NSAIDs - prescribing issues
Exam Tips
- In OSCE prescribing stations, always state: lowest effective dose, shortest duration, and check OTC NSAID use.
- Know hard contraindications: active GI bleed/ulcer, previous NSAID-related GI bleed/perforation, severe renal/hepatic failure, severe heart failure, third-trimester pregnancy, serious NSAID hypersensitivity.
- High-yield safety rule: avoid diclofenac/coxibs/high-dose ibuprofen in established cardiovascular disease; avoid etoricoxib if BP is uncontrolled.
- For high GI risk, pair NSAID with a PPI and document counselling on red flags (melaena, haematemesis, reduced urine output, chest pain, breathlessness).
- Common viva question: explain COX-1 vs COX-2 and link mechanism directly to efficacy and adverse effects.
Definition
Nonsteroidal anti-inflammatory drugs (NSAIDs) are medicines used for analgesic, antipyretic, and dose-dependent anti-inflammatory effects in acute and chronic painful inflammatory conditions. In prescribing practice, the key issue is balancing symptom benefit against gastrointestinal, renal, and cardiovascular harm by selecting the right agent, dose, duration, and monitoring strategy for each patient.
Pathophysiology
Most NSAIDs reversibly inhibit cyclo-oxygenase (COX) enzymes, reducing prostaglandin synthesis both peripherally and centrally (predominantly peripheral effect). COX-1 inhibition reduces protective gastric prostaglandins and platelet thromboxane activity, contributing to dyspepsia, ulceration, and bleeding risk; COX-2 inhibition reduces inflammatory prostaglandins and therefore pain/swelling, but selective or relatively COX-2-favouring agents can increase thrombotic cardiovascular risk in susceptible patients. Renal adverse effects arise because prostaglandins help maintain renal perfusion, especially when renal blood flow is already compromised (for example CKD, heart failure, dehydration, diuretic/RAAS blockade use). See Figure: arachidonic acid-COX pathway diagram in core pharmacology texts.
Risk Factors
- Ageing/frailty and multimorbidity (higher GI, renal, CV toxicity burden)
- Previous NSAID-related GI bleed or perforation
- Recurrent peptic ulcer disease or recurrent GI haemorrhage
- Concomitant interacting medicines (for example anticoagulants, antiplatelets, corticosteroids, SSRIs, ACE inhibitors/ARBs, diuretics)
- Established cardiovascular disease (ischaemic heart disease, stroke/TIA, peripheral arterial disease, heart failure)
- Hypertension, especially uncontrolled (>140/90 mmHg for etoricoxib/high-dose ibuprofen)
- Renal impairment, diabetes mellitus, or heart failure
- Severe hepatic impairment (Child-Pugh 10 or more, albumin <25 g/L)
- NSAID hypersensitivity history (asthma, rhinitis, nasal polyps, urticaria, angioedema after NSAID/aspirin)
- Third-trimester pregnancy
- Current varicella infection
Clinical Features
Symptoms
- Epigastric pain, dyspepsia, reflux, nausea
- Melaena or haematemesis suggesting upper GI bleeding
- Reduced urine output, lethargy, or thirst suggesting AKI/dehydration
- Wheeze or breathlessness after NSAID exposure in aspirin-exacerbated respiratory disease
- Ankle swelling or worsening breathlessness from fluid retention/heart failure exacerbation
- Headache or dizziness
- Poor BP control after NSAID initiation
Signs
- Epigastric tenderness
- Pallor or tachycardia in occult/overt GI blood loss
- Hypotension in significant GI haemorrhage
- Peripheral oedema, raised JVP, bibasal crackles in heart failure worsening
- Elevated blood pressure on repeat measurements
- Wheeze on chest examination
- Reduced hydration status (dry mucosae, postural drop)
Investigations
Management
Lifestyle Modifications
- Use shared decision-making: explain benefit-risk balance and red flags (melaena, haematemesis, oliguria, dyspnoea, chest pain)
- Use the lowest effective dose for the shortest possible duration
- Avoid duplicate OTC NSAID/aspirin self-medication unless specifically advised
- Consider non-NSAID options early (physiotherapy, exercise-based rehabilitation, weight reduction, heat/ice, pacing)
- Prefer topical NSAID for localised osteoarthritis pain where suitable
Pharmacological Treatment
Standard oral NSAIDs (non-selective or relatively COX-2 preferential)
- Ibuprofen 200-400 mg orally three times daily (max 2400 mg/day)
- Naproxen 250-500 mg orally twice daily (usual max 1000 mg/day)
- Diclofenac 50 mg orally two to three times daily (max 150 mg/day; avoid in significant CV disease)
- Mefenamic acid 500 mg initially then 250-500 mg three times daily for short courses
Choose agent by GI/CV/renal risk and prior response. Do not prescribe if active GI ulcer/bleed, severe renal impairment (eGFR <30), severe heart failure, severe hepatic impairment, third-trimester pregnancy, or prior severe NSAID hypersensitivity.
COX-2 selective NSAIDs (coxibs)
- Celecoxib 100 mg once or twice daily (up to 200 mg twice daily depending indication)
- Etoricoxib 30-60 mg once daily (higher doses such as 90 mg for selected inflammatory indications)
Lower GI ulcer risk than some non-selective NSAIDs but CV risk remains important. Avoid in ischaemic heart disease, cerebrovascular disease, peripheral arterial disease, NYHA II-IV heart failure; avoid etoricoxib in uncontrolled hypertension.
Gastroprotection
- Omeprazole 20 mg once daily
- Lansoprazole 15-30 mg once daily
Co-prescribe PPI when GI risk is increased (older age, prior ulcer, concomitant anticoagulant/antiplatelet/steroid, long-term NSAID use, dyspepsia history).
Alternatives when NSAID risk outweighs benefit
- Paracetamol 1 g up to four times daily (max 4 g/day in adults)
- Codeine phosphate 30-60 mg every 4-6 hours as short-term rescue (max 240 mg/day)
Use opioid options only for short, infrequent rescue due to dependence and adverse-effect risk; reassess diagnosis if ongoing need.
Complications
- Peptic ulcer disease, upper GI bleeding, or perforation
- Acute kidney injury and progression of chronic kidney disease
- Sodium/fluid retention with worsening heart failure
- Hypertension destabilisation
- Thrombotic cardiovascular events (MI, stroke) in higher-risk patients
- Bronchospasm/anaphylactoid reactions in NSAID-sensitive individuals
- Hepatic injury (uncommon but clinically important)
Prognosis
With careful patient selection, short-course use, and appropriate gastroprotection/monitoring, most people gain symptomatic benefit without major toxicity. Prognosis worsens when NSAIDs are used long term in patients with unrecognised GI, renal, or cardiovascular risk, or when contraindications and interacting drugs are missed.
Sources & References
✅NICE Guidelines(1)
- NSAIDs - prescribing issues[overview]
📖Textbook References(3)
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1791)[context]
- [Oxford Medical Handbooks] Ian Wilkinson, Tim Raine, Kate Wiles, Anna Goodhart, Catriona Ha - Oxford Handbook of Clinical Medicine (2017, Oxford University Press) - libgen.li.pdf(pp. 889, 890)[context]
- [Oxford Medical Handbooks] Ian Wilkinson, Tim Raine, Kate Wiles, Anna Goodhart, Catriona Ha - Oxford Handbook of Clinical Medicine (2017, Oxford University Press) - libgen.li.pdf(pp. 888, 889)[context]