What is the hierarchy of opioids from weakest to strongest for an adult patient with no significant medical history?

Opioid Hierarchy from Weakest to Strongest

Opioids are classified into weak opioids (WHO Level II) and strong opioids (WHO Level III), with oral morphine serving as the reference standard for potency comparisons among strong opioids. 1

Weak Opioids (WHO Level II)

These agents are used for mild to moderate pain, though their clinical utility is increasingly questioned 1:

• Codeine - Requires metabolism via CYP2D6 to morphine for analgesic effect; essentially ineffective in poor metabolizers and potentially toxic in ultrarapid metabolizers 1
• Tramadol - Approximately 10 times less potent than oral morphine; has a relative effectiveness of 0.1-0.2 compared to oral morphine 1, 2
• Dihydrocodeine - Relative effectiveness of 0.17 compared to oral morphine 1

Important caveat: The 2018 ESMO guidelines note that many experts now advocate skipping weak opioids entirely and starting with low-dose morphine for moderate pain, as weak opioids have a "ceiling effect" and limited evidence of superiority over non-opioids 1. The effectiveness of WHO Level II opioids typically plateaus after 30-40 days 1.

Strong Opioids (WHO Level III)

Listed from weakest to strongest based on relative potency compared to oral morphine 1:

Oral Formulations (relative to oral morphine = 1.0):

1. Morphine (oral) - Reference standard (potency = 1.0) 1
2. Oxycodone (oral) - Potency = 2.0 (twice as potent as oral morphine) 1
3. Methadone (oral) - Potency = 4-12 (varies with dose: factor of 4 for daily morphine <90mg, factor of 8 for 90-300mg, factor of 12 for >300mg) 1
4. Hydromorphone (oral) - Potency = 7.5 1
5. Buprenorphine (oral) - Potency = 75 1

Parenteral Formulations (relative to oral morphine = 1.0):

1. Morphine (parenteral) - Potency = 3.0 1
2. Transdermal buprenorphine - Potency = 1.7 1
3. Transdermal fentanyl - Potency = 4.0 1
4. Buprenorphine (IV) - Potency = 100 1

Fentanyl is 50-100 times more potent than morphine when comparing equivalent routes of administration 3, 4. Sufentanil is approximately 10 times more potent than fentanyl 4.

Critical Clinical Considerations

Morphine remains the first-line strong opioid because it is widely available, well-studied, inexpensive, and has no upper dose limit 1. The 2023 ASCO guidelines confirm no opioid demonstrates clear superiority over others in efficacy or tolerability 1.

Methadone requires specialist consultation due to marked interindividual variability in half-life and complex pharmacokinetics 1. It should only be prescribed by experienced clinicians 1.

Tramadol and codeine have significant limitations including genetic variability in metabolism, dose-dependent neurotoxicity (tramadol), and unpredictable efficacy, making them less desirable than low-dose morphine 1, 5. Recent evidence suggests these "weak" opioids may be no less risky than morphine at equivalent analgesic doses 5.

Route conversion: When converting from oral to parenteral morphine, divide the oral dose by 2-3 to achieve equianalgesic effect 1.