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Patients with gout should be advised to lose weight, moderate their use of alcohol (especially beer), avoid dehydration and repetitive trauma, and control hypertension and hyperlipidemia.
A purine-restricted diet may be unpalatable to many patients and may reduce serum urate levels by only 1 mg/dL.
A more reasonable dietary approach is to reduce consumption of fat, cholesterol, and meat (especially organ meats, which contain high levels of purines).
Patients should also be advised to drink at least eight glasses of liquids daily to prevent dehydration and help reduce uric acid levels.
Use of thiazides and loop diuretics may decrease the clearance of uric acid and reduce plasma volume and therefore should be discontinued or avoided if possible.
Other drugs, such as low-dose aspirin, ethambutol hydrochloride (Myambutol), pyrazinamide, and niacin, decrease uric acid excretion by competing for secretion in renal tubules and also should be avoided.
Early treatment to reduce inflammation and pain is important in an acute attack of gout. The current pharmacologic options include nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, glucocorticoids, and corticotropin.
Acute attack
NSAIDs
Indomethacin (Indocin), 50-75 mg PO initially, then 50 mg q6h, tapered over 7 days
Ibuprofen, 800 mg q8h, tapered over 7 days
Colchicine, 0.6 mg PO q1-2h (maximum, 4 mg/24 hr)
Corticosteroids
Prednisone, 0.5-0.75 mg/day PO, tapered over 7 days
Triamcinolone acetonide, 10-40 mg intra-articularly, depending on size of joint
Corticotropin, 40-80 IU IM q24-72h
Prevention of recurrence
Colchicine, 0.6 mg/day PO
NSAIDs
Indomethacin, 50 mg bid
Ibuprofen, 400-800 mg q8h
Reduction of uric acid levels
Probenecid (Benemid, Benuryl), 250 mg bid x 7 days, increased to 500-1,000 mg bid for maintenance dosage
Indications: Underexcretion of uric acid (<700 mg/24 hr), GFR >50 mL/min, no acute gout, no history of nephrolithiasis
Precautions: Avoid concomitant salicylate therapy
Sulfinpyrazone (Anturane), 50 mg bid x 7 days, advance to 100 mg bid; maintenance dosage, 200 mg bid
Indications: Same as for probenecid
Precautions: Avoid concomitant salicylate therapy and use in patients with sulfa allergy
Allopurinol (Purinol, Zyloprim), 300-600 mg/day, adjusted according to renal function (ie, GFR, glomerular filtration rate)
Indications: Hyperuricemia associated with overproduction, urinary uric acid excretion >700 mg/24 hr, nephrolithiasis, prophylaxis before chemotherapy, hyperuricemia associated with enzyme defects, intolerance to uricosuric agents, inability to lower uric acid level to <7 mg/dL with uricosuric drugs
Precautions: Reduce dose by 75% if patient is also taking azathioprine (Imuran) or mercaptopurine (Purinethol)
NSAIDs
NSAIDs have become first-line therapy for acute episodes because of the many side effects experienced with colchicine and its lack of efficacy if administered beyond 24 hours after onset of an attack.
Any NSAID is effective for acute attacks, but agents with a short half-life (eg, indomethacin [Indocin], ibuprofen) are most popular because of their rapid onset of action.
Indomethacin provides relief within hours when given in an initial oral dose of 50 to 75 mg with subsequent doses of 50 mg every 6 hours. Once symptoms abate, the dose can be tapered gradually over 5 to 7 days (5). The usual oral dosage of ibuprofen is 800 mg every 8 hours. These doses usually provide fast relief, but lower doses may be required for several days after an attack.
Use of NSAIDs should be avoided or monitored carefully in patients with preexisting renal dysfunction or a history of gastrointestinal bleeding. Also, because these agents affect platelet function, they should not be given to patients who have a bleeding propensity or are receiving anticoagulation therapy.
Whether use of the newer cyclooxygenase-2 inhibitors will be beneficial or safer in such patients is yet to be determined. These are a relatively new type of anti-inflammatory drug that are currently under scrutiny. By inhibition of cyclooxygenase-2, the vicious cycle of inflammation and pain caused by gout is impeded. COX-2 expression in monocytes has been suggested to be induced in response to urate crystals.
Colchicine
Colchicine. This agent is an effective alternative to NSAIDs in the treatment of acute gouty arthritis.
Colchicine is most beneficial when it is given in the first 12 to 36 hours of an attack. It apparently exerts its effect by inhibiting the phagocytosis of uric acid and blocking the release of chemotactic factor.
Colchicine has anti-inflammatory
activity but no analgesic activity.
Colchicine can be given orally or parenterally. With oral administration, two
0.5- or 0.6-mg tablets are taken initially. Then one tablet is taken every hour
until joint symptoms are relieved, gastrointestinal side effects develop
(nausea, vomiting and diarrhea) or a total of 5 to 7 mg has been given.
Colchicine can be given intravenously in 1-mg doses (not to exceed 4 mg per day) if the oral route is not available or gastrointestinal side effects have to be avoided.
Intravenous administration has been associated with an increased risk of toxic side effects, including bone marrow suppression and renal or hepatic cell damage.
