Opioids & opioid use disorder

Equianalgesic dosing, naloxone, OUD treatment (methadone, buprenorphine, naltrexone), pregnancy considerations.

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◆Common opioids — knowing the family

•Morphine — gold standard; AVOID in renal failure (active metabolite M6G accumulates)
•Hydromorphone (Dilaudid) — preferred in renal failure
•Oxycodone — oral; combined with APAP (Percocet) or naloxone (Targin)
•Fentanyl — IV or transdermal patch; 100× morphine potency; preferred in renal failure + hemodynamic instability
•Methadone — long half-life; OUD maintenance; QT prolongation
•Tramadol — weak μ agonist + SNRI activity; seizure risk; serotonin syndrome with SSRIs
•Codeine — prodrug requiring CYP2D6 → morphine; AVOID in children + nursing mothers (CYP2D6 ultra-rapid metabolizers → infant death)
•Meperidine — AVOID (toxic metabolite normeperidine → seizures); serotonin syndrome with MAOIs

•Respiratory depression — leading cause of overdose death
•Sedation, AMS
•Constipation (does NOT improve with tolerance) — schedule a bowel regimen (senna + docusate; methylnaltrexone for refractory)
•Nausea, pruritus, urinary retention
•Tolerance (need more drug for same effect) + physical dependence (withdrawal on discontinuation)
•Hyperalgesia with long-term high-dose use (paradoxical pain ↑)
•Miosis (pinpoint pupils)

•Overdose triad: miosis + respiratory depression + AMS
•Antidote: NALOXONE — IV/IM/intranasal (Narcan); short half-life (30–90 min) → may need repeat dosing; PRECIPITATES withdrawal
•Withdrawal: NOT life-threatening (vs alcohol/benzo which are) — nausea, diarrhea, mydriasis, piloerection ('cold turkey'), yawning, lacrimation, restless legs, anxiety, dilated pupils, muscle aches
•Treat withdrawal: clonidine (autonomic), loperamide (diarrhea), ondansetron (nausea), NSAIDs (myalgia)
•Neonatal abstinence syndrome (NAS): irritability, high-pitched cry, hypertonia, seizures — treat with MORPHINE or methadone taper

•Methadone — full μ agonist; reduces craving; only at federally certified opioid treatment programs
•Buprenorphine — PARTIAL μ agonist; ceiling effect on respiratory depression (safer); office-based prescribing (X-waiver no longer required)
•Combination buprenorphine-naloxone (Suboxone): if injected, naloxone precipitates withdrawal (deterrent)
•Naltrexone — μ ANTAGONIST; oral or monthly IM (Vivitrol); requires 7–10 day opioid-free period (precipitates withdrawal if not)
•Naloxone for take-home (lay reversal) — co-prescribe for any high-risk patient
•Pregnancy + OUD: methadone or buprenorphine maintenance; NEVER detox during pregnancy (relapse + miscarriage risk)

•Morphine 30 mg PO = oxycodone 20 mg PO = hydrocodone 30 mg = hydromorphone 7.5 mg
•Morphine 10 mg IV = morphine 30 mg PO (3:1 oral-to-IV ratio)
•Fentanyl: 25 µg/hr patch ≈ morphine 60 mg/day PO (for chronic use)
•Always reduce by 25–50% when switching drugs (incomplete cross-tolerance)

◆Codeine forbidden in kids + breastfeeding (CYP2D6 ultra-rapid metabolizer → fatal infant respiratory depression)
◆Meperidine OUT — toxic metabolite normeperidine causes seizures; serotonin syndrome with MAOIs
◆Morphine + renal failure → switch to hydromorphone or fentanyl (no active metabolites)
◆Buprenorphine: partial agonist with ceiling on respiratory depression — SAFER than methadone for outpatient OUD
◆Naltrexone needs 7–10 days opioid-free before starting (else precipitated withdrawal)
◆Pregnant + OUD → methadone or buprenorphine; do NOT detox in pregnancy
◆Tramadol = SNRI + opioid; AVOID with SSRIs (serotonin syndrome) + epilepsy (seizures)

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