GI Drugs

  1. Acid-Peptic Diseases (3)
    • GERD
    • Peptic Ulcers (Gastric & Duodenal)
    • Stress-related Mucosal Injury
  2. Acid-Peptic Diseases:
    Most common bacteria cause?
    Most common drug cause?
    • Cause:  Mucosal erosions or ulceration by Acid, Pepsin, or Bile
    • Most Common Bacteria:  H. Pylori
    • Most Common Drug:  NSAIDs
  3. Two mechanisms by which H. pylori predisposes to peptic ulcer disease.
    1.  Inflammatory mediators produced by H. pylori inhibit somatostatin secretion (D cells) in the stomach antrum --> Disinhibition of gastrin secretion (G cells) --> Gastrin secretion --> Parietal cell proliferation --> increases the functional capacity of the gastric mucosa to secrete H+ ions

    2.  Ammonium hydroxide (produced by H. pylori) lowers gastric pH --> gastrin secretion
  4. GERD
    Stomach acid/ bile refluxes back into esophagus --> constant irritationof the lining f the esophagus --> inflammation
  5. GERD Complcations (3)
    • Narrowing of the esophagus
    • Ulcers
    • Higher risk of esophogeal cancer
  6. Peptic Ulcer:
    1)  What is it?
    2)  An imbalance occurs between protecting factors and damaging factors in the GI mucosa.
    3)  Can result in (3):
    • Break in the lining of the stomach or duodenum.
    • 3) Pain and bleeding, Obstruction, perforation
  7. Acid-Peptic Disease Treatment
    • Antacids
    • H2-receptor antagonists
    • Proton pump inhibitors
  8. Antacids (Description)
    • Neutralize gastric HCl, used for intermittent heartburn, dyspepsia
    • Promote mucosal defense mechanisms
    • Have been in use for a long time
    • Act quickly but for a short duration
  9. Antacids (Drugs)
    • Magnesium aluminum hydroxide
    • Calcium carbonate/ Sodium bicarbonate
  10. Magnesium Aluminum Hydroxide
    Type of drug?
    How effective is it compared to other drugs?
    Most common adverse effect?
    • Antacid
    • Most effective antacid
    • Diarrhea is the most common adverse side effect
  11. Calcium carbonate:
    Type of drug?  Also used for?
    Common Adverse Effects:
    • Antacid, also used for hypocalcemia (ex. Tums)
    • Consitpation, flatulence, acid rebound can occur.
  12. H2 Receptor Antagonists:
    1) Action?
    2) Clearance?
    3) 1/2 life/ acid reduction profile compared to antacids?
    4)  Is inhibition of acid secretion dose dependent?
    5)  Inhibits  ____ acid secretion better than _____ acid secretion.
    • 1) Competitive inhibition at H2 receptors.
    • 2) Clearance lowered in hepatic/ renal insufficiency and elderly (requires dosage adjustment).
    • 3) Longer 1/2 life than antacids, better at reducing acid profile
    • 4)  Linear dose dependent inhibition of acid secretion
    • Commonly used into role of H. pylori discovered
    • 5)  Inhibits nocturnal acid secretion better than meal stimulated acid secretion

    • Proton pump inhibitors are more useful (better bang for buck)
    • Prescription doses maintain > 50% decrease for 10 horus; less than 6 hrs for OTC
  13. H2 Antagonists used to treat:
    • 1) GERD:  High doses promote healing
    • 2) Peptic Ulcer Disease (not recommended when H. pylori involved; NSAID-induced ulcers can be healed if NSAID discontinued)
    • 3) Non-Ulcer Dyspepsia
    • 4) Bleeding Prevention in Stress-Related Gastritis
  14. Name the 4 H2 Antagonists
    • Cimetidine
    • Ranitidine
    • Nizatidine
    • Famotidine
  15. Which H2 Receptor Antagonist is most potent?
  16. H2 Antagonist adverse effects?
    • Mental status change (elderly ICU patients)
    • Cimetidine has endocrine effects (rare) -->  Gynecomastia or impotence in men; Galactorrhea in women
  17. Which H2 Receptor Antagonist inhibits hepatic biotransformation by cytochrome P450's?
    Cimetidine (don't use when patient is on several other drugs)
  18. Which type of GI drugs are pro-drugs?
    What are their active species?
    Proton Pump Inhibitors

