Gouty arthritis, acute

Indomethacin is available for the short-term treatment of acute gouty arthritis, acute pain of ankylosing spondylitis, and osteoarthritis. An injectable form to be reconstituted also is available as the sodium trihydrate salt for IV use in premature infants with patent ductus arteriosus. Because of its ability to suppress uterine activity by inhibiting prostaglandin biosynthesis, indomethacin also has an unlabeled use to prevent premature labor. 

Thus, the presence of uric acid crystals in joints triggers a vicious cycle, resulting in an extremely painful inflammation. A typical localization of acute gouty arthritis is the first metatarsal joint of the foot (podagra). The diagnosis of acute gouty arthritis is confirmed by the detection of urate crystals in the joint or tophus. 

Daily doses of 3-8 mg (6-8 times 0.5-1.0 mg) are used for the treatment of acute gouty arthritis. For prophylaxis, daily doses of 0.5-1.5 mg are used, but the use of colchicine for prophylaxis is controversial. 

Hyperuricemia is defined as serum uric acid concentration >416 p mol/L or 7.0 mg/dL. With increasing serum uric acid concentration, the risk of acute gouty arthritis increases, but asymptomatic hyperuricemia does not have to be treated pharmacologically. 

Tubulin is a major component of the cellular cytoskele-ton. Tubulin polymers (microtubules) are important for cell division (mitotic spindle) and the chemotaxis and phagocytosis of neutrophils. Prevention of tubulin polymerisation by colchicine accounts for the therapeutic effects of this drug in acute gouty arthritis and its anti-mitotic effects. 

Short-term management of acute ankylosing spondylitis, acute and subacute bursitis, acute nonspecific tenosynovitis, acute gouty arthritis, psoriatic arthritis, rheumatoid arthritis, post-traumatic osteoarthritis, synovitis of osteoarthritis, epicondylitis... 

Certain drugs bind to microtubules and thus interfere with their assembly or disassembly. These include colchicine (used for treatment of acute gouty arthritis), vinblastine (a vinca alkaloid used for treating certain types of cancer), paclitaxel (Taxol) (effective against ovarian cancer), and griseoflilvin (an antifungal agent). 

Develop a pharmacotherapeutic plan for a patient with acute gouty arthritis or uric acid nephropathy that includes individualized drug selection and monitoring for efficacy and safety. 

Treatment of gout involves (1) acute relief of a gouty arthritis attack and (2) in some patients long-term maintenance treatment to prevent future attacks. 

If the diagnosis is an acute attack of gouty arthritis, what treatment plan would you outline for this patient ... 

Allopurinol is well absorbed with a short half-life of 2 to 3 hours. The half-life of oxypurinol approaches 24 hours, allowing allopurinol to be dosed once daily. Oxypurinol is cleared primarily renally and can accumulate in patients with reduced kidney function. Allopurinol should not be started during an acute gout attack because sudden shifts in serum uric acid levels may precipitate or exacerbate gouty arthritis. Rapid shifts in serum uric acid can change the concentration of monosodium urate crystals in synovial fluid, causing more crystals to precipitate. Thus some clinicians advocate a prophylactic dose of colchicine (0.6 mg/day) during initiation of antihyperuricemic therapy. Acute episodes should be treated appropriately before maintenance treatment is started. 

Schlesinger N. Management of acute and chronic gouty arthritis. Drugs 2004 64 2399-2416. 

Pyrazinamide Adults Based on IBW 40-55 kg 1000 mg 56-75 kg 1500 mg 76-90 kg 2000 mg Children 15-30 mg/kg Hepatotoxicity, gastrointestinal symptoms (nausea, vomiting), non-gouty polyarthralgia, asymptomatic hyperuricemia, acute gouty arthritis, transient morbilliform rash, dermatitis Serum uric acid can serve as a surrogate marker for compliance FFTs in patients with underlying liver disease... 

Tophi (urate deposits) are uncommon in gouty subjects and are a late complication of hyperuricemia. The most common sites of tophaceous deposits in patients with recurrent acute gouty arthritis are the base of the great toe, helix of the ear, olecranon bursae, Achilles tendon, knees, wrists, and hands. 

Acute attacks of gouty arthritis are characterized by rapid onset of excruciating pain, swelling, and inflammation. The attack is typically monoarticular... 

When joint aspiration is not a viable option, a presumptive diagnosis of acute gouty arthritis may be made on the basis of the presence of the characteristic signs and symptoms, as well as the response to treatment. 

The goals in the treatment of gout are to terminate the acute attack, prevent recurrent attacks of gouty arthritis, and prevent complications associated with chronic deposition of urate crystals in tissues. 

FIGURE 1-1. Treatment algorithm for acute gouty arthritis. (NSAID, nonsteroidal antiinflammatory drug.)... 

TABLE 1-1 Dosage Regimens of Nonsteroidal Antiinflammatory Drugs for Treatment of Acute Gouty Arthritis... 

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. 

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. 

Patients with a history of recurrent acute gouty arthritis and a significantly elevated serum uric acid concentration are probably best managed with uric acid-lowering therapy. 

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 <50 mL/min) or a history of renal calculi, and in patients who are overproducers of uric acid. 

Patients with acute gout should be monitored for symptomatic relief of joint pain as well as potential adverse effects and drug interactions related to drug therapy. The acute pain of an initial attack of gouty arthritis should begin to ease within about 8 hours of treatment initiation. Complete resolution of pain, erythema, and inflammation usually occurs within 48 to 72 hours. 

The most important side effects of the thiazide diuretics, chlorthalidone, furosemide, ethacrynic acid and metolazone are potassium losses with resultant hypokalemia, and hyperuricemia. Hyperuricemia may result in acute attacks of gouty arthritis in individuals with a gouty diathesis. 

Hyperuricemia may be produced by overproduction of uric acid or under-excretion of uric add by the kidneys. Kyperuricemia may progress to acute and chronic gouty arthritis if uric acid (monosodium urate) is deposited in joints and surrounding soft tissue, where it causes inflammation, Uric add is produced from excess endogenous purines as shown in Figure 1-18-5, and is also produced from dietary purines (digestion of nucleic acid in the intestine) by intestinal epithe-lia. Both sources of uric acid are transported in the blood to the kidneys for excretion in urine. 

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