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PHARMACOLOGIC TREATMENT OF OPIATE DEPENDENCE

PHARMACOLOGIC TREATMENT OF OPIATE DEPENDENCE

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PHARMACOLOGIC TREATMENT OF OPIATE DEPENDENCE

  1. 1. PHARMACOLOGIC TREATMENT OF OPIATE DEPENDENCE Paula Colescott MD Diplomat of The American Board of Addiction Medicine Board Certification in Internal Medicine
  2. 2. Objectives The student will understand: • The Brain changes in the addict • The Historical Approaches of Treatment • Agonist Treatment • Blockade of the Opiate Receptor • Those who qualify for Buprenorphine/Naltrexone • The Clitheroe Protocol
  3. 3. In Reflection • 25 yo Native Female, IV heroin user ,being released from Hiland Prison. She is tremulous as she tells me she doesn’t think she can stay clean. • 30 yo white female, narcotic/heroin user, who is in RSAT @ Hiland Prison. She confides to me that despite treatment she fears her inability to resist relapse.
  4. 4. W H Y
  5. 5. OPIUM 1898 1804 1832
  6. 6. OPIATES Derived from extracts of the juice of opium poppy. OPIOIDS Any exogenous substance that acts as an agonist at any of several receptors Neurobiology of Addiction George F. Koob
  7. 7. Take a Drug Change Your Brain DRUG ADDICTION IS A COMPLEX ILLNESSDRUG ADDICTION IS A COMPLEX ILLNESS www.drugabuse.gov
  8. 8. Steward, 1987, p. 166 “It’s staying off that is the hard part. It takes a lot of willpower. But seeing smack eats away at your willpower; it makes it very hard. When I stop I just feel vacant with no direction or energy and that lasts for months.’
  9. 9. Behavioral Mechanisms of Addiction “The special role the drug comes to play in the personality organization of these patients. They have not successfully established familiar defensive, neurotic, characterological or other common adaptive mechanisms as a way of dealing with their distress. Instead, they have resorted to the use of opioids as a way of coping with a range of problems including ordinary human pain, disappointment, anxiety, loss, anguish, sexual frustration, and other suffering”
  10. 10. Opioids relieve emotional pain and this is one of the behavioral mechanisms implicated in the addiction cycle (Khantzian, 1985, 1990, 1997)
  11. 11. Opioid Intoxication 1st Profound euphoria the rush Visceral sensations, a facial flush, deepening of the voice. The rush is resistant to tolerance. 2nd The High feeling of well-being over several hours, no tolerance 3rd The Nod state of escape from reality ranging from sleepiness to virtual unconsciousness 4th Being Straight User no longer experiencing the rush or nod or high, but also not in withdrawal. This can last up to 8 h following an injection or smoking of heroin.
  12. 12. NATURAL REWARDS DISPLACED SPIRITUALLY PHYSICALLY SOCIALLY INTELLECTUALLY EMOTIONALLY Salient
  13. 13. Substance Dependence (brief) • Organization around acquisition, use, recovery from effects, of the drug—behavior is rewarding • Dosage and frequency not the issue • Consequences are the issue • Adaptation and deterioration are hallmarks • Ambivalence is the psychodynamic – Loss of CONROL
  14. 14. WITHDRAWAL
  15. 15. Acute Withdrawal 5-7 Days • Runny nose, sneezing, • Sweating, yawning • Restless, insomnia • Piloerection, myalgia • Twitching, arthralgia • Abd. Cramps, diarrhea • Vomiting, dehydration • Tachycardia, HBP, Fever • Psychosis • Autonomic rebound locus ceruleus •
  16. 16. Protracted (1-12 months) Abstinence • Anergia, Anhedonia • Sleep disturbance • Poor appetite • Emotional lability/dysphoria • Stress incompetence • Drug craving, obsession • Muscle aches and pains • Reduced libido, impotence • Dopaminergic deficiency, nucleus accumbens, VTA
  17. 17. WHY TREAT OPIOID DEPENDENCE WITH OPIOID AGONISTS? Repeated Exposure Neuronal Adaptation Tolerance, physical dependence, craving Chronic relapsing nature of opioid dependence
  18. 18. Natural History of Narcotic Addiction: Male Heroin Addicts • Hser et al.,2001
  19. 19. Therapeutic Options Available to Benjamin Rush, MD
  20. 20. Coming in For Treatment
  21. 21. Medical Withdrawal from Opioids 1. Cold Turkey 2. Symptomatic Medications/Social Support Clonidine, ibuprofen, hydoxyzine, methocambanol, loperamide… 3. Taper ( Goodman & Gilman: 20-50% decrease/day) 4. Federally regulated methadone clinic 5. Ultra-Rapid Opioid Detox (UROD), Rapid Opioid Detox 6. Buprenorphine –(suboxone/subutex) 7. Blockade of the Opiate Receptor ? Medical Withdrawal or “Detox” is not treatment
  22. 22. OPIATES Just Detox Alone And then Aftercare??
