MEPERIDINE

OFFICIAL NAMES: Meperidine, meperidine hydrochloride, Demerol, Pethidine

STREET NAMES: Demmies

DRUG CLASSIFICATIONS: Schedule II, narcotic

OVERVIEW

Meperidine is a synthetic, opioid analgesic. An analgesic is any drug or substance that, when ingested or injected, diminishes or relieves pain. Another word for analgesic is "painkiller." Many different drugs act as analgesics. One method of classifying analgesics is to distinguish between those that require a doctor's prescription and those that do not. Medications obtainable without a doctor's prescription are known as over-the-counter (OTC) drugs. OTC analgesics are the most familiar, and include such medications as acetaminophen (Tylenol), aspirin, and ibuprofen (Advil; Midol).

The most effective and widely used prescription analgesics belong to a class of drugs known as opioids. Opioid drugs can be classified as natural, semi-synthetic, or synthetic. Natural opioids are also frequently referred to as opiates. Both terms, opiate and opioid, are derivations of opium. The drug groups were so-named because they produce effects similar to opium, which itself is a plant-based, chemically complex drug. Opium has been used throughout recorded history for both medicinal and recreational purposes.

Opium is made by drying the liquid that comes from the unripe seed capsule of the opium poppy, a flowering plant common to certain parts of the world. References to opium and its medicinal value have been found in writings dating from several thousand years ago. Up until the twentieth century, opium was prized for its ability to alleviate pain, treat diarrhea, and elevate mood. In addition to its well-established use as a treatment for pain and diarrhea, opium was touted and used as a cure for a wide range of other medical problems. In truth, however, opium had little or no real medical effects on the majority of those conditions. Instead, its ability to produce euphoria, a profound sense of well-being and calmness (elevated mood), made opium appear to be a highly effective medicine. After all, regardless of the illness or condition, a person who used opium nearly always felt better, whether or not they were truly getting better. In higher quantities, opium is also effective at inducing sleep. In fact, the scientific name for the opium poppy is Papaver somniferum, Greek for "poppy that causes sleep." In even greater quantities, opium can induce coma and death.

Although opium has genuine medical benefits, it also poses significant risks. Perhaps most important is the inherent difficulty in predicting how weak or strong opium's effects will be on any particular occasion. The concentrations of the primary active chemicals, morphine and codeine, can vary significantly from one batch of opium to the next. One reason a drug abuser might prefer prescription over illegal drugs is that they always know how much of a prescription drug they are taking. Someone who buys heroin, for instance, could be getting a nearly pure drug, or could be purchasing mostly cornstarch. Used as a medicine, opium was a risky proposition. Once the technologies in chemistry were developed, researchers in medicine and pharmacology were eager to purify the active chemicals in opium.

Along with knowledge of its desirable effects, people in ancient times were no doubt also aware of opium's undesirable effects. Serious forms of psychological and physical addiction can develop after even short-term opium use. The highly addictive nature of opium, and by extension the opioids, tends to overshadow all other issues related to the drugs. Aside from developing predictable drugs, the primary reason for previous and ongoing research in this area is to develop a powerful analgesic with as few of the harmful side effects of opium and the current opioids as possible. Addictive potential is the side effect researchers would most like to eliminate.

It was not until 1806 that a German chemist was able to isolate morphine from opium. This was a major breakthrough in pharmacology; a pure, highly effective analgesic was finally available. Unlike opium, morphine's potency is always the same, which allows for accurate scientific study of its effects. Data from studies of morphine have provided specific information about the safest and most effective dosages to use.

Morphine was the first limited success of attempts to improve on opium. The medical community was initially hopeful that, in addition to its analgesic power, morphine would be the break-through drug for treating opium addiction. In fact, morphine was successful in that regard; opium addicts that were given morphine were often cured of their addiction. However, it became painfully clear that those same patients developed an equally powerful addiction to morphine. The isolation of codeine in 1832 was also a limited success; it produces fewer side effects and is less addictive, but is much less potent than morphine.

Meperidine was first synthesized in the late 1930s, and was one of the first synthetic opioids. The fact that both morphine and codeine are still widely used, though, indicates that meperidine, along with all of the opioids produced since that time, have been only modest successes. Research continues with the hope of discovering the "perfect" opioid analgesic.

