A presentation on Gout management 2.pptx

A presentation on Gout management

1. Lecture- 25 Lecture Title Gou t

2. Objectives At the end of this lecture, student will be able to: Discuss the treatment goals of Gout Explain the treatment of Gout

3. Treatment The goals in the treatment of gout are To terminate the acute attack Prevent recurrent attacks of gouty arthritis Prevent complications associated with chronic deposition of urate crystals in tissues Prevent or reverse features commonly associated with the illness including obesity, elevated triglycerides, and hypertension This can be accomplished through a combination of nonpharmacologic and pharmacologic methods

4. Treatment ACUTE GOUTY ARTHRITIS For most patients without contraindications, acute attacks of gouty arthritis may be treated successfully with short courses of high-dose NSAIDs, corticosteroids, or colchicine Nonsteroidal Antiinflammatory Drugs NSAIDs are the mainstay of therapy for acute attacks of gouty arthritis because of their excellent efficacy and minimal toxicity with short-term use

5. Treatment Indomethacin has been favoured as the NSAID of choice for acute gout flares, but there is little evidence to support one NSAID as being more efficacious than another The most important determinant of therapeutic success with NSAIDs appears not to be which one is chosen but rather how soon it is initiated Therapy should be initiated with maximum dosages at the onset of symptoms and continued for 24 hours after complete resolution of an acute attack, then tapered quickly over 2 to 3 days

6. Treatment Resolution of an acute attack for most patients generally occurs within 5 to 8 days after initiating therapy All NSAIDs have the potential to cause similar adverse effects The most common areas affected include the Gastrointestinal system (gastritis, bleeding, perforation) Kidneys (renal papillary necrosis, reduced creatinine clearance) Cardiovascular system (sodium and fluid retention, increased blood pressure) Central nervous system (impaired cognitive function, headache, dizziness)

7. Treatment Caution should be exercised when using NSAIDs for individuals with a history of Peptic ulcer disease Congestive heart failure Uncontrolled hypertension Renal insufficiency Coronary artery disease Patients with active peptic ulcer disease, uncompensated congestive heart failure, severe renal impairment, or a history of hypersensitivity to aspirin or other NSAIDs should not be prescribed an NSAID

8. Treatment Corticosteroids Corticosteroids have typically been reserved for treatment of acute gout flares when contraindications to NSAIDs exist, largely due to lack of evidence from controlled clinical trials Evidence that is more recent indicates that corticosteroids are equivalent to NSAIDs in the treatment of acute gout flares They can be used either systemically or by intra articular injection

9. Treatment Oral corticosteroids are usually administered in doses of 30 to 60 mg of prednisone equivalent for 3 to 5 days Patients with multiple joint involvement may be good candidates to consider for this regimen A hypothetical risk for a rebound attack upon steroid withdrawal exists Therefore, the dose of corticosteroid should be tapered gradually in 5 mg decrements spread over 10 to 14 days and then discontinued

10. Treatment Intraarticular administration of triamcinolone acetonide in a dose of 20 to 40 mg may be useful in treating acute gout limited to one or two joints Injection should be done under aseptic technique in a joint determined not to be infected A single intramuscular injection of a long-acting corticosteroid, such as methylprednisolone, can be used as an alternative to the oral route if patients are unable to take oral therapy

11. Treatment If not contraindicated, low-dose colchicine can be used as adjunctive therapy to injectable corticosteroids to prevent rebound flare-ups The adverse effects of corticosteroids are generally dose and duration dependent Short-term use for treatment of acute attacks is generally well tolerated Corticosteroids should be used with caution for patients with diabetes as they can increase blood sugar

12. Treatment In addition, patients with a history of gastrointestinal problems, bleeding disorders, cardiovascular disease, and psychiatric disorders should be monitored closely Long-term corticosteroid use should be avoided because of the risk for osteoporosis, hypothalamic– pituitary axis suppression, cataracts, and muscle deconditioning that can occur with their use Corticotropin , or adrenocorticotropic hormone (ACTH), which stimulates the adrenal cortex to produce cortisol and corticosteroid, can be administered in acute gout

13. Treatment Doses of 40 to 80 United States Pharmacopeia (USP) units are given intramuscularly every6 to 8 hours for 2 to 3 days, and then discontinued When administered alone or in combination with colchicine, ACTH may provide earlier efficacy compared with indomethacin but with fewer adverse effects

14. Treatment Colchicine Colchicine is an antimitotic drug that is highly effective at relieving acute attacks of gout but has the lowest benefit-to-toxicity ratio of the available pharmacotherapy for gout When begun within the first 24 hours of an acute attack, colchicine produces a response in two thirds of patients within hours of administration If the initiation of colchicine is delayed longer than 48 hours after the onset of acute symptoms, the probability of success with the drug diminishes substantially

