Buprenorphine and Naloxone Clinical Pharmacology Abuse …丁丙诺啡和纳洛酮的临床药理学的滥用….ppt

Buprenorphine and Naloxone: Clinical Pharmacology Abuse Liability John Mendelson MD California Pacific Medical Research Institute and the University of California at San Francisco Presentation Goals Review Buprenorphine Pharmacology Basic Pharmacology Sublingual pharmacokinetics Review Rational for Suboxone (Buprenorphine Naloxone combo tablet) Predicted effects in Buprenorphine treated patients MMT patients Untreated Heroin Addicts Onward Review Buprenorphine Pharmacology Basic Pharmacology Sublingual pharmacokinetics Review Rational for Suboxone (Buprenorphine Naloxone combo tablet) Predicted effects in Buprenorphine treated patients MMT patients Untreated Heroin Addicts Buprenorphine Pharmacology Semisynthetic, highly lipophylic Thebaine derivative 25 to 50 times more potent than morphine Partial μ-agonist Some kappa antagonist effects Clinical significance unclear Pharmacotherapy with Buprenorphine Used as parenteral analgesic in Europe (1o England) for cancer pain and in obstetrics Never caught on in USA May produce less respiratory depression than traditional μ-agonists AnalgesiaBuprenorphine vs. Morphine 0.4 mg Buprenorphine IM equianalgesic with 10 mg Morphine IM Analgesia lasts longer (6 hours) Maximal effects occur later Peak respiratory depression at 3 hours Peak miosis at 6 hours Pharmacological Properties Partial agonist effects suggested by Ceiling on analgesic effects Antagonizes fentanyl induced respiratory depression without complete loss of anesthesia Indicates high affinity for μ-receptor Can precipitate opiate withdrawal in highly μ-dependent people Advantages of Buprenorphine Tolerable dose range (4 to 32 mg SL daily to every 3rd day) for addiction pharmacotherapy Partial agonist Ceiling effects so safer in overdose Less/absent effects in μ-dependent addicts Kappa antagonist Less euphoria Disadvantages of Buprenorphine Can be abused Risk may be greatest in new abusers Is only a partial agonist not suitable for addicts with high