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OPIOID RELATED DISORDERS




                       Dr. Srinath G
                  Dr. Gowri Devi M
Plan of Presentation

       Introduction
       Epidemiology
       Psychiatric classification
       DSM Criteria
       Management
Introduction
   Opioid= natural opiates+ others
   Narcotic- “stupor”
   Rush/ high
   Oxycodone- Rolls Royce
   Chasing the dragon
ENDOGENOUS OPIOIDS

                         • POMC
          Endorphins     • ß- Endorphin, MSH, ACTH, LPH



                         • Preproencephalin
         Encephalins     • Leu & Met Encephalin



                         • Preprodynorphin
         Dynorphins      • Dynorphin A & B


   Opioid motif- Tyr- Gly- Gly- Phe (Leu or Met)
Opioids
                                             Semi-
           Naturally      Semi-           synthetics
                                       Synthetic
           occurring     Synthetic
         • Morphine    • Heroin      • Methadone
         • Codeine     • Oxycodone   • Meperidine



   Full agonists
   Partial agonists
   Antagonists
Opioid Receptors


                    Opioid receptors

 µ receptors
  DAMGO         δ receptors      К receptors
    CTOP         DPDPE                            Orphanin
 Analgesia,                     DPDTE Nor-
                Naltrindole    binaltorphimine    Nociceptin
Respiration,    Analgesia,
GI, Feeding,                    Analgesia, GI,
               Feeding, GH     Psychomimetis,
  Prolactin,
  GH, Ach,                    Feeding, Sedation
DA, Sedation
Neurobiology

   G protein coupled- Gi
   Inhibit Adenyl cyclase, effect potassium channels and calcium
    channels during acute administration
   Chronic administration causes superactivation of adenyl
    cyclase
   Reward circuit
   Drive/ Motivation
   Emotional circuit
   Executive function
   Learning
Functions of Opioids

   Analgesia
   Psychomimesis
   Respiratory depression
   Hormones
   GIT                  Cornerstone of
                             pain
   Feeding               management      Mood altering
                                           properties
   Sedation
   NT
EPIDEMIOLOGY
Life time prevalence of
 Opiate use in India- 0.4%

 In US 0.2%
Psychiatric co-morbidity

   24% non substance Axis I disorders
   35% Axis II disorders
   47% overall non substance illness
   MC- Mood disorders, Antisocial PD, Anxiety
   Females- BPD, Depression
Medical disorders

   CVS effects
   TB
   HIV/AIDS
   Liver disease
   Immune system
Special population

   Criminal patients
   Pregnant mothers
   Neonatal Narcotic Abstinence Syndrome
       Hyper excitable CNS
       GIT
       Respiratory system
       ANS
Terms

        Misuse- incorrect use of a medication

        • Amount, Longer time and frequency

        Abuse- maladaptive pattern of use leading
        to clinical distress or impairment
        • Harmful use in ICD-10

        Addiction- chronic neurobiologic disease
        with various factors

        Dependence- set of behaviors, a
        neurobiological adaptation

        Pseudo addiction- iatrogenically produced
        in pain patients
Laboratory testing

   Emergency testing, rehabilitation testing, diagnostic testing
   Tested drugs- Opioids, PCP, LSD, Cannabis, Amphetamines
   Tests
       Thin layer chromatography
       Enzyme Immuno Assays
       Medtox Profile II ER
       On Trak TesTCup
   Specimens
       Urine screening
       Oral fluids
   Other
Drugs

Methadone
   Full µ agonist
   Very high lipid solubility
   Half life - 15 to 60 hours
   Methadone clinic
Clonidine
   α- 2 agonist
   reduces nausea, vomiting, diarrhea, abdominal cramps, and
    sweating
   Not helpful in insomnia, opioid craving
Buprenorphine
   Partial agonist at mu and kappa receptors- Ceiling effect
   Poor oral availability- sublingual administration
   Buprenorphine: Naloxone = 4:1
   Less abuse potential
   Office based maintenance
LAAM (l-Alpha Acetyl Methadol)
Opioid antagonists- Naltrexone, Nalmefene
Withdrawal
                 • Dysphoria, nausea & vomiting, lacrimation & rhinorrhoea, Pupillary
                   dilatation, piloerection, sweating, diarrhea, yawning, fever and insomnia,
                   cold turkey, aches-kick the habit
  Features       • Depends upon the half life of the drug



