What are the types of opioids and their relative strengths for adult patients?

Opioid Types and Relative Strengths for Adult Patients

Oral morphine is the gold standard first-line opioid for moderate to severe pain, with all other opioids compared to it using equianalgesic conversion ratios. 1

Classification of Opioids by Strength

Strong Opioids (WHO Level III)

These are pure mu-opioid receptor agonists used for moderate to severe pain, with no ceiling effect for analgesia: 1

Relative potency compared to oral morphine (1.0 as reference): 1

• Morphine sulfate oral: 1.0 (reference standard)

  • Starting dose: 20-40 mg oral; 5-10 mg IV/subcutaneous 1
  • Oral to IV/subcutaneous conversion ratio: 1:2 to 1:3 1
  • No upper dose limit (titrate to effect) 1

• Oxycodone oral: 1.5-2.0 times more potent than oral morphine

  • Starting dose: 20 mg 1
  • No upper dose limit 1

• Hydromorphone oral: 7.5 times more potent than oral morphine

  • Starting dose: 8 mg 1
  • IV hydromorphone is 3 times more potent than oral 1

• Fentanyl transdermal: Approximately 4 times more potent (calculated from mg/day to mcg/hour)

  • Starting dose: 12-25 mcg/hour patch 1
  • Reserved for opioid-tolerant patients with stable pain only 1
  • Not for opioid-naïve patients or unstable pain requiring titration 1

• Methadone oral: Variable potency ratio of 4-12 depending on baseline morphine dose

  • Factor of 4 for morphine doses <90 mg/day
  • Factor of 8 for doses 90-300 mg/day
  • Factor of 12 for doses >300 mg/day 1
  • Starting dose: 10 mg 1
  • Requires specialist expertise due to long, unpredictable half-life and QTc prolongation risk 1

• Buprenorphine (partial agonist):

  • Oral: 75 times more potent than oral morphine
  • IV: 100 times more potent
  • Transdermal: approximately 4 times more potent (calculated conversion) 1
  • Has ceiling effect for analgesia, limiting use in severe pain 1
  • Preferred in renal impairment as mainly excreted in stool 1

Weak Opioids (WHO Level II)

These are used for mild to moderate pain: 1

• Tramadol: 0.1-0.2 times the potency of oral morphine

  • Starting dose: 50-100 mg
  • Maximum: 400 mg/day 1
  • Approximately one-tenth as potent as morphine 1
  • Avoid with SSRIs/tricyclics due to serotonin syndrome risk 1

• Dihydrocodeine: 0.17 times the potency of oral morphine

  • Starting dose: 60-120 mg
  • Maximum: 240 mg/day 1

• Codeine: Highly variable potency due to CYP2D6 genetic polymorphism

  • Avoid in renal failure due to toxic metabolite accumulation 1
  • Not recommended due to unpredictable metabolism 2

Critical Prescribing Principles

Route and Onset Considerations

For severe pain requiring urgent relief, use parenteral opioids (IV or subcutaneous): 1

• Morphine IV: Relative onset approximately 6 minutes, duration 96 minutes 3
• Hydromorphone IV: Relative onset approximately 5 minutes, duration 120 minutes 3
• Fentanyl IV: Relative onset approximately 2 minutes, duration only 7 minutes 3

Titration intervals based on pharmacokinetics: 3

• Morphine and hydromorphone: Can be titrated IV every 5 minutes
• Fentanyl: Can be titrated every 3 minutes due to rapid onset

Opioid Rotation/Conversion

When converting between opioids, reduce the equianalgesic dose by 25-50% to account for incomplete cross-tolerance if pain was well-controlled: 1

If pain was poorly controlled, may use 100% of equianalgesic dose or increase by 25%: 1

Special Populations

Renal impairment: 1

• Avoid morphine and codeine due to accumulation of toxic metabolites causing confusion, drowsiness, hallucinations, and myoclonus 1
• Preferred opioids: Buprenorphine or fentanyl 1

Cardiac concerns:

• Methadone doses >100 mg/day require baseline and follow-up ECG monitoring for QTc prolongation 1
• Buprenorphine transdermal limited to maximum 20 mcg/hour due to QTc concerns 1

Agents to Avoid

Mixed agonist-antagonists (pentazocine, nalbuphine, butorphanol) should NOT be used in cancer pain: 1

• Should never be combined with pure agonists
• Can precipitate withdrawal in opioid-dependent patients 1

Meperidine and propoxyphene are not recommended due to CNS toxic metabolites (normeperidine, norpropoxyphene) 1