Pharmacology GI
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- What are some symptoms of GI dysfunction?
- - heart burn - abdominal pain - dyspepsia - nausea/vomiting - diarrhea/constipation - GI bleeding
- What are the 3 phases of gastric acid secretion?
- 1. cephalic 2. gastric 3. intestinal
- What are some pathological conditions of the GI tract that are improved by decreasing gastric acid and pepsin activity?
- - GERD - esophagitis - gastric ulcer - duodenal ulcer - gastritis - zollinger-elison syndrome
- What are factors associated with ulcer disease?
- - erosive and protective factors - erosive (or aggresive factors) included HCl, pepsin, bile salts, H. pylori, drugs - protective factors include: rapid turnover of epithelial cells and prostaglandin synthesis (produced mucus and bicarbonate secretion)
- How do pepsin and bile cause ulcer disease?
- - pepsin and bile cause direct mucosal injury - pepsin is a protelytic enzyme that causes mucosal injury, especially if pH is less than 4
- Give an example of how certain drugs can cause ulcer disease
- - NSAIDs can cause ulcers by decreasing prostaglandin synthesis - prostaglandins have a protective function and help to neutralize acidity
- What are some drugs that can cause GI mucosal injury?
- - aspirin - bisphosphonates (fosamax) - chemo agents - ethanol - NSAIDs (naproxen, ibuprofen) - potassium supplementation
- Why is potassium supplementation often enteric coated or time-released?
- so that potassium with not be released in the stomach and cause GI upset
- What are some complications of GERD?
- - esophageal stricture - esophageal ulcer - erosive esophagitis - Barrett's esophagus - pulmonary aspiration (can cause aspiration pneumonia)
- How could a patient with GERD present?
- can present with: - heart burn - regurgitation - dysphagia - chest pain - hoarseness - asthma - dental erosions
- How do proton pump inhibitors work?
- - proton pump inhibitors work by inhibiting the release of H+ by the parietal cell - inhibit H+/K+ ATPase enzyme
- How do Histamine 2-receptor antagonists (H2 Blockers) work?
- - H2 receptor blockers prevent histamine from binding to the receptor site on the parietal cell and prevents activation of the parietal cell
- How do you diagnose GERD?
- - history and physical - barium studies - endoscopy
- What are some recommended lifestyle modifcations for patients with GERD?
- - change dietary habits - do not sleep directly after eating - elevate head of bed - stop smoking - lose weight
- What is the mechanism of action for antacids and alginic acid?
- - neutrilize stomach acid and deactivate pepsin - forms a viscous solution creating a more alkaline environment
- What are some adverse drug events (ADEs) associated with antacids?
- - diarrhea with magnesium antacids - constipation with aluminium - maalox and mylanta contain magnesium and aluminum - acid reboud
- What are some drug interactions that occur with antacids?
- - antacids can bind with other drugs and eliminate them through the feces - drugs like ferrous sulfate, digoxin, quinolones, isoniazid
- You should avoid give sodium bicarbonate to patients with this condition
- CHF, because sodium bicarbonate contains high levels of sodium
- Which antacids can cause constipation?
- aluminum hydroxide and calcium carbonate
- With what patients should you avoid giving magnesium hydroxide?
- - patients with chronic diarrhea or C. Dificil
- Name 4 histamine 2 receptor antagonist (H2 blockers)
- - cimetidine (tagamet) - famotidine (pepcid) - nizatidine (axid) - ranitidine (Zantac)
- Patients with mild or moderate GERD are usually given these drugs
- H2 blockers
- What are 2 major drug interactions with cimedtidine?
- - cimetidine can inhibit warfarin and phenytoin
- What are some causes of higher doses of cimetidine?
- - gynecomastia (enlargement of the breasts, especially in men) - mental confusion
- Patients with moderate to severe GERD symptoms are given these drugs
- proton pump inhibitors
- What are some adverse drug events (ADEs) with proton pump inhibitors?
- - GI disturbances - CNS disturbance - Gastric tumors - C. Dificil in patient on long-term PPI
- What are some genetic or environmental factors that can increase the chance of development of peptic ulcer disease?
- - first-degree relative having PUD - smoking - alcohol - diet
- What is a leading cause of recurrent ulcers?
- H. Pylori
- What are some characteristics of H. Pylori?
