buprenorphine {suboxone , subutex }

1. Buprenorphine{Suboxone�, Subutex�} Herbert D. Kleber, M.D. Professor of Psychiatry, Columbia University College of Physicians & Surgeons Director, Division on Substance Abuse, NYSPI

3. How Does Buprenorphine Work? High Affinity for Mu Opioid Receptor Competes with other opioids and blocks their effects Displaces heroin or other opiates from receptors(This can produce withdrawal if patient has opiates in system) Slow Dissociation from Mu Opioid Receptor Prolonged therapeutic effect > 24 hours �Ceiling Effect� on Opiate Effects Poor drug for intoxication purposes Safer in an overdose Formulated with Naloxone Naloxone is poorly absorbed if taken orally Naloxone blocks opiate effects if injected

4. Agonist Heroin, Morphine, Codeine, Methadone, LAAM Mild-moderate binding to mu receptors Short-acting = Powerful opiate high Long-acting = Weak opiate high Partial Agonist Buprenorphine Strong and long binding to mu receptors But � Relatively weak opiate effect Antagonist Naloxone, Naltrexone Strong binding to mu receptors but does not activate them Thus, blocks all opiates with no opiate effects

5. Methadone Maintenance Treatment As part of a comprehensive rehabilitation program methadone maintenance has been shown to: Decrease illicit opiate use Normalizes immune and endocrine systems Decrease criminal activities Increase pro-social activities

6. Why Not Use Blockers? Naltrexone High non-compliance rates Early gastrointestinal discomfort Possible dysphoric effects No opiate effect �benefits� Useful only in highly selected, highly leveraged, patient populations (i.e., doctors & nurses)

9. Clinical Uses of Buprenorphine Withdrawal & Detoxification Maintenance Prevents withdrawal Diminishes craving Does not produce a �high� Blocks (or reduces effect of) heroin Increases treatment retention

10. Comparison Trials:BUP vs. Methadone Johnson et al. (1992) n=162 BUP 8 mg vs. METH 20 mg vs. METH 60 mg Strain et al. (1994) n=164 BUP 8 mg vs. METH 50 mg for 26 weeks Ling et al. (1996) n=225 BUP 8 mg vs. METH 30 mg vs. METH 80 mg for 52 weeks,

12. Opioid Agonist Medications

13. Buprenorphine Blockade of Hydromorphone Opiate Effects

14. Buprenorphine Summary A Partial Mu-Opioid Agonist As effective as Methadone or LAAM Lower level of physical dependence Lower risk of respiratory depression Abusable, but the combination with naloxone (opiate blocker) reduces diversion to street

15. Buprenorphine Summary WELL ACCEPTED MAINTENANCE THERAPY MILD WITHDRAWAL DECREASES OPIOID USE GREATER SAFETY LOWER DIVERSION POTENTIAL