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Liver Connect: Opiate Addiction and Treatment

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Liver Connect: Opiate Addiction and Treatment Aryeh Levenson, M.D. South Central Foundation April 16, 2013 (Thank you Paula Colescott M.D. : Clithroe) – PowerPoint PPT presentation

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Title: Liver Connect: Opiate Addiction and Treatment


1
  • Liver Connect Opiate Addiction and Treatment
  • Aryeh Levenson, M.D.
  • South Central Foundation
  • April 16, 2013
  • (Thank you Paula Colescott M.D. Clithroe)

2
OPIATESDerived from extracts of the juice of
opium poppy. OPIOIDSAny exogenous substance
that acts as an agonist at any of several
receptors
  • Neurobiology of Addiction
  • George F. Koob

3
Epidemiology of drug Addiction
  • Survey Results
  • Opiates 35
  • Tobacco 32
  • Stimulants/Cocaine 25
  • Alcohol 15
  • Sedatives/anxiolytics/hypnotics 10
  • Cannabis 10
  • Odds of becoming dependent after first non
    medical use
  • Opiate/Opioid Abuse 1.8 mil (0.7) in US

4
Opiate Addiction
  • Opiates are leading cause of substance related
    deaths in USA
  • (often after period of withdrawal/abstinence
  • Heroine users have up to 30X death rate as non
    heroine users
  • Hep B and C and HIV Transmission
  • A door to enslavement into prostitution
  • High percentage of pregnant opiate abusers
  • Long term users develop abstinence Syndrome
  • Criminality

5
Opiate Addiction
  • gt600 incr of Opiate RX b/n 1997 2007
  • Current yearly use 700 mg of morphine
    equivalents per American
  • OR5 mg dose of Vicodin (hydrocodone and
    acetaminophen) every 4 hours for 3 weeks per
    American

6
Tolerance Vs. Dependence Vs. Abuse Vs Addiction
  • Tolerance require to take more of the
    medication to get same clinical effect
  • Dependence sudden discontinuation of medication
    results in withdrawal symptoms
  • Addiction Maladaptive behaviors around the use
    of the substance
  • Drug Dependence Addiction involves abuse
    tolerance/withdrawal

7
Chronic Pain
  • Chronic Pain affects every aspect of an
    individuals life..social, functional,
    psychological, spiritual
  • gt 50 of chronic pain patients will misuse/abuse
    opiate pain meds
  • Therapeutic Dependence ? fear ? drug seeking
    behaviors

8
Chronic Pain and Pseudo addiction
  • Pseudo-addiction Undertreated pain ?
    drug-seeking behaviors ("doctor shopping," etc.)
    to relieve their pain
  • However, pseudo-addicted patients legitimately
    need more analgesics to adequately treat their
    pain, and their behavior will stop once pain is
    adequately treated.

9
Opiate Addiction
  • Differential characteristics of opiate dependence
  • Ultra high relapse rate due to physiological
    effects of chronic opiate use ? severe cravings
  • TX Failure rate for opiate addiction 80 -90
  • True for all non medication assisted options
    (e.g. outpatient, inpatient, long term
    residential, incarceration

10
Natural History of Opioid dependence
  • Repeated Exposure
  • Neuronal Adaptation
  • Tolerance, physical dependence, craving
  • Abstinence state
  • Chronic Relapse

11
Acute Withdrawal1-5 Days (short Acting)1 14
days long Acting
  • Runny nose, sneezing,
  • Sweating, yawning
  • Restless, insomnia
  • Piloerection, myalgia
  • Twitching, arthralgia
  • Abd. Cramps, diarrhea
  • Vomiting, dehydration
  • Tachycardia, HBP, Fever
  • Psychosis (Ive not seen)
  • Autonomic rebound locus ceruleus

12
  • Protracted (weeks, months, ? years) 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

13
Receptor Binding at Mu Opiate receptor
  • Agonist
  • Partial Agonist
  • Antagonists
  • Morphine-like effect, increasing dose increases
    effect, Highly reinforcing
  • (Oxymorphine, methadone, codeine, tramadol,
    hydromorphone, etc, etc, etc
  • Morphine-like effect with strong receptor
    affinity, slow dissociation, ceiling effect (bup,
    Pentazocin )
  • Binds to Receptor, blocks opiates. No morphine
    like effect (e.g., oral or IM naltrexone)

14

15
Options to manage Opioid Dependence
  • 1. Cold Turkey
  • 2. Symptomatic Medications/Social Support
  • Clonidine, ibuprofen, hydoxyzine,
    methocambanol, loperamide, phenergan valuim
  • 3. Taper ( Goodman Gilman 20-50
    decrease/day)
  • 4. Ultra-Rapid Opioid Detox (UROD), Rapid Opioid
    Detox
  • 5. Federally regulated methadone clinic
  • 6. Buprenorphine (suboxone/subutex)
  • 7. Antagonist (blockade) therapy (e.g. Natrexone)
  • Medical Withdrawal or Detox is not treatment