- - gram negative, spiral shaped, flagellated organism - penetrates and colonized gastric mucosa - acid sensitive - toxic to epithelial cells
- What is an example of a non-invasive test to screen for H. Pylori?
- - test for the presence of urease with a urea breath test
- What does urease do?
- - urease cleaves urea into bicarbonate and ammonium
- What are some common agents used in the treatment for H. Pylori?
- 1. amoxicillin - type of penicillin 2. bismuth subsalicylate (Pepto Bismol) 3. Clarithromycin (Biaxin) - in the class called macrolytes 4. H2 Blockers 5. Lansoprazole (Prevacid) - PPI 6. Metornidazole (Flagyl) - antimicrobial agents 7. Omeprazole (prilosec) - PPI 8. Tetracyclin - can cause yellowing of the teeth, diarrhea 9. Ranitidine Bismuth Subscitrate - Pepto Bismol with Ranitidine (H2 blocker)
- What is the best regiment for treating H. Pylori?
- a regiment with 2 antibiotics
- What is the 1st line treatment regiment of choice of treatment of H. Pylori?
- - PPI, amocillin 1 gm, clarithromycin 500 mg (all twice daily for 7-14 days) - can substitute metronidazole 500 mg BID for amoxicillin with penicillin allergic patients
- What is another option for 1st line treatment of H. Pylori?
- - Bismuth Subscitrate 525 mg, metronidazle 500 mg, tetracycline 500 mg (all QID) with a PPI (BID) for 7-14 days - generally reserved for retreatment
- What is the 1st line treatment for patient with macrolide allergy (allergic to clarithromycin)?
- PPI, amoxicillin 1 gm, metronidazole 500 mg (all BID) for 14 days
- What are 3 regiments that can be used as "rescue therapy"?
- 1. PPI, levofloxacin 250-500 mg, amoxicillin 1 gm (all BID for 14 days) 2. PPI, rifabutin 150 mg, amoxicillin 1 gm BID for 14 days - change rifabutin to rifampin with HIV patients 3. PPI twice daily plus amoxicillin 1 gm TID - not a good regiment since there is only one antibiotic
- Give some examples of NSAIDs
- - aspirin - naproxen - diclofenac - ibuprofen
- How do NSAIDs cause ulcers?
- NSAIDS inhibit prostaglandins which have a protective function in the GI
- What is the treatment for NSAID ulcers?
- - discontinue NSAIDs - check for presence of H. Pylori by endoscopy - use H2 blocker or PPI
- How long is the treatment regiment with a gastric NSAID ulcer?
- 4-8 weeks
- How long is the treatment regiment for a patient with a duodenal NSAID ulcer?
- 8-12 weeks
- What drug is used in combination with a NSAID to increase prostaglandin?
- Misoprostol (Misoprostol 200 mg and diclofenac 50 mg) in combination is called Arthrotec
- Why are patients in the ICU given stess ulcer prophylaxis?
- because 75% of ICU patients develop stress ulcers
- What are risk factors for stress ulcers?
- - coagulopathy (which can cause DIC) - head trauma - hepatic failure - mechanical ventrilation - major surgery - servere burns - organ failure
- What are some agents used for stress ulcer prophylaxis?
- - antacids (although they are not indicated in ICU setting) - H2 antagonist is the drug of choice
- What are two H2 blockers that can be given for stress ulcer prophylaxis?
- Ranitidine (Zantac) or Famotidine (Pepcid)
- What are the dosages for ranitidine (zantac) and famotidine (pepcid) for stress ulcer prophylaxis when given IV? when given PO?
- IV: Ranitidine 50 mg IV 8 hrs or Pepcid 20 mg IV Q 12 hrs PO: Ranitidine 150 mg PO BID or Pepcid 20 mg PO BID
- What are some characteristics of sucralfate (carafate)?
- - used for stress ulcer prophylaxis - coats the stomach lining to stop bleeding (acts like a bandaid) - only comes PO - can not be given with other drugs because it can bind with other drugs (needs to be given at least 2 hrs before given other medication)
- What is the dosing for sucralfate (carafate)?
- 1 gm PO QID
- Why can giving proton pump inhibitors in the ICU setting increase the risk for nosocomial infections?
- - PPI decrease the acidity in the stomach which creates a medium that bacteria can grow