Chapter 13  ·  Module 5

Clinical Applications and Management of Opioid Use Disorder

WHO analgesic ladder, medications for opioid use disorder, and special populations

World Health Organization Analgesic Ladder

Step 1

Mild Pain

  • Acetaminophen
  • Nonsteroidal anti-inflammatory drugs
  • Adjuvant agents
  • No opioids at this step

Step 2

Mild to Moderate Pain

  • Add weak opioid or low-dose strong opioid
  • Codeine, tramadol, low-dose oxycodone
  • Continue Step 1 non-opioids
  • Continue adjuvants

Step 3

Moderate to Severe Pain

  • Strong opioids titrated to effect
  • Morphine, oxycodone, fentanyl, hydromorphone
  • No fixed ceiling dose for cancer pain
  • Guiding principles: by mouth, by the clock, by the ladder

Medications for Opioid Use Disorder Compared

Agent Mechanism Setting Key Requirement Key Monitoring
Methadone Full mu agonist Licensed opioid treatment programs only Daily observed dosing initially; take-home earned with stability QTc interval monitoring; cytochrome P450 3A4 drug interactions
Buprenorphine/ naloxone Partial mu agonist plus naloxone deterrent Office-based — any prescriber with standard registration Patient must be in spontaneous withdrawal before induction Hepatic function; signs of precipitated withdrawal at induction
Extended-release naltrexone Pure mu antagonist Office-based or outpatient Full detoxification first: 7–10 days minimum off short-acting opioids Adherence; relapse risk during detoxification period

Special Populations: High-Yield Rules

Avoid or Reduce

Renal Impairment

  • Morphine: morphine-6-glucuronide accumulates → prolonged respiratory depression
  • Meperidine: normeperidine accumulates → seizures — avoid entirely
  • Preferred: fentanyl or hydromorphone (less active metabolite accumulation)
  • Oxycodone: dose reduction required

Adjust Doses

Elderly and Hepatic Disease

  • Elderly: start lower, titrate slower; avoid meperidine (Beers Criteria)
  • Hepatic disease: reduced first-pass metabolism increases bioavailability
  • Buprenorphine: use cautiously in severe hepatic impairment
  • All opioids: extended dosing intervals in hepatic disease

Pregnancy and Neonatal Opioid Withdrawal Syndrome

Preferred treatment for opioid use disorder in pregnancy: methadone or buprenorphine maintenance — not abstinence. Abrupt withdrawal in pregnancy risks fetal distress and preterm labor.

Neonatal opioid withdrawal syndrome: onset 24–72 hours after birth in exposed neonates. Symptoms: irritability, high-pitched crying, tremors, poor feeding, vomiting, diarrhea, seizures in severe cases. Treatment: supportive care; oral morphine or methadone weaning if needed. Not a contraindication to maternal opioid use disorder treatment.