To understand the benefits and drawbacks of opioid drugs, one needs to understand their primary effects on the body; specifically, how they function as pain relievers. In the broadest sense, there are two types of pain—physical and emotional. Physical pain, while unpleasant, is necessary for survival. It serves as notification of the presence of injury or disease, which in turn prompts a person to take appropriate, possibly even life-saving action. Half of all individuals who seek medical attention report pain as their primary complaint.

Opioids produce their effects by interacting with cell-surface proteins known as opioid receptors. An opioid, whether endogenous (naturally produced by the body) or in drug form, fits into a receptor somewhat like a key in a lock. This activates the receptor and initiates complex changes in the nerve cell. Activated opioid receptors produce chemical changes that reduce the ability of a nerve cell to transmit pain signals. They also decrease the "perception" of pain by neurons in the brain. If opioids are used when one is not in pain, those same chemical changes in the brain's nerve cells can produce feelings of euphoria.

In a basic sense, both the good (analgesia) and bad (addiction) effects of opioids are caused by the same process: the interaction of drugs with nerve cells, especially those in the brain. As a neuron transmits or processes pain signals, it is functioning in an abnormal, hyperactive state. Opioids work to reduce that activity and bring the neuron back toward a more normal state. Applying the opioid effect to a neuron that is already in a normal state, however, tends to force the response of neurons in the opposite direction of pain, toward pleasure (euphoria). If neurons remain in this artificially produced state for any length of time, they become tolerant of the effect. Once the opioid is removed, the affected neurons move back toward the pain end of the spectrum, something known as the "rebound effect."

People that use meperidine for acute pain, such as after an injury, typically do not have long enough exposure to develop tolerance and addiction. People with chronic pain, however, may develop some tolerance and physical addiction in the sense that, if they stop the drug, their pain returns. Only rarely, though, do people using opioids long-term for legitimate medical reasons develop psychological addiction. A person who begins abusing an opioid drug to get high, and continues using the drug, will develop both physical and psychological tolerance and addiction. Eventually, they will need the drug not to get high, but to keep from having the pain of withdrawal. These scenarios also apply to endogenous opioids, although to a much lesser extent. For instance, athletes that produce high levels of endorphins—one of the endogenous opioids—after exercise often report that they feel depressed if they stop exercising.

CHEMICAL/ORGANIC COMPOSITION

Meperidine hydrochloride (the full name) is a synthetic opioid. It is synthesized by the reaction of chemicals not found in opium. Specifically, meperidine hydrochloride is produced by the reaction of dichlorodiethyl methylamine with benzyl cyanide, to produce ethyl 1-methyl-4-phenyl-isonipecotate hydrochloride (meperidine's chemical name). Some references to meperidine classify it as a totally synthetic opioid. Semi-synthetic opioids are produced by using one of the opiates as a starting material. Two examples of semi-synthetic opioids are hydrocodone and heroin. Hydrocodone is produced by the chemical modification of codeine, while heroin is made by chemically altering morphine.

Although morphine and meperidine are quite similar in their clinical effects, they are not that similar in chemical composition. The important chemical determinant of an opioid analgesic, however, is not its structural resemblance to morphine, but its ability to bind with and activate an opioid receptor.

INGESTION METHODS

Meperidine can be taken orally or injected. Oral forms include tablets and syrup. Dosages of tablets range from 25 mg to 100 mg meperidine per tablet. The syrup form contains 50 mg meperidine per 5 ml. The typical dosage is from 50 mg to 150 mg every three to four hours.

Injections of meperidine can be given intramuscularly (in the muscle), subcutaneously (under the skin), and intravenously (directly into the bloodstream). The body responds more readily to meperidine when it is injected, so dosages are usually about half that of the oral form, again every three to four hours. As with other opioids, intravenous administration of meperidine is often given at a low, continual dose.

Patients recovering from surgery can request that meperidine be administered through a system known as patient controlled anesthesia (PCA). This system allows a patient to administer his or her own medication in small doses. The machine has an electronic control mechanism that allows only a specific amount of meperidine to be administered by the patient each hour. PCA alleviates the need for a nurse to give the patient an intramuscular injection every three to four hours, and keeps meperidine in the body at a more constant level.

