Buprenorphine: A Promising Pharmacotherapy for the Treatment of Opioid Dependence

1. Buprenorphine: A Promising Pharmacotherapy for the Treatment of Opioid Dependence Laura Haynes and Larissa Williams

2. Overview • Heroin • Leading treatment in the U.S.: Methadone • Experimental treatment: Buprenorphine • Naltrexone • Combination Treatment: Buprenorphine and Naltrexone • Differing Approaches and Pharmaco-Philosophy

3. History of Heroin Use in the U.S. • Civil War • New wonder drug: Heroin • Drug Kits • Unregulated and sold legally in the U.S. until 1920 when Congress enacted the Dangerous Drug Act. http://www.heroinaddiction.com/heroin_hist.html

4. Heroin: Why is it so addictive? Heroin is converted to morphine. Physical dependence/addiction. Psychological dependence

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6. Structure of Heroin and Agonists Used to Treat Its Addiction Heroin Methadone Buprenorphine

7. Common Treatment for Addiction • Methadone is used as a replacement for heroin, in treatments aimed at either abstinence or maintenance. 

8. New Treatment • Buprenorphine hydrochloride is a derivative of the morphine alkaloid thebaine. • Buprenorphine is a partial agonist at the µ-opioid receptor and an antagonist at the κ-receptor www.chemfinder.com

9. Side Effects (actual functions?) • Drowsiness • Vomiting • Nausea • Constipation • Itching and Perspiration • Mood Changes

10. Comparison of Methadone with Buprenorphine • Agonist type • full agonist at m-opioid receptor • Partial agonist at m-opioid receptor and weak agonist at k-receptor • Medication form • tablets, solution (oral and parenteral) • parenteral form and sublingual tablet • Dose • 20 to 100 mg, orally • 8 to 24 mg, sublingually • Frequency of administration • daily • daily to three times per week • Potential for abuse • studies in monkeys show to be not as effective at suppressing self administration • efficacy of dose reaches a plateau • high dose increases risk of precipitated withdrawal • Withdrawal • slow dissociation kinetics from receptor result in less severe withdrawal than methadone

11. Naltrexone • Opioid antagonist • blocks opioid induced effects, such as euphoria • lessens reinforcing effects • Limited usefulness • low patient compliance because requires abstinence www.chemfinder.com

12. STOP USE Buprenorphine Naltrexone Combination Treatment: Buprenorphine and Naltrexone • Direct transfer from buprenorphine to naltrexone without detoxification • Combination product

13. Social Implications • Scientific evidence of usefulness is NO indication of acceptance • Available in Europe since 1996 • Approved relatively recently in the United States • Why?

14. Differing Approaches www.flags.net

15. Three Different Approaches(France, Australia, United States) • Acceptance of scientific research • easily accepted and liberal implementation of use in 1996 • large clinical studies and synthesis of worldwide data; approved in 2001 • slow to conduct large-scale clinical trials; long approval process • Distribution and Use • widely available, 10 times more people treated than with methadone • guidelines for use set forth by the government • methadone treatment facilities outside of mainstream medical community • Results • some illegal use resulting in overdose and death • decrease in the number of heroin related deaths

16. Philosophy of Addiction Treatments in the United States • Current Situation… • ideology of abstinence • suspicious of medicinal treatments • What could be done… • inform and involve medical community • lessen paperwork and red tape • Resulting in… • shift from treatment system based in ideology to science • pharmacological treatment within a social and political context

17. Conclusion • Heroin and methadone are highly addictive • Buprenorphine and naltrexone are less addictive • New way of approaching opioid addiction/disease

18. References Journals • Bickel, W.K. and Ammasm L. 1995. Buprenorphine treatment of opioid dependence: A review. Experimental and Clinical Psychopharmacology, 3: 477-489. • Cherubin, C.E.; Sapira, J.D. 1993. The medical complications of drug addiction and the medical assessment of the intravenous drug user: 25 years later. Annals of Internal Medicine, 119: 1017-1028. • Chiang, C.N., and Hawks, R.L. 2003. Pharmacokinetics of the combination tablet of buprenorphine and naloxone. Drug and Alcohol Dependence, 70: S39-S47. • Johnson, R.E., Strain, E.C., and Ammas, L. 2003. Buprenorphine: how to use it right. Drug and Alcohol Dependence, 70: S59-S77. • Ling, W., and Wesson, D.R. 2003. Clinical efficacy of buprenorphine: comparisons to methadone and placebo. Drug and Alcohol Dependence,70: S49-S57. • Ling, W. and Smith, D. 2002. Buprenorphine: blending practice and research. Journal of Substance Abuse Treatment, 23: 87-92. • Mather, L.E. 1987. Opioid pharmacokinetics in relation to their effects. Anaesth Intensive Care,1:15-22. • O’Conner, P.G.; Fiellin, D.A. 2000. Pharmacologic Treatment of Heroin-Dependent Patients. Annals of Internal Medicine, 133: 40-54. • Zhi-Min, L., Xian-Xiang, L., Yue, M., Ping, O., and Xin, A. 2003. Evaluation on drug dependence of buprenorphine. Acta Pharmacol Sin, 24: 428-452. Websites • http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/C/CNS.html • http://www.doctorsreviewservice.com/opiates.htm • http://www.adf.org.au/drughit/smackcat13.html • http://www.chemfinder.com Books • Blain, Jack, D., ed. Bruprenorphine: An Alternative Treatment for Opioid Dependence. Rockville, MD: US Department of Health and Human Services, 1992.

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