renal handling of uric acid Uric acid is a weak organic acid. It is excreted primarily (66%) through the kidney. Up to a third is excreted through the GI tract. In cases of renal failure, GI excretion is increased. There are four components of renal excretion of uric acid : 1. Glomerular filtration: near complete excretion …
allopurinol hypersensitivity syndrome (AHS)? • AHS is a rare (0.1%–0.4% of patients) complication of allopurinol use with high morbidity and mortality (25% in some studies). • AHS typically occurs 2 to 4 weeks after initiating therapy. • Clinical manifestations include severe skin rash (e.g., Stevens–Johnson syndrome, toxic epidermal necrolysis), fever, eosinophilia, hepatic necrosis, leukocytosis, and renal failure. • Treatment …
What are the most common reasons for inadequate response of serum uric acid to allopurinol? Poor adherence and under-dosing of allopurinol by physicians (failure to titrate dose to goal serum uric acid level) are the two most common causes. Adherence may be as low as 50%. Patients are asymptomatic in the intercritical period, and there …
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Comparison of xanthine oxidase inhibitors Allopurinol Febuxostat Mechanism of action XOIHypoxanthine analog XOI (more potent than allopurinol)Not a hypoxanthine analog Pharmacokinetics 80%–90% bioavailabilityHalf-life of 60 minutesOxipurinol metabolite long-lived (t 1/2 14–28 hours)Max antihyperuricemic effect seen after 7–10 days ∼50% bioavailabilityExtensive hepatic metabolismEqual hepatic and renal excretionMax antihyperuricemic effect seen after 5–7 days Adverse events CommonAcute gouty arthritis: …
What types of urate lowering agents are available? • XOIs inhibit uric acid synthesis by inhibiting xanthine oxidase, the final enzyme involved in the production of uric acid . XOIs are first-line ULT. • Uricosurics reduce the serum urate concentration by enhancing the renal excretion of uric acid. Typically used as add-on therapy with XOIs. • Uricase converts uric acid into allantoin, …
How to avoid precipitating gout flares when initiating ULT? • Gradual dose increases. Start at 100 mg/day and increase by 100-mg increments (or 50 mg if glomerular filtration rate [GFR] <30 mL/minute), every 2 to 4 weeks. • Use of prophylaxis with colchicine, nonsteroidal antiinflammatory drugs (NSAIDs) or low-dose prednisone
Indications for ULT in patients with gout • Recurrent attacks (>= 2 per year). • Tophus or tophi (can take months to years to resorb). • History of nephrolithiasis. • Renal insufficiency (chronic kidney disease [CKD] stage 3 or worse; creatinine clearance < 60mL/minute). • Asymptomatic hyperuricemia alone is not an indication for ULT. The decision to use ULT in …