ic13.2, 17 gout Flashcards
What is the cause of gout
Imbalance in purine metabolism
Adenine and Guanine converted to hypoxanthine, xanthine, uric acid
Underexcretion of uric acid
Deposition of Monosodium Urate (MSU) crystals in tissues
Pathogenesis of gout
Neutrophils phagocytose crystals
Neutrophils lyse, releasing crystals
Neutrophils release prostaglandins to recruit more neutrophils, causing a (+) feedback loop
Risk factors for gout (4 points)
Purine rich diet (red meat, seafood)
Sedentary lifestyle
Obesity
If in males < 30yo and premenopausal women → suggest inherited enzyme defect or presence of renal disease
Presentation of gout
Monoarticular (1 joint), on 1st MTP of great toe
Early morning onset, sudden
Feels like joint on fire
Lab test to diagnose gout
Must have symptoms (pain, swelling)
If asymptomatic and hyperuricemia, not considered Gout
Presence of monosodium urate crystals in synovial fluid
Definition of hyperuricemia
Treatment goals
Males: Uric acid > 7mg/dL or 450umol/L
Females: Uric acid > 6mg/dL or 360umol/L
Non-tophaceous: 6mg/dL or 360 umol/L
Tophaceous gout: 5mg/dL or 300 umol/L
What can be used for acute flare?
Colchicine (1st line)
PO NSAIDs
PO Corticosteroids
MOA of Colchicine
1) Bind to tubulin, prevent tubulin polymerisation into microtubules
2) Inhibit leukocyte migration and phagocytosis
3) Inhibit leukotriene B4 and Prostaglandin production
Dose of Colchicine for acute flare
Dose of Colchicine in flare prophylaxis
Acute flare
1mg loading dose, followed by 0.5mg one hour later
OR 0.5mg BD / TDS until acute flare resolves
Flare prophylaxis
0.5mg OD for 3-6 months
Colchicine SE and how (3 points)
Nausea, Vomiting
Diarrhea
Colchicine inhibits cell division at higher doses eg. GI cells
Reducing Colchicine dose should reduce diarrhea SE
Muscle weakness
Tubulin inhibition → Affect transport of growth factors along nerves to muscles
Does Colchicine need dose adjustment in renal or hepatic impairment
renal
What are the indications for Colchicine (2 points)
1) For acute flare, should be used within 24 hours!
If (+) feedback start, Colchicine will not be useful
2) Prophylaxis against acute flares (ie. taking Colchicine with ULT to prevent acute flare)
MOA of NSAID or Coxib in gout
Inhibit prostaglandins and urate crystal phagocytosis
Which NSAID should not be used in gout? Why?
Aspirin, as it has anti-uricosuric effect (reduce uric acid excretion, increase uric acid reabsorption in kidney)
What does uricosuric mean
Increase uric excretion via kidneys, reduce uric acid reabsorption
Contraindication of NSAID
Contraindicated in CrCl < 30ml/min
Principles of treating acute gout flare (3 points) eg. When to start ULT
If on ULT during flare, continue ULT (eg. Allopurinol) during flare
Stop Colchicine after flare resolves
If starting ULT, wait 2-4 weeks after flare resolve (as ULT can worsen flare)
Unless flare is too frequent or patient feels motivated to start therapy, then dont need wait for 2-4 weeks to start ULT
ULT lowers serum uric acid level, causing uric acid crystals to exit the joint
How long should prophylaxis of acute gout flare be given
Examples
Given with ULT
3-6 months
Colchicine 0.5mg OD
Low dose oral NSAID / Coxib, eg. Celecoxib 200mg OD
Low dose oral Corticosteroid, eg. Prednisolone 5 - 7.5mg OD
When to start ULT? (4 points)
Frequent acute gout flares (≥ 2 per year)
Presence of tophi
Clinical or imaging findings of gouty arthropathy
History of urolithiasis (uric acid stones in kidney)
Treatment target for ULT
Non-tophaceous gout: < 6 mg/dL (360umol/L)
Tophaceous gout: < 5 mg/dL (300umol/L)
rmb 7665
7 males, 6 females
Dose of allopurinol
Start: 100mg/day
Maintenance: 300mg/day
Max: 900mg/day
What to consider for Allopurinol
Risk of SJS / TEN (HLAB 58:01)
Lower Allopurinol dose in renal impairment
Indication of Allopurinol
First line
For patients with major CVD / MACE (hence cannot take Febuxostat)
Counselling for Allopurinol
Look out for flu-like symptoms (eg. fever, body aches), skin peeling, mouth ulcers, sore throat, red or sore eyes, rash
