Gout Flashcards
What causes gout?
Imbalances in purine metabolism
Deposition of monosodium urate (MSU) crystals in articular and periarticular tissues –> lead to inflammation, swelling, pain –> gouty attack
Clinical spectrum of diseases due to gout
- Recurrent acute gouty arthritis (assoc. w urate crystals in synovial fluid)
- Tophi (deposits of monosodium urate crystals in tissue in & surrounding joint) → chronic
- Interstitial renal disease (gouty nephropathy) → extra articular presentations
- Uric acid nephrolithiasis (uric acid kidney stones) → extra articular presentations
What dietary and lifestyle factors worsens gout?
Alcohol consumption
Sugary beverages
Red meat
Sedentary lifestyle –> obesity
Does gout occur more freq in male or female?
Males
What are 2 ways that causes hyperuricemia?
Increased purine/urate production
Decrease uric acid clearance
What are some drugs that decrease uric acid clearance?
Diuretics
Levodopa
Cyclosporine nad tacrolimus
Ethambutol
Low dose salicylates
Salt restriction
What are presentations of a gout attack?
- Usually monoarticular @ 1st great toe
- wakes up from sleep by pain
- severe pain for severe hours
- swelling and discomfort continues for days to weeks
Why does gout attack commonly start from big toe?
Uric acid in cold temp, lowers its solubility causing it to precipitate and since the big toe is furthest from circulatory, it is coldest part of the body
Does asymptomatic hyperuricemia suggests gout?
No
How to diagnose gout?
Diagnosis based on presence of monosodium urate crystals in…
- Synovial fluid (detected in joint aspirate)
- Tissue sections of tophaceous deposits (Tophi)
- Joint aspiration → from joint fluid then view under microscope to check for birefringent like crystals (needle shape, yellow)
How would the joint aspirate look like in gout attack?
Yellow colour and cloudy
Presence of uric acid crystals
What is Tx goal of gout?
- Provide rapid, SAFE, & effective pain relief
- Reduce future attacks (reduce SU concentration): do baseline serum urate lvl
- Address associated comorbidities
- Prevent joint destruction and tophi formation
- Increase quality of life
What are common pharmacotherapy for acute gout?
Colchicine
NSAID
CS
What are common pharmacotherapy for chronic gout?
Allopurinol
Febuxostat
Probenecid
What is usually given for 1st line in acute flares?
Colchicine (within 24hrs)
What is nonpharm for flares?
Topical ice
What is colchicine dose for acute flares?
- One off treatment with 1mg loading dose, followed by 1 dose of 0.5mg 1hr ltr
OR
- 0.5mg 2-3times/day until flare resolves
What is NSAID dose for acute flares?
Celecoxib 400mg LD, 200mg 12hrs ltr on day 1 then continue 200mg BD daily thereafter. Max: 400mg/day. Tx duration usually 5-7days
What is CS dose for acute flares?
Prednisolone 30-40mg QD or in 2 divided doses for 2-5days or until smx resolves. Then taper down gradually for another 7 days by halving dose then discontinue
Can also dose by weight: 0.5mg/kg
Colchicine SE
N/V, diarrhoea
Should colchicine and NSAID be cautioned in renal impairment?
Yes.
Consider reducing dose of colchicine.
NSAID is CI in CrCl <30ml/min
When should Urate Lowering Therapy (ULT) be initiated?
- Freq acute gout flares (>=2/yr)
- Presence of any tophus
- Clinical or imaging findings of gouty arthropathy
- Hx of urolithiasis
What is Tx target for ULT?
Non-thopaceous gout: <6mg/dl
Tophaceous gout: <5mg/dl
How does allopurinol and febuxostat help in gout?
Decrease prdtn of uric acid
How does probenecid help in gout?
Prevent reabsorption of uric acid which increases uric acid excretion
What is the most impt point to counsel for allopurinol?
Risk of SCAR
Febuxostat should be used in caution in what conditions?
HF and CHD
Probenecid is CI in __ and not rec in __
Urolithiasis: prevents tubular reabsorption of urate
Not rec if CrCl < 50ml/min
What is first line for ULT?
Allopurinol. Cheaper than febuxostat
What is allopurinol dose for ULT?
- Initiation: ≤ 100 mg/day [start w lower doses in CKD stage ≥ 3 e.g. ≤ 50 mg/day]
- Titration: in 50 to 100 mg increments every 2-8 weeks [Monitor serum urate- <6mg/dL, clinical response & drug tox- SCAR]
- Usual maintenance: > 300 mg/day [ok for renal impairment too]
- Max dose: 800-900 mg/day [if normal renal function] since we treat to target, can increase dose.
What is febuxostat dose for ULT?
- Initiation: ≤ 40 mg/day
- Titration: 80 mg/day if treatment target not met after 2-4 weeks
When will febuxostat be considered over allopurinol?
When pt is intolerant to allopurinol i.e SCAR
What is probenecid dose for ULT?
- Initiation: 250 mg BD x 1 week, then 500 mg BD
- Titration: in 500 mg every 4 weeks as tolerated if smx not controlled
- Usual maintenance: ≤ 2 g/day
What to counsel pts on probenecid?
Keep hydrated (>=2L of water) to prevent kidney stones from forming –> urolithiasis
Why should we “start low, go slow” for ULT?
Dont want to precipitate another gout flare
Pts w G6PD def on probenecid has a risk of __
Hemolytic anemia
When does SCAR usually occur after Tx initiation?
First few wks to months
What is the allele that increases the risk of allopurinol-induced SCAR
HLA-B*5801
Is routine genotyping done before starting allopurinol and why?
No, low positive predictive value (PPV) of 2% & the lack of alternative cost-effective ULT options.
Allopurinol genotyping is more useful in pts with __
Renal impairment
Older age
What smx to counsel pts on SCAR?
- Flu like smx like fever, body aches, unwell
- Mouth ulcers, sore throat
- Red or sore eyes
- Rashes
Usually in first 3 months but may also happen after 3months
What DDI w allopurinol increases bone marrow suppression?
6-mercaptopurine
Azathioprine
Cyclophosphamide
What DDI w allopurinol increases hypersensitivity rxn?
- ACEi
- Loop diuretics
- Thiazide / Thiazide-like diuretics
- Ampicillin/amoxicillin
What should you monitor if allopurinol is taken with carbamazepine or warfarin?
Carba - SJS/TEN
Warfarin - bleeding
ULT-prophylaxis against acute flares treatment
- Colchicine 0.5 mg OD
- Low-dose oral NSAID / Coxib (e.g. celecoxib 200mg OD)
- Low-dose oral corticosteroid (e.g. prednisolone 5 – 7.5 mg OD)
For 3 – 6 months
Usually when will ULT Tx be stopped
No flares for >=1yr and no tophi
What is non-pharm to reduce flares?
Limit alcohol intake
Limit purine-rich foods
Limit high-fructose corn syrup
Weight management
Can you initiate ULT during acute flares?
NO
unless pt is alr on ULT, can still continue during flares
What foods are high in purine?
Asparagus
Cauliflower
Mushroom
Red meat
Anchovies (ikan bilis)
Durain
Peanuts
Organ meat eg. liver
Alcohol
Which HTN is preferred in gout?
ACEi (enalapril and captopril) or ARB (losartan) has uricosuric effect
Dont give HCTZ