THERAPEUTIC USE

Meperidine is used for the treatment of moderate-to-severe pain, most commonly following surgery. It is sometimes given as an adjunct to anesthesia just before and during surgery. Meperidine also remains one of the more frequently used opioid analgesics in obstetric departments for severe pain during labor and delivery. Meperidine may be preferred over morphine after surgery because it produces less nausea and constipation in most people.

Meperidine is generally not recommended for use in infants and small children. Likewise, the elderly may have underlying medical conditions that present special risks with meperidine use.

Meperidine is occasionally used in outpatients for the treatment of acute pain, especially if other opioids prove ineffective. Its use for chronic pain is less accepted. Meperidine is eliminated from the body more quickly than other opioids, which means it must be taken more frequently, and its analgesic effects fluctuate more rapidly.

USAGE TRENDS

A study published in the Journal of the American Medical Association in 2000, obtained Drug Enforcement Administration (DEA) data on trends in legitimate medical use of several opioid medications, including meperidine, for the period of 1990 to 1996. In that seven-year span, meperidine use in the United States decreased by 35% (5,200 kg to 3,400 kg).

In the early 1980s, approximately 15,400 kg of meperidine were consumed worldwide each year. By 1999, that figure decreased to 12,200 kg, a 20% drop. Most of the decrease in the use of meperidine may be due to the ongoing development of other safer, longer lasting Schedule II opioids.

Scope and severity

One method of analyzing the issue of drug abuse is to compare and contrast the abuse of illegal drugs (marijuana, cocaine, etc.) with that of legal drugs (OTC and prescription medications). The majority of national and international attention and resources go toward illicit drug abuse. However, prescription drug abuse is a large and growing proportion of the complete drug abuse picture.

Each year, the National Household Survey on Drug Abuse (NHSDA)—the United States Department of Health and Human Services—collects statistical data on five drug groups: marijuana and hashish; psychotherapeutic drugs; cocaine and crack; hallucinogens; and inhalants. Psychotherapeutic drugs include stimulants, sedatives, tranquilizers, and pain relievers. Meperidine and other opioids constitute the majority of the pain relievers in that group.

In 2000, the NHSDA found 1.7% of all people 12 years and older reported nonmedical use of any psychotherapeutic medication during the previous month. More than nine million Americans over age 12 reported use at any time during the year. Those in the 18 to 25-year-old age group have the highest rates of drug abuse. In 2000, 3.6% of individuals in that age group reported nonmedical use of prescription drugs in the month prior to the date on which they were surveyed, but less than half that many, 1.6%, reported the same type of drug abuse in 1994. An estimated 1.6 million Americans used prescription pain relievers nonmedically for the first time in 1998. During the 1980s, there were generally fewer than 500,000 first-time users per year.

The study in the Journal of the American Medical Association mentioned previously also analyzed data from The Drug Abuse Warning Network (DAWN). As mentioned, the study showed a 35% decrease in the medical use of meperidine. However, use of the other four opioid drugs studied (morphine, fentanyl, oxycodone, and hydromorphone) increased, such that the group as a whole showed a cumulative increase of nearly 250%. Data collected from DAWN for the same time-period showed a 7% increase in emergency room mentions of abuse of these drugs. By comparison, the reports of abuse of illicit drugs increased 110%. Admittedly, the data collected by DAWN evaluates only one facet of the drug abuse problem—drug abuse that contributes to emergency room visits. However, from these data at least, it does not appear that a significant increase in medical use of opioid drugs resulted in a proportionate increase in abuse. Further studies looking at a broader picture of opioid analgesic abuse are needed.

Age, ethnic, and gender trends

Between 1990 and 1998, abuse of some illegal drugs among teens and young adults leveled off or decreased slightly. However, increases in new users of prescription pain relievers were reported in young teens, age 12–17, as well as in young adults age 18–25. In 2000, the NHSDA found that the youngest teens, age 12–14, reported psychotherapeutic medications as the most frequent drugs of abuse, making up 53% of the total of all drug abuse reports. Teens and young adults in the 18–25 age group reported prescription drug abuse at a rate of 36%, while 28% of those over age 26 reported that type of abuse. Most teenagers begin prescription drug abuse by taking another person's medication, usually someone from their family. Teens are also more likely than adults to be acquainted with someone illegally who sells prescription drugs like meperidine.

