What is analgesic potency?

Analgesic Potency

Analgesic potency refers to the relative dose of one analgesic medication required to produce the same pain-relieving effect as another analgesic—essentially, it is a comparative measure of how much drug is needed to achieve equivalent analgesia. 1

Core Definition and Mechanism

Analgesic potency is determined by the binding affinity and selectivity of opioids for mu, kappa, and delta opioid receptors, with variations in these properties directly affecting how much drug is needed to achieve pain relief 1. Opioids vary in their binding affinity and selectivity for different opioid receptors, which fundamentally determines their potency 2.

• Potency is expressed as a ratio comparing one drug to another (e.g., fentanyl is approximately 80 times as potent as parenteral morphine, meaning 1 mg of fentanyl produces the same analgesic effect as 80 mg of morphine) 1
• For local anesthetics used intrathecally, the analgesic potency ratio for levobupivacaine compared to bupivacaine is 0.8, and for ropivacaine is 0.65 1
• Sufentanil demonstrates an intrathecal potency ratio to fentanyl of 4.4:1, and during intermediate-term infusions in chronic pain patients, sufentanil is approximately 7.5 times as potent as fentanyl 1, 3

Critical Clinical Distinction: Potency vs. Efficacy

A crucial misconception is that higher potency implies superior pain relief or greater danger—this is false. 4 Pharmacologic potency per se does not necessarily imply more effective analgesia or higher abuse liability 4.

• Differences in pharmacologic potency are largely accounted for by adjusting the actual doses prescribed according to individualized patient need 4
• All full opioid agonists like morphine have no ceiling effect for analgesia—dosage is titrated to provide adequate analgesia and may be limited by adverse reactions rather than potency 5
• Less-potent opioids are not inherently less effective, and more-potent opioids are not inherently more dangerous when dosed appropriately 4

Pharmacokinetic Factors Affecting Potency

Beyond receptor binding, pharmacokinetics and bioavailability determine the rapidity and duration of action, which influence clinical potency 1, 2.

• Route of administration significantly affects potency—rapid delivery to the brain (intravenous, intranasal) produces stronger effects but does not change the fundamental potency of the drug 2
• Oral bioavailability varies substantially: oxycodone has 60-90% bioavailability, making its equianalgesic oral dose between half and two-thirds that of oral morphine 1
• Morphine has less than 40% oral bioavailability due to extensive pre-systemic metabolism, requiring higher oral doses compared to parenteral administration 5

Tolerance and Cross-Tolerance Impact on Potency

Long-term opioid exposure fundamentally alters effective potency through tolerance and cross-tolerance. 1

• Analgesic tolerance develops differentially across opioid properties—tolerance to analgesia develops faster than tolerance to respiratory depression, creating a narrowing therapeutic window 1, 2
• Cross-tolerance between opioids used for maintenance therapy and other opioids used for analgesia explains why patients receiving opioid agonist therapy often require higher and more frequent doses to achieve adequate pain control 1
• Patients receiving maintenance methadone therapy demonstrate cross-tolerance to morphine's analgesic effects, with pain relief not lasting as long as expected 1
• Opioid-induced hyperalgesia can develop even after a few administrations, effectively diminishing analgesic effectiveness and altering the practical potency of the drug 1, 2

Clinical Application: Equianalgesic Dosing

Published dose conversion tables may not accurately calculate doses for safe opioid rotation in patients receiving long-term therapy because they are based on limited data that may not apply to chronic pain. 4

• The conversion ratio of 10 mg parenteral morphine = 30 mg oral morphine is based on clinical experience in chronic pain patients, while the ratio of 10 mg parenteral morphine = 60 mg oral morphine is based on acute pain studies 6
• When converting to transdermal fentanyl, the recommended starting dose is intentionally conservative and likely too low for 50% of patients to minimize overdose risk with the first dose 6
• Hydromorphone is 5-10 times as potent as morphine, with no major differences in efficacy and adverse effects when used in equianalgesic doses 1

Common Pitfall: Maintenance Opioids and Analgesia

A critical misconception is that maintenance opioids (methadone or buprenorphine) prescribed for addiction treatment provide sustained analgesia—they do not. 1

• Methadone and buprenorphine have a duration of action for analgesia (4-8 hours) that is substantially shorter than their suppression of opioid withdrawal (24-48 hours) 1
• Because most patients receiving opioid agonist therapy are dosed every 24-48 hours, the period of even partial pain relief is minimal 1
• Methadone has pronounced interindividual differences in plasma half-life, relative analgesic potency, and duration of action, making it more complicated to use compared with other opioids 1