15. Treatment Although it is a highly effective therapy, oral colchicine can cause dose-dependent gastrointestinal adverse effects, including nausea, vomiting, and diarrhea , in 50% to 80% of patients Other important nongastrointestinal adverse effects include neutropenia axonal neuromyopathy, It may be worsened for patients taking other myopathic drugs such as β- hydroxy- β- methylglutaryl -coenzyme A reductase inhibitors (statins) or for those with renal insufficiency

16. Treatment Colchicine should be used carefully for patients with renal insufficiency, with dosing repeated no more than once every 2 weeks Patients undergoing dialysis should receive a reduced dose of 0.6 mg, administered as a one-time dose only

17. Treatment Nonpharmacologic Therapies Gout is influenced by several dietary factors, including obesity, alcohol intake, hyperlipidemia , and the insulin resistance syndrome Because of the elevated risk for development of gout that exists with hyperuricemia even the asymptomatic patient should receive interventions directed toward modifying or correcting some of these underlying contributors Patients suffering from acute gouty arthritis should be advised to reduce their dietary intake of saturated fats and meats high in purines (e.g., organ meats)

18. Treatment NEPHROLITHIASIS The medical management of uric acid nephrolithiasis includes Hydration sufficient to maintain a urine volume of 2 to 3 L/day Alkalinization of urine Avoidance of purine-rich foods Moderation of protein intake Reduction of urinary uric acid excretion.

19. Treatment Maintenance of a 24-hour urine volume of 2 to 3 L with an adequate intake of fluids is desirable for all gout patients, but especially for those with excessive [>1 g/day (>6 mmol /day)] uric acid excretion Alkalinizing agents should be used with the objective of making the urine less acidic. Urine pH should be maintained at 6 to 6.5 In this pH range, up to 85% of uric acid will be in the form of the soluble urate ion Reduction of urine acidity is usually accomplished by the administration of potassium bicarbonate or potassium citrate 60 to 80 mEq /day

20. Treatment Second, older patients with uric acid kidney stones may also have hypertension, congestive heart failure, or renal insufficiency Because of these conditions, they should not be overloaded with alkalinizing sodium salts or unlimited fluid intake, as these agents can worsen these conditions Acetazolamide, a carbonic anhydrase inhibitor, produces rapid and effective urinary alkalinization and sometimes is used in conjunction with alkali therapy

21. Treatment Such a diet is still palatable and reduces appreciably the amount of uric acid in the urine The mainstay of drug therapy for recurrent uric acid nephrolithiasis is xanthine oxidase inhibitors They are effective in reducing both serum and urinary uric acid levels, thus preventing the formation of calculi Xanthine oxidase inhibitors are recommended as prophylactic treatment for patients who will receive cytotoxic agents for the treatment of lymphoma or leukemia

22. Treatment PROPHYLACTIC THERAPY OF INTERCRITICAL GOUT After the first attack of acute gouty arthritis or after the passage of the first renal stone, a decision to institute prophylactic therapy must be considered This decision should carefully balance risk and benefit Prophylactic therapy has been found to be cost-effective if patients have two or more attacks per year, even if the serum uric acid concentration is normal or only minimally elevated

23. Treatment Then prophylactic treatment should be instituted immediately after resolution of the acute episode Patients with tophi should also be administered prophylactic therapy When implemented, urate-lowering therapy should not commence during an acute attack but 6 to 8 weeks after resolution Prophylactic therapy with low-dose oral colchicine, 0.6 mg once daily, may be effective in preventing recurrent arthritis for patients with no evidence of visible tophi and a normal or slightly elevated serum urate concentration

24. Treatment Patients do not become resistant to or tolerant of daily colchicine, and if they sense the beginning of an acute attack Increase the dose to 1.2 mg, followed by one repeat dose of 0.6 mg in 1 hour If the serum urate concentration is within the normal range and the patient has been symptom free for 1 year, maintenance colchicine may be discontinued The patient should be advised, however, that discontinuation of the treatment program may be followed by an exacerbation of acute gouty arthritis

25. Treatment Patients with a history of recurrent acute gouty arthritis and a significantly elevated serum uric acid concentration probably are best managed with uric acid–lowering therapy The goal of initiating urate -lowering therapies is to achieve and maintain a serum uric acid concentration of less than 6 mg/ dL (357 μmol /L), and preferably below 5 mg/ dL (297 μmol /L) Reduction of the serum urate concentration can be accomplished pharmacologically by decreasing the synthesis of uric acid (xanthine oxidase inhibitors) or by increasing the renal excretion of uric acid ( uricosurics )

