NR 566 Week 4 Study Guide Chapter 25: Drugs Used in Treating Inflammatory Processes

Drugs: Anti-gout agents: allopurinol (Zyloprim), colchicine, and febuxostat (Uloric) Uricosuric agents: probenecid (Benemid) and sulfinpyrazone (Anturane) o Peak incidence 70 to 79 years old, more common in men than women o Gout in women occurs exclusively post-menopausal and is associated with HTN, renal insufficiency, and diuretics o Gout Syndrome: Caused by an alteration in purine metabolism: end product is uric acid o Hyperuricemia and deposition of urate crystals in various tissues o Four phases: asymptomatic hyperuricemia, acute gouty arthritis, inter-critical gout, and chronic tophaceous gout o Those with asymptomatic hyperuricemia do not require treatment (diet and lifestyle changes) o Acute gout is characterized by sudden onset of pain, erythema, limited ROM, and swelling of the involved joint  50% of cases involve the first metatarsal joint of the great toe o Key elements in Tx include management of the acute pain and use of antigout and uricosuric agents o Pain: NSAIDS and corticosteroids Pharmacodynamics Antigout Drugs (allopurinol, colchicine, and febuxostat) o Act to reduce the inflammatory process or to prevent the synthesis of uric acid o Allopurinol and febuxostat inhibit xanthine oxidase: enzyme responsible for conversion of hypoxanthine and xanthine to uric acid o Allopurinol has a metabolite (alloxanthine): also an inhibitor of xanthine oxidase o Allopurinol acts directly on purine metabolism, reducing the production of uric acid, without disrupting biosynthesis of vital purines o Allopurinol and febuxostat are the only drugs that act directly on the pathophysiological cause of gout o Allopurinol decreases both serum and urinary uric acid in 2 to 3 days: dose dependent  A week or more of Tx may be necessary before the full effects can be seen o Febuxostat is used to treat hyperuricemia in patients with gout o Goal is to have uric acid level of less than 6 mg/dL o Can take 2 weeks or more to see the effects of febuxostat o Colchicine: does not affect purine metabolism o Binds to the microtubular proteins to interfere with the function of the mitotic spindles and inhibit migration of granulocytes to the inflamed area o Reduces lactic acid production by granulocytes: decreases deposition of uric acid o Interferes with kinin formation and reduces phagocytosis o Taken together: these actions decrease the inflammatory response to the deposited urate crystals o Relives pain in acute attack: not an analgesic o Its prophylactic, suppressive effect helps reduce the incidence of acute attack and relives patient’s occasional residual pain and mild discomfort Uricosuric drugs: probenecid (Benemid) and sulfinpyrazone (Anturane o These drugs increase the rate of uric acid secretion in the urine o Both drugs inhibit renal tubular reabsorption of urate and thus increase the renal excretion of uric acid and decrease serum uric acid levels. o Effective uricosuria reduces the miscible urate pool, retards urate deposition, and promotes reabsorption of urate deposits o Sulfinpyrazone competitively inhibits platelet prostaglandin synthesis: prevents platelet aggregation (antithrombotic effects) o Both drugs lack anti-inflammatory activity o Most useful in patients with reduced urinary excretion of uric acid o Not intended for Tx of acute attacks Pharmacotherapeutics o Allopurinol (Zyloprim) colchicine, probenecid (Benemid, and sulfinpyrazone (Anturane): poor urate clearance in the presence of renal impairment o Use with caution: renal function tests performed regularly to determine dosage o Data is insufficient regarding febuxostat in renal impairment o Allopurinol and colchicine: hepatotoxicity o Not recommended for patients with severe hepatic dysfunction o If anorexia, weight loss, or pruritus, evaluate LFTs o For milder hepatic disorders: close monitoring of LFTs is required o Colchicine, probenecid