1 / 28

Initiating Methadone Treatment: Induction and stabilisation

Initiating Methadone Treatment: Induction and stabilisation. Nichole Riese, MD CCFP June 11, 2010. Disclosure of Conflict of Interest. Methadone: an introduction to clinical practice Winnipeg Manitoba June 11, 2010 No conflict of interest to declare. Objectives.

hada
Download Presentation

Initiating Methadone Treatment: Induction and stabilisation

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Initiating Methadone Treatment:Induction and stabilisation Nichole Riese, MD CCFP June 11, 2010

  2. Disclosure of Conflict of Interest Methadone: an introduction to clinical practice Winnipeg Manitoba June 11, 2010 • No conflict of interest to declare

  3. Objectives • Considerations in initiation of methadone dosing • Use & interpretation of methadone blood levels • Early, Late & Split dose inductions

  4. Methadone Pharmacology • Almost pure mu agonist • Oral: 80-90% bioavailability • Extended duration of action in suppressing opioid withdrawal (T-1/2=24-36 hours) • Analgesic properties of methadone differ significantly from maintenance properties • Accumulation with repeated use for pain can result in sedation and respiratory depression in the non-tolerant patient Source: Goodman & Gilman

  5. Tolerant/Dependent Drug States “Abnormal Normality” Drug effects scale 00 Time in Hours 24

  6. “Anatomy” of a Fix “Abnormal Normality” Amount “Tolerance Threshold” Time in hours

  7. Methadone vsOxycontin -- Methadone -- Oxycontin “Abnormal Normality” Amount “Tolerance Threshold” 0 4 8 12 16 20 Time in hours

  8. Methadone Absorption • Detected in 30 min following oral dosing • Peak plasma levels occur at 2 to 4 hours • Large amounts stored in liver and other tissues for later release into circulation to maintain steady-state (reservoir effect) • Protein binding extensive, up to 90% of therapeutic dose • Highly lipophilic, parental doses readily cross blood-brain barrier Source: Goodman and Gilman, Kreek , and others.

  9. Methadone Metabolism/Excretion • Extensive bio-transformation in liver • N-demethylation and cyclization to form principal metabolites: • PYRROLIDINES (EDDP) • PYRROLINE (EMDP) • Metabolites are essentially inactive • Metabolites and unchanged methadone are excreted in bile and in urine Source: Goodman and Gilman, Kreek, Bassett and others

  10. Benefits of Pharmacotherapy for Opioid Dependence • Increasing employment • Improved physical and mental health • Improved social function Source: J Thomas Payte

  11. Issues in Methadone treatment • Dose • Duration

  12. How long does MMT last?

  13. Profile for Potential Psychotherapeutic Agent • Effective after oral administration • Long biological half-life (>24 hours) • Minimal side-effects during chronic administration • Safe – no true toxic or serious adverse effects • Efficacious for a substantial % of persons with the disorder Source: MJ Kreek, Rational for Maintenance Pharmacotherapy of Opiate Dependence

  14. Steady-State Simulation – Maintenance PharmacotherapyAttained after 4-5 half-times - 1 “dose” q half-life Time (multiples of elimination half-time)Dose level remains constant Source: Goodman and Gilman

  15. Initial Dose

  16. Early Induction • Early dose adjustments to “approximate” established “Tolerance Threshold” • Remember STEADY-STATE PHARMACOLOGY! Today’s dose repeated tomorrow will have a greater effect and the next day, and the next... until steady state is achieved • Provide full relief and prevention of withdrawal signs and symptoms and ensure reduction in drug hunger/craving

  17. Late induction • Gradual continued dose adjustment beyond initial relief in order to: • Establish adequate level of cross-tolerance or “blockade” • Provide a dose adequate to achieve the desired effects: • Prevention of withdrawal, drug hunger and relapse

  18. Desired Response from Methadone in Methadone Maintenance Treatment • Prevention of onset of withdrawal syndrome for 24 hours or more • Reduction or elimination of drug hunger or craving • Blockade of euphoric effects of illicit narcotics Source: Kreek 1987

  19. Individualized! Adequate Dose • Based on clinical and laboratory data

  20. How much? Enough!

  21. How much is enough? The amount required to produce the desired response for the desired duration of time with an allowance for a margin of effectiveness and safety. Source: Payte and Kun, 1992

  22. Retention in Treatment Relative to DoseRelative Risk of Leaving Treatment 80 + mg 60-79 mg < 60 mg(Baseline) Source: Caplehorn & Bell 22

  23. Blood levels: When and Why • Clinical picture – Dose incongruities • Suspected drug interactions • Ensure adequacy of dose • Documentation of “need” for dose level • Determine need for and effectiveness of split-dose practices

  24. Interpretation of Methadone Blood Levels • 24-hour/trough level at 150-200 ng/ml or more • Peak/trough ration around 2.0 or less, 500/250 = 2.0 (values > 2 suggest rapid metabolism or elimination) Rate of change – more important than absolute numbers or levels!

  25. My dose isn’t holding me… • Environment? • Stressors? • Alcohol? • Other drugs/medications? • Vitamins? • Urinary pH? • Methadone blood levels?

  26. “Not Holding” Strategies • Cognitive, behavioural interventions • Increased contact, counselling, therapy • Alter urinary pH? • IV drugs? • Faster metabolizers? • Raise dose? Is patient fixing? • Split dose?

  27. Split-dose Induction • Day 1: • 100% of dose observed • 50% of dose taken in 12 hours • Day 2: • 50% of dose every 12 hours Note: Poor results from starting with half the ordinary dose on day 1

  28. Questions?

More Related