AS8.3 | Pharmacologic Management of Pain — Summary & Reflection

KEY TAKEAWAYS

The WHO analgesic ladder structures pain pharmacotherapy in three steps — non-opioids alone (Step 1), weak opioids added (Step 2), strong opioids (Step 3) — guided by 'by mouth, by the clock, by the ladder.' Paracetamol acts centrally (mechanism partly unclear; not primarily via peripheral COX inhibition) and is hepatotoxic in overdose through NAPQI accumulation. NSAIDs inhibit COX-1 and COX-2, reducing prostaglandin synthesis; adverse effects (GI, renal, cardiovascular, platelet) are mechanism-based and COX-selectivity determines the safety profile. Opioids act at μ, δ, and κ GPCRs; μ-receptor activation produces analgesia, respiratory depression, miosis, constipation, and euphoria. Morphine's active metabolite M6G accumulates in renal failure — fentanyl is preferred in significant renal impairment. Opioid adverse effects include respiratory depression (reversed with naloxone), constipation (no tolerance — laxative always co-prescribed), nausea, sedation, and urinary retention. Adjuvant analgesics — gabapentinoids (α₂δ Ca²⁺ channel subunit blockade), TCAs (reuptake inhibition in descending pathways), SNRIs, sub-anaesthetic ketamine (NMDA antagonism) — are first-line for neuropathic pain and perioperative opioid reduction. Multimodal analgesia combines agents at multiple targets to maximise efficacy while minimising individual drug doses and adverse effects.

REFLECT

Reflect on a clinical situation — real or hypothetical — where a patient was prescribed an opioid analgesic without co-prescribing a laxative, an antiemetic, or a non-opioid analgesic. What were the consequences? How might a multimodal analgesic plan have improved the outcome? Consider also the social and systemic dimensions of opioid prescribing: in your community, what are the barriers to accessing adequate analgesia (cost, stigma, prescriber reluctance, drug availability)? As a future doctor, how will you balance the duty to treat pain effectively against the duty to prescribe opioids responsibly in a context where opioid misuse causes significant harm?