Addiction opiates

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. 

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. 

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. 

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... 

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

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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... 

In the treatment of chronic diseases, a long term zero order release dosage form is highly desirable as it reduces fluctuations of drug levels, reduces toxicity and increases patient compliance. Problems in the treatment of both hypertension, a lifetime disorder, and opiate addiction are associated with compliance. The goal of this research is to develop a subcutaneously injectable system which can release drug at constant rates over a long period of time. 

Children of opiate addicts have been shown to have poorer social, educational and health status and to be at higher risk of abuse than their peers (Keen et al., 2000). However, given the high rates of psychiatric comorbidity (in particular, depression) in opiate-dependent patients (Brooner et al., 1997 Khantzian and Treece, 1985), it may be that some of the increased risk in children stems from this greater parental depression. Nunes et al. (1998) reported higher incidence of conduct disorder and global and social impairment for children of addicts with major depression compared to addicts without depression and controls, but not compared with children of depressed patients without substance use disorders. 

Finally, intravenous drug administration and the sharing of needles and syringes is common among opiate addicts this creates a serious risk of cross-infection. Many studies have shown a high incidence of HIV and hepatitis B and C among heroin addicts. This risk is somewhat reduced in medically controlled narcotic prescription... 

Gossop M, Green L, Phillips G and Bradley BP (1989). Lapse, relapse and survival among opiate addicts after treatment A prospective follow-up study. British Journal of Psychiatry, 154, 348-353. 

Sell LA, Morris J, Bearn J, Frackowiak RSJ, Friston KJ and Dolan RJ (1999). Activation of the reward circuitry in opiate addicts. European Journal of Neuroscience, 11, 1042-1048. 

Upregulation of the cyclic AMP pathway is one mechanism underlying opiate addiction 411... 

The study of protein phosphorylation has helped to clarify the mechanisms involved in the causes and manifestation of disorders of the nervous system. Two illustrative examples are given here Alzheimer s disease and opiate addiction. 

Upregulation of the cyclic AMP pathway is one mechanism underlying opiate addiction. The mechanisms by which opiates induce tolerance, dependence and withdrawal in specific target neurons has been a major focus of research for many years. The inability to account for prominent aspects of opiate addiction solely on the basis of alterations in endogenous opioid peptides or in opiate receptors has shifted attention to postreceptor mechanisms [66]. 

The noradrenergic neurons of the locus ceruleus have provided a useful model system for the study of opiate addiction (see Ch. 56). Acutely, opiates inhibit these neurons, in part by inhibiting the cAMP pathway via inhibition of adenylyl cyclase. Chronically, these neurons become tolerant to opiates that is, their firing rates recover toward normal levels with continued exposure to the... 

Suboxone (buprenorphine and naloxone), is used in maintenance treatment of opiate addiction. 

Fischer G, Etzersdorfer P, Eder H, Jagsch R, Langer M, Weninger M. (1998). Buprenorphine maintenance in pregnant opiate addicts. Eur Addict Res. 4(suppl 1) 32-36. 

Naloxone (Narcan). Naloxone, like naltrexone, is a potent opioid receptor blocker. Its primary use has been to reverse opiate toxicity after an overdose. However, some physicians have found it is also useful for a process known as rapid opiate detoxification. Although opiate withdrawal is not life threatening, it can be extremely unpleasant. Most opiate addicts are fearful of the withdrawal symptoms therefore, it usually requires a slow, deliberate detoxification to keep the withdrawal symptoms in check. Rapid opiate detoxification is an alternative approach that keeps the taper and detoxification as brief as possible. In this approach, naloxone is used in conjunction with general anesthesia or a nonopiate sedative such as the benzodiazepine mid-... 

In October 2002, the FDA approved two new medications for treating opiate addiction, both developed by Reckitt Benckiser Pharmaceuticals. The new drugs, Subutex (buprenorphine hydrochloride) and Suboxone tablets (buprenorphine hydrochloride and naloxone hydrochloride) contain buprenorphine, a partial opioid agonist. Like methadone, buprenorphine binds to the brain s opioid receptors, but produces significantly reduced pleasurable effects than heroin. 

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