On the other end of the age spectrum, prescription drug abuse among older adults is also a growing concern. Persons 65 and older comprise 13% of the United States population, but consume about 33% of all prescription drugs. A study of 1,500 elderly patients found that 3% were abusing prescription drugs. Unlike people in younger age groups, however, the elderly are more likely to misuse prescription drugs than abuse them. If abuse does occur, it may begin with misuse due to inappropriate prescribing or the patient not following instructions correctly.

The NHSDA study showed that boys in the youngest age group (12–17) are more likely to experiment with illegal drugs, but girls of that age have a 20% higher rate of prescription drug abuse. In addition, for all teens of that age who abuse prescription drugs, girls are twice as likely to become addicted as boys are. Women are also more likely to abuse and become addicted to prescription drugs in the young-and middle-adult age groups. Part of this may be that women are prescribed potential drugs of abuse more often than men are. Finally, a survey of elderly persons admitted to a treatment program found that 70% were female. Of the various drugs of abuse in that group, 70% were opioids. At all age groups, whites are more likely than other racial or ethnic groups to abuse prescription drugs.

Health professionals (doctors, nurses, dentists, veterinarians, etc.) and their staff may be at risk for meperidine abuse because of their ready access to the drug. Several highly publicized cases involving health care workers who removed injectable meperidine from vials for their own use—and replaced it with some other (harmless) liquid to give to the patient—would seem to lend credence to that argument. On the other hand, one would expect health care workers to be at lesser risk due to their training and knowledge of the effects of drug abuse. In fact, the publicized cases of meperidine theft present an unbalanced picture, since health care workers do not appear to have rates of meperidine or other opioid abuse much different from the rest of the population.

MENTAL EFFECTS

As with all opioids, meperidine is capable of producing euphoria. A few people may get a mild stimulant effect and a feeling of elation. However, instead of euphoria after a meperidine dose, some people report a feeling of dysphoria—a general feeling of discomfort and restlessness—or even disorientation and confusion. Still other people may just feel drowsy, with no noticeable positive or negative effect on their mood.

It remains a misconception that opioids offer no true analgesic effect, but instead produce a type of euphoria that simply results in one not caring about one's pain. With the available detailed knowledge of the interaction between opioids and opioid receptors in the central nervous system, that myth has been dispelled. Up to a limit (usually an amount great enough to produce serious side effects), the more meperidine ingested in a single dose, the greater the analgesia and the more pronounced the mental effects.

PHYSIOLOGICAL EFFECTS

Other than analgesia, the most common physiological effects produced by medicinal quantities of meperidine are nausea, vomiting, dry mouth, dizziness, constipation, and itchy skin. These relatively harmless side effects typically disappear in most people after taking the drug for several days, or by reducing the dosage. For most people, higher doses of meperidine are more likely to produce side effects. For those who experience side effects at lower doses, any higher dose is likely to make them more pronounced.

Harmful side effects

The complication of greatest concern is respiratory depression. Opioids affect the area of the brain that controls breathing. A large enough single dose of any opioid, including meperidine, can stop breathing completely, resulting in death. Combining meperidine with another central nervous system depressant, such as alcohol or sedatives, is especially risky. While drowsiness itself is not a harmful side effect, it can be dangerous if someone drives or engages in some other activity that requires them to be alert.

Meperidine presents a higher risk for seizures than other opioids. Seizures induced by meperidine also tend to be resistant to treatment with opioid antagonists. Therefore, people with a history of seizures, and those at increased risk for first occurrence of a seizure (such as someone with head trauma) should avoid meperidine if possible. Other potential neurological side effects include tremors, delirium, and hallucinations. These side effects are uncommon, but serious. Some people may have an allergic reaction to meperidine, and severe cases can involve respiratory arrest; cold, clammy skin; generalized weakness; and unconsciousness or coma.

