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history of peptic ulcer disease or alcoholism, and age over 70 Twenty-five percent of all hospitalizations and deaths from peptic ulcer disease result from traditional NSAID therapy Each year, 1:1000 patients with rheumatoid arthritis will require hospitalization for NSAID-related gastrointestinal bleeding or perforation Although all traditional NSAIDs can cause massive gastrointestinal bleeding, the risk may be higher with indomethacin and piroxicam, probably because these drugs preferentially inhibit COX-1 in the stomach One approach to reducing the gastrointestinal toxicity of traditional NSAIDs is to add either a proton pump inhibitor (eg, omeprazole 20 mg orally daily) or misoprostol The expense of proton pump inhibitors and misoprostol dictates that their use should be reserved for patients with risk factors for NSAID-induced gastrointestinal toxicity (noted above) Patients who have recently recovered from an NSAID-induced bleeding gastric ulcer appear to be at high risk for rebleeding (about 5% in 6 months) when an NSAID is reintroduced, even if prophylactic measures such as proton pump inhibitors are used NSAIDs can also affect the lower intestinal tract, causing perforation or aggravating inflammatory bowel disease Acute liver injury from NSAIDs is rare, occurring in about 1 of every 25,000 patients using these agents Having rheumatoid arthritis or taking sulindac may increase the risk 2 Renal side effects All of the NSAIDs, including aspirin and the COX-2 inhibitors, can produce renal toxicity, including interstitial nephritis, nephrotic syndrome, prerenal azotemia, and aggravation of hypertension Hyperkalemia due to hyporeninemic hypoaldosteronism may also be seen The risk of renal toxicity is low but is increased by age over 60, a history of renal disease, congestive heart failure, ascites, and diuretic use COX-2 inhibitors appear to cause as much nephrotoxicity as traditional NSAIDs 3 Platelet effects All NSAIDs except the nonacetylated salicylates and the COX-2 inhibitors interfere with platelet function and prolong bleeding time For all older NSAIDs except aspirin, the effect on bleeding time resolves as the drug is cleared Aspirin irreversibly inhibits platelet function, so the bleeding time effect resolves only as new platelets are made COX-2 inhibitors, which differ from other NSAIDs in not inhibiting platelet function, do not increase the risk of bleeding with surgical procedures as most NSAIDs do Unfortunately, this failure to inhibit platelets is now known to lead to increased risks of myocardial infarction and stroke, particularly when the medications are used in high doses for prolonged periods of time Patients requiring low-dose aspirin who are not compliant have a greater risk of developing a thrombotic event while taking a coxib than while taking a traditional NSAID Whether combination therapy with low-dose aspirin and a coxib maintains the gastrointestinal advantage of selective COX-2 inhibitors is not yet known Although groups of patients with rheumatoid arthritis respond similarly to NSAIDs, individuals may respond differently an NSAID that works for one patient may not work for another Thus, if the first NSAID chosen is not effective after 2 3 weeks of use, another should be tried
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Low-dose corticosteroids (eg, oral prednisone 5 10 mg daily) produce a prompt anti-inflammatory effect in rheumatoid arthritis and slow the rate of bony destruction However, their multiple side effects limit their long-term use Corticosteroids may be used on a short-term basis to tide patients over acute disabling episodes, to facilitate other treatment measures (eg, physical therapy), or to manage serious extra-articular manifestations (eg, pericarditis, necrotizing scleritis) They may also be indicated for active disease that persists despite treatment with DMARDs No more than 10 mg of prednisone or equivalent per day is appropriate for articular disease Many patients do reasonably well on 5 75 mg daily (The use of 1 mg tablets, to facilitate doses of < 5 mg/d, is encouraged) When the corticosteroids are to be discontinued, they should be tapered gradually on a planned schedule appropriate to the duration of treatment All patients receiving long-term corticosteroid therapy should take measures to prevent osteoporosis Intra-articular corticosteroids may be helpful if one or two joints are the chief source of difficulty Intra-articular triamcinolone, 10 40 mg depending on the size of the joint to be injected, may be given for symptomatic relief but not more than four times a year
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