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Is There a Better or a Best Opioid?

Is There a Better or a Best Opioid?. S. Lawrence Librach MD,CCFP,FCFP Professor, Family & Community Medicine Sun Life Financial Chair in Bioethics. The Simple Answer. It depends!. Pharmacogenetics & Role in Opioid Selection.

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Is There a Better or a Best Opioid?

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  1. Is There a Better or a Best Opioid? S. Lawrence Librach MD,CCFP,FCFP Professor, Family & Community Medicine Sun Life Financial Chair in Bioethics

  2. The Simple Answer It depends!

  3. Pharmacogenetics & Role in Opioid Selection • Increasing evidence that perception of pain & response to analgesics especially opioids have genetic components • Pain thresholds & processing • Drug pharmacokinetics & pharmacodynamics • Single nucleotide polymorphism in a number of genes may be responsible for individual variation

  4. Pharmacogenetics & Role in Opioid Pharmacokinetics • Metabolism of opioids mostly dependent on 2 pathways • Cytochrome P450 2D6 & 3A enzymes (CYT) • Uridine-diphosphoglucuronosyltransferase (UGT) • e.g. codeine • Ultrarapid metabolizers in children responsible for caution re: use in children • Poor metabolizers have functionally impaired CYP2D6 (7-10% Caucasians, 3% Blacks, 1% Asians)limited effect because cannot convert to morphine

  5. Pharmacogenetics & Role in Opioid Receptors • Opioid receptorsmu, delta, kappa & “orphan receptor” ORL 1 have all been found to have genetic variants • For mu receptors • Different binding to receptors • Receptor density, location, dimers • Addiction • Require more opioid for same effect • No clear info re: impact on or receptors

  6. Pharmacogenetics & Multidrug Resistance-1 Gene (MDR-1) • MDR-1 limits GI absorption & excretion via liver, kidneys or GI tract • Certain genotypes associated with increased adverse effects • ORLs associated with better response

  7. Pharmacogenetic Testing • The next horizon • As genome testing becomes less expensive may be a factor in the future

  8. Opioid Metabolism • Clearance of metabolites an issue with morphine, hydromorphone, oxycodone as metabolites can build up in renal failure • Hepatic failure requires adjustment of all opioids

  9. Opioid Pharmacokinetics

  10. Lipid Solubility of Some CommonOpioid Drugs DRUG HEPTANE - BUFFER PARTITION COEFFICIENT • Morphine • Hydromorphone • Fentanyl • Methadone • 000001 • 00001 • 196 • 446

  11. Opioids Tolerance & Hyperalgesia • Experience with chronic administration of opioids in cancer or other illnesses has shown us that analgesia is not always maintained • OT defined as reduction in response to same dose of opioid after repeated exposure or when  doses required to achieve same effect

  12. Opioids & Tolerance • Clearly seen in animal models fairly early on • Clinical trials are difficult to do especially in cancer pain • Certain effects of opioids like respiratory depression, nausea, sedation are often tolerated quickly but analgesic tolerance may not be seen or diagnosed

  13. Opioid Tolerance & Clinical Relevance • Not clear but some interesting possibilities to consider • If pain is  even in presence of disease , need to consider tolerance • May justify opioid rotation more frequently • Should every patient we treat have a cocktail of opioids plus co-analgesics? • Need studies

  14. Poor Choices for Opioids • Pethidine (meperidine) • Poor oral absorption • Metabolite toxicity • Pentazocine • Dextropropoxyphene • Tramadol • For severe pain

  15. Pain Severity • Start with strong opioids in moderate to severe pain • Little to gain by starting with weak drugs

  16. Type of Pain • All opioids effective in neuropathic pain • Methadone may have an advantage • All opioids similarly effective in inflammatory (nociceptive pain)

  17. Adverse Effects • No evidence that any opioid better than another for adverse effects • However, some patients report differences

  18. Physician Factors • Experience • “my favourite opioid is…..” • Fear or ignorance

  19. Opioid Availability • Menu should be full of choices

  20. Dr. Larry Librach Temmy Latner Centre for Palliative Care 20

  21. Costs • Sustained release drugs may not be necessary • Affordability for patients • Affordability for the system • e.g. transmucosal fentanyl products

  22. Special Issues • Drug interactions • Additive effects • CYP 450 inhibition • e.g. tramadol, methadone, fentanyl • Universal precautions for opioids

  23. Summary • Really is no one best opioid • Need more than morphine in your formulary as tolerance may be an issue

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