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Buprenorphine in the treatment of addiction


Title: Treatment options for the Opioid Dependent Patient: Buprenorphine for opiate dependence and more Last modified by: Matthew Torrington Document presentation format – PowerPoint PPT presentation

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Title: Buprenorphine in the treatment of addiction

Buprenorphine in the treatment of addiction
  • Matthew A. Torrington MD
  • Clinical Research Physician
  • UCLA Integrated Substance Abuse Programs
  • Matrix Institute on Addictions
  • Addiction Medicine Clinic
  • November 4, 2004

Scope of this Talk
  • What are we talking about? Addiction then
  • Buprenorphine For the treatment of opioid
  • Buprenorphine As an analgesic
  • Buprenorphine On the horizon

AAPainMed,APainS, ASAMdefined ADDICTON in 2001
  • Addiction is a primary, chronic, neurobiologic
    disease, with genetic, psychosocial, and
    environmental factors influencing its development
    and manifestations. It is characterized by
    behaviors that include one or more of the
    following impaired control over drug use,
    compulsive use, continued use despite harm, and
  • Savage et al., 2001

DSM 4 criteria for opiate abuse
  • Significant impairment or distress resulting from
  • Failure to fulfill roles at work, home, or school
  • Persistent use in physically hazardous situations
  • Recurrent legal problems related to use
  • Continued use despite interpersonal problems

DSM 4 criteria for Opiate Depend. 3 of the
following occurring in the same 12- month period
  • 1. Desire or unsuccessful efforts to cut down on
    opiate use
  • 2. Large amount of time spent obtaining opiates,
    using opiates, or recovering from opiate effects
  • 3. Social, occupational, or recreational
    activities reduced because of opiate use
  • 4. Opiate use continued despite knowledge that a
    physical or psychological problem is being caused
    or exacerbated by use

5. Tolerance
  • Need for increased amounts of opiates to achieve
    desired effect or
  • Diminished effect with continued use of the same
    amount of opiate
  • Tolerance develops normally with repeated use
  • Tolerance to sedating effect develops quickly
  • Tolerance to respiratory depression can be marked

6. Withdrawal
  • withdrawal syndrome with cessation of use,
    reduction of use, or use of opiate antagonist
  • Opiates or related substance taken to relieve or
    avoid withdrawal symptoms

  • operationally defined as aberrant drug-related
    behaviors that make patients with chronic pain
    look like addicts.
  • these behaviors stop if opioid doses are
    increased and pain improves (Weissman and Haddox,
  • This indicates that the aberrant drug-related
    behaviors were actually a search for relief
  • Little data on the subject, but evidence in rats

Magnitude of the Problem
  • There are 1,110 licensed OTPs in the U.S.
  • 225,000 patients in methadone treatment
  • 800,000 persons addicted to heroin
  • 4.7 million prescription opioid users
  • First time users are on the increase

Treatment Admissions
Schematic of Opiate Receptor
Source Goodman and Gillman 9th ed, p. 526
Effect of Common Opiates at mu receptor
  • Heroin, morphine, methadone
  • Buprenorphine
  • Naltrexone (Revia, Vixo)
  • Naloxone (Narcan)
  • Nalmefene
  • Agonist
  • Partial Agonist
  • Antagonist

Receptor Binding at Mu receptor
  • Morphine like effect
  • Weak morphine like effects with strong receptor
  • No effect in absence of an opiate or opiate
  • AgonistOpens door
  • Partial Agonist
  • Opens door with safety chain
  • Antagonists
  • Dummy key

Buprenorphine pharmacology contd.
  • Less bounce to the ounce
  • Ceiling effect on respiratory depression
  • Less physical dependence capacity
  • Blocks withdrawal in mildly dependent people
  • Precipitates withdrawal in moderate to severely
    dependent people

