Pathophysiology and Treatment of Gout
Pathophysiology of Gout
Gout is a metabolic disorder caused by hyperuricemia and the deposition of monosodium urate crystals in joints and tissues.
Stages of Gout:
- Asymptomatic Hyperuricemia: Elevated uric acid without symptoms.
- Acute Gouty Arthritis: Sudden onset of pain, redness, and swelling, often in the big toe.
- Intercritical Gout: Symptom-free intervals between gout attacks.
- Chronic Tophaceous Gout: Persistent joint inflammation with visible urate deposits.
Mechanism: Hyperuricemia leads to monosodium urate crystal precipitation, triggering inflammation mediated by cytokines like IL-1β.
Classification of Drugs Used in Gout
Drugs for Acute Gout
- NSAIDs: Indomethacin, naproxen.
- Colchicine.
- Corticosteroids: Prednisone, methylprednisolone.
Drugs for Chronic Gout
- Urate-Lowering Therapies:
- Xanthine oxidase inhibitors: Allopurinol, febuxostat.
- Uricosuric agents: Probenecid, lesinurad.
- Uricase-based agents: Pegloticase.
Mechanism of Action and Adverse Effects of Drugs
1. NSAIDs
Mechanism: Inhibit COX, reducing prostaglandin synthesis and inflammation.
Adverse Effects: Gastric irritation, renal dysfunction.
2. Colchicine
Mechanism: Inhibits neutrophil microtubule polymerization, reducing inflammation.
Adverse Effects: Diarrhea, abdominal pain, myopathy.
3. Corticosteroids
Mechanism: Suppress inflammation by inhibiting cytokines and phospholipase A2.
Adverse Effects: Hyperglycemia, osteoporosis.
4. Xanthine Oxidase Inhibitors
Mechanism: Inhibit uric acid synthesis.
Adverse Effects: Hypersensitivity, liver dysfunction.
5. Uricosuric Agents
Mechanism: Increase uric acid excretion by inhibiting renal reabsorption.
Adverse Effects: Kidney stones, GI disturbances.
6. Uricase-Based Agents
Mechanism: Converts uric acid into soluble allantoin.
Adverse Effects: Infusion reactions, gout flares.
