What's new: proton pump inhibitors and pediatrics.

Abstract

1. Ashish S. Patel, MD* 2. John F. Pohl, MD* 3. David J. Easley, MD* 1. *Department of Pediatrics, Division of Gastroenterology, Scott and White Hospital, Texas A&M Health Science Center, Temple, TX After completing this article, readers should be able to: 1. Explain why proton pump inhibitors are more effective than histamine2-receptor antagonists. 2. Describe how proton pump inhibitors work. 3. Describe the best delivery system for patients requiring medication through a tube. 4. Identify the proton pump inhibitor currently approved in the United States for intravenous administration. Proton pump inhibitors (PPIs) have become the mainstay of treatment for acid-related gastrointestinal disease in adults since their introduction in 1989. There are several inherent advantages of PPIs compared with the older medication classes of antacids or histamine2-receptor antagonists (H2-RAs). H2-RAs reduce acid secretion only by competing with histamine receptors located in the parietal cell membrane; other cellular receptors that respond to endocrine (gastrin) and neuroendocrine (vagal stimulation) pathways are not affected. As a consequence, H2-RAs do not completely block gastric parietal cell acid production. Unlike H2-RAs, PPIs demonstrate consistent gastric pH control and do not develop tachyphylaxis with repeated dosing. The pharmacology of every PPI involves targeting the gastric acid or proton pump (H+-K+ ATPase), which is situated in parietal cell membranes. After extensive first-pass metabolism in the liver, prodrug accumulates in the canalicular space of the parietal cell and is converted to an active metabolite through an acid-catalyzed reaction. Active drug then irreversibly binds to cysteine residues within the H+-K+ ATPase via a covalent bond. Consequently, PPIs inhibit the final step of gastric acid secretion by blocking proton production. PPIs require an acidic environment within the canalicular space for activation, and proton pumps are maximally exposed on the surfaces of meal-stimulated parietal cells. As a result, administration optimally should occur in a fasting state 30 minutes prior to the first meal of the day. In general, most PPIs …