                 • OWS, SOWS, COWS
Measurement




                 • Opioid agonists, Non-opioids
                 • Rapid and Ultra rapid Detoxification, in physician office,
Detoxification
Detoxification
•   Short term
•   Long term
•   Rapid
•   Ultra Rapid
Short term             Rate of tapering is 5%
detoxification         to 10% per day
• 15-30 mg methadone
• 30 days
Long term detoxification




15-30 mg
methadone


Up to 180 days
Rapid detoxification

Antagonist administration        Precipitate withdrawal




                  Supportive Treatment

         Antiemetics, analgesics, buprenorphine
Ultra rapid detoxification



    Under general anesthesia
Antagonist precipitated withdrawal




   Supportive Treatment
Methadone maintenance

         Phase                  Purpose                        Range


• Initial dose          • Relieves abstinence       •   20-40 mg
• Early induction       • Reach tolerance level     •   +/- 5- 10 mg q 3-4 hrs
• Late induction        • Establish adequate dose   •   +/- 5- 10 mg q 3-4 hrs
• Maintenance/          • Steady state occupation   •   60-120 mg/ day
  Stabilization           of receptors
• Maintenance to        • Medically supervised      • 10% q 5- 10 days
  abstinence              withdrawal
• Medical maintenance   • Indefinite management     • Adequate dose
                          in medical setting




   Lapse
   Relapse
   Plasma levels of methadone- 150-200ng/ml
   Adequate blockade achieved at 400+ng/ml
   Methadone drug interactions
   ADR- constipation, sweating, transient skin rash, weight gain,
    water retention, libido changes
   3 phases-


                             Vocational      Continued
            Stabilsation
                             programs       maintenance
Psychosocial Treatment
   Narcotic anonymous
   Therapeutic communities
   Relapse Prevention
   Cue prevention
   Harm Reduction
   Psychodynamic/interpersonal
   Group and Family therapy
   Alternate groups- SOS,
Narcotic Anonymous
Therapeutic communities
Relapse prevention- Risk factors, Social
pressure, Cravings




Internal/        Cognitive/ Behavioral/
External            Pharmacologic



                         Self
                      Management/
                        Others
Relapse process


                                    Stop
     Time                          relapse

                                  Full blown
                                   relapse


   Relapse warning signs- mood, attitude, behavioral, thought
    change
References
   CTP- Kaplan and Sadock
   Comprehensive text book of substance abuse
   Clinical practice guidelines- IPS
   Tasman Psychiatry
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Opioids

