Aspiration: Proton Pump Inhibitors

PROTON PUMP INHIBITORS

Mechanism of Action

Th ese agents, including omeprazole (Prilosec), lan-soprazole (Prevacid), rabeprazole (Aciphex), esome-prazole (Nexium), and pantoprazole (Protonix), bind to the proton pump of parietal cells in the gas-tric mucosa and inhibit secretion of hydrogen ions.

Clinical Uses

Proton pump inhibitors (PPIs) are indicated for the treatment of duodenal ulcer, GERD, and Zollinger– Ellison syndrome. They may promote healing of peptic ulcers and erosive GERD more quickly than H₂-receptor blockers. There are ongoing ques-tions regarding the safety of PPIs in patients taking clopidogrel (Plavix) because of concerns of inad-equate antiplatelet therapy when these drugs are combined.

Side Effects

PPIs are generally well tolerated, causing few side effects. Adverse side effects primarily involve the GI system (nausea, abdominal pain, constipation, diarrhea). On rare occasions, these drugs have been associated with myalgias, anaphylaxis, angioedema, and severe dermatological reactions. Long-term use of PPIs has also been associated with gastric entero-chromaffin-like cell hyperplasia and an increased risk of pneumonia secondary to bacterial coloniza-tion in the higher-pH environment.

Dosage

Recommended oral doses for adults are omeprazole, 20 mg; lansoprazole, 15 mg; rabeprazole, 20 mg; and pantoprazole, 40 mg. Because these drugs are pri-marily eliminated by the liver, repeat doses should be decreased in patients with severe liver impairment.

Drug Interactions

PPIs can interfere with hepatic P-450 enzymes, potentially decreasing the clearance of diazepam, warfarin, and phenytoin. Concurrent administra-tion can decrease clopidogrel (Plavix) effectiveness, as the latter medication is dependent on hepatic enzymes for activation.