OTC drugs matched the number of ED visits involving illicit drugs.¹⁵

Illicit drug use generates significant costs to the health care system. In 2001, the hospital and ambulatory care costs of illicit drug use as a whole were an estimated $1.34 billion. The cost for illicit drug–related skin and soft tissue infections alone was estimated to be more than $193 million.¹⁶ More recently in 2008, the cost of hospital days stemming from drug overdoses without alcohol involvement was estimated to be $737 million.¹⁷

Pharmacology

Knowledge of drug interactions assists in the diagnosis and care of substance abuse victims. A careful medication history for all legal and illegal drugs, including ethanol, may pinpoint the source of an adverse reaction. For example, a variety of agents can increase the effects of cocaine. The coingestion of ethanol and cocaine results in an active metabolite, cocaethylene, that also enhances and magnifies cocaine’s effects. Serotonin syndrome, manifested by muscle rigidity, hyperthermia, diarrhea, and seizures, may result when sympathomimetic drugs are taken concurrently with selective serotonin reuptake inhibitors such as fluoxetine. Amphetamines elevate serotonin either directly or by reversible inhibition of monoamine oxidase. In fact, a selective serotonin reuptake inhibitor can result in flashbacks in prior amphetamine users. Monoamine oxidase inhibitors can provoke hypertensive crisis in patients taking sympathomimetics. Interactions between medications commonly prescribed for patients with human immunodeficiency virus (HIV) infection and recreational drugs may be associated with serious clinical consequences because protease inhibitors and non-nucleoside reverse transcriptase inhibitors (NNRTIs) can inhibit or induce the cytochrome P₄₅₀ system, which could result in either drug accumulation or toxicity or withdrawal reactions.¹⁸ For example, patients maintained with methadone who are subsequently treated with NNRTIs are at risk for development of methadone withdrawal by NNRTI-mediated enzyme induction.¹⁸

Household products and medications also have abuse potential. For example, dextromethorphan in common cough medications is converted into a substance (dextrorphan) similar to ketamine and PCP, which causes dissociative effects by antagonizing the N-methyl-D-aspartate (NMDA) receptor. Recreational users describe mild hallucinations and an “out-of-body” state.¹⁹ Some common chemicals in the home and workplace have an intoxicating effect that may be unexpected. Solvents, paint, lacquers, glues, aerosols, refrigerants, and other propellants (Fig. 186-1) are readily accessible for abuse among children and teens. Inhaled hydrocarbons, such as toluene, are rapidly absorbed and easily pass through the lipophilic blood-brain barrier to give an inexpensive high.

Illicit drug laboratories have poor quality control, and many drugs are combined or “cut” with other substances to increase profits. Up to 50% of street samples lack the alleged drug. Some additives, such as local anesthetics or sugars, may be innocuous, but others, such as strychnine, may be lethal. Levamisole, a widely available anthelmintic agent, is now a common cocaine adulterant and can result in life-threatening agranulocytosis, leukoencephalopathy, and cutaneous vasculitides.²⁰ Other drugs, such as PCP, are misleadingly sold as a different drug, such as lysergic acid diethylamide (LSD). During the 1990s, many doses of purported ecstasy (MDMA) actually contained amphetamine drug mixtures or even simple caffeine or ephedrine.^21,22 Drug combinations and unanticipated additives or substitutions may produce a clinical picture discordant with what the patient claims to have taken.

“Look-alike” drugs may also have toxic effects. Teens in particular may take look-alike or “knock-off” drugs that look like a desired product, such as Ritalin or Coricidin, in the hope of getting high, when in reality they may suffer unanticipated effects from an unrelated medication sold by an unscrupulous dealer. Teenagers can present with dystonias after unsuspectingly taking haloperidol instead of diazepam (each can have a “letter” inscribed in the middle of the pill).