16
Overview of curent outcomesOpioid Dependence
lt 20 CAN ACHIEVE THIS
ABSTINENCE
Naltrexone
HARM REDUCTION
OPIOID REPLACEMENT
Methadone or buprenorphine
Needle Exchange Program
DEATH
17
Problems with Methadone Maintenance
  • Methadone still has high abuse potential
  • Limited Access Extremely high requirements
    for certification limits the program availability
  • Anchorage Methadone program has extensive
    waitlist
  • Poor community acceptance

18
Buprenorphine
  • Two formulations (Schedule III)
  • Buprenorphine alone Subutex
  • Partial Agonist
  • (now in generic)
  • Used primarily in pregnancy
  • Buprenorphine Naloxone (Suboxone) -41 RATIO
  • Naloxone is antagonist

19
Buprenorphine
  • Poorly bioavailability orally
  • fair sublingual bioavailability
  • Good IV bioavailability
  • Versus Naloxone an Opiate Antagonist
  • Good IV bioavailability
  • Poor oral and sublngual bioavailability
  • Thus Abuse of Buprenorphine will precipiate
    withdrawal

20
Is Buprenorphine an Analgesic?
  • Yes
  • 20-40 X as potent as morphine
  • Analgesic in US, Buprenex (injectible) approved
    1985
  • Butrans transdermal for pain approved 2010

21
Buprenorphine
  • Partial agonist
  • Relatively long therapeutic half-life (24-60
    hours)
  • Relatively mild withdrawal syndrome
  • Low risk of overdose
  • Preferentially binds to mu receptors over other
    agonists limits mu receptor activation
  • Blocks effects of other opiates

22
Receptor Dissociation
  • Speed (slow or fast) of disengagement or
    uncoupling of a drug from the receptor
  • Buprenorphines dissociation is slow
  • Blocks other opioids (ie morphine) from binding
  • Prolonged therapeutic effect (gt 24 hours)

Slide Courtesy of John T. Pichot, MD
23
94 to 98
85 to 92
100
90
80
70
27 to 47
60
Receptor Occupancy
50
40
30
20
10
0
2 mg
16 mg
32 mg
Dose
Source Greenwald, MK et al, Neuropsychopharmacol
ogy 28, 2000-2009, 2003.
24
Effects of IV Heroin without Buprenorphine
High
Normal
Rush
Opiate Effects
Withdrawal
25
Usual Effect of Buprenorphine Induction in an
Opiate Dependent Patient
High
Opiate Effects
Normal
Withdrawal
26
Effects of Using Heroin while on Buprenorphine
High
Attenuated rush
Normal
Opiate effects
Withdrawal
27
Buprenorphine
  • Highly Effective
  • Significantly increased Abstinence Rates
  • ( gt 60 at SCF Suboxone program, gt 80 for those
    maintained 2 weeks)
  • 2 year data
  • 80-90 relapse upon discontinuation

28
Patient Selection 10 Assessment Questions
  • Is the patient dependent/addicted to opioids?
  • Can the patient meet program requirements ?
  • 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?
  • 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?

29
Less Likely to be an Appropriate Candidate
  • High BNZ doses, alcohol, other CNS depressants
  • Significant psychiatric co-morbidity/instability
  • 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 systemCannot be living
    with IV opiate user . Cannot be employed by
    Business linked to drug use

30
Naltrexone
  • Opiate Antagonist - competitively binds to mu,
    kappa, delta opiate receptors
  • Blocks all effects
  • Lowers tolerance levels ? ? risk of overdose on
    relapse
  • Side effects prec, withdrawal, nausea, HA,
    dizziness, anxiety, fatique, insomnia
  • Medical Alert Bracelet
  • Issues with pain management

31
Naltrexone Oral vs Injectable
  • Oral Vs Injectable
  • Oral efficacy related to compliance
  • Compliance Limited
  • Reductions on craving??
  • Injectable (Vivitrol)
  • Reduces cravings, increases abstinence rates
  • Long term efficacy unknown

32
SCF Medication Assisted Opiate Treatment program
  • Philosophy
  • Based on research, not on theory
  • NOT BASED ON ABSTINANCE MODEL
  • E.g. use of opiate replacement treatment
  • Risk reduction model
  • E.g. THC use
  • Relapses

33
SCF Medication Assisted Opiate Treatment program
  • 2X/week suboxone group.
  • PRN meetings with counselor
  • Community Support groups (mandatory)
  • Establishment of community sober support system
    (mandatory)
  • Pill Counts
  • Tox and Buprenorphine Screens
  • On going evaluation of THC, etoh use

34
SCF Medication Assisted Opiate Treatment program
  • Use of negative reinforcement Docking to ensure
    compliance

35
SCF Treatment Program
  • Ongoing assessment of functionality and well
    being
  • Integration of Mental Health Counseling
  • Integration of psychiatric treatment
  • On going dialogue regarding treatment response
    and limitations

36
Vaccines
  • Drug vaccines - designed to enable antibodies to
    recognize and bind to drug molecules, so that
    they become too large to penetrate the
    blood-brain barrier.
  • Goal reduce the pleasurable effects of drug use
    and subsequent cravings.
  • Still in preliminary investigation
  • Studies in cocaine addiction
  • In development for Meth, Opiate, Nicotine
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