Patients with kidney or liver disease should exercise caution when using meperidine for any length of time. A by-product of meperidine, normeperidine, is broken down in the liver and excreted by the kidneys. Someone with impaired function of either organ may develop high levels of normeperidine, which can be toxic to the nervous system. Some people, especially the elderly, may have no history of kidney or liver disease, but can have reduced kidney and liver function following surgery. Therefore, if elderly patients must be given meperidine, the safest course may be to limit its length of use as much as possible.

Long-term health effects

Direct, negative effects on long-term health from chronic meperidine use are mostly limited to the slight possibility of central nervous system damage. There are surprisingly few other adverse health effects as far as organ or tissue damage is concerned. This is in contrast to most other abused drugs, with alcohol and tobacco being the obvious examples, and does not match the social stigma associated with opioid drugs.

Compared with other drugs, the relative lack of direct organ or tissue damage from meperidine use is counterbalanced by its high risk for abuse and addiction. High addiction potential in a drug typically means a high risk for long-term use. Long-term use can include either years of continual use or a repeated cycle of use and abstinence. The latter can be especially difficult with meperidine, given the potentially serious withdrawal symptoms associated with abruptly stopping the drug. People with meperidine or other prescription drug addiction are less likely to seek professional help than those who abuse illegal drugs. This may be due to a misperception that addiction to prescription drugs cannot or should not be as serious as illegal drug addiction. Unfortunately, self-treating an addiction usually involves abrupt cessation of the drug, with negative health effects.

The longer and more heavy the abuse, and the more suddenly the drug is ceased, the more serious and painful the withdrawal symptoms will be. Symptoms of withdrawal associated with physical addiction can include restlessness, muscle and bone pain, insomnia, diarrhea, runny nose, chills with goose bumps, and involuntary leg movements. The involuntary leg movements associated with opioid withdrawal are what originally led to the phrase "kicking the habit." In addition, the goose bumps that often occur during withdrawal originated the use of the phrase "quitting cold turkey," since the person's skin resembles that of cold turkey skin. Signs of withdrawal associated with psychological addiction include strong dysphoria (feeling badly) and a nearly uncontrollable craving for the drug.

REACTIONS WITH OTHER DRUGS OR SUBSTANCES

Some who abuse opioids are under the mistaken impression that using alcohol with the drug will enhance its effects. Like meperidine, alcohol is a cental nervous system depressant, so when both are used together, the risk for respiratory depression and death increases. Also, because alcohol impairs judgment, a drunk person is more likely to believe he can handle more of the drug than he truly can, just as many intoxicated people dangerously believe they are much better drivers than they are. Most people who end up in hospital emergency rooms after an opioid overdose were also using alcohol.

Other classes of drugs that should be avoided when using meperidine include benzodiazepines (drugs in the same class as Valium), most antihistamines, and sedatives/hypnotics (sleeping pills). Several types of antidepressants, including tricyclics, selective serotonin reuptake inhibitors (SSRIs, drugs in the same class as Prozac), and especially monoamine oxidase inhibitors (MAOIs), should be used with great caution or not at all in combination with meperidine. In general, any other central nervous system depressant should either be avoided or used under the guidance of a physician when taking meperidine.

TREATMENT AND REHABILITATION

As a Schedule II opioid narcotic, meperidine is highly addictive. Treatment for opioid overdose usually involves administration of an opioid antagonist such as Narcan (naloxone), which reverses or blocks the effects of the drug. However, in some cases, those who overdose on meperidine do not respond well to opioid antagonists.

Most people who overcome meperidine addiction do so by themselves, but some may need professional assistance. In either case, it is invaluable for someone to have the help and support of friends and family. For chronic addiction (drug use and addiction lasting more than one year), meperidine may be replaced by methadone, another opioid medication. The patient receives methadone either through a physician or through a qualified drug treatment program. In a structured setting, the patient and health care professionals have a much better chance of controlling drug use with methadone, and eventually may achieve complete abstinence. Methadone need only be taken once a day, it reduces or eliminates withdrawal symptoms and the craving for meperidine, and it has fewer side effects.

