Dyspepsia with NSAID

The most common adverse effects of NSAIDs involve the gastrointestinal tract. Minor complaints (nausea, dyspepsia, anorexia, and abdominal pain) are common (up to 60% of patients). Serious GI complications associated with NSAIDs including perforations, gastric outlet obstruction, and GI bleeding, occur in 1.5% to 4% of patients per year. 

A higher incidence of abdominal pain, diarrhoea, nausea and dyspepsia occurred when diclofenac was combined with misoprostol. Concurrent use of indometacin and misoprostol also resulted in an increase in frequency and severity of abdominal symptoms, frequency of bowel movements and a decrease in faecal consistency. The most frequent adverse effect of misoprostol alone is diarrhoea, and this may limit the dose tolerated. When using misoprostol with NSAIDs, warn patients about the possibility of increased stomach pain and diarrhoea. Preparations combining diclofenac or naproxen with misoprostol are available. 

The indications for these agents are in principle identical to those of the non-selective NSAIDs although the substances have not yet received approval for the whole spectrum of indications of the conventional NSAIDs. Because they lack COX-1-inhibiting properties, COX-2-selective inhibitors show fewer side effects than conventional NSAIDs. However, they are not free of side effects because COX-2 has physiological functions that are blocked by the COX-2 inhibitors. The most frequently observed side effects are infections of the upper respiratory tract, diarrhoea, dyspepsia, abdominal discomfort and headache. Peripheral oedema is as frequent as with conventional NSAIDs. The frequency of gastrointestinal complications is approximately half that observed with conventional NSAIDs. 

The most common adverse reactions seen with celecoxib include dyspepsia, abdominal pain, diarrhea, nausea, and headache Like other NSAIDs, celecoxib may compromise renal function. Elevation of aminotransferase levels also occurs. 

NSAIDs are one of the most widely used classes of medications in the United States, particularly in the elderly.4 More than 20,000 deaths occur in the United States per year as a direct result of adverse events related to NSAID use. Chronic NSAID ingestion leads to symptoms of nausea and dyspepsia in nearly half of patients. Peptic ulceration occurs in up to 30% of patients who use NSAIDs chronically, with gastrointestinal bleeding or perforation occurring in 1.5% of patients who develop an ulcer. NSAID-related peptic ulcers usually occur in the stomach duodenal ulcers are much less common. 

Patients at increased risk of NSAID-induced gastrointestinal adverse effects (e.g., dyspepsia, peptic ulcer formation, and bleeding) include the elderly, those with peptic ulcer disease, coagulopathy, and patients receiving high doses of concurrent corticosteroids. Nephrotoxicity is more common in the elderly, patients with creatinine clearance values less than 50 mL/minute, and those with volume depletion or on diuretic therapy. NSAIDs should be used with caution in patients with reduced cardiac output due to sodium retention and in patients receiving antihypertensives, warfarin, and lithium. 

GI complaints are the most common adverse effects of NSAIDs. Minor complaints such as nausea, dyspepsia, anorexia, abdominal pain, flatulence, and diarrhea occur in 10% to 60% of patients. NSAIDs should be taken with food or milk, except for enteric-coated products (milk or antacids may destroy the enteric coating and cause increased GI symptoms in some patients). 

The doctor may decide to stop the NSAID and see how Mrs PJ manages without the diclofenac or may consider adding in a proton pump inhibitor, in line with Clinical Knowledge Summaries (2008) guidance, to manage the incidence of NSAID-induced dyspepsia. If it is felt that the problem is related to the sulfasalazine and the nausea does not abate, the doctor may try an alternative treatment. As Mrs PJ is currently only on a low dose of sulfasalazine it would not really be possible to reduce the dose and still maintain efficacy. 

Some 500 million prescriptions for NSAIDs are written each year in the UK, and 10-15% of patients develop dyspepsia whilst taking these drugs. Gastric erosions develop in up to 80%, but these are usually self-limiting. Gastric or duodenal ulcers occur in 1-5%. The incidence increases sharply with age in those over 60, and the risk of ulcers and their complications is doubled in patients over 75 and those with cardiac failure or a history of peptic ulceration or bleeding. Ibuprofen may be less prone to cause these problems than other NSAIDs. 

Dyspepsia may or may not be associated with an ulcer, and in itself is of little clinical value when trying to identify subsets of patients who are most likely to have an ulcer. As many as 50% of patients who take NSAIDs report having dyspepsia. " Patients with dyspeptic symptoms may have either uninvestigated (no upper endoscopy) dyspepsia or investigated (underwent upper endoscopy) dyspepsia. If an ulcer is not confirmed in a patient with ulcer-like symptoms at the time of endoscopy, the disorder is referred to as nonulcer dyspepsia. ... 

Patients with PUD should eUminate or reduce psychological stress, cigarette smoking, and the use of nonselective NSAIDs (including aspirin). Although there is no antiulcer diet, the patient should avoid foods and beverages (e.g., spicy foods, caffeine, and alcohol) that cause dyspepsia or that exacerbate ulcer symptoms. If possible, alternative agents such as acetaminophen, nonacetylated... 

Whereas the toxicity of sulindac is lower than that observed for indomethacin and other NSAIDs, the spectrum of adverse reactions is very similar. The most frequent side effects reported are associated with irritation of the Gl tract (e.g., nausea, dyspepsia, and diarrhea), although these effects generally are mild. Effects on the CNS (e.g., dizziness and headache) are less common. Dermatological effects are less frequently encountered. 

As a result of the OMNIUM and ASTRONAUT studies, the Helicobacter status of a large number of patients taking NSAIDs had been established. These and others entered a study in which patients with current or past known peptic ulcer and/or current moderate/severe dyspepsia who were H. pylori positive were randomised to receive omeprazole 20 mg bid, clarithromycin 500 mg bid, amoxycillin 1 g bid or omeprazole with placebo... 

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