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Buprenorphine

Explore the course, treatment, and role of buprenorphine in long-term management of Opioid Use Disorder. Understand the effects, withdrawal symptoms, overdose, and strategies for effective treatment.

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Buprenorphine

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  1. Buprenorphine Daryl Shorter, MD Michael E. DeBakey VA Medical Center Menninger Department of Psychiatry and Behavioral Science Baylor College of Medicine

  2. 22.5 million Americans (8.7%) current users of illicit substances 2.33 million persons with Opioid Use Disorder 426,000 persons with heroin abuse or dependence 1.8 million persons with pain reliever abuse or dependence Alcohol Medical Scholars Program

  3. This Lecture Reviews • Definitions • Course of Opioid Use Disorder (OUD) • Treatment of OUD • Role of buprenorphine in long-term Rx Alcohol Medical Scholars Program

  4. Opioid Brain Effects • Decrease pain (via μ-opioid receptor) • Suppress cough • Increase constipation • Cause euphoria (μ-opioid receptor) Alcohol Medical Scholars Program

  5. Opioids • Heroin – no medical use • Morphine – Rx for pain • All prescription pain meds (unless anti-inflammatory) • Oxycodone (Oxycontin) • Hydrocodone (Vicodin, Lorcet, Lortab) • Methadone (Dolophine) • Buprenorphine (Subutex) • Tramadol (Ultram) Alcohol Medical Scholars Program

  6. DSM-5 Opioid Use Disorder • Tolerance • Withdrawal • Attempts to cut down • Much time spent using • Use larger amounts • Neglecting roles • Hazardous use • Physical/psychological problems from use • Social/interpersonal problems from use • Activities given up • Craving Alcohol Medical Scholars Program

  7. Opioid Withdrawal • Dysphoric (sad) mood • Muscle aches • Lacrimation (tearing) or rhinorrhea (runny nose) • Pupillary dilation, piloerection (goose flesh), or sweating • Nausea/vomiting • Diarrhea • Yawning • Fever • Insomnia Alcohol Medical Scholars Program

  8. Opioid Overdose • 2nd highest cause of accidental death • 17,000 opioid overdose deaths (2010) • Cause of death = respiratory depression • ~7 non-fatal OD for every fatal OD Alcohol Medical Scholars Program

  9. Opioid Overdose • ↓ consciousness • ↓ respirations (< 12/min) • Miotic(pinpoint) pupils • Evidence of opioid use (needle track marks) • Management: Opioid antagonist, naloxone Alcohol Medical Scholars Program

  10. This Lecture Reviews • Definitions • Course of Opioid Use Disorder (OUD) • Treatment of OUD • Role of buprenorphine in long-term Rx Alcohol Medical Scholars Program

  11. Course of OUD OUD Nonmedical Use Prescription Rx or street drugs Exposure to Pain Relievers or seek opioid high Alcohol Medical Scholars Program

  12. Health Risks OUD • Accidental injury • 2-5x ↑ risk of falls & fractures • ~3x ↑ risk of mortality from vehicular accidents • 4x ↑ risk of overall mortality • ↑ risk of HIV & Hepatitis C Alcohol Medical Scholars Program

  13. Social Consequences • ↑ Criminal behavior & crime-related costs • Education •  GPA; ↑ truancy • Violence • Loss job and family Alcohol Medical Scholars Program

  14. Relapse • 6 months after treatment ~50% abstinent • 10 years after treatment ~25% abstinent There is a need for effective treatment. Alcohol Medical Scholars Program

  15. This Lecture Reviews • Definitions • Course of Opioid Use Disorder (OUD) • Treatment of OUD • Role of buprenorphine in long-term Rx Alcohol Medical Scholars Program

  16. Goals of OUD Treatment 1. ↓ withdrawal symptoms 2. ↓ craving 3. Prevent relapse 4. ↑ physiologic state/ improve functioning Alcohol Medical Scholars Program

  17. Case - Jimmy • 32y male, presents to ER • Reports 12+ year hx of opioid misuse • Last use of heroin ~12 hours ago • Anxious, sweating, nauseous, pupils dilated Alcohol Medical Scholars Program

  18. Clinical Opioid Withdrawal Scale • 11-item COWS assessment: pulse, sweating, pupil size, yawning, anxiety • Scores characterize withdrawal: • 5-12 = mild • 13-24 = moderate • 25-36 = moderately severe • ≥36 = severe Alcohol Medical Scholars Program

  19. Withdrawal Management • Use clonidine (Catapres) to  withdrawal • α2-adrenergic agonist to  adrenalin • Treats hypertension • Rx other symptom as needed • Loperamide (Imodium) for diarrhea • Ibuprofen (Advil) for bone/muscle pain • Medications for insomnia Alcohol Medical Scholars Program

