Drugs

What precautions need to be taken when prescribing and administering pegloticase? • Low G6PD enzyme activity (deficiency) is a contraindication due to risk of hemolytic anemia and methemoglobinemia. All patients must be screened for G6PD deficiency. • Pegloticase profoundly lowers the uric acid level in 24 hours; without prophylaxis, 80% of patients will suffer an acute gout flare. Start prophylaxis …

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Bone Strengthening Agents 1. Nonpharmacologic measures that are effective for prevention and treatment of osteoporosis include adequate calcium and vitamin D nutrition, regular exercise, fall prevention, smoking cessation, and limitation of alcohol and caffeine intake. 2. Pharmacologic therapy should be initiated in patients who have had a fragility fracture, a bone mineral density (BMD) T-score <–2.5, or …

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What is pegloticase? In contrast with other mammals, homo sapiens (and other higher primates) lack uricase, an enzyme which converts uric acid to the more soluble allantoin. Pegloticase is a recombinant mammalian uricase attached to polyethylene glycol (PEGylated). Due to cost (∼2000 $US per infusion) and risk of adverse events, it is recommended for cases …

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How can the risk of uric acid nephropathy and nephrolithiasis be minimized when prescribing uricosurics? 1. Adequate fluid intake, 2 L/day. 2. Urine alkalinization (not needed in most patients); may use sodium bicarbonate (3–7.5 g daily) or potassium citrate (7.5 g daily) to maintain an alkaline urine (pH > 6.0).

When should ULT be initiated? Classic teaching is that initiation of ULT should be avoided in the presence of acute flares. American College of Rheumatology Guidelines from 2012 provide leeway as long as appropriate antiinflammatory management is in place, with prophylaxis against flares continued following the acute treatment regimen (prophylaxis commonly extended for ≥6 months).

What medications have uricosuric effect even if not prescribed for this reason? Losartan: modest uricosuric effect, plateaus at 50 mg daily. Fenofibrate: may induce ∼20% decrease in serum uric acid. Atorvastatin (note the risk of myopathy with statins + fibrates). High-dose (>4 g/day) salicylates. Pearl: consider choosing medications with urate-lowering “side effect” for patients with gout …

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Uricosuric medications Clinical Pharmacology of Probenecid Probenecid Mechanism of action Competitively inhibits URAT1 & GLUT9 → decreased tubular reabsorption urate → increased uricosuria Pharmacokinetics Hepatic metabolismHalf-life 6–12 hours → BID dosingDecreases serum uric acid by ∼33% Adverse events PreventableAcute gouty attacks: use prophylaxisUrate nephropathy: obtain baseline urine testsUrate nephrolithiasis: obtain baseline urine testsRelatively commonNausea, loss …

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