What is the most potent nonsteroidal anti-inflammatory drug (NSAID)?

Most Potent NSAID

Ketorolac is the most potent nonsteroidal anti-inflammatory drug (NSAID) currently available for clinical use. 1, 2

Comparative Potency of NSAIDs

• Ketorolac stands out as the most potent NSAID, with analgesic efficacy comparable to opioids like morphine and meperidine for moderate to severe pain 1, 3
• Ketorolac is the only NSAID widely available in injectable form, highlighting its unique potency profile among NSAIDs 1
• Other NSAIDs with significant but lesser potency include diclofenac, indomethacin, and dexketoprofen 4
• Naproxen is recommended as a preferred NSAID in certain clinical contexts due to its favorable efficacy and safety profile, though it is not the most potent 4

Mechanism of Action and Potency

• Ketorolac is a pyrrolo-pyrrole NSAID that achieves its potent analgesic effects through strong inhibition of cyclooxygenase enzymes 3, 2
• Like other NSAIDs, ketorolac inhibits prostaglandin synthesis, but does so with greater potency than most other agents in this class 1
• Ketorolac has been described as "the most potent NSAID known" in clinical literature 2
• Its potency is sufficient to provide opioid-sparing effects, reducing narcotic requirements by approximately 40-45% when used in combination therapy 5, 2

Clinical Applications of Ketorolac

• Ketorolac is particularly effective for post-surgical pain management either alone or in combination with opioids 1, 5
• For acute pain management, ketorolac can be administered via multiple routes:
  • Intravenous: 0.5 mg/kg initial dose followed by 1.0 mg/kg every 6 hours or 0.17 mg/kg/h infusion 5
  • Intramuscular: 60 mg IM every 15-30 minutes with maximum daily dosage of 120 mg 4
  • Oral: 0.25 mg/kg to maximum of 1.0 mg/kg/day 5
• Maximum duration of treatment should be limited to 48 hours for parenteral administration and 7 days for oral administration 5

Important Considerations and Limitations

• Despite its potency, ketorolac has limitations for acute pain management:
  • Delayed onset of action (30-60 minutes) compared to opioids 6
  • Approximately 25% of patients may have inadequate response 6
• Ketorolac carries significant risks that require careful patient selection:
  • Increased risk of GI complications including ulceration even when administered parenterally 3
  • Reversible inhibitory effect on platelet aggregation that may increase bleeding risk 3, 5
  • Contraindicated in patients with aspirin/NSAID-induced asthma, pregnancy, and cerebrovascular hemorrhage 4
• The elimination half-life increases in elderly patients and those with renal impairment 3

Comparative Efficacy in Pain Management

• In studies of postoperative pain, ketorolac has demonstrated analgesic efficacy equivalent to commonly used doses of morphine and meperidine 6
• When combined with opioids, ketorolac exhibits synergistic effects that improve pain relief while reducing opioid-related adverse effects 5
• For pediatric postoperative pain management, ketorolac has shown efficacy equal to major opioid analgesics and superior to codeine 5

When selecting the most appropriate NSAID for a patient, clinicians should consider not only potency but also the safety profile, route of administration needed, and patient-specific risk factors for adverse effects.