Surgery & Perioperative/Analgesia (WHO ladder & opioids)

Analgesics & the WHO pain ladder

also: opioids · morphine · WHO analgesic ladder · codeine · naloxone · PCA

Overview

Acute, post-operative and palliative pain management — the WHO ladder, the opioids, and the safety points (naloxone, renal impairment, codeine pharmacogenetics).

Mechanism

Step the WHO ladder: non-opioid (paracetamol/NSAID) → weak opioid (codeine/dihydrocodeine/tramadol) → strong opioid (morphine/oxycodone/fentanyl). Opioids agonise µ-opioid receptors (Gi → ↓cAMP, ↓neuronal excitability) → analgesia + the class effects. Naloxone is a competitive opioid antagonist (reversal).

Indications

Acute / post-operative pain (incl. PCA)
Chronic & cancer pain (WHO ladder)
Opioid overdose reversal (naloxone)

The agents

Morphinestrong opioid

PO/IV/SC

Standard; active metabolites accumulate in renal impairment → use oxycodone/alfentanil if eGFR low.

Oxycodonestrong opioid

Less active-metabolite accumulation; renal impairment.

Fentanylstrong opioid

transdermal/IV/buccal

Transdermal for stable chronic pain; safer in renal failure.

Codeine / dihydrocodeine / tramadolweak opioid

Codeine is a prodrug (CYP2D6) — avoid <12y / variable metabolisers; tramadol also lowers seizure threshold + serotonergic.

Naloxoneantagonist (reversal)

IV/IM/intranasal

Short half-life — repeat/infuse; titrate to respiratory rate, not full reversal in palliative patients.

Adverse effects

Respiratory depressionserious

The dangerous effect; reverse with naloxone.

Constipationclassic

Co-prescribe a laxative — tolerance does NOT develop.

Nausea, sedation, pruritus, urinary retentioncommon

Dependence / tolerancecommon

Toxicity: pinpoint pupils + ↓RR + ↓GCSserious

Cautions & contraindications

Morphine in significant renal impairmentrenal

Active metabolite (M6G) accumulation → toxicity; use oxycodone/fentanyl/alfentanil.

Codeine/tramadol in children <12 / breastfeedingpaediatric

CYP2D6 ultra-rapid metabolism → respiratory depression.

Caution with other CNS depressants (benzodiazepines, alcohol)all

Interactions

Additive sedation/respiratory depression with benzodiazepines, gabapentinoids, alcohol
Tramadol + SSRIs → serotonin syndrome

Monitoring & kinetics

Respiratory rate, sedation, pain score; bowels (laxative); convert doses carefully (oral→SC morphine ÷2; opioid switch tables)

PO/IV/SC/transdermal. Always co-prescribe an antiemetic + laxative when starting strong opioids.

Source: WHO — Analgesic ladder · BNF — Opioid analgesics