GI Pharmacology Review PDF

Review: GI Pharmacology Discussed the structure of the esophagus and the gastroesophageal (GE) junction Normal anti-reflux barrier = 1) diaphragm and 2) lower esophageal sphincter Gastroesophageal reflux disease (GERD) = symptoms and/or esophageal mucosal damage secondary to reflux of...

Review: GI Pharmacology Discussed the structure of the esophagus and the gastroesophageal (GE) junction Normal anti-reflux barrier = 1) diaphragm and 2) lower esophageal sphincter Gastroesophageal reflux disease (GERD) = symptoms and/or esophageal mucosal damage secondary to reflux of normal gastric content (i.e., heartburn) - Symptoms include burning/regurgitation, postprandial, aggravated by change in position, antacids help GERD is caused by a defective anti-reflux barrier, which can allow stomach acid to damage the esophagus Complications of GERD: 1) Erosive esophagitis (damage to the mucosal lining), which could lead to 2) peptic stricture (scar tissue closing the esophagus), or 3) Barrett’s esophagus (tissue changes from squamous epithelium to intestine-like columnar epithelium) which could lead to 4) esophageal cancer Antacids: weak base to neutralize stomach acid, protect esophageal mucosa. Can combine: magnesium hydroxide, aluminum hydroxide, sodium bicarbonate or calcium carbonate. Quick onset (5-10 min) but short duration (30-60 minutes) Useful for intermittent, mild symptoms that occur less than once a week. See slide 22 for Adverse Events Anti-Secretory therapies for GERD focus on blocking the ability of parietal cells (cells in the gastric mucosa) to secrete acid.  H2-receptor antagonists (H2-RAs) block the histamine 2 receptor on parietal cells (different than the allergy-associated H1 receptor). - Examples: Ranitidine (Zantac) or Famotidine (Pepcid), or Cimetidine (Tagemet). - Work by competitive inhibition of the H2 receptor, decreasing gastric acid secretion after a single dose. - Takes 30-45 minutes for onset, lasts 4-10 hours. - Adverse events rare (headache, dizziness, diarrhea), but Cimetidine is a CYP450 inhibitor, so can cause drug-drug interactions - Ranitidine (Zantac) recently withdrawn after FDA confirmed unacceptably high levels of the carcinogen NMDA - Problem: not effective in healing erosive esophagitis, patients develop tachyphylaxis (reduced response to the drug) after 2-6 weeks. Typically used therapeutically for mild GERD. Proton Pump Inhibitors (PPIs): Omeprazole (Prilosec), Lansoprazole (Prevacid), many others. - Most potent inhibitors of gastric acid secretion, binding directly to the proton pump in parietal cells. - Forms stable, irreversible bond with the proton pump, so effects are long-lasting. - Can inhibit basal and stimulated gastric acid by 90% - Take 30 minutes before first meal, daily (not on-demand), can help heal erosive esophagitis - Adverse effects are rare (headache, diarrhea, abdominal pain) - However, long-term use can cause some possible safety concerns, including vitamin B12 deficiency, hypomagenesemia, bone fractures, etc. - May cause some drug-drug interactions. - Preferred drug choice for treating GERD.  Lifestyle modifications still cornerstone of GERD therapy: elevate head of bed while sleeping, no food 3 hours before bedtime, no smoking, decrease fat and volume, avoid peppermint, chocolate, alcohol and coffee, try weight loss, avoid certain medications. Peptic Ulcer Disease (PUD): defects in gastric mucosa that persist due to gastric secretions - Presents with pain 1-3 hours after meals, relieved by food or antacids, but can include nausea, vomiting, dyspepsia, heartburn, weight loss, hematemesis (vomiting blood) - Commonly caused by H. pylori infection or overuse of NSAIDS. - H. pylori – gram negative bacteria that lives on top of gastric epithelium. Causes 50-75% of PUD. - NSAID use – accounts for most other cases of PUD. Endogenous prostaglandins are cytoprotective in the gut, so blocking their production by inhibiting Cox1 or Cox2 weakens the gut (increases acid, reduces mucus, etc). Selective Cox-2 inhibitors have less effects on the gut. Other causes of PUD = Severe psychological stress (CNS trauma, surgery, severe medical illness), or hypersecretory states (uncommon) Discussed myths about causes and treatment of PUD Severe PUD can lead to bleeding in the gut Treatment of H. Pylori PUD is triple-therapy: PPI and 2 antibiotics, each twice daily for 10-14 days, then continue 2-6 weeks more of anti-acid therapy. Cures about 80% of patients. To treat NSAID-caused PUD: stop the NSAID and start a PPI (more effective than H2-RA).  Discussed cytoprotective therapies: Misoprostol, Sucralfate, Bismuth Mioprostol = blocks parietal cell ability to make cAMP in response to histamine. Approved for use for those on NSAIDs to prevent problems. Often causes cramping and diarrhea, contraindicated for pregnant women. Sucralfate (Carafate) = binds to injured tissue in the stomach, reducing exposure to pepsin and acid. Still not as effective as PPIs, but OK for pregnant women. Bismuth (Pepto-Bismol) = does not block acid secretion or neutralize it, but can inhibit pepsin activity, suppress H. Pylori infection, may coat and protect the ulcer. Can cause black stool, cannot be used with aspirin (salicylates), possible to induce toxicity with long-term use.