PERSONAL AND SOCIAL CONSEQUENCES

Meperidine and the other opioids do offer great personal and social medical benefits. However, these benefits must be weighed against the potential costs of abuse and addiction. The social consequences of having a broad range of effective analgesics to treat chronic pain are significant. Conditions associated with chronic pain are the largest contributors to lost work time and decreased productivity. In addition, in the long-term, many individuals with ineffectively treated pain only add to the medical costs society must bear. Therefore, doctors must weigh the risks and benefits of prescribing meperidine for each individual. Careful use of meperidine and other opioids would seem to present much greater social benefits than costs.

Personal costs—financial, physical, and emotion-al—can be huge for those individuals who abuse meperidine and become addicted. An established addiction can be expensive to maintain. Many people describe a serious opioid addiction as "all consuming"; everything in their lives eventually revolves around obtaining more of the drug. With the drug as their focus, they lose friends, alienate family members, and may be unable to hold a job. Those who are caught committing crimes to maintain their addiction may pay a very high price—loss of their freedom. Finally, whether through overdose or violence, those who abuse prescription or illicit drugs may pay the ultimate price—loss of their life.

Evidence indicates that proper meperidine prescription for legitimate medical concerns does not greatly increase the risk of addiction and abuse. Those in the medical community agree that more education is needed by both doctors and patients to help prevent the potential for abuse and addiction, so that patients truly in need are not denied access to meperidine based on misperceptions and fear. The benefits for individuals and society are great when pain is treated safely and effectively.

LEGAL CONSEQUENCES

As a Schedule II drug, meperidine is strictly controlled in the United States, as well as in other parts of the world. Its manufacture and distribution in the United States are controlled by the Food and Drug Administration (FDA) and the Drug Enforcement Administration (DEA). International control is overseen by the International Narcotic Control Board (INCB).

Hospital and community pharmacies exercise special caution when dispensing meperidine and other controlled substances. In an emergency, a doctor may choose to telephone the patient's pharmacy with the prescription. However, for medications such as meperidine, telephoned prescriptions can usually only provide a small amount of the drug, and the doctor must provide their DEA number and some relevant medical information. Refills for Schedule II medications are not allowed; a patient must obtain a new prescription from their doctor.

It is illegal to write a prescription or an order for meperidine without a valid medical license. Professionals who may legally write prescriptions or orders for meperidine include medical doctors, doctors of osteopathy, podiatrists, dentists, and veterinarians. Physicians or dentists who knowingly write multiple prescriptions for patients without a valid medical reason may end up in prison. Writing and filling bogus prescriptions for profit is an even more serious offense.

Likewise, it is illegal to obtain, or try to obtain, prescriptions for meperidine or other opioids under false pretenses (fabricated symptoms and scenarios). Nineteen states have a law (a felony in some) prohibiting patients from obtaining the same controlled substance from multiple prescribers within a limited time-period ("doctorshopping"). The perpetrators of crimes involving prescription drugs are most often white, middle-class women. Their crimes usually involve doctor-shopping and/or prescription forgery.

Many people argue that increased production of opioid drugs leads to increased rates of abuse and addiction. The national attention on burglarized pharmacies, and drugs pilfered from hospitals, seem to bolster this argument. However, studies have consistently shown that patients with chronic pain who use opioids appropriately rarely become addicted. In 2001 and 2002, a number of groups that advocate for effective pain management joined with government agencies, including the DEA, to begin a long-term effort to increase the availability of effective pain-management drugs for patients, while decreasing the chances for illegal use and abuse.

See also Codeine; Designer drugs; Fentanyl; Heroin; Morphine; Opium; Oxycodone

RESOURCES

Books

American Cancer Society. American Cancer Society's Guide to Pain Control. Atlanta: American Cancer Society Health Content Products, 2001.

Booth, Martin. Opium: A History. New York: St. Martin's Press, 1996.

Courtwright, David T. Forces of Habit: Drugs and the Making of the Modern World. Cambridge, MA: Harvard University Press, 2001.

Kuhn, Cynthia, et al. Buzzed: The Straight Facts about the Most Used and Abused Drugs from Alcohol to Ecstasy. New York:W.W. Norton and Company, Inc., 1998.

