Pharmacologic Management of Pain
Match drug to mechanism
Acetaminophen is first-line for mild pain but has hepatic ceilings. NSAIDs are effective for inflammatory nociceptive pain; their risks include GI bleeding, renal injury (especially with ACE inhibitors and diuretics), and cardiovascular events. Topical NSAIDs and lidocaine reduce systemic exposure.
Neuropathic pain responds to gabapentinoids, SNRIs, and TCAs. Gabapentin and pregabalin require renal dose adjustment and carry sedation and misuse risk. Duloxetine suits coexisting depression; nortriptyline is a common TCA but is anticholinergic and risky in the elderly and in cardiac disease. Topical capsaicin and lidocaine are useful adjuvants. Opioids remain appropriate for selected severe pain but require goals, monitoring, and an exit strategy.
Opioid pharmacology
Morphine and hydromorphone are renally cleared. Methadone prolongs QT and has variable equianalgesia. Buprenorphine is a partial agonist with a ceiling and high affinity. Tramadol and meperidine are serotonergic, and meperidine is neurotoxic with repeated dosing because of normeperidine accumulation. Codeine and tramadol depend on CYP2D6, so ultrarapid metabolizers risk toxicity. Rotate with a 25–50% dose reduction for incomplete cross-tolerance.
Trap: milligram-per-milligram equivalence is false; use morphine milligram equivalents cautiously. Another trap: naloxone reverses respiratory depression but may precipitate withdrawal and is short-acting.
Rule of thumb: match drug to mechanism, and review interactions and renal or hepatic function every time you escalate.