26. Treatment Colchicine at a dose of 0.6 mg once daily should be administered for at least the first 8 weeks of antihyperuricemic therapy Xanthine Oxidase Inhibitors Xanthine oxidase inhibitors reduce uric acid by impairing the ability of xanthine oxidase to convert hypoxanthine to xanthine and xanthine to uric acid

27. Treatment Allopurinol was the only agent available in the United States; however, a second xanthine oxidase inhibitor ( febuxostat ; Uloric ) was recently made available Allopurinol lowers uric acid levels in a dose-dependent manner It is typically initiated at a dose of 100 mg/day and then titrated by 100 mg/day at 1-week intervals to achieve a serum uric acid level of 6 mg/dL Serum uric acid levels can be checked approximately 1 week after initiating or modifying the dose of allopurinol

28. Treatment Typical doses of 100 to 300 mg/day are used, although tophaceous gout may require doses of 400 to 600 mg/day and the maximum recommended dose of allopurinol is 800 mg/day Allopurinol should be considered for long-term use when prescribed, as intermittent administration has been found to be less effective in controlling gouty attacks Allopurinol is an effective urate-lowering agent, but up to 5% of patients are unable to tolerate it because of adverse effects Long term adherence with allopurinol is low

29. Treatment Mild adverse effects such as skin rash, leukopenia, gastrointestinal problems, headache, and urticaria can occur with allopurinol administration More severe adverse reactions including severe rash hepatitis, interstitial nephritis, and eosinophilia reportedly occur in approximately 2% of patients and are associated with a 20% mortality Although direct evidence is lacking, the presence of renal insufficiency is believed to predispose patients to this “allopurinol hypersensitivity syndrome”

30. Treatment It is traditionally recommended that the dose of allopurinol be reduced for patients with renal insufficiency Similar to allopurinol, febuxostat lowers serum urate concentrations in a dose-dependent manner In clinical trials, 40 mg/day of febuxostat was noninferior to conventionally dosed allopurinol in achieving the primary endpoint of serum urate concentration

31. Treatment The incidence of gout flares occurring during the initial months of administration was similar for both drugs Febuxostat is well tolerated, with adverse events mostly limited to nausea, arthralgias , and minor liver transaminase elevations An advantage of febuxostat is that it does not require dose adjustment for patients with mild to moderate hepatic or renal impairment

32. Treatment Uricosuric Drugs Uricosuric drugs increase the renal clearance of uric acid by inhibiting postsecretory renal proximal tubular reabsorption of uric acid The drugs used most widely to increase uric acid excretion are probenecid and sulfinpyrazone Therapy with uricosuric drugs should be started at a low dose to avoid marked uricosuria and possible stone formation The maintenance of adequate urine flow and alkalinization of the urine during the first several days of uricosuric therapy further diminish the possibility of uric acid stone formation

33. Treatment Probenecid is given initially at a dose of 250 mg twice a day for 1 to 2 weeks and then 500 mg twice a day 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 is reached The initial dose of sulfinpyrazone is 50 mg twice a day for 3 to 4 days and then 100 mg twice a day, increasing the daily dose by 100 mg increments each week up to 800 mg/day

34. Treatment The major adverse effects associated with uricosuric therapy are gastrointestinal irritation, rash and hypersensitivity, precipitation of acute gouty arthritis, and stone formation Of the two agents, probenecid is the most frequently used uricosuric , as sulfinpyrazone is associated with more severe adverse effects A disadvantage of uricosurics is that salicylates may interfere with this mechanism and result in treatment failure; however, low doses (325 mg/day or less) of enteric-coated aspirin may be used cautiously

35. Treatment In addition, probenecid can inhibit the tubular secretion of other organic acids Increased plasma concentrations of penicillins , cephalosporins, sulfonamides , and indomethacin can occur Because it is chemically related to phenylbutazone , sulfinpyrazone can act as an antiplatelet agent and should be used with great caution for anticoagulated patients or for those with peptic ulcer disease Uricosuric drugs are contraindicated for patients who are allergic to them and for patients with impaired renal function

36. Treatment Miscellaneous Agents Lipid-lowering agents, in particular fenofibrate , can also be prescribed for patients with gout Although dyslipidemia is common in gout patients, the fibrates are believed to exert their effects as an ancillary benefit by increasing the clearance of hypoxanthine and xanthine, leading to a sustained reduction in serum urate concentrations Reductions of 20% to 30% in urate levels are observed with fenofibrate use

37. Treatment Importantly, fenofibrate does not appear to not cause an acute gout flare when initiated and is well tolerated overall Losartan, an angiotensin II receptor antagonist, has also demonstrated benefit in reducing serum urate concentrations independently of angiotensin receptor antagonism Losartan inhibits renal tubular reabsorption of uric acid and increases urinary excretion, and this effect seems to be a unique property of losartan that is not shared with other angiotensin II receptor antagonists