Pharmacology of analgesics and other agents used to treat major symptom complexes

Overview

Palliative symptom management draws on a defined pharmacological toolkit spanning analgesics (opioid and non-opioid) and drugs targeting other common end-of-life symptom complexes (nausea, secretions, agitation, dyspnoea) - selection is matched to the underlying mechanism, not applied generically
Polypharmacy is common in this population given the number of symptoms often present simultaneously, making rational, mechanism-based drug selection (rather than empirical stacking of agents) particularly important

Matching the drug class to the specific symptom mechanism (e.g. neuropathic vs nociceptive pain, mechanism-specific antiemetic choice) produces more effective symptom control than a one-size-fits-all approach, and reduces unnecessary polypharmacy

Symptom	First-line agent(s)	Mechanism
Nociceptive pain	Opioids, paracetamol, NSAIDs (if appropriate)	Standard analgesic ladder
Neuropathic pain	Gabapentinoids, tricyclic antidepressants, sometimes adjunct opioids	Membrane stabilisation/descending pain modulation
Nausea (opioid-related)	Haloperidol, metoclopramide	Dopamine antagonism
Nausea (obstruction-related)	Hyoscine butylbromide, octreotide (antisecretory); avoid prokinetics if complete obstruction	Reduced GI secretion/motility
Terminal respiratory secretions	Hyoscine butylbromide/hyoscine hydrobromide, glycopyrronium	Antimuscarinic - reduced secretion production
Terminal agitation/delirium	Haloperidol, or benzodiazepines for specific indications	Antipsychotic/sedative, mechanism-dependent

Dose selection and route (oral, subcutaneous, syringe driver) are adjusted as swallowing/absorption become unreliable near the end of life, generally shifting to the subcutaneous route via syringe driver for continuous symptom control
Combination regimens are common and should be reviewed regularly for continued indication, given the risk of cumulative side effects (particularly sedation and anticholinergic burden) from multiple agents used together

Opioid toxicity, terminal secretions ("death rattle" - distressing to families though not typically to the patient), terminal delirium/agitation, subcutaneous infusion pump (syringe driver) use

Rational, mechanism-matched symptom management (rather than empirically adding drugs) is both more effective and reduces the cumulative burden of polypharmacy in a population where drug clearance and tolerance of side effects are often already compromised

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