What Is Gout?
Gout is a painful inflammatory arthritis caused by the deposition of monosodium urate (MSU) crystals in joints and soft tissues due to elevated levels of uric acid (hyperuricemia). It most commonly affects the base of the big toe but can involve other joints as well.
While gout has metabolic and dietary causes, it is often drug-induced, especially in hospitalized or chronically medicated patients.
How Drugs Can Cause Gout
Certain medications increase uric acid levels by:
- Reducing renal urate excretion
- Increasing uric acid production
- Competing for excretion channels in the kidney
Understanding which drugs increase this risk can help in early identification, substitution, and prevention of painful gout attacks.
CANDLE-CAP Mnemonic: Drug List Simplified
This colorful and clever mnemonic helps remember the major gout-inducing drugs:
| Mnemonic | Drug |
|---|---|
| C | Chlorthalidone |
| A | Aspirin |
| N | Nicotinic Acid |
| D | Diuretics |
| L | Levodopa |
| E | Ethambutol |
| C | Cyclosporine |
| A | Alcohol |
| P | Pyrazinamide |
This tool is especially useful for medical students, interns, and pharmacists who want a quick recall during case discussions or exams.
Mechanisms of Each Drug in Gout Pathogenesis
Let’s break down how each drug contributes to hyperuricemia:
1. Chlorthalidone (Thiazide diuretic)
- Decreases uric acid excretion in the renal tubule
- Causes volume depletion → increases urate reabsorption
2. Aspirin (Low dose)
- Paradoxically reduces uric acid clearance
- High doses increase uric acid excretion but are rarely used
3. Nicotinic Acid (Niacin)
- Used in dyslipidemia; raises uric acid via decreased excretion
4. Diuretics (Loop & Thiazide)
- Lead to volume depletion
- Compete for organic anion transporters in kidney
5. Levodopa
- Alters renal hemodynamics
- Can lead to decreased uric acid clearance
6. Ethambutol
- Antitubercular drug that impairs renal urate excretion
7. Cyclosporine
- Used post-transplant and in autoimmune diseases
- Nephrotoxic effects impair uric acid filtration
8. Alcohol
- Increases lactic acid, which competes with uric acid for renal excretion
- Promotes purine breakdown → more uric acid
9. Pyrazinamide
- Anti-TB drug that inhibits uric acid secretion in kidneys
Risk Factors That Increase Susceptibility
Even among users of these medications, not everyone develops gout. Certain factors increase risk:
- Chronic kidney disease
- Male sex (especially > 40 years)
- High purine diet (red meat, seafood)
- Alcohol abuse
- Family history of gout
- Metabolic syndrome (diabetes, hypertension, obesity)
Clinical Signs of Drug-Induced Gout
- Sudden, intense joint pain (especially at night)
- Swelling, redness, and warmth over joints
- Tophi (chalky uric acid nodules in chronic cases)
- Restricted joint movement
- Often monoarticular (one joint involved initially)
Diagnosis and Monitoring
Investigations:
- Serum uric acid level
- Joint aspiration (urate crystals under polarizing microscope)
- Renal function tests (especially if on diuretics or cyclosporine)
- Drug history and duration
Tip: Always correlate timing of symptoms with start or dose increase of offending medication.
Drug Substitutions and Safer Alternatives
| Offending Drug | Possible Substitution |
|---|---|
| Chlorthalidone | Amlodipine or ARBs |
| Thiazide Diuretics | Loop diuretics (with caution) |
| Aspirin (low-dose) | Consider Clopidogrel (if CV risk allows) |
| Ethambutol | Replace with Streptomycin or other TB regimens if appropriate |
| Pyrazinamide | Monitor closely or adjust dose |
| Cyclosporine | Tacrolimus (less gout risk) |
Always involve a specialist before making changes, especially in transplant or TB patients.
Preventive Measures for High-Risk Patients
- Avoid purine-rich foods
- Maintain good hydration
- Limit alcohol intake
- Regular uric acid monitoring
- Use urate-lowering therapy (e.g., Allopurinol, Febuxostat)
- Patient education on early warning signs
Case Study: Polypharmacy and Gout Flare
Mr. K, a 58-year-old diabetic and hypertensive, was prescribed:
- Chlorthalidone
- Aspirin (low-dose)
- Nicotinic acid (for dyslipidemia)
Two weeks later, he developed acute pain in the right big toe. Uric acid was 9.2 mg/dL.
After revising his medications and starting Allopurinol, symptoms resolved.
👉 Lesson: Polypharmacy with “CANDLE-CAP” drugs multiplies gout risk.
Patient Education Tips
- Don’t stop medications without consulting your doctor
- Report sudden joint pains, especially if new meds were started
- Stay hydrated
- Avoid binge drinking
- Follow up regularly for uric acid testing
- Ask if safer alternatives are available
Summary Table: Drugs Causing Hyperuricemia
| Category | Examples | Effect |
|---|---|---|
| Diuretics | Chlorthalidone, Furosemide | ↓ Urate excretion |
| Anti-TB drugs | Pyrazinamide, Ethambutol | ↓ Renal urate clearance |
| Immunosuppressive | Cyclosporine | Nephrotoxicity, ↓ filtration |
| Analgesics | Low-dose Aspirin | ↓ Urate clearance |
| Lipid-lowering | Niacin (Nicotinic acid) | Promotes urate retention |
| Neurologic | Levodopa | Alters renal function |
| Others | Alcohol | ↑ Purine load + ↓ excretion |
Key Takeaways
- CANDLE-CAP is a powerful tool to remember drugs causing gout.
- Not all patients on these drugs develop gout — assess individual risk.
- Monitor renal function and serum uric acid regularly.
- Educate patients on diet, hydration, and early symptoms.
- Collaborate across disciplines for medication management.
FAQs on Drug-Induced Gout
Q1: Can I continue taking aspirin if I have gout?
A: Low-dose aspirin may worsen gout, but it's essential for cardiovascular protection. Discuss alternatives with your doctor.
Q2: Is allopurinol effective for drug-induced gout?
A: Yes, it's a standard urate-lowering therapy but requires careful monitoring during initiation.
Q3: Are all diuretics unsafe in gout?
A: Thiazides are more likely to cause gout than loop diuretics. Use the lowest dose possible.
Q4: Is gout curable?
A: Gout is manageable with the right medication and lifestyle. Early identification of triggers is key.
Q5: Do TB medications always cause gout?
A: Not always, but Pyrazinamide and Ethambutol are known offenders. Risk increases with duration and comorbidities.
