Pharmacology Flashcards: GI Drugs, Proton Pump Inhibitors, H2 Blockers, Antiemetics

Proton pump inhibitors, or PPIs, like omeprazole, pantoprazole, and esomeprazole irreversibly block the hydrogen-potassium ATPase pump in gastric parietal cells, reducing stomach acid secretion by up to 90 percent. They treat gastroesophageal reflux disease, peptic ulcers, and Helicobacter pylori infection as part of combination therapy. Long-term risks include increased fracture risk from impaired calcium absorption, hypomagnesemia, vitamin B12 deficiency, Clostridioides difficile infection, and chronic kidney disease.

Proton pump inhibitors block the final common pathway of acid secretion by inhibiting the proton pump directly, producing more potent and longer-lasting acid suppression than H2 blockers. H2 receptor blockers like ranitidine, famotidine, and cimetidine block histamine-2 receptors on parietal cells, reducing only the histamine-stimulated component of acid secretion. PPIs are more effective for healing erosive esophagitis and ulcers, while H2 blockers are adequate for mild heartburn and prevention of stress ulcers.

Ondansetron, brand name Zofran, is an antiemetic that works by blocking serotonin 5-HT3 receptors in the chemoreceptor trigger zone and the vagus nerve, preventing nausea and vomiting signals from reaching the vomiting center in the brain. It is highly effective for chemotherapy-induced, postoperative, and radiation-induced nausea and vomiting. Ondansetron can be given orally, intravenously, or as an orally disintegrating tablet. Side effects are generally mild and include headache and constipation.

Metoclopramide is a prokinetic and antiemetic drug that works by blocking dopamine receptors and enhancing upper gastrointestinal motility. It is used for gastroparesis, nausea, and gastroesophageal reflux disease. The FDA issued a black box warning because long-term use beyond 12 weeks significantly increases the risk of tardive dyskinesia, an often irreversible movement disorder causing involuntary facial and tongue movements. Elderly patients, particularly women, are at highest risk.

Helicobacter pylori infection is treated with combination therapy called triple or quadruple therapy. Standard triple therapy uses a proton pump inhibitor plus two antibiotics, typically clarithromycin and amoxicillin or metronidazole, for 14 days. Bismuth quadruple therapy uses a PPI, bismuth subsalicylate, metronidazole, and tetracycline. The PPI suppresses acid to allow mucosal healing while the antibiotics eradicate the bacteria. Antibiotic resistance, particularly to clarithromycin, is increasing, making local resistance patterns important for regimen selection.

Sucralfate is a mucosal protectant that forms a paste-like protective barrier over ulcerated tissue in the stomach and duodenum. In the acidic environment of the stomach, sucralfate polymerizes and binds to positively charged proteins at the ulcer base, creating a physical shield that prevents further acid, pepsin, and bile damage. It does not reduce acid secretion. Sucralfate must be taken on an empty stomach, one hour before meals, because food interferes with its ability to bind to the ulcer site. ---