    Active species (thiophilic sulfonamide cation) forms a disulfide linkage to actively secrete (H+/K+ ATPase)
  19. Proton Pump Inhibitors
    1)  Acid or base?
    2)  Where are they absorbed?
    • 1)  Lipophilic weak bases
    • 2)  Absorbed in intestine
    • Takes several days to reach maximal acid secretion inhibition
    • Prodrugs (concentrated an protonated in acidic compartments)
    • Form a covalent bond with a cysteine in the proton pump
    • Very effective
  20. Which GI drugs should you eat with an empty stomach?  Why?
    PPIs because their bioavailability is decreased by food.
  21. Name the 5 Proton Pump Inhibitors
    • Lansoprazole (Prevacid)
    • Pantoprazole (Protonix)
    • Rabeproazole (Aciphex)
    • Omeprazole (Prilosec)
    • Esomeprazole (Nexium; S-isomer of Omeprazole)
  22. PPIs used to treat
    • GERD (very effective)
    • Peptic Ulcer Disease
    • Non-Ulcer Dyspepsia (no proven superior to H2 antagonists)
    • Bleeding Prevention in Stress-Related Mucosal Bleeding (Omeprazole- immediate release)
    • Gastrinoma and other hypersecretory conditions (provides superior acid supression)
  23. PPIs: Adverse Effects
    • Very safe
    • Nutrition (B12 is lowered)
    • Resperitaory and Enteric infections
    • Drug interactions (drugs w/ gastric acidity-dependent bioavailabilities; hepatic CP450 biotransformation)
    • Omeprazole may inhibit Plavix formation
  24. Which 2 PPIs have the highest bioavailability?
    • Esomeprazole
    • Lansoprazole
  25. What is the pKa of most PPIs?  What is the exception?

    Rabeprazole's pKa = 5
  26. Name the Mucosal Protective Agents (3)
    • Bismuth Subsalicylate
    • Misoprostol (PGE1 analog)
    • Sucralfate (reacts with gastric HCl to form a "paste", binds duodenal ulcer and forms a protective barrier)
  27. Which drug causes GI motility increase?
    Which receptor is it an antagonist for?
    Which one does not cross the BBB?
    • Metoclopramide/Domperidone
    • D2
    • This blocks inhibition of cholinergic smooth muscle stimulation
    • Enhances gastric emptying
    • Anti-nausea, anti-emetic effects
    • Domperidone
  28. Anti-Diarrheal Agents (6)
    • Loperamide
    • Diphenoxylate
    • Kaolin and Pectin
    • Bile Salt binding resins (cholestyramine, colestipol, colesevelam)
    • Octreotide
    • Alosetron

    • For tx of mild/moderate acute diarrhea
    • Should be stopped if condition worsens
    • Can be used to control chronic diarrhea
  29. Loperamide (Imodium) and Diphenoxylate (Lomotil) are known as what?
    Loperamide increases?
    Which one can lead to dependence due to its ability to cross the CNS?
    • Opiod Agonists
    • Loperamide increases 1) colonic transit time 2)fecal water absorption
    • Diphenoxylate has CNS effects and can lead to dependence
  30. Octreotide:
    1)  Actions similar to ___
    2)  Inhibits effects of what?
    3)  Used in?
    • Anti-Diarrheal
    • 1) Actions similar to somatostatin
    • 2)  Inhibits endocrine tumor effects
    • 3)  Used in short-bowel syndrome and AIDS
  31. Irritable Bowel Syndrome (IBS) Drugs
    • Alosetron (diarrheal-predominant IBS)- 5-HT3 antagonist
    • Tegaserod (constipation-predominant IBS)- 5-HT4 agonist
    •          Cardiovascular effects caused it to be pulled of the marker
    • Antispasmodics (Anticholinergics): Dicyclomine, hyoscyamine
  32. Most common anti-emetic (anti-vomiting) drug combination?
    Dexamethasone & ondansetron
  33. Name the anti-emetics (5)
    • Odansetron, Ganisetron
    • Metoglopramide
    • Aprepitant
    • Corticosteroids (dexamethasone, methylprednisone)
    • Cannabinoids (Cronabinol and Nabilone)
  34. Irritable Bowel Disease
    • Spectrum of chronic idiopathic inflammatory intestinal conditions
    • 1) Ulcerative colitis
    • 2) Chron's Disease

    Associated w/ a spectrum of extraintestinal conditions (ie. arthritis)
  35. Ulcerative Colitis
    Confluent mucosal inflammation of the colon starting at the anal verge and extending proximally for a variable extent
  36. Chron's Disease
    Transmural inflammation of any part of hte GI tract, but most commonly the area adjacent to the ileocecal valve
  37. Aminosalicylates (4)
    • Sulfasalazine
    • Olsalazine
    • Balsalazide
    • Mesalamine
  38. Delivery is important for this drug because it works topically.
  39. Inflammatory Bowel Disease:
    Treat with?
    • 1) Glucocorticoid therapy (prednisone or prednisolone)
    • 2)  Zathiprine and 6-Mercaptopurine (induce and maintain remission)
    • 3)  Methotrexate (interferes w/ inflammatory action of IL-1)
    • 4) Anti-tumor necrosis factor (infliximab)
  40. Methrotrexate interferes with _____ and is used to treat ____
    Methotrexates interferes with inflammatory action of IL-1 and is used to treat Inflammatory Bowel Disease
Card Set
GI Drugs
Pharmacology Test 2