Drug abuse: What hospital pharmacists need to know
By Thomas G. Hall, PharmD, MS
Director of Pharmacy
Columbia Las Encinas Hospital
Pasadena, CA
Addiction is a disease with physical, genetic, and psychological components that act together to create a chronic state that is progressive and eventually fatal unless effectively treated. With addictive drugs, repeated administration or abuse causes changes in the functioning of the brain. All addictive drugs activate the meso-limbic dopamine system.
That area is responsible for both rewards and basic drives (food, sex, etc.). At some point, the abused drug becomes the primary reward in the abuser’s life. The transition can occur with dramatic swiftness or as a gradual and relentless progression. But at some time, a point of no return is passed where the abuser suffers almost a complete loss of the ability to control the tempo of drug use. Implicit in this disease definition is the idea that addiction is a chronic disease and that a cure is not, at the present time, possible.
The reality that addiction is a disease of the brain is based on more than 25 years of research. This is a disease that disrupts the mechanisms responsible for controlling, modulating, and generating cognitive, emotional, and social behavior.
The physical component of the disease of addiction consists of the changes created by drugs. Those changes occur in homeostasis as well as in the anatomy of receptors in the central nervous system. The primary site of all addictive drug dysfunction is the meso-limbic dopamine system. Following are the categories of addictive drugs as categorized by the Drug Enforcement Agency.
• Stimulants: cocaine, amphetamines, and related substances, including MDMA (ecstasy);
• Opiates: morphine, heroin, codeine, and propoxyphene;
• Marijuana and hashish derivatives;
• Depressants: benzodiazepines, barbiturates, meprobamate, methaqualone, and alcohol (beer, wine, distilled spirits);
• Hallucinogens: LSD, mescaline, psilocybin including MDMA, and phencyclidine (PCP and PCP analogues);
• Inhalants: solvents, aerosol, anesthetics, nitrates.
While some addicting drugs can be considered more quickly addicting than others, and some literature has described both inhalants and LSD as non-addicting, all the listed drugs have significant addiction potential. Use of members of any of the listed drug categories will precipitate a quick return to the drug of choice, or relapse. The following is a description of a few representatives of the drug classes.
1. Cocaine: Cocaine is a powerfully addictive drug. The major routes of administration of cocaine are sniffing or snorting, injecting, and smoking (including free-base and crack cocaine). Smoking involves inhaling cocaine vapor or smoke into the lungs where absorption into the bloodstream is as rapid as by injection. "Crack" is the street name given to cocaine that has been processed from cocaine hydrochloride to a free base for smoking.
Rather than requiring the more volatile method of processing cocaine using ethyl ether, crack cocaine is processed with ammonia or sodium bicarbonate (baking soda) and water and heated to remove the hydrochloride, thus producing a form of cocaine that can be smoked. The term "crack" refers to the crackling sound heard when the mixture is smoked (heated), presumably from the sodium bicarbonate.
Cocaine poses a great risk whether it is ingested by inhalation (snorting), injection, or smoking. It appears that compulsive cocaine use may develop even more rapidly if the substance is smoked rather than snorted. Smoking allows extremely high doses of cocaine to reach the brain quickly and brings an intense and immediate high.
Health hazards: Cocaine is a strong central nervous system stimulant that interferes with the reabsorption process of dopamine. Physical effects of cocaine use include constricted peripheral blood vessels, dilated pupils, and increased temperature, heart rate, and blood pressure. The duration of cocaine’s immediate euphoric effects, which include hyperstimulation, reduced fatigue, and mental clarity, depends on the route of administration.
The faster the absorption, the more intense the high. But the faster the absorption, the shorter the duration of action. The high from snorting may last 15 to 30 minutes, while that from smoking may last five to 10 minutes. Increased use can reduce the period of stimulation.
Some users of cocaine report feelings of restlessness, irritability, and anxiety. Prolonged cocaine snorting can result in ulceration of the mucous membrane of the nose and can damage the nasal septum enough to cause it to collapse. Cocaine-related deaths are often a result of cardiac arrest or seizures followed by respiratory arrest.
Added danger: When people mix cocaine and alcohol, they are compounding the danger each drug poses. Researchers have found that the liver combines cocaine and alcohol and manufactures a third substance, cocaethylene. Cocaethylene intensifies cocaine’s euphoric effects and is highly cardiotoxic, increasing the risk of sudden death.
2. Ecstasy: MDMA, (3-4 methylenedioxymethamphetamine) called "Adam," "ecstasy," or "X-TC" on the street, is a synthetic, psychoactive (mind-altering) drug with hallucinogenic and ampheta mine-like properties. Its chemical structure is similar to two other synthetic drugs, MDA and methamphetamine, which are known to cause brain damage. (MDA is the parent drug of MDMA. It is an amphetamine-like drug that has also been abused and is similar in chemical structure to MDMA.)