Rudgley, Richard. Essential Substances: A Cultural History of Intoxicants in Society. New York: Kodansha America, Inc., 1994.

Periodicals

Brookoff, Daniel. "Chronic Pain: 1. A New Disease?" Hospital Practice 35 (July 15, 2000): 45-59.

Brookoff, Daniel. "Chronic Pain: 2. The Case for Opioids." Hospital Practice 35 (September 15, 2000): 69-84.

Carver, Alan. "Medical Use and Abuse of Opioid Analgesics." Neurology Alert 18 (June 2000): 77.

Demott, Kathryn. "Opioids Still Worthwhile Despite Street-Drug Taint." Clinical Psychiatry News 29 (June 2001): 46.

Foster, Roxie L. "Pain Management." Journal of the Society of Pediatric Nurses 1 (July-Sept. 1996): 93.

Joranson, David E., et al. "Trends in Medical Use and Abuse of Opioid Analgesics." The Journal of the American Medical Association 282 (April 5, 2000): 1710-4.

Kettelman, Karen. "What's So Bad About Meperidine?" Nursing30 (October 2000): 20.

Mitka, Mike. "Abuse of Prescription Drugs: Is a Patient Ailing or Addicted?" The Journal of the American Medical Association283 (March 1, 2000): 1126.

Potter, Michael, et al. "Opioids for Chronic Nonmalignant Pain." Journal of Family Practice 50 (February 2001): 145.

Reidenberg, Marcus M. "Clinical Pharmacology." The Journal of the American Medical Association 273 (June 7, 1995): 1664-5.

Rich, Ben A. "Physicians' Legal Duty to Relieve Suffering." The Western Journal of Medicine 175 (September 2001): 151.

Rowbotham, David J. "Endogenous Opioids, Placebo Response, and Pain." The Lancet 357 (June 16, 2001): 1901.

Self, Timothy H. "Minimizing Risk of Meperidine Neurotoxicity." The Journal of Critical Illness 16 (May 2001): 237.

Sullivan, Louis W. "The Painkiller Prescription: Protect Use, Prevent Abuse." The Journal of Musculoskeletal Medicine 18 (September 2001): 438.

Other

Painfully Obvious: The Effects of Abusing Prescription Drugs.2002. <http://www.painfullyobvious.com>.

United Nations Office for Drug Control and Crime Prevention. (April 4, 2002). <http://www.undcp.org>.

The Vaults of Erowid: Documenting the Complex Relationship between Humans and Psychoactives. 2002. <http://www.erowid.org>.

Organizations

Drug Enforcement Administration (DEA), Information Services Section (CPI), 2401 Jefferson Davis Highway, Alexandria, VA, USA, 22301, <http://www.usdoj.gov/dea>.

National Institute on Drug Abuse (NIDA), National Institutes of Health, 6001 Executive Boulevard, Room 5213, Bethesda, MD, USA, 20892-9561, (301) 443-1124, (888) 644-6432, [email protected], <http://www.drugabusegov/NIDAHome.html>.

Office of Disease Prevention and Health Promotion, U.S. Department of Health and Human Services, 200 Independence Avenue SW., Room 738G, Washington, DC, USA, 20201, (202) 401-6295, <http://odphp.osophs.dhhs.gov>.

Office of FirstGov c/o GSA, 750 17th Street, N.W., Suite 200, Washington, DC, USA, 20006-4634, <http://www.whitehousedrugpolicy.gov>.

Substance Abuse and Mental Health Services Administration (SAMHSA), U.S. Dept. of Health and Human Services, 5600 Fishers Lane, Rockville,, MD, USA, 20857, (301) 443-6239, [email protected], <http://www.samhsa.gov>.

Substance Abuse and Mental Health Services Administration (SAMHSA)/Center for Substance Abuse Treatment (CSAT), 5600 Fishers Lane, Rockville, MD, USA, 20857, (301) 443-5700, [email protected], <http://www.samhsa.gov>.

U.S. Food and Drug Administration (FDA), 5600 Fishers Lane, Rockville, MD, USA, 20857-0001, (888) 463-6332, <http://www.fda.gov>.

Scott J. Polzin, MS