  23. 23. Treatment Overview of Opioid Dependence DEATH HARM REDUCTION OPIOID REPLACEMENT Methadone or buprenorphine ABSTINENCE < 20% CAN ACHIEVE THIS Naltrexone Needle Exchange Program
  24. 24. Is Clean & Sober too Much to ask with Opiates?? Opioid Replacement Methadone=76% Buprenorphine=? Abstinence Detox only 3% @ 1 yr MJ Kreek <20% in lifetime WA state MDs 85% @ 10 yrs.
  25. 25. New History 1960-70s Dole, Nyswander, and Kreek • Proposed addiction to be a change in brain from prolonged exposure to opiates • Started evaluating methadone in the early 1960s • Methadone for dependence/addiction Rx in special clinics
  26. 26. Buprenorphine (Subutex) Orphan drug developed by NIDA and private pharmaceutical interest over 25 years
  27. 27. 2000 Drug Addiction Treatment Act • Addiction is a chronic disease • Physicians may offer buprenorphine treatment, as a replacement therapy in their office “OBOT” –Office Based Opioid Therapy (need 8h CME) • PCP knows the patient, the family, “the story” • Reduces stigma, increases access to care • Aligns addiction with other chronic relapsing conditions (asthma, HBP, DM, Obesity, depression, mental illness, etc.)
  28. 28. Cognitive Behavioral Therapies Substance abuse is related to maladaptive social learning/adverse life situations. • Improve interpersonal &Coping skills – Evaluating feelings, thoughts • Self-efficacy – Teach problem solving Reduce risk of relapse – Triggers, cues – Coping with urges “As a Man thinks, so is he” Solomon
  29. 29. Is Buprenorphine an Opioid? Yes
  30. 30. Is Buprenorphine an Analgesic? • Yes • 20-40 X as potent as morphine • Analgesic in US, Buprenex (IV/IM), for decades • Worldwide use for pain as Temgesic • There is no FDA approval for pain(SL), but it is prescribed to pain patients “off-label” [problematic]
  31. 31. Opioid Receptors and Effect of Agonist Mu1 (μ1) analgesia, euphoria Mu2 (μ2) constipation, respiratory depression Kappa spinal analgesia, dysphoria Delta unknown
  32. 32. Receptor Binding at Mu receptor Agonist Partial Agonist Antagonists Morphine-like effect, increasing dose increases effect Morphine-like effect with strong receptor affinity, slow dissociation, ceiling effect (bup) No effect in absence of an opiate or opiate dependence (e.g., naltrexone)
  33. 33. Function at Receptors: Full Agonists Mu receptor Full agonist binding …  activates the mu receptor at higher levels with higher doses  is highly reinforcing  is the most abused opioid type  includes, oxycodone, morphine,methadone, others Slide Courtesy of John T. Pichot, MD
  34. 34. Opioid Receptor Partial Agonists Mu receptor  activates the receptor at lower levels but plateaus at lower levels  is relatively less reinforcing  is a less abused opioid type  includes buprenorphine Partial agonist binding … Slide Courtesy of John T. Pichot, MD
  35. 35. Full Agonist Bound to Receptor Bup affinity is higher Therefore Full Agonist is displaced Partial Agonist (Bup) Receptor Affinity Mu Receptor • Strength: Drug physically binds to a receptor  Buprenorphine affinity is very strong and it will displace full agonists like morphine and methadone  Can precipitate withdrawal Slide Courtesy of John T. Pichot, MD
  36. 36. Receptor Dissociation • Speed (slow or fast) of disengagement or uncoupling of a drug from the receptor • Buprenorphine’s dissociation is slow – Blocks other opioids (ie morphine) from binding – Prolonged therapeutic effect (> 24 hours) Mu Receptor Bup dissociation is slow Therefore Full Agonists can’t bind Slide Courtesy of John T. Pichot, MD
  37. 37. 0 10 20 30 40 50 60 70 80 90 100 2 mg 16 mg 32 mg Dose %ReceptorOccupancy Source: Greenwald, MK et al, Neuropsychopharmacology 28, 2000-2009, 2003. μ Effects of Buprenorphine Maintenance Dose on Mu Opioid Receptor Availability 27 to 47% 85 to 92% 94 to 98%
  38. 38. Benefits of Buprenorphine • Mild withdrawal syndrome • Prolonged therapeutic effect • Safe and effective as an analgesic • Blockade of “illicit” opioids • Greater safety margin compared to methadone • Decreased risk of abuse and diversion with combination tablet • Efficacy comparable to methadone