Health hazards: Many problems that users encounter with MDMA are similar to those found with the use of amphetamines and cocaine:
• Psychological difficulties, including confusion, depression, sleep problems, drug craving, severe anxiety, and paranoia during and sometimes weeks after taking MDMA. Psychotic episodes also have been reported.
• Physical symptoms such as muscle tension, involuntary teeth clenching, nausea, blurred vision, rapid eye movement, faintness, and chills or sweating.
• Increases in heart rate and blood pressure, a special risk for people with circulatory or heart disease.
Research shows that MDMA destroys serotonin-producing neurons, which play a direct role in regulating aggression, mood, sexual responses, sleep, and sensitivity to pain. It is probably this action on the serotonin system that gives MDMA its purported properties of heightened sexual experience, tranquility, and conviviality. MDMA also is related in structure and effects to methamphetamine, which has been shown to cause degeneration of neurons containing the neurotransmitter dopamine.
Damage to these neurons is the underlying cause of the motor disturbances seen in Parkin son’s disease. In laboratory experiments, a single exposure to methamphetamine at high doses or prolonged use at low doses destroys up to 50% of the brain cells that use dopamine. Although this damage may not be immediately apparent, scientists believe that with aging or exposure to other toxic agents, Parkinsonian symptoms eventually may emerge. These symptoms begin with lack of coordination and tremors and eventually may result in a form of paralysis.
3. Heroin: Recent studies suggest a shift from injecting heroin to snorting or smoking it, because of increased purity and the misconception that those forms of use will not lead to addiction. Heroin is processed from morphine, a naturally occurring substance extracted from the seedpod of the Asian poppy plant. Heroin usually appears as a white or brown powder.
Health hazards: The short-term effects of heroin abuse appear soon after a single dose and disappear in a few hours. After an injection of heroin, the user reports feeling a surge of euphoria ("rush") accompanied by a warm flushing of the skin, a dry mouth, and heavy extremities. Following this initial euphoria, the user goes "on the nod," an alternately wakeful and drowsy state. Mental functioning becomes clouded due to the depression of the central nervous system.
Long-term effects of heroin appear after repeated use for some period of time. Chronic users may develop collapsed veins, infection of the heart lining and valves, abscesses, cellulitis, and liver disease. Pulmonary complications, including various types of pneumonia, may result from the poor health condition of the abuser, as well as from heroin’s depressing effects on respiration. In addition to the effects of the drug itself, street heroin may have additives that do not readily dissolve and result in clogging the blood vessels that lead to the lungs, liver, kidneys, or brain.
Reports from the Department of Health and Human Services’ 1995 Drug Abuse Warning Network, which collects data on drug-related hospital emergency room episodes and drug-related deaths from 21 metropolitan areas, rank heroin second to cocaine as the most frequently mentioned drug in overall drug-related deaths. From 1990 through 1995, the number of heroin-related episodes doubled. Between 1994 and 1995, there was a 19% increase in heroin-related emergency department episodes as heroin use became popular again.
Major withdrawal symptoms peak between 48 and 72 hours after the last dose and subside after about a week. Sudden withdrawal by heavily dependent users who are in poor health is occasionally fatal, although heroin withdrawal is considered much less dangerous than alcohol or barbiturate withdrawal.
4. Marijuana: Marijuana is a green or gray mixture of dried, shredded flowers and leaves of the hemp plant Cannabis sativa. It is usually smoked as a cigarette or in a pipe or water pipe. In recent years, it has appeared in blunts, which are cigars emptied of tobacco and re-filled with marijuana, often in combination with another drug, such as crack cocaine.
Some users also mix marijuana into foods or use it to brew tea. The main active chemical in marijuana is THC (delta-9-tetrahydrocannabinol). In 1988, it was discovered that the membranes of certain nerve cells contain protein receptors that bind THC. Once securely in place, THC triggers a series of cellular reactions that ultimately lead to the high that users experience when they smoke marijuana.
The short-term effects of marijuana use include problems with memory and learning; distorted perception; difficulty in thinking and problem solving; loss of coordination; and increased heart rate, anxiety, and panic attacks.
Hybridization of marijuana crops has created a product that contains as much as 24% THC by weight. Compare this to the average of 2% in the marijuana common in the early 1960s.
Effects on the brain: Researchers have found that THC changes the way sensory information gets into and is acted on by the hippocampus. This is a component of the brain’s limbic system that is crucial for learning, memory, and the integration of sensory experiences with emotions and motivations. Investigations have shown that THC suppresses neurons in the information processing system of the hippocampus and the activity of the nerve fibers. In addition, researchers have discovered that learned behaviors, which depend on the hippocampus, also deteriorate.
