Key Facts

Opioids remain the most effective analgesics for severe acute and cancer pain. However, their role in chronic non-cancer pain is increasingly questioned due to limited long-term efficacy and substantial harms including dependence, hyperalgesia, and death.

Epidemiology

• UK: ~5.6 million opioid prescriptions per quarter
• ~500,000 people prescribed opioids for >3 years in England
• Opioid-related deaths: ~2,000/year in England and Wales (rising)
• ~1 in 8 adults prescribed an opioid in any year

Pharmacology

• Mechanism: agonism at opioid receptors (mu > kappa > delta) → inhibit ascending pain pathways, activate descending inhibition
• Mu receptor effects: analgesia, euphoria, respiratory depression, constipation, miosis, dependence
• Kappa effects: analgesia, sedation, dysphoria
• Metabolism: most metabolised hepatically
  • Morphine → M6G (active, renally excreted) and M3G (neuroexcitatory)
  • Codeine → morphine (CYP2D6) — pro-drug
  • Oxycodone → oxymorphone (CYP2D6)

Pathophysiology of Complications

• Tolerance: receptor desensitisation → need increasing doses for same effect
• Physical dependence: neuroadaptation → withdrawal symptoms on cessation
• Opioid-induced hyperalgesia: paradoxical increased pain sensitivity with chronic use
• Respiratory depression: mu-receptor mediated suppression of brainstem respiratory centres

Indications

• Severe acute pain: trauma, post-operative, renal colic, MI
• Cancer pain: integral part of palliative care; WHO Step 3
• Chronic non-cancer pain: only after failure of non-opioid strategies; time-limited trial

Common Side Effects

• Constipation: affects >90%; tolerance does NOT develop — always prescribe laxative
• Nausea/vomiting: affects ~30%; usually resolves in 5–7 days; antiemetic (cyclizine, ondansetron)
• Sedation/drowsiness: usually resolves; warn about driving
• Pruritus: particularly with morphine; can try antihistamine or switch opioid
• Urinary retention: particularly post-operative

Serious Complications

• Respiratory depression: most dangerous; RR <8, pinpoint pupils, reduced consciousness — naloxone 400 mcg IV
• Opioid dependence: physical and psychological; risk increases with duration and dose
• Opioid-induced hyperalgesia: paradoxical worsening of pain → reduce/rotate opioid
• Hypogonadism: chronic opioids suppress HPG axis → reduced testosterone/oestrogen
• Immunosuppression: chronic opioids may impair immune function

Red Flags

• Respiratory rate <8 breaths/min — immediate naloxone
• Escalating doses without benefit → consider hyperalgesia, dependence, reassess
• Requests for early prescriptions/lost prescriptions → assess for misuse
• Concurrent benzodiazepine/gabapentinoid use → additive respiratory depression risk

Before Starting Opioids

• Pain assessment: type, severity, functional impact
• Risk assessment: history of substance misuse, mental health, concurrent medications
• U&Es: renal function (morphine accumulation in CKD)
• LFTs: hepatic function (metabolism)

Monitoring

• Pain scores and functional assessment: regularly — document benefit or lack thereof
• Side effects: constipation, nausea, sedation, respiratory rate
• Review at 2–4 weeks: if chronic pain trial — is there meaningful benefit? If not, wean off
• Longer-term: regular 3–6 monthly review; assess ongoing indication, dose, side effects, addiction risk

Special Tests

• Urine drug screen: if concerns about compliance, misuse, or diversion
• CYP2D6 genotyping: if codeine/tramadol ineffective or excessive effect

Acute Pain

• Morphine: 5–10 mg PO 4-hourly PRN (opioid-naïve) or 2.5–5 mg SC/IV
• PCA (patient-controlled analgesia): post-operative — morphine bolus with lockout interval
• Multimodal approach: combine with paracetamol + NSAID to reduce opioid requirement
• Wean off as acute pain resolves — do not discharge on strong opioids without clear plan

Cancer Pain

• WHO Step 3: strong opioid — morphine first-line
• Immediate-release morphine (Oramorph/Sevredol): titrate to find effective dose
• Convert to modified-release: once stable dose established (MST Continus BD)
• Breakthrough dose: 1/6 of total 24-hour morphine dose as immediate-release PRN
• Fentanyl patches: for stable pain, swallowing difficulty, or renal impairment
• Opioid rotation: if side effects intolerable — use equianalgesic conversion chart

Chronic Non-Cancer Pain

• FPM Opioids Aware guidance: time-limited trial (2–4 weeks); SMART goals; stop if no benefit
• Maximum recommended: ~120 mg oral morphine equivalent/day
• Regular review: every 3 months minimum
• Deprescribing/tapering: reduce by 10% of dose every 1–2 weeks

Opioid Conversion

• Use equianalgesic tables; reduce by ~25–50% when switching (incomplete cross-tolerance)

Naloxone for Overdose

• IV/IM/SC naloxone 400 mcg: repeat every 2–3 minutes (max 10 mg)
• Half-life of naloxone (~60 min) is shorter than most opioids → monitor for re-sedation
• Continuous infusion: may be needed for long-acting opioid overdose

Referral Criteria

• Pain clinic: chronic pain not responding to primary care management; opioid reduction support
• Palliative care: cancer pain management
• Addiction services: opioid dependence/misuse
• Pharmacy: complex opioid conversion calculations

• Acute pain: opioids very effective; should be short-term
• Cancer pain: opioids are essential; effective with appropriate dose titration
• Chronic non-cancer pain: limited evidence for long-term benefit; significant harms
• Opioid-related deaths: increasing in UK; ~2,000/year
• Dependence: develops in ~8–12% of patients prescribed opioids for chronic pain
• Deprescribing: possible in most patients with gradual taper — pain scores often unchanged or improved

Opioid Equianalgesic Conversion Table

Opioid Side Effect Management