Gout Flashcards
What turns uric acid into the more soluble allantoin?
Uricase (humans don’t have this)
Do gout patients typically have an issue with overproduction or underexcretion?
underexcretion (90%)
overproduction (10%)
Purine rich foods
- anchovies
- brain
- kidney
- liver
- sardines
Drugs that can induce hyperuricemia and gout
- Diuretics
- Nicotinic acid
- Salicylates
- Ethanol
- Pyrazinamide
- Ethambutol
- Cytotoxic drugs
8 Cyclosporine - Levodopa
Where does acute gout most commonly affect?
1st MTP (“podagra”)
-typically in one joint of LE
Tophaceous gout
- chronic gout
- monosodium urate in soft tissues and joints
If someone has asymptomatic hyperuricemia do they need treatment?
Not necessarily
What happens to serum uric acid levels during acute attacks?
it drops
What is the clinical triad for gout?
- Inflammatory monoarthritis
- Elevated serum uric acid level
- Response to colchicine
Acute gout-Mild/moderate: treatment
Monotherapy (NSAID, colchicine, systemic corticosteroid)
Acute gout - Severe: treatment
Combination therapy
- Colchicine + NSAID
- Colchicine + corticosteroid
- NSAID + intra articular steroid
- Colchicine + intra articular steroid injection
Where does colchicine work on the arachidonic acid cascade?
Lipoxygenase –> leukotriene B4
Which NSAID is the most used agent for gout?
Indomethacin
Colchicine: ADE
dose-dependent GI effects (diarrhea, nausea, vomiting)
Colchicine: metabolism
CYP3A4, so adjust dose if on other agents like this
When should colchicine be started to help stop a gout attack?
Start within 36 hours
When can you think about injecting steroid for gout?
- If only affecting 1-2 joints
- Always use in combination
Which oral steroid should be used for acute gout attack?
methylprednisolone pack
Ultimately allopurinol is the drug of choice to prevent gout attacks. What are the anti-inflammatory regimens that need to be in place before starting allopurinol?
1. Colchicine or 2. NSAIDs + PPI or 3. Prednisone <10mg/day
When should urate-lowering therapy xanthine oxidase inhibitors (ex. allopurinol) be initiated?
- 2 or more gout attacks/year
- 1 or more tophus
- Chronic Kidney Disease (stage 2 or worse)
- History of urolithiasis
What is the goal serum urate concentration after starting a xanthine oxidase inhibitor like allopurinol?
<6mg/dL*****
What is 1st line urate lowering therapy?
Allopurinol
Allopurinol: Acute hypersensitivity syndrome
AVOID/Consider genetic testing in high risk populations:
- Koreans with CKD
- Han Chinese and Thai (irrespective of renal function)
Allopurinol: ADE
pruritis, rash, elevated LFT
What is the difference in mechanism and dose adjustment between allopurinol and Febuxostat?
Allopurinol - irreversibly inhibits xanthine oxidase. Needs to be adjusted in renal patients
Febuxostat - reversible inhibitor of xanthine oxidase. No need for dose adjustments in patients with kidney issues.
What is drug is contraindicated with Febuxostat?
Azathioprine
Febuxostat: ADE
liver enzyme elevation (ALT, AST)
What is another approach to help uric acid excretion if patients can’t do it the normal way?
Xanthine oxidase inhibitor + fenofibrate or losartan
Pegloticase: Indication
3rd line therapy for refractory gout. Heavy disease burden with chronic tophaceous disease
Pegloticase: MOA
recombinant porcine-like uricase (biologic) which metabolizes uric acid to allantoin
If patient is on max dose of Allopurinol what can be added??
- Lesinurad
- Probenacid
When can prophylactic treatment be discontinued?
- 6 months
or - 3 months following achieving urate target