Effects on the lungs: Someone who smokes marijuana regularly may have many of the same respiratory problems that tobacco smokers have. These individuals may have daily cough and phlegm, symptoms of chronic bronchitis, and more frequent chest colds. Continuing to smoke marijuana can lead to abnormal functioning of lung tissue, which is due to injury by marijuana smoke. Regardless of the THC content, the amount of tar inhaled by marijuana smokers and the level of carbon monoxide absorbed are three to five times greater than among tobacco smokers. This may be due to the marijuana users inhaling more deeply and holding the smoke in the lungs.
Effects on heart rate and blood pressure: Recent findings indicate that smoking marijuana while injecting cocaine has the potential to cause severe increases in heart rate and blood pressure. In one study, experienced marijuana and cocaine users were given marijuana alone, cocaine alone, and then a combination of both.
Each drug alone produced cardiovascular effects; when they were combined, the effects were greater and lasted longer. The heart rate of the subjects in the study increased 29 beats per minute with marijuana alone and 32 beats per minute with cocaine alone. When the drugs were given together, the heart rate increased by 49 beats per minute, and the increased rate persisted for a longer time.
In this study, the drugs were given with the subjects sitting quietly. In normal circumstances, an individual may smoke marijuana and inject cocaine in a setting that is much less controlled, possibly becoming physically active and significantly increasing risks of cardiovascular overload.
Effects on learning and social behavior: A study of college students has shown that critical skills related to attention, memory, and learning are impaired among people who use marijuana heavily, even after discontinuing its use for at least 24 hours.
Researchers compared 65 "heavy users," who had smoked marijuana a median of 29 of the past 30 days, and 64 "light users," who had smoked a median of one day in the past 30. After a closely monitored 19- to 24-hour period of abstinence from marijuana and other illicit drugs and alcohol, the undergraduates were given several standard tests measuring aspects of attention, memory, and learning.
Compared to the light users, heavy marijuana users made more errors and had more difficulty sustaining attention, shifting attention to meet the demands of changes in the environment, and in registering, processing, and using information.
5. LSD: LSD (lysergic acid diethylamide) is one of the major drugs in the hallucinogen class. It was discovered in 1938 and is among the most potent mood-changing chemicals. It is manufactured from lysergic acid, which is found in ergot, a fungus that grows on rye and other grains.
LSD, commonly referred to as "acid," is sold on the street in tablets, capsules, and, occasionally, liquid form. It is odorless, colorless, and has a slightly bitter taste and is usually taken by mouth. It can be added to absorbent paper, such as blotter, and divided into small decorated squares, each square representing one dose. The Drug Enforcement Administration reports that the strength of LSD samples obtained currently from illicit sources ranges from 20 to 80 mcg of LSD per dose. This is considerably less than the levels reported during the 1960s and early 1970s, when the dosage ranged from 100 to 200 mcg or higher per unit.
Health hazards: LSD’s effects are unpredictable. They depend on the amount taken; the user’s personality, mood, and expectations; and the surroundings in which the drug is used. Usually, the user feels the first effects of the drug 30 to 90 minutes after taking it. The physical effects include dilated pupils, higher body temperature, increased heart rate and blood pressure, sweating, loss of appetite, sleeplessness, dry mouth, and tremors.
Sensations and feelings change much more dramatically than the physical signs. The user may feel several different emotions at once or swing rapidly from one emotion to another. If taken in sufficient quantity, the drug produces delusions and visual hallucinations.
Some LSD users experience severe, terrifying thoughts and feelings, fear of losing control, fear of insanity and death, and despair while using LSD. It is difficult to determine the extent and mechanism of the LSD involvement in these experiences. Over time, most users voluntarily decrease or stop LSD use. LSD is not considered an addictive drug because it does not produce compulsive drug-seeking behavior as do cocaine, amphetamines, heroin, alcohol, and nicotine.
However, like many of the addictive drugs, LSD produces tolerance, so some users who take the drug repeatedly must take progressively higher doses to achieve the state of intoxication they previously had achieved.
6. Phencyclidine: Phencyclidine (PCP) is most often used in areas where other more desirable agents are less available. PCP is incorrectly considered to be less addictive than opiates or cocaine and carries the potential of creating addictions that require treatments as compre hensive as those given to users of other classic addictive substances.
Common results of its abuse include nystagmus; hypertension; acute brain syndrome (disorientation, confusion, lack of judgment, inappropriate affect, recent memory loss); behavior that is violent, agitated, or bizarre; tachycardia; and hallucinations or delusions.
Less common results are coma, lethargy, generalized rigidity, generalized seizures, localized dystonias, and dyskinesias. Rare effects of its use include facial grimacing, athetosis, hypersalivation, bronchorrhea, and cardiac arrest.