  20. Withdrawal Management (2) • Symptom-triggered clonidine Rx • For COWS > 8, give 0.1-0.2mg clonidine • On day 1, target dose of 0.3-0.6mg • May  to 0.6-1.2mg/day, as necessary • Once stabilized, reduce daily dose by 50% per day Alcohol Medical Scholars Program

  21. Alcohol Medical Scholars Program

  22. Withdrawal Management (3) Use opioid agonist to  symptoms • Methadone • Up to 30mg/day •  10-20% every 1-2 days over 2-3 weeks • Better than α2-adrenergic agonist based Rx • Buprenorphine • Up to 8mg/day • ↓ by 2mg every 1-2 days over 7-10 days Alcohol Medical Scholars Program

  23. Alcohol Medical Scholars Program

  24. Long-term Rx of OUD • Opioid Antagonist Therapy • Intramuscular naltrexone (Trexan) • Administer every 30 days • Prevents opioid high • Low compliance • No other FDA-approved medications Alcohol Medical Scholars Program

  25. Long-term Rx of OUD (2) • Methadone maintenance treatment (MMT) • Taken daily by mouth • Obtained through federally-regulated program • Optimal dose varies (target = 80mg/day) -- Must ↑ dose slowly to avoid OD Alcohol Medical Scholars Program

  26. MMT Drawbacks • Overdose common in early treatment • Cannot be prescribed from general practice • Strict government control and paperwork • Stigma of daily clinic attendance Alcohol Medical Scholars Program

  27. This Lecture Reviews • Definitions • Course of Opioid Use Disorder (OUD) • Treatment of OUD • Role of buprenorphine in long-term Rx Alcohol Medical Scholars Program

  28. Office-Based Buprenorphine • Taken daily, sublingually • Rx in offices of physicians with special training • Individual dose varies (target = 16-24mg/day) • Daily visits not necessary Alcohol Medical Scholars Program

  29. Buprenorphine Pharmacology • Partial agonist at μ-opioid receptor • Slow dissociation from receptor • Half-life = 24-36 hrs • Metabolizes quickly, if give orally • So Rx is sublingual or buccal Alcohol Medical Scholars Program

  30. Buprenorphine Pharmacology (2) • Clinical impact • Less subjective euphoria than methadone • Long-lasting clinical action • Partially blocks intoxication • Reduced overdose risk Alcohol Medical Scholars Program

  31. Formulations • Buprenorphine alone (Subutex) • Buprenorphine + naloxone (Suboxone) • Naloxone = antagonist •  risk of diversion and IV misuse • Combined in 4 mg bup:1 mg naloxone • Combo in sublingual or buccal film Alcohol Medical Scholars Program

  32. More Buprenorphine Info • Side effects • Neuro: Sedation, dizziness, headache • GI: Constipation, nausea/vomiting • Respiratory depression • Availability and cost • Prescribed by MDs with special training • Reimbursed by Medicaid, health insurances --But costs more than methadone Alcohol Medical Scholars Program

  33. Buprenorphine Treatment • Initiation • Goal: avoid precipitated withdrawal & OD • Patient stops opioid misuse 12-36 hrs prior • Patient demonstrates early withdrawal • COWS rating > 8 Alcohol Medical Scholars Program

  34. Buprenorphine Induction • Induction phase (days 1-7) • Day 1 • First dose = 4mg • Assess for adverse effects • Repeat 4mg dose if withdrawal symptoms persist • Maximum dose day 1 = 8 mg Alcohol Medical Scholars Program

  35. Buprenorphine Induction (2) • Days 2-7 •  dose until withdrawal symptoms  (w/in 2 hrs) • Day 2 dose: often  to 16mg •  dose by Day 7 (usual to 8 – 24mg/day) Alcohol Medical Scholars Program

  36. Buprenorphine Stabilization • Weeks 2-8 • Dose adjustment continues (up to 32mg/day) • Characterized by •   opioid craving • No withdrawal symptoms •  or absent opioid misuse Alcohol Medical Scholars Program

  37. Buprenorphine Maintenance • Months 3-12 • Optimal dose reached • Relapse prevention Alcohol Medical Scholars Program

  38. Buprenorphine Effectiveness Buprenorphine (16mg/day) Better than placebo and naltrexone ↑Treatment retention  Opioid positive urines Alcohol Medical Scholars Program

  39. Buprenorphine v. Methadone • Both improve outcomes • Methadone → greater patient retention • Buprenorphine benefits Office-based Rx Safer during induction Alcohol Medical Scholars Program

  40. Conclusions • OUD is common and dangerous • Buprenorphine is A partial μ-opioid receptor agonist Is safer Is effective for office-based Rx • Combined with naloxone → ↓ misuse Alcohol Medical Scholars Program

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