Analguesics relieve pain, classified by WHO into Step 1 (non-opioids), Step 2 (weak opioids) and Step 3 (strong opioids). Paracetamol (analgesic and antipyretic — central mechanism, COX-3/PC-2 inhibition) is the most widely used drug, but with hepatotoxicity risk in overdose. NSAIDs (ibuprofen, naproxen, diclofenac, nimesulide, piroxicam, meloxicam) inhibit cyclo-oxygenases COX-1 and/or COX-2, reducing prostaglandin synthesis — analgesic, anti-inflammatory and antipyretic actions, but with GI and cardiovascular risk. Metamizole (pyrazolone) has potent antipyretic and spasmolytic effects, but with agranulocytosis risk. Weak opioids — codeine (prodrug converted to morphine by CYP2D6), tramadol (serotonergic/noradrenergic reuptake inhibition + partial mu agonism) — are used in moderate pain. Strong opioids — morphine (pure mu agonist — gold standard), fentanyl (50-100x more potent than morphine — patches and injectable), methadone (mu agonist + NMDA antagonist — used in opioid substitution therapy) — are used in severe pain and palliative care. (Sources: DailyMed/FDA, EMC-UK/MHRA, WHO Analgesic Ladder)