The usual dosage is 0.6 mg every 1 to 2 hours (maximum dose, 4 mg/24 hr). Therapy is continued until symptoms are relieved or gastrointestinal effects occur. The oral regimen can be difficult for patients who have concomitant medical problems necessitating such measures as bed rest, nothing by mouth, and electrolyte correction. In such patients, an alternative treatment option should be used.
When oral medications are contraindicated, some clinicians give intravenous colchicine in an initial dose of 2 mg with two additional doses of 1 mg every 6 hours if needed. The maximum dose should not exceed 4 mg/24 hr, and intravenous dosing should not be repeated for at least 2 weeks.
However, intravenous colchicine therapy is generally unnecessary for an acute flare of gout, and when administered incorrectly, it can cause bone marrow toxicity and irritation of the soft tissues and veins.
After intravenous therapy, administration of additional oral colchicine must be avoided for a full week, according to manufacturers' recommendations.
Glucocorticoids
Glucocorticoid therapy, either oral or parenteral, is effective in patients who are unable to take or tolerate NSAIDs and colchicine.
The usual initial dosage of prednisone is 0.5 to 0.75 mg/kg a day, with rapid tapering over the next 7 to 10 days. Side effects of this regimen are rare but may include glucose intolerance, electrolyte shifts, hypertension, and increased susceptibility to infection. A symptom flare may occur after tapering of corticosteroid therapy.
Intra-articular steroids are useful in patients with multiple medical problems, involvement of only a few joints, or contraindications to other therapies. A typical dose of triamcinolone acetonide is 10 to 40 mg, depending on the size of the affected joint.
A postinjection flare caused by the steroid crystals themselves may occur but is usually short-lived. This approach has been particularly successful in postoperative patients with a single affected joint who are unable to take oral medications.
Corticotropin
Corticotropin (ACTH) (an exogenously produced corticotropin that stimulates the adrenal cortex to secrete cortisol, corticosterone, and several androgens) is still an option for treating gout.
An intramuscular dose of 100 IU produces 100 mg of cortisol over 16 hours. Peak plasma concentrations of ACTH usually occur within an hour. The usual intramuscular dosage of corticotropin is 40 to 80 IU every 24 to 72 hours.
Although this agent has been shown to be as effective as indomethacin, it carries a higher risk of rebound attacks, and multiple injections may be required. Some investigators have reported efficacy in acute attacks, especially in patients with multiple medical conditions.
Prophylactic drugs
When attacks of gout recur despite conservative measures (eg, dietary modifications, reduction in alcohol consumption), treatment with urate-lowering agents is indicated. Serum urate levels of less than 6 mg/dL generally reduce recurrence of gouty arthritis, but levels below 5 mg/dL may be necessary for the resorption of tophi.
The physiologic basis for these recommended levels is that serum uric acid levels of 7 mg/dL or higher are supersaturated with monosodium urate crystals at 37°C (98.6°F), whereas at the cooler temperatures found in the extremities (eg, 30°C [86°F]), saturation is reached at levels below 5 mg/dL.
The two classes of medications available for reducing serum urate levels are uricosuric agents and xanthine oxidase inhibitors.
In most cases, lifetime treatment with one of these agents is indicated.
Uricosuric drugs
Therapy with uricosuric agents is generally recommended for patients less than 60 years of age who have normal renal function, underexcretion of uric acid (<700 mg/24 hr), and no history of nephrolithiasis .
Although 24-hour uric acid measurement is not required in all patients with gout, it may be useful when uricosuric drug therapy is being considered.
Two common uricosuric agents are probenecid (Benemid, Benuryl) and sulfinpyrazone (Anturane). The usual dosage of probenecid is 500 to 1,000 mg twice daily.
Sulfinpyrazone has an antiplatelet effect that may be beneficial for patients with a cardiac condition who are unable to take low-dose aspirin.
The major side effects of these drugs--hypersensitivity reactions and an increased risk of uric acid nephro-lithiasis--may be avoided by alkalization of the urine. However, this process involves use of additional medications, which may decrease patient compliance.
Xanthine oxidase inhibitors
Allopurinol (Purinol, Zyloprim) decreases uric acid production by inhibiting the enzyme xanthine oxidase. The usual dosage in patients with normal renal function is 300 mg/day (maximum dose, 600 mg/day).
Dosage adjustments are necessary in patients with impaired creatinine clearance.
The increased risk of precipitating an acute attack during drug initiation can be decreased by starting with a dosage of 50 to 100 mg/day.
In addition, medications such as azathioprine (Imuran) and mercaptopurine (Purinethol) are inactivated by xanthine oxidase.
When allopurinol is given concomitantly with these agents, the dose level should be reduced to 25% to 30% of the initial dose to avoid catastrophic hematologic consequences.
Allopurinol is indicated in patients with a history of nephrolithiasis, renal impairment, and an inadequate response to uricosuric drug therapy. Most patients with tophaceous gout need allopurinol therapy.
It is also indicated in patients with myeloproliferative disease who are undergoing chemotherapy and in those with hyperuricemia due to HGPRT deficiency or PRPP synthetase overactivity.
General treatment recommendations <.....More>
The above opinionated views and information serves to educated and informed consumer . The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. .It should not replaced professional advise and consultation.A licensed physician should be consulted for diagnosis and treatment of any and all medical conditions
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