Methadone
Dolophine
Synthetic μ-opioid agonist + NMDA antagonist + monoamine reuptake inhibitor
μ-opioid agonist with NMDA-receptor antagonism (blunts tolerance + opioid-induced hyperalgesia) and monoamine reuptake inhibition. Very long, variable half-life.
Indications
- •Single intraop dose for prolonged opioid-sparing postop analgesia
- •Opioid use disorder maintenance
- •Chronic/cancer pain
Dosing
| Context | Adult | Pediatric |
|---|---|---|
| Intraop single dose | 0.1–0.3 mg/kg IV | — |
| Maintenance/chronic | Individualized (specialist) | — |
Pharmacokinetics
Onset 10–20 min IV; analgesia 4–8 h but elimination t½ 8–59 h → accumulates with repeat dosing.
Hemodynamic effects
Minimal.
Respiratory effects
Dose-dependent and DELAYED/prolonged due to long half-life.
Side effects
- !QT prolongation → torsades (dose-dependent)
- !Delayed/prolonged respiratory depression
- !Accumulation with repeat dosing
Contraindications
- ×Long QT / other QT-prolonging drugs (relative)
- ×MAOI within 14 days (relative)
Reversal / antidote
Naloxone (may need an infusion — methadone outlasts a single naloxone dose)
Clinical pearls
- ★A single intraop dose delivers long opioid-sparing postop analgesia (NMDA antagonism reduces OIH/tolerance).
- ★Check a baseline QTc; avoid stacking QT-prolonging drugs.
- ★Respiratory-depressant effect outlasts naloxone — re-dose/monitor.
Other drugs in Narcotics & Analgesics
- Fentanyl
μ-opioid receptor agonist. ~100× potency of morphine.
- Remifentanil
μ-opioid agonist. Ester linkage hydrolyzed by nonspecific tissue + plasma esterases — no organ-dependent clearance.
- Morphine
μ-opioid receptor agonist. Active metabolite morphine-6-glucuronide (M6G) is analgesic and renally cleared — accumulates in renal failure → prolonged sedation/respiratory depression. Causes histamine release.
- Hydromorphone
μ-opioid agonist ~5–7× more potent than morphine. No clinically significant active metabolites → safer than morphine in renal failure. Less histamine release.
- Sufentanil
Most potent opioid in common clinical use — ~1000× morphine, ~10× fentanyl. High lipid solubility.
- Alfentanil
μ-opioid agonist ~1/5–1/10 the potency of fentanyl but FASTEST onset of the family — low pKa means a high non-ionized fraction at physiologic pH.
- Meperidine
μ-opioid agonist ~1/10 morphine, plus κ-agonism (anti-shivering). Active metabolite normeperidine is renally cleared, proconvulsant, and neurotoxic.
- Nalbuphine
κ-receptor agonist + μ-receptor antagonist. Ceiling on respiratory depression. Reverses μ-mediated pruritus/respiratory depression while preserving some analgesia.
Browse all classes: /reference/drugs
Suggested reading
- •Stoelting & Hines, Pharmacology & Physiology in Anesthetic Practice, 6e
- •Miller's Anesthesia, 9e
- •FDA package insert
