GOUT
✅ Pathogenesis & Pathophysiology
● Hyperuricemia → deposition of sodium urate crystals in joints/kidneys.
● Causes inflammation via:
○ Neutrophil infiltration
○ Phagocytosis of crystals → lysosomal rupture → release of hydrolytic enzymes
○ Leukotriene release → acute inflammation
● Caused by:
○ Overproduction of uric acid OR
○ Underexcretion (most common) in renal elimination
● Target urate level: below the saturation point <6 mg/dL
Risk factors
● Alcohol, high-purine diet (seafood, meat), sugary drinks, CKD.
Clinical Features
Acute attack
● Sudden, severe pain in early morning in (large toe)
● Swollen, warm, red joint. Red, purple skin around joint
● Classically: 1st metatarsophalangeal joint
Treatment Strategies
(1) Acute Gout – treat inflammation
Goal: Reduce inflammation from urate crystals.
, Drugs
🔹 NSAIDs (Indomethacin = classic first choice)
● Rapid pain relief
● Avoid in renal impairment, ulcers, HF.
🔹 Corticosteroids
● Intra-articular for 1–2 joints
● Systemic for multiple joints or NSAID/colchicine intolerance
🔹 Colchicine
MOA:
● Binds tubulin → microtubule depolymerization
● ↓ leukocyte motility + blocks cell division
● Must give within 36 hours of attack
● Relief within 12 hours
● Prevent acute attacks of gout
PK:
● Oral, enterohepatic circulation
● Excreted unchanged in feces/urine
Adverse effects:
● Severe diarrhoea (most common), N/V, abdominal pain
● Long term: myopathy, alopecia, bone marrow suppression (NSAIDS hv largely replaced colchicine)
Contraindications:
● Pregnancy
● Renal, hepatic, CV disease
● Dose adjustment with CYP3A4 inhibitors (clarithromycin, itraconazole, protease inhibitors)
Note: Stop colchicine if saturation point of uric acid> 6mg or diarrhoea
✅ Pathogenesis & Pathophysiology
● Hyperuricemia → deposition of sodium urate crystals in joints/kidneys.
● Causes inflammation via:
○ Neutrophil infiltration
○ Phagocytosis of crystals → lysosomal rupture → release of hydrolytic enzymes
○ Leukotriene release → acute inflammation
● Caused by:
○ Overproduction of uric acid OR
○ Underexcretion (most common) in renal elimination
● Target urate level: below the saturation point <6 mg/dL
Risk factors
● Alcohol, high-purine diet (seafood, meat), sugary drinks, CKD.
Clinical Features
Acute attack
● Sudden, severe pain in early morning in (large toe)
● Swollen, warm, red joint. Red, purple skin around joint
● Classically: 1st metatarsophalangeal joint
Treatment Strategies
(1) Acute Gout – treat inflammation
Goal: Reduce inflammation from urate crystals.
, Drugs
🔹 NSAIDs (Indomethacin = classic first choice)
● Rapid pain relief
● Avoid in renal impairment, ulcers, HF.
🔹 Corticosteroids
● Intra-articular for 1–2 joints
● Systemic for multiple joints or NSAID/colchicine intolerance
🔹 Colchicine
MOA:
● Binds tubulin → microtubule depolymerization
● ↓ leukocyte motility + blocks cell division
● Must give within 36 hours of attack
● Relief within 12 hours
● Prevent acute attacks of gout
PK:
● Oral, enterohepatic circulation
● Excreted unchanged in feces/urine
Adverse effects:
● Severe diarrhoea (most common), N/V, abdominal pain
● Long term: myopathy, alopecia, bone marrow suppression (NSAIDS hv largely replaced colchicine)
Contraindications:
● Pregnancy
● Renal, hepatic, CV disease
● Dose adjustment with CYP3A4 inhibitors (clarithromycin, itraconazole, protease inhibitors)
Note: Stop colchicine if saturation point of uric acid> 6mg or diarrhoea
