NMT150 Stomach Acid Suppression & H. Pylori Eradication PDF

STOMACH ACID SUPPRESSION AND H. PYLORI ERADICATION Dr. Adam Gratton NMT150 MSc ND March 23, 2023 LECTURE COMPETENCIES Compare and contrast the mechanisms of action, indications, and adverse effects of drugs used to alleviate the effects of, or suppress excess stomach acid secretio...

STOMACH ACID SUPPRESSION AND H. PYLORI ERADICATION Dr. Adam Gratton NMT150 MSc ND March 23, 2023 LECTURE COMPETENCIES Compare and contrast the mechanisms of action, indications, and adverse effects of drugs used to alleviate the effects of, or suppress excess stomach acid secretion - Antacids and alginates - H2 receptor antagonists - Proton pump inhibitors - Prostaglandin analogues Describe quadruple therapy within the context of H. pylori eradication Describe the adverse effects of quadruple therapy GI DISORDERS Dyspepsia - pain or discomfort located in the upper abdomen Gastroesophageal reflux disease (GERD) – acid reflux into the lower esophagus most commonly associated with heartburn and regurgitation ranging from silent to severe Peptic ulcer disease (PUD) - the development of breaks in the mucosa of the stomach (gastric ulcers) and/or proximal duodenum (duodenal ulcers). ALGINATES Natural polysaccharide polymers derived from seaweed Precipitate into a gel on contact with gastric acid Gel floats on top of stomach contents forming a physical barrier between acid and the lower esophageal sphincter Gel refluxes instead of acid ALGINATE/MAGNESIUM HYDROXIDE Tablet form Typically 2 – 4 tablets chewed PRN after meals followed by a glass of water Adverse effects include nausea, vomiting, eructation, flatulence ANTACIDS Just acid-neutralizing agents Aluminum and magnesium hydroxides, in combination, are one of the most common Aluminum hydroxide causes constipation Magnesium hydroxide causes diarrhea Often only work for a short time as acid is involved in the negative feedback of acid regulation ALUMINUM AND MAGNESIUM HYDROXIDE COMBINATION Typically administered PRN after meals Adverse effects include constipation and diarrhea H2 RECEPTOR ANTAGONISTS Generic naming convention: -tidine Histamine is a potent inducer of acid secretion Structurally similar to histamine but do not activate H2 receptors on parietal cells resulting in competitive inhibition Results in potent inhibition of both meal-stimulated secretion and basal secretion of gastric acid RANITIDINE Have no effect on gastric emptying time, esophageal sphincter pressure, or pancreatic enzyme secretion Indications: Dyspepsia/GERD/heartburn Peptic ulcer disease: at doses that raise gastric pH above 4 for at least 13 hours a day Require 6-8 weeks of continuous therapy to heal 90% of ulcers RANITIDINE Adverse effects include diarrhea, constipation, headache, fatigue, confusion (most commonly in elderly patients with reduced renal function), cardiac effects, rash Dose: 150 mg BID – QID PO or 300 mg QHS PO PROTON PUMP INHIBITORS Generic naming convention: -prazole Prodrugs administered orally as sustained-release, enteric- coated preparations as they are inactivated by stomach acid Activated by protonation, which occurs in areas of the body below their pKa (~4.0) The only place that happens is in the parietal cell canaliculi Once activated they bind to H+/K+ ATPase and irreversibly inactivate the pump OMEPRAZOLE Must be taken 30 minutes before a meal to ensure pumps are active when peak concentration of PPI are present in the blood Takes about 3 days to reach steady state inhibition (after factoring in the inactivation of active pumps, stimulation of inactive pumps, and creation of new pumps) Rapid CYP2C19 metabolizers may require higher doses OMEPRAZOLE Indications Peptic ulcer disease Better than H2 antagonists Heal 80-90% of ulcers in 2 weeks or less Drug of choice for Zollinger-Ellison syndrome Most effective for treating dyspepsia/GERD/heartburn May be used to prevent ulcers in patients taking NSAIDs OMEPRAZOLE Common adverse effects include headache, nausea, diarrhea, abdominal pain, constipation, dizziness, fatigue, rash, pruritis May cause allergic reactions, kidney disorders, dementia (inconclusive) Long-term use associated with pneumonia, GI infections, vitamin and mineral deficiencies (B12, iron, Mg), osteoporosis, and fractures OMEPRAZOLE Dose: 20 – 40 mg once daily PO 30 minutes AC If partial or no response, dose BID AC Half the usual dose may be enough for less severe symptoms or for maintenance after remission CYTOPROTECTIVE DRUGS The two common drugs here are sucralfate and misoprostol Sucralfate is essentially a chemical bandage Sucrose sulfate and aluminum hydroxide complex that binds to ulcers creating a physical barrier from stomach acid Misoprostol has a more complicated mechanism of action MISOPROSTOL Prostaglandin E1 analog Binds to prostaglandin receptors in the stomach and enhances mucus production, mucosal blood flow, and bicarbonate secretion in epithelial cells Binds to prostaglandin receptors on parietal cells and inhibits adenylate cyclase (decreases cAMP) which downregulates H+/K+ ATPase and decreases acid secretion MISOPROSTOL Indicated for gastric and duodenal ulcers in patients taking NSAIDs long-term. Rather expensive and typically reserved for high-risk patients (elderly and those with a previous history of ulcer disease) Contraindicated in pregnancy as it can stimulate uterine contractions and induce labour MISOPROSTOL Adverse effects include dose-related diarrhea, abdominal cramps, flatulence Risk of diarrhea increased when used alongside magnesium-based antacids Dose: 200 mcg QID PO HELICOBACTER PYLORI Most infections are asymptomatic When symptoms do occur, they are typically related to gastritis or peptic ulcers Infection significantly increases the risk of gastric cancer First line management for eradication is “quadruple therapy” for 14 days QUADRUPLE THERAPY First-line First-line or prior treatment failure PPI BID PPI BID Amoxicillin BID Bismuth subsalicylate QID Metronidazole BID Metronidazole TID - QID Clarithromycin BID Tetracycline QID QUADRUPLE THERAPY Both regimens achieve a minimum eradication rate of at least 85% Risk of reinfection after successful eradication is about 1% a year QUADRUPLE THERAPY Adverse effects are generally related to the component parts Headache and diarrhea are most commonly reported Clarithromycin can cause altered taste, GI upset, and diarrhea Amoxicillin can cause diarrhea and rash Bismuth can lead to darkening of stool and tongue, nausea, and constipation Adverse effects are more common with quadruple therapy containing PPI, bismuth, metronidazole, tetracycline SAMPLE QUESTION Which of the following drug options is the best for treating peptic ulcer disease? A. Alginate B. Misoprostol C. Ranitidine D. Omeprazole