  • 1. OPIOID RELATED DISORDERS Dr. Srinath G Dr. Gowri Devi M
  • 2. Plan of Presentation  Introduction  Epidemiology  Psychiatric classification  DSM Criteria  Management
  • 3. Introduction  Opioid= natural opiates+ others  Narcotic- “stupor”  Rush/ high  Oxycodone- Rolls Royce  Chasing the dragon
  • 4. ENDOGENOUS OPIOIDS • POMC Endorphins • ß- Endorphin, MSH, ACTH, LPH • Preproencephalin Encephalins • Leu & Met Encephalin • Preprodynorphin Dynorphins • Dynorphin A & B  Opioid motif- Tyr- Gly- Gly- Phe (Leu or Met)
  • 5. Opioids Semi- Naturally Semi- synthetics Synthetic occurring Synthetic • Morphine • Heroin • Methadone • Codeine • Oxycodone • Meperidine  Full agonists  Partial agonists  Antagonists
  • 6. Opioid Receptors Opioid receptors µ receptors DAMGO δ receptors К receptors CTOP DPDPE Orphanin Analgesia, DPDTE Nor- Naltrindole binaltorphimine Nociceptin Respiration, Analgesia, GI, Feeding, Analgesia, GI, Feeding, GH Psychomimetis, Prolactin, GH, Ach, Feeding, Sedation DA, Sedation
  • 7. Neurobiology  G protein coupled- Gi  Inhibit Adenyl cyclase, effect potassium channels and calcium channels during acute administration  Chronic administration causes superactivation of adenyl cyclase  Reward circuit  Drive/ Motivation  Emotional circuit  Executive function  Learning
  • 8.
  • 9. Functions of Opioids  Analgesia  Psychomimesis  Respiratory depression  Hormones  GIT Cornerstone of pain  Feeding management Mood altering properties  Sedation  NT
  • 10. EPIDEMIOLOGY Life time prevalence of  Opiate use in India- 0.4%  In US 0.2%
  • 11. Psychiatric co-morbidity  24% non substance Axis I disorders  35% Axis II disorders  47% overall non substance illness  MC- Mood disorders, Antisocial PD, Anxiety  Females- BPD, Depression
  • 12. Medical disorders  CVS effects  TB  HIV/AIDS  Liver disease  Immune system
  • 13. Special population  Criminal patients  Pregnant mothers  Neonatal Narcotic Abstinence Syndrome  Hyper excitable CNS  GIT  Respiratory system  ANS
  • 14. Terms Misuse- incorrect use of a medication • Amount, Longer time and frequency Abuse- maladaptive pattern of use leading to clinical distress or impairment • Harmful use in ICD-10 Addiction- chronic neurobiologic disease with various factors Dependence- set of behaviors, a neurobiological adaptation Pseudo addiction- iatrogenically produced in pain patients
  • 15.
  • 16.
  • 17. Laboratory testing  Emergency testing, rehabilitation testing, diagnostic testing  Tested drugs- Opioids, PCP, LSD, Cannabis, Amphetamines  Tests  Thin layer chromatography  Enzyme Immuno Assays  Medtox Profile II ER  On Trak TesTCup  Specimens  Urine screening  Oral fluids  Other
  • 18. Drugs Methadone  Full µ agonist  Very high lipid solubility  Half life - 15 to 60 hours  Methadone clinic Clonidine  α- 2 agonist  reduces nausea, vomiting, diarrhea, abdominal cramps, and sweating  Not helpful in insomnia, opioid craving
  • 19. Buprenorphine  Partial agonist at mu and kappa receptors- Ceiling effect  Poor oral availability- sublingual administration  Buprenorphine: Naloxone = 4:1  Less abuse potential  Office based maintenance LAAM (l-Alpha Acetyl Methadol) Opioid antagonists- Naltrexone, Nalmefene
  • 20. Withdrawal • Dysphoria, nausea & vomiting, lacrimation & rhinorrhoea, Pupillary dilatation, piloerection, sweating, diarrhea, yawning, fever and insomnia, cold turkey, aches-kick the habit Features • Depends upon the half life of the drug • OWS, SOWS, COWS Measurement • Opioid agonists, Non-opioids • Rapid and Ultra rapid Detoxification, in physician office, Detoxification
  • 21. Detoxification • Short term • Long term • Rapid • Ultra Rapid
  • 22. Short term Rate of tapering is 5% detoxification to 10% per day • 15-30 mg methadone • 30 days
  • 23. Long term detoxification 15-30 mg methadone Up to 180 days
  • 24. Rapid detoxification Antagonist administration Precipitate withdrawal Supportive Treatment Antiemetics, analgesics, buprenorphine
  • 25. Ultra rapid detoxification Under general anesthesia Antagonist precipitated withdrawal Supportive Treatment
  • 26. Methadone maintenance Phase Purpose Range • Initial dose • Relieves abstinence • 20-40 mg • Early induction • Reach tolerance level • +/- 5- 10 mg q 3-4 hrs • Late induction • Establish adequate dose • +/- 5- 10 mg q 3-4 hrs • Maintenance/ • Steady state occupation • 60-120 mg/ day Stabilization of receptors • Maintenance to • Medically supervised • 10% q 5- 10 days abstinence withdrawal • Medical maintenance • Indefinite management • Adequate dose in medical setting  Lapse  Relapse
  • 27. Plasma levels of methadone- 150-200ng/ml  Adequate blockade achieved at 400+ng/ml  Methadone drug interactions  ADR- constipation, sweating, transient skin rash, weight gain, water retention, libido changes  3 phases- Vocational Continued Stabilsation programs maintenance
  • 28. Psychosocial Treatment  Narcotic anonymous  Therapeutic communities  Relapse Prevention  Cue prevention  Harm Reduction  Psychodynamic/interpersonal  Group and Family therapy  Alternate groups- SOS,
  • 31. Relapse prevention- Risk factors, Social pressure, Cravings Internal/ Cognitive/ Behavioral/ External Pharmacologic Self Management/ Others
  • 32. Relapse process Stop Time relapse Full blown relapse  Relapse warning signs- mood, attitude, behavioral, thought change
  • 33. References  CTP- Kaplan and Sadock  Comprehensive text book of substance abuse  Clinical practice guidelines- IPS  Tasman Psychiatry