Pharmacologic Management of Pain
Principles
Multimodal analgesia combines agents with different mechanisms to improve efficacy and reduce dose-related toxicity. Nonopioid foundations include acetaminophen and NSAIDs, but screen for hepatic, renal, gastrointestinal, and cardiovascular risk. Topical NSAIDs or lidocaine can reduce systemic exposure. Adjuvant classes include gabapentinoids (alpha-2-delta ligands; renally dosed), tricyclics (caution in cardiac disease, glaucoma, and older adults), SNRIs such as duloxetine, and selected anticonvulsants. Opioids remain appropriate for some acute and cancer-related pain but require individualized risk assessment, a PDMP check, baseline and periodic urine drug testing when indicated, and a documented treatment agreement.
Know the toxicity signatures: meperidine accumulates normeperidine (seizures), tramadol lowers seizure threshold and can cause serotonin syndrome, methadone prolongs QT and has variable conversion, and codeine and tramadol depend on CYP2D6. Buprenorphine is a partial mu agonist with high affinity-it can precipitate withdrawal and has a ceiling for respiratory depression, but not for analgesia in all contexts. Opioid-induced hyperalgesia and tolerance are not the same as addiction.
Conversion traps are common. Equianalgesic tables are starting points, not precise calculators; when rotating, reduce the calculated dose by 25–50% for incomplete cross-tolerance, then titrate. Watch for opioid plus benzodiazepine or gabapentinoid sedation.
Worked example: a patient on oral morphine 60 mg/day is switched to hydromorphone because of nausea. Using standard equianalgesia, calculate the new dose, reduce for cross-tolerance, and reassess in 24–48 hours. Rule of thumb: start low, go slow, treat function as the target, and never adjust a controlled substance without checking the PDMP and documenting rationale.