c. Prevention of rebleeding from peptic ulcers—In patients with acute gastrointestinal bleeding due to peptic ulcers, the risk of rebleeding from ulcers that have a visible vessel or adherent clot is increased. Rebleeding of this subset of high-risk ulcers is reduced significantly with PPIs administered for 3–5 days either as high-dose oral therapy (eg, omeprazole, 40 mg orally twice daily) or as a continuous intravenous infusion. It is believed that an intragastric pH higher than 6 may enhance coagulation and platelet aggregation. The optimal dose of intravenous PPI needed to achieve and maintain this level of near-complete acid inhibition is unknown; however, initial bolus administration of esomeprazole or pantoprazole (80 mg) followed by constant infusion (8 mg/h) is commonly recommended.
3.
Nonulcer dyspepsia—PPIs have modest efficacy for treatment of nonulcer dyspepsia, benefiting 10–20% more patients than placebo. Despite their use for this indication, superiority to H2 antagonists (or even placebo) has not been conclusively demonstrated.
4.
Prevention of stress-related mucosal bleeding—As discussed previously (see H2-Receptor Antagonists), PPIs (given orally, by nasogastric tube, or by intravenous infusions) may be administered to reduce the risk of clinically significant stress-related mucosal bleeding in critically ill patients. The only PPI approved by the US Food and Drug Administration (FDA) for this indication is an oral immediate-release omeprazole formulation, which is administered by nasogastric tube twice daily on the first day, then once daily. Although not FDA approved for this indication, other PPI suspension formulations (esomeprazole, omeprazole, pantoprazole) may also be used. For patients with nasoenteric tubes, PPI suspensions may be preferred to intravenous H2 antagonists or PPIs because of comparable efficacy, lower cost, and ease of administration.
For patients without a nasoenteric tube or with significant ileus, intravenous H2 antagonists are preferred to intravenous PPIs because of their proven efficacy. Although PPIs are increasingly used, there are no controlled trials demonstrating efficacy or optimal dosing.
5. Gastrinoma and other hypersecretory conditions—
Patients with isolated gastrinomas are best treated with surgical resection. In patients with metastatic or unresectable gastrinomas, massive acid hypersecretion results in peptic ulceration, erosive esophagitis, and malabsorption. With PPIs, excellent acid suppression can be achieved in all patients. Dosage is titrated to reduce basal acid output to less than 5–10 mEq/h. Typical doses of omeprazole are 60–120 mg/d.
1. General—Although PPIs have been considered to be extremely safe, a number of recent safety concerns have been raised. As with most drugs, PPIs should be prescribed at the lowest effective dose and the risks versus benefits of long-term use carefully weighed. Diarrhea, headache, and abdominal pain are reported in 1–5% of patients, although the frequency of these events is only slightly increased compared with placebo. In large observational studies, PPIs have been associated with an increased risk of acute interstitial nephritis and chronic kidney disease compared to nonusers or users of H2-receptor antagonists. A mechanism by which kidney damage might occur has not been determined. Some epidemiologic studies have also detected an increased risk of dementia in long-term PPI users, although causality has not been established. PPIs are not teratogenic in animal models; however, safety during pregnancy has not been established.
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