Agents for Gastroesophageal Reflux Disease

Ca Conclusion ST was started on a PPi for the treatment of his stage ii moderate to severe GEPD symptoms. He wilt need treatment for at least 4 to 8 weeks. STs recent immobility has led to his weight gain and possibly his worsening symptoms. ST was also counseled on nondrug therapies to help relieve his GERD symptoms. 

Available agents Omeprazole Lansoprazole Pantoprazole Pabeprazole Esomeprazole Metoclopramide Cisapride 

MOA PPIs are substituted benzimidazoles that irreversibly inhibit gastric parietal cell release of acid. PPIs are prodrugs that must be activated in the acidic environment of the secretory canaliculus located in the parietal cell. PPIs inhibit the ATPase pump and can inhibit nearly 100% of the gastric acid secretion Promotility agents increase LES tone and accelerate gastric emptying. 

Pharmacokinetics All oral PPIs are rapidly absorbed and undergo hepatic metabolism. The bioavailability of the oral PPIs ranges from 30% to 85%. All of the PPIs have a short elimination PA ( 2 hr), but this has minimal effect on the duration of antisecretory action due to irreversible binding to the proton pump. Both cisapride and metoclopramide have a rapid onset of action, 1 hr. Both agents have a similar oral bioavailability 50%-80% and are extensively metabolized by the liver to inactive metabolites. 

Adverse reactions PPIs are very well tolerated. Rarely, headache, diarrhea, constipation, nausea, and pruritus have been observed. Metoclopramide is associated with CNS side effects, especially in the elderly or in those with decreased renal function. Metoclopramide also leads to drowsiness, diarrhea, abdominal cramps, and extrapyramidal reactions. Cisapride, at high doses, is associated with QT segment prolongation. When used at the recommended doses in patients with normal renal and hepatic function, cardiac effects are rare. 

---