Complications: Rhabdomyolysis is reported in about 2.2%; it may progress to myoglobin - uric renal failure. Rare complications include aspiration pneumonia, pulmonary embolism, intracranial hemorrhage, diffuse intravascular clotting, liver necrosis, drowning, and traumatic injury.
Hypertension is a hallmark sign (incidence 57%), usually resolving within four hours but uncommonly persisting for more than 24 hours. Onset of hypertensive crisis may be delayed for several days, usually precipitated by complications (agitation, seizures, intracerebral hemorrhage, or hemodynamic changes during dialysis). Mild tachycardia also is common.
Apnea and laryngealstridor often are related to grand mal seizures and usually are self-limited. Rarely, mechanical ventilation is required for hours or days. Tachypnea, bronchospasm, and bronchorrhea also may occur.
Marked paranoid behavior, combativeness, seizures, muscle rigidity, respiratory depression, and coma with the eyes open are common diagnostic clues. Although extremely rare in the absence of trauma, intracranial hemorrhage may occur.
PCP crosses the placenta and may result in neonatal irritability, jitteriness, coarse tremors, nystagmus, and poor feeding.
Contaminants: Illicit phencyclidine is rarely available as the pure crystalline substance. Liquid products contain solvents used in the manufacturing process, such as benzene, toluene, cyclohexanol, isopropanol, phenol, and ether.
A common contaminant is PCC, an intermediate in synthesis that releases hydrogen cyanide when smoked or heated; amounts range from 10% to 70%. At the usual recreational doses of 2.5 to 6 mg, acute cyanide toxicity is possible; nausea, vomiting, abdominal cramps, cyanosis, and coma have been attributed to PCC. Other pharmacologically active adulterants include phenylpropanolamine, benzocaine, procaine, ephedrine, caffeine, ketamine, and piperidine.
7. Inhalants: Inhalants are breathable chemical vapors that produce psychoactive (mind-altering) effects. Although people are exposed to volatile solvents and other inhalants in the home and in the workplace, many do not think of inhalable substances as drugs because most of them were never meant to be used in that way.
Young people are likely to abuse inhalants, in part because inhalants are readily available and inexpensive. Sometimes, children unintentionally misuse inhalant products that are found in household products. Parents should see that their children do not have access to them. Inhalants fall into the following categories:
— Solvents:
• industrial or household solvents or solvent-containing products, including paint thinners or solvents, degreasers (dry-cleaning fluids), gasoline, and glues;
• art or office supply solvents, including correction fluids, felt-tip marker fluid, and electronic contact cleaners.
— Gases:
• gases used in household or commercial products, including butane lighters and propane tanks, whipping cream aerosols or dispensers (whippets), and refrigerant gases;
• household aerosol propellants and associated solvents in items such as spray paints, hair or deodorant sprays, and fabric protector sprays.
• medical anesthetic gases, such as ether, chloroform, halothane, and nitrous oxide (laughing gas).
— Nitrites: aliphatic nitrites, including cyclohexylnitrite, which is available to the general public; amyl nitrite, which is available only by prescription; and butyl nitrite, which is now an illegal substance.
Health hazards: When inhaled via the nose or mouth into the lungs in sufficient concentrations, inhalants can cause intoxicating effects. Intoxica tion can last only a few minutes or several hours if inhalants are taken repeatedly. Initially, users may feel slightly stimulated; with successive inhalations, they may feel less inhibited and less in control; finally, a user can lose consciousness.
Sniffing highly concentrated amounts of the chemicals in solvents or aerosol sprays can directly induce heart failure and death. This is especially common from the abuse of fluorocarbons and butane-type gases. High concentrations of inhalants also cause death from suffocation by displacing oxygen in the circulation.
Other irreversible effects caused by inhaling specific solvents are as follows:
• hearing loss: toluene (paint sprays, glues, de-waxers) and trichloroethylene (cleaning fluids, correction fluids);
• peripheral neuropathies or limb spasms: hexane (glues, gasoline) and nitrous oxide (whipping cream, gas cylinders);
• central nervous system or brain damage: toluene (paint sprays, glues, de-waxers);
• bone marrow damage: benzene (gasoline).
Serious but potentially irreversible effects include:
• liver and kidney damage: toluene-containing substances and chlorinated hydrocarbons (correction fluids, dry-cleaning fluids);
• blood oxygen depletion: organic nitrites ("poppers," "bold," and "rush") and methylene chloride (varnish removers, paint thinners).
Death from inhalants usually is caused by a very high concentration of fumes. Deliberately inhaling concentrated fumes in a paper or plastic bag or in a closed area greatly increases the chances of suffocation.
Amyl and butylnitrites have been associated with Kaposi’s sarcoma (KS), the most common cancer reported among AIDS patients. Early studies of KS showed that many people with KS had used volatile nitrites.
Researchers are continuing to explore the hypothesis of nitrites as a factor contributing to the development of KS in people infected with HIV.
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