Which has the strongest binding affinity, buprenorphine, fentanyl, hydrocodone, or codeine?

Buprenorphine Has the Strongest Binding Affinity

Among buprenorphine, fentanyl, hydrocodone, and codeine, buprenorphine has the highest binding affinity for the mu-opioid receptor, exceeded only by sufentanil (which is not among the options listed). 1

Binding Affinity Hierarchy

The mu-opioid receptor binding affinity from highest to lowest among these medications is:

• Buprenorphine: Very high binding affinity, described as having affinity "exceeded only by sufentanil" 1
• Fentanyl: High binding affinity, but lower than buprenorphine 1
• Hydrocodone: Moderate binding affinity 1
• Codeine: Lowest binding affinity among these options 1

Clinical Implications of Buprenorphine's High Binding Affinity

The exceptionally high binding affinity of buprenorphine creates significant clinical challenges when managing acute pain in patients on buprenorphine therapy. 1

Key Pharmacologic Characteristics

• Buprenorphine is a partial mu-opioid receptor agonist with very high receptor affinity and slow dissociation from the receptor 2, 3, 4
• This high affinity allows buprenorphine to effectively block or compete with full opioid agonists (like fentanyl, morphine, or hydromorphone) when administered concurrently 1, 2
• The binding is so strong that effects are not easily reversed by competitive antagonists like naloxone at standard doses 5

Acute Pain Management Considerations

When patients on buprenorphine require acute pain management:

• Continue the baseline buprenorphine dose to prevent withdrawal and maintain stability 1
• Higher doses of full mu-agonists may be required to compete with buprenorphine at the receptor level, with fentanyl and hydromorphone being preferred due to their stronger binding affinity compared to other options 1
• Hydromorphone, morphine, and fentanyl are recommended as the full agonists of choice because their binding affinity and lipophilicity allow them to better compete with buprenorphine 1
• Codeine and hydrocodone would be particularly ineffective in this scenario due to their much lower binding affinity 1

Important Cautions

• Mixed agonist-antagonists (nalbuphine, butorphanol) must be avoided as they can precipitate acute withdrawal by displacing buprenorphine 1
• If buprenorphine is abruptly discontinued after adding full agonists, patients may experience increased sensitivity to respiratory depression and sedation 1