Good Effect
Intensity of abstinence
Buprenorphine Morphine
60 50 40 30 20 10 0
Himmelsbach scores
Days after drug withdrawal
Buprenorphine for Opiate Dependence
  • Suppresses withdrawal
  • Substitutes for street opiates
  • Blocks subsequently administered opiates
  • Safety in long term use

Overview to theDrug Addiction Treatment Act of
2000 An Amendmentto the Controlled Substances
Act(October, 2000)
Amended Controlled Substances Act
  • Narcotic drug
  • Approved by the FDA for use in maintenance or
    detoxification treatment of opioid dependence
  • Schedule III, IV, or V
  • Drugs or combinations of drugs

Amended Controlled Substances Act
  • Practitioner requirements
  • Qualifying physician
  • Has capacity to refer patients for appropriate
    counseling and ancillary services
  • No more than 30 patients (individual or group

Amended Controlled Substances Act
  • Qualifying physician
  • A licensed physician who meets one or more of the
  • 1. Board certified in Addiction Psychiatry
  • 2. Certified in Addiction Medicine by ASAM
  • 3. Certified in Addiction Medicine by AOA
  • 4. Investigator in buprenorphine clinical trials

Amended Controlled Substances Act
  • Qualifying physician (continued)
  • Meets one or more of the following
  • 5. Has completed 8 hours training provided by
    ASAM, AAAP, AMA, AOA, APA (or other organizations
    which may be designated by HHS)
  • 6. Training/experience as determined by state
    medical licensing board
  • 7. Other criteria established through regulation
    by the Secretary of Health and Human Services

Buprenorphine Potent Analgesic
  • 20-50 times potency of morphine
  • Available worldwide for pain treatment
  • Injectable formulation available in U.S.
  • Usual analgesic dose .2-.4 mg sl
  • Higher dose for opiate dependence

Buprenorphine and Pain
  • Animal data dont predict human data
  • Good potent analgesic
  • No ceiling effect or inverted U curve
  • Mild CVS effect, mild G-I effect
  • Limited dependence, slow mild withdrawal
  • Ceiling on respiratory depression
  • Analgesia not compromised by ceiling.
  • Effective for long term use mos. to yrs.

(No Transcript)
Buprenorphine Analgesic Profile
  • Rapid onset of action
  • Long duration of peak effect (60-120 min)
  • Long half life (3.5 hrs)
  • Analgesic action up to 8 hrs.
  • Ceiling effect on respiratory depression
  • Low physical dependence profile

Buprenorphine Clinical Analgesic Use
  • Surgical pain
  • Intra-operative, peri-operative, post-operative
  • Labor pain
  • Back pain
  • Phantom pain
  • Post-herpetic neuralgia
  • Cancer pain

Buprenorphine for Pain
  • Good for trans-dermal application
  • Lipophilic
  • High level analgesia
  • Low adverse effects
  • Patch
  • Consistent delivery, desirable time course
  • Flexible dosing and compliance

Myths about buprenorphine and pain
  • Partial agonist, limited clinical effects
  • Not reversible by naloxone
  • Cant be given after other opioids.
  • Reality
  • High affinity, mod intrinsic activity, slow
    dissociation from mu, highly lipophilic

Treating Acute pain in buprenorphine patients
  • Keep on buprenorphine
  • Increase buprenorphine dose
  • Add high potency opioidfentanyl
  • Add or switch to methadone (Caution)
  • Regional analgesia
  • PCA
  • Non-opioids

Treating Chronic pain in buprenorphine patients
  • Keep on sublingual buprenorphine
  • Consider buprenorphine patches (when available)
  • Switch to morphine
  • Switch to methadone (CAUTION)
  • Use opioid rotation
  • High potency opioids for break thru pain
  • Non-opioid analgesics
  • Adjunct medications and local anesthetics
  • Non-pharmacological treatments

Issues on the horizon
  • Buprenorphine access 30 pt rule, inability of
    NTPs to use buprenorphine, cost
  • Buprenorphine abuse liability
  • Studies underway
  • Bup 3, CTN, outpatient detox schedules
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