gout 1.pdf

Assisst.prof. HASSAN KHUDER RAJAB 2ND CLASS LECT. GOUTE ARTHRITIS Objective :►Defenition of gout. ►treatment of acute attack. ►prophylaxis of gout therapy ►how we evaluate our treatment of gout. ACUTE GOUTY ARTHRITIS Nonpharmacologic Therapy Patients may be advised to reduce their intake of foods hi...

Assisst.prof. HASSAN KHUDER RAJAB 2ND CLASS LECT. GOUTE ARTHRITIS Objective :►Defenition of gout. ►treatment of acute attack. ►prophylaxis of gout therapy ►how we evaluate our treatment of gout. ACUTE GOUTY ARTHRITIS Nonpharmacologic Therapy Patients may be advised to reduce their intake of foods high in purines (e.g., organ meats), avoid alcohol, increase fluid intake, and lose weight if obese. Joint rest for 1 to 2 days should be encouraged, and local application of ice may be beneficial. Nonsteroidal Antiinflammatory Drugs Colchicine Colchicine is an antimitotic drug that is highly effective in relieving acute gout attacks but has a low benefit-toxicity ratio. When colchicine is started within the first 24 hours of an acute attack, about two-thirds of patients respond within several hours. The likelihood of success decreases substantially if treatment is delayed longer than 48 hours after symptom onset. Oral colchicine causes dose-dependent GI adverse effects (nausea, vomiting, and diarrhea) in 50% to 80% of patients before relief of the attack. Non-GI adverse effects include neutropenia and axonal neuromyopathy, which may be worsened in patients taking other myopathic drugs (e.g., statins) or in those with renal insufficiency. Colchicine should not be used concurrently with macrolide antibiotics (especially clarithromycin) because reduced biliary excretion may lead to increased plasma colchicine levels and agranulocytosis. Colchicine should be reserved for patients with insufficient relief, intolerance, or contraindications to NSAIDs. The usual oral colchicine dose is 1 mg initially, followed by 0.5 mg every 1 hour until the joint symptoms subside, the patient develops abdominal discomfort or diarrhea, or a total dose of 8 mg has been given. IV colchicine should be avoided because it is associated with serious adverse effects (e.g., bone marrow suppression, tissue necrosis from local extravasation, disseminated intravascular coagulation, hepatocellular toxicity, and renal failure). If considered necessary, the recommended initial IV dose is 2 mg (if renal function is normal) diluted in 10 to 20 mL of normal saline administered slowly over 10 to 20 minutes in a secure, free- flowing IV line to avoid extravasation. This may be followed by two additional doses of 1 mg each at 6-hour intervals, with the total dose not exceeding 4 mg. After a full IV course, patients should not receive colchicine by any route for at least 7 days. Corticosteroids Corticosteroids may be used to treat acute attacks of gouty arthritis, but they are reserved primarily for patients with a contraindication or who are unresponsive to NSAID or colchicine therapy. Patients with multiple-joint involvement may also benefit. The recommended dose is prednisone 30 to 60 mg (or an equivalent dose of another corticosteroid) orally once daily for 3 to 5 days. Because rebound attacks may occur upon steroid withdrawal, the dose should be gradually tapered in 5-mg over 10 to 14 days and discontinued. A single intramuscular injection of a long-acting corticosteroid (e.g., methylprednisolone acetate) can be used as an alternative to the oral route if patients are unable to take oral therapy. If not contraindicated, low-dose colchicine can be used as adjunctive therapy to injectable corticosteroids to prevent rebound flare-ups. Intraarticular administration of triamcinolone hexacetonide 20 to 40 mg may be useful for acute gout limited to one or two joints. Adrenocorticotropic hormone (ACTH) gel, 40 to 80 USP units, may be given intramuscularly every 6 to 8 hours for 2 to 3 days and then discontinued and it should be reserved for patients with contraindications to first-line therapies (e.g., heart failure, chronic renal failure, history of GI bleeding). PROPHYLACTIC THERAPY OF GOUT General Approach Prophylactic treatment can be withheld if the first episode of acute gouty arthritis was mild and responded promptly to treatment, the patient’s serum urate concentration was only minimally elevated, and the 24-hour urinary uric acid excretion was not excessive (less than 1,000 mg/24 hours on a regular diet). If the patient had a severe attack of gouty arthritis, a complicated course of uric acid lithiasis, a substantially elevated serum uric acid (greater than 10 mg/dL), or a 24-hour urinary excretion of uric acid of more than 1,000 mg, then prophylactic treatment should be instituted immediately after resolution of the acute episode. Prophylactic therapy is cost-effective for patients with frequent attacks of gouty arthritis Colchicine given in low oral doses (0.5 to 0.6 mg twice daily) may be effective in preventing recurrent arthritis in patients with no evidence of visible tophi and a normal or slightly elevated serum urate concentration. The oral dose should be reduced to no more than 0.6 mg daily or every other day in patients with renal or hepatic dysfunction. Treated patients who sense the onset of an acute attack should increase the dose to 1 mg every 2 hours; in most instances, the attack aborts after 1 or 2 mg. Discontinuation of prophylaxis may be attempted if the serum urate concentration remains normal and the patient is symptom-free for 1 year. Uricosuric Drugs Probenecid and sulfinpyrazone increase the renal clearance of uric acid by inhibiting the renal tubular reabsorption of uric acid. They should only be used in patients with documented underexcretion of uric acid. Therapy with uricosuric drugs should be started at a low dose to avoid marked uricosuria and possible stone formation. Maintenance of adequate urine flow and alkalinization of the urine with sodium bicarbonate or Shohl’s solution during the first several days of uricosuric therapy further diminish the possibility of uric acid stone formation. Probenecid is given initially at a dose of 250 mg twice daily for 1 to 2 weeks, then 500 mg twice daily for 2 weeks. Thereafter, the daily dose is increased by 500-mg increments every 1 to 2 weeks until satisfactory control is achieved or a maximum dose of 2 g/day is reached. The initial dose of sulfinpyrazone is 50 mg twice daily for 3 to 4 days, then 100 mg twice daily, increasing the daily dose by 100-mg increments each week up to 800 mg/day. The major side effects associated with uricosuric therapy are GI irritation, rash and hypersensitivity, precipitation of acute gouty arthritis, and stone formation. These drugs are contraindicated in patients who are allergic to them and in patients with impaired renal function (CLcr