Addictive opiates

As seen in Figure 3.7, the most widely abused opiate pain relievers are Darvocet , Darvon , and Tylenol with codeine , followed by Vicodin, Lortab , and Lorcet . Methadone is the least addicting of the opiate pain relievers and stays in the body the longest. Because of this, methadone is often used as a substitute for morphine, heroin, and other more addictive opiates to wean people off the drug to which they are addicted. 

A common strategy for treating chronic opiate addiction iavolves the substitution of methadone which can either be provided as maintenance therapy or tapered until abstinence is achieved. Naltrexone and buprenorphine [52485-79-7] have also been used ia this manner. The a2 adrenergic agonist clonidine [4205-90-7] provides some rehef from the symptoms of opiate withdrawal, probably the result of its mimicking the inhibitory effect of opiates on the activity of locus coerukus neurons. 

Another agent of this general type is nalmefene (47) Despite their useful characteristics, opiates display tolerance, addiction, abuse, and some toxic side effects Antagonists combat some of these effects, most notably respiratory depression and addiction Nalmefene reputedly has significant oral activity as a narcotic antagonist The synthesis of nalmefine concludes by Wittig olefination of naltrexone (46) to nalmefene (47) This molecular transformation resulted in a significant increase in oral potency as well (141... 

Individuals experiencing dmg withdrawal can become conditioned to environmental situations. Previously neutral stimuli can elicit many of the symptoms of dmg withdrawal, and this conditioned withdrawal has motivational significance especially in alcohol and opiate addiction. Thus conditioned withdrawal may trigger craving and relapse in a particular situation. 

Drug addiction is defined as a syndrome in which drug use (e.g., psychostimulants, opiates, alcohol) pervades all life activities of the user. Life becomes governed by the drug and the addicted patient can lose social compatibility (e.g., loss of partner and friends, loss of job, crime). Behavioral characteristics of this syndrome are compulsive drug use, craving, and chronic relapses that can occur even after years of abstinence. 

Substitution therapy with methadone or buprenorphine has been veiy successfiil in terms of harm reduction. Some opiate addicts might also benefit from naltrexone treatment. One idea is that patients should undergo rapid opiate detoxification with naltrexone under anaesthesia, which then allows fiuther naltrexone treatment to reduce the likelihood of relapse. However, the mode of action of rapid opiate detoxification is obscure. Moreover, it can be a dangerous procedure and some studies now indicate that this procedure can induce even more severe and long-lasting withdrawal symptoms as well as no improvement in relapse rates than a regular detoxification and psychosocial relapse prevention program. 

Two opioids are used in the treatment and management of opiate dependence levomethadyl and methadone. Levomethadyl is given in an opiate dependency clinic to maintain control over the delivery of the drug. Because of its potential for serious and life-threatening proarrhythmic effects, levomethadyl is reserved for use in the treatment of addicted patients who have no response to other treatments. Levomethadyl is not taken daily the drug is administered three times a week (Monday/Wednesday/Thursday or Tuesday/Thursday/ Saturday). Daily use of the usual dose will cause serious overdose. 

Bond C, LaForge KS, Tian M, et al Single-nucleotide polymorphism in the human mu opioid receptor gene alters beta-endorphin binding and activity possible implications for opiate addiction. Proc Natl Acad Sci U S A 95 9608-9613, 1998 Borron SW, Monier C, Risede P, et al Flunitrazepam variably alters morphine, bu-prenorphine, and methadone lethality in the rat. Hum Exp Toxicol 21 399-603, 2002... 

Gossop M, Bradley B, Phillips GT An investigation of withdrawal symptoms shown by opiate addicts during and subsequent to a 21 -day in-patient methadone detoxification procedure. Addict Behav 12 1-6, 1987 GreenJ, Jaffe JH Alcohol and opiate dependence. J Stud Alcohol 38 1274-1293,1977 Green L, Gossop M Effects of information on the opiate withdrawal syndrome. Br J Addict 83 305-309, 1988... 

Jones RT Dependence in non-addict humans after a single dose of morphine, in Endogenous and exogenous opiate agonists and antagonists. Edited by Way EL. New York, Pergamon, 1979, pp 557-560... 

Kleber HD Ultrarapid opiate detoxification. Addiction 93 1629-1633, 1998 Kleber HD, Kosten TR Naltrexone induction psychologic and pharmacologic strategies. J Clin Psychiatry 43 29-38, 1984... 

Krausz M, Degkwitz P, Kuhne A, et al Comorbidity of opiate dependence and mental disorders. Addict Behav 23 767-783, 1998... 

Krausz M, Verthein U, Degkwitz P Psychiatric comorbidity in opiate addicts. Eur Addict Res 5 55-62, 1999... 

Ling W, Weiss DG, Charuvastra VC, et al Use of disulfiram for alcoholics in methadone maintenance programs. Arch Gen Psychiarry 40 851—854, 1983 Ling W, Charuvastra C, Collins JF, er al Buprenorphine maintenance treatment of opiate dependence a multi-center, randomized clinical trial. Addiction 93 475-486, 1998... 

Ross J, Darke S The nature of benzodiazepine dependence among heroin users in Sydney, Australia. Addiction 95 1785-1793, 2000 Rounsaville BJ, Kleber HD Untreated opiate addicts. Arch Gen Psychiatry 42 1072— 1077, 1985b... 

San L, Arranz B Pros and cons of ultrarapid opiate detoxification. Addiction 94 1240-1241, 1999... 

Strang J, Bearn J, Gossop M Lofexidine for opiate detoxification review of recent randomized and open controlled trials. Am J Addict 8 337—348, 1999... 

Woody GE, Luborsky L, McLellan AT, et al Psychotherapy for opiate addicts does it help Arch Gen Psychiatry 40 639—645, 1983 Woody GE, McLellan AT, Luborsky L, et al Severity of psychiatric symptoms as a predictor of benefits from psychotherapy the Veterans Administration-Penn study. Am J Psychiatry 141 1172—1177, 1984 Woody GE, McLellan AT, Luborsky L, et al Twelve-month follow-up of psychotherapy for opiate dependence. Am J Psychiatry 144 590-596, 1987 Yabaluri N, Medzihradsky F Down-regulation of mu-opioid receptor by full but not partial agonists is independent of G protein coupling. Mol Pharmacol 52 896-902, 1997... 

Williams H, Oyefeso A, Ghodse AH Benzodiazepine misuse and dependence among opiate addicts in treatment. It J Psychol Med 13 62-64, 1996 Wiseman SM, Spencer-Peet J Prescribing for alcoholics a survey of drugs taken prior to admission to an alcoholism unit. Practitioner 229 88—89, 1985 Wolf B, Grohmann R, Biber D, et al Benzodiazepine abuse and dependence in psychiatric inpatients. Pharmacopsychiatry 22 54—60, 1989 Wood MR, Kim JJ, Han W, et al Benzodiazepines as potent and selective bradykinin B1 antagonists. J Med Chem 46 1803—1806, 2003 Zawertailo LA, Busto UE, Kaplan HL, et al Comparative abuse liability and pharmacological effects of meprobamate, triazolam, and butabarbital. J Clin Psycho-pharmacol 23 269-280, 2003... 

Ledent C, Valverde L, Cossu G, et al Unresponsiveness to cannabinoids and reduced addictive effects of opiates in CBl receptor knockout mice. Science 283 401-404, 1999... 

---