Clinical Uses

The principles of drug interactions can be used clinically for the treatment of acute INTOXICATION and for WITHDRAWAL—by transforming, reducing, or blocking the pharmacological properties and/or the toxic effects of drugs used and abused for nonmedical purposes. Although these interactions often involve a competition with the abused drug for similar central nervous system RECEPTOR sites, other mechanisms are also clinically relevant.

Disulfiram and Alcohol (Ethanol). One such nonreceptor-mediated interaction involves DISULFIRAM (Antabuse) and ethanol (alcohol). Since an ethanol-receptor site has not yet been conclusively identified, specific receptor agonists and antagonists are not yet available for the treatment of ethanol intoxication, withdrawal, and abstinence (as they are for opioids). Disulfiram is sometimes used in the treatment of chronic ALCOHOLISM, although the drug does not cure alcoholism; rather, it interacts with ethanol in such a way that it helps to strengthen an individual s desire to stop drinking. Although disulfiram by itself is relatively nontoxic, it significantly alters the intermediate metabolism of ethanol, resulting in a five- to tenfold increase in plasma acetaldehyde concentrations. This acetal-dehyde syndrome results in vasodilatation (dilation of blood vessels), headache, difficulty breathing, nausea, vomiting, sweating, faintness, weakness, and vertigo. All of these reactions are obviously unpleasant, especially at the same time, thus well worth avoiding. The acetaldehyde syndrome therefore helps to persuade alcoholics to remain abstinent, since they realize that they cannot drink etha-nol for at least three or four days after taking disulfiram. The consumption of even small or moderate amounts of ethanol following disulfiram pretreatment can result in extremely unpleasant drug interactions through the acetaldehyde syndrome.

Opioids. Drug interactions involving opioids (morphine-like drugs) and opioid receptors are classic examples of how knowledge of the molecular mechanisms of the actions of a class of drugs can assist in the treatment of acute intoxication, withdrawal, and/or abstinence. Naloxone, the opi-oid-receptor antagonist, can be used as a diagnostic aid in emergency rooms. In the case of a comatose patient with unknown medical history, the intravenous administration of naloxone can provide infor mation on whether or not the coma is the result of an opioid overdose. The antagonist competes with the agonist (usually heroin or morphine) for the opioid-receptor sites, displacing the agonist from the binding sites to reverse the symptoms of an overdose effectively and rapidly. Continued naloxone therapy and supportive treatment are often still necessary.

If, however, naloxone is administered to an individual dependent on opioids but not in a coma, a severe withdrawal syndrome develops within a few minutes and peaks after about thirty minutes. Depending on the individual, such precipitated withdrawal can be more severe than that following the abrupt withdrawal of the opioid-receptor agonist (e.g., heroin). In the former instance, the binding of the agonist to opioid receptors is suddenly inhibited by the presence of the antagonist (e.g., naloxone); even relatively large doses of the agonist (e.g., heroin) cannot effectively overcome the binding of the antagonist. Quite the contrary, respiratory depression can develop if higher doses of the agonist are administered. Therefore, opioid-receptor antagonists are not recommended for the pharmacological treatment of opioid withdrawal. Rather, longer acting, less potent, opioid receptor-agonists, such as METHADONE, are more commonly prescribed. Methadone. The symptoms associated with metha-done withdrawal are milder, although more protracted, than those observed with morphine or heroin. Therefore, methadone therapy can be gradually discontinued in some heroin-dependent people. If the patient refuses to withdraw from methadone, the person can be maintained on meth-adone relatively indefinitely. TOLERANCE develops to some of the pharmacological effects of metha-done, including any reinforcing or rewarding effects (e.g., the euphoria or "high"). Therefore, the patient cannot attain the same magnitude of euphoria with continued methadone therapy, although the symptoms associated with opioid withdrawal will be prevented or attenuated. Cross-tolerance also develops to other opioid drugs, so the patient will not feel the same high if heroin is again used on the street.

This type of maintenance program makes those who are heroin dependent more likely to accept other psychiatric or rehabilitative therapy. It also reduces the possibility that methadone patients will continue to seek heroin or morphine outside the clinic. In this way, the principles of drug interac tions involving opioid receptors in the central nervous system have helped to stabilize TREATMENT

strategies for opioid withdrawal and abstinence.

(SEE ALSO: Accidents and Injuries; Complications;

Neurological; Drug Abuse Warning Network)

BIBLIOGRAPHY

Cloninger, C. R., Dinwiddie, S. H., & Reich, T. (1989). Epidemiology and genetics of alcoholism. Annual Review of Psychiatry 8, 331-346.

CREGLER, L. L. (1989). Adverse consequences of cocaine abuse. Journal of the National Medical Association 81, 27-38.

GRIFFIN, J. P. & D'Arcy, P. F. (1997). Manual of adverse drug interactions, Fifth Edition. Oxford: Elsevier Science.

Karalliedde, L. & Henry, J. (Eds.)(1998). Handbook of drug interactions. New York: Oxford University Press, Inc.

KORSTEN, M. A., & LIEBER, C. S. (1985). Medical complications of alcoholism. In J. H. Mendelson & N. K. Mello (Eds.), The diagnosis and treatment of alcoholism, pp. 21-64. New York: McGraw-Hill.

Liebowitz, N. R., Kranzler, H. R. & Meyer, R. E. (1990). Pharmacological approaches to alcoholism treatment. Alcohol Health & Research World, 14, 144-153.

Redmond, D. E., Jr., & Krystal, J. H. (1984). Multiple mechanisms of withdrawal from opioid drugs. Annual Review of Neuroscience 7, 443-478.

Sands, B. F., Knapp, C. M. & Domenic, A. (1993). Medical consequences of alcohol-drug interactions. Alcohol Health & Research World, 17, 316-320.

Drug Free Life

Drug Free Life

How To Beat Drugs And Be On Your Way To Full Recovery. In this book, you will learn all about: Background Info On Drugs, Psychological Treatments Statistics, Rehab, Hypnosis and Much MORE.

Get My Free Ebook


Post a comment