  39. 39. “Normal” Withdrawal Effects of IV Heroin without Buprenorphine High Opiate Effects Rush
  40. 40. Usual Effect of Buprenorphine Induction in an Opiate Dependent Patient “Normal” Withdrawal High Opiate Effects
  41. 41. “Normal” Withdrawal Effects of Using Heroin while on Buprenorphine High Attenuated rushOpiate effects
  42. 42. CESAR FAX U n i v e r s i t y o f M a r y l a n d , C o l l e g e P a r k A Weekly FAX from the Center for Substance Abuse Research April 9, 2012 Vol. 21, Issue 14 Northeastern and Southern Regions of Country Account for Largest Increases in Buprenorphine Found in Law Enforcement Drug Seizures 2003 2004 2005 2006 2007 2008 2009 2010 0 500 1,000 1,500 2,000 2,500 3,000 3,500 4,000 4,500 831 1,689 4,161 3,856 West Midwest Northeast South Estimated Number of Buprenorphine Reports, U.S. Law Enforcement-Seized Drug Exhibits Analyzed by Forensic Laboratories, by U.S. Census Region*, 2003-2010 *Northeast: CT, MA, ME, NH, NJ, NY, PA, RI, VT South: AL, AR, DC, DE, FL, GA, KY, LA, MD, MS, NC, OK, SC, TN, TX, VA WV Midwest: IA, IL, IN, KS, MI, MN, MO, ND, NE, OH, SD, WI West: AK, AZ, CA, CO, HI, ID, MT, NM, NV, OR, UT, WA, WY Buprenorphine estimates for the South and West regions do not meet the DEA’s standard of precision and reliability.
  43. 43. Who is Appropriate for Buprenorphine Treatment?
  44. 44. Patient Selection: 10 Assessment Questions • Is the patient dependent/addicted to opioids? • Does the Client live in Anchorage? • Is the patient aware of other available treatment options? • Does the patient understand the risks, benefits, and limitations of buprenorphine treatment? • Is the patient expected to be reasonably compliant, with all treatment modalities? • Is the patient able to follow safety procedures?
  45. 45. Patient Selection: 10 Assessment Questions • Is the patient psychiatrically stable? • Is the patient taking other medications that may interact with buprenorphine? • Are the psychosocial circumstances of the patient stable and supportive? • Is the patient interested in office-based buprenorphine treatment? • Are there resources available in the office to provide appropriate treatment, and support? • Do they have a means of paying for the Suboxone?
  46. 46. Less Likely to be an Appropriate Candidate: • High BNZ doses, alcohol, other CNS depressants • Significant psychiatric co-morbidity • Multiple addiction treatment episodes (+ -??) • Actively or chronic suicidal or homicidal ideation • Needs that cannot be addressed with existing office- based resources or through referrals • High daily doses of methadone ( 40mg+/day) • Poor social support system—Cannot be living with IV opiate user . Cannot be employed by Business linked to drug use
  47. 47. How do you determine Dependence? DSM-IV requirements: 3 or more needed x 12 months – Tolerance – Withdrawal – Larger amt. longer period than intended – Any unsuccessful effort / persistent desire to cut down /control substance use – A lot of time spent obtaining / recovering – Important social, occupational, or recreational activities given up / reduced – Continuation despite consequences caused or exacerbated by the substance
  48. 48. Narcotic / Alcohol Dependent • Do CIWA and COWS scale • Treat according to the CIWA/ETOH protocol • This patient is NOT a candidate for suboxone • This patient is a good candidate for NALTREXONE maintenance once they finish withdrawing from ETOH. • They can be made comfortable with BZDs, clonidine, phenergan or zofran
  49. 49. The Narcotic/Alcohol Dependent • Suboxone possible If – they contract to remain in residential treatment for 90 days – Their counselors confirm their investment in recovery – They have no underlying psych co-morbidity – Upon release they have a stable living situation – Upon release they remain in IOP – Upon release they have the finances to obtain suboxone consistently. – They agree to be on a monitored ANTABUSE PROGRAM
  50. 50. $$ Subutex: 2 mg: $14.49. #30 $173.49 8mg: $20.99 #30 $317.49 CARRS—6/2010

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