GI MTM: Pharmacology of GERD, PUD, IBS, and Pancreatitis

  1. H2 receptor antagonist examples
    • 1. Cimetidine
    • 2. Famotidine
    • 3. Nizantidine
    • 4. Ranitidine
  2. H2 receptor locations
    • 1. Blood vessels: lower BP
    • 2. Heart
    • 3. Skin: dilation and increased permeability of skin
    • 4. Parietal cells of the stomach: stimulation of gastric acid secretion
  3. Pharmacologic MOA of H2 receptor antagonists
    Potentially inhibit basal, food-stimulated, and nocturnal secretion of gastric acid after a single dose

    Binds to the histamine/gastrin receptor and is a reversible competitive antagonist
  4. Pharmacology and pharmacokinetics of H2 receptor antagonists
    • Admin: oral
    • Distribution: placenta and breast milk
    • Half life: cimetidine is the least all others are the same
    • Potency: cimetidine is least the ranitidine then famotidine
    • excretetion: urine
    • Metabolism: cimetidine inhibits CYP450
  5. Side effects of H2 Receptor antagonists
    Minor: headache, dizziness, diarrhea, muscle pain

    Cimetidine: can act as an antiandrogen (gynecomastia and reduced sperm count)

    Can increase the concentration of warfarin, diazepam, phenytoin, quinidine, theophylline, imiprimine due to CYP450
  6. Misoprostol Pharmacology
    Inhibits the secretion of gastic acid and stimulates the secretion of mucus and bicarb

    • Less effective the H2 antagonists and CONTRAINDICATED in pregnancy
    • USES: prevention of gastic ulcers induced by NSAIDS
  7. Examples of PPIs
    • 1. Omeprazole (R-S)
    • 2. Esomeprazole (R)
    • 3. Lansoprazole
    • 4. Rabeprazole
    • 5. Pantoprazole
  8. Pharmacology of PPIs
    • MOA: inhibits basal, food-stimulated, and nocturnal secretion of gastic acid w/in 1-2 hrs of first dose (stops secretion dose not neutralize whats there)
    • It is a prodrug that is converted to the active form by low pH once in binds to the H+/K+ ATPase proton pump it binds IRREVERSIBLY
  9. Pharmacokinetics of PPIs
    • Admin: oral ONE HOUR PRIOR to meals
    • Bioavailability: decreased by 50% with food
    • Half-life: takes 3-4 days to take effect but binds irreversilby and takes 18hrs to make a new pump once the drug is gone
    • Benefits: short serum half life, concentrated and active only at SOA, long duration of action
  10. PPIs side effects
    • 1. headache, diarrhea, constipation, abdominal pain
    • 2. Increased risk of bacterial infections (pneumonia, C. diff) stomach pH increases and makes it a more ideal environment
    • 3. Increased risk of fractures
    • 4. DD interactions: warfarin, clopidogrel, phenytoin, diazepam
  11. Antispasmotics (anticholinergics) examples
    • 1. Hyoscamine
    • 2. Dicyclomine
    • 3. Glyopyrrolate
    • 4. Methscopalamine
  12. Pharmacology of Antispasmotics/anticholinergics
    works as a non-specific antagonist of muscarinic receptors where it inhibits secretion of gastric acid, inhibits gastric motility, and relieve abdominal pain/discomfort
  13. Side effects of antispasmotics/anticholinergics
    • 1. Dry mouth
    • 2. visual disturbances
    • 3. urinary retention
    • 4. constipation
  14. Sucralfate Pharmacology
    • Forms gel complex with mucus to create a physical barrier that prevents HCl and pepsin from reaching gastic cells and it binds to ulcers for 6hrs
    • It also stimulates prostaglandin release and bicarb secretion
    • This prevents mucosal injury, inflammation, and helps heal ulcers
  15. Bismuth Compounds pharmacology
    Coats ulcers to create a physical barrier, stimulates prostaglandin release, simulates bicarb secretion, and reduces stool frequency
  16. 5-HT3 Serotonin Receptor Antagonists Examples
    • 1. Ondasetron
    • 2. Granisetron
    • 3. Dolesetron
    • 4. Palonosetron
    • 5. Proisetron
    • 6. Alosetron (HIGH POTENCY)
  17. Pharmacology of 5-HT3 SRA
    vagal signaling of nausea and produce colonic motility
  18. Pharmacology of Alosetron
    Reduction of GI contractility and motility, increased fluid absorption...used in WOMEN with severe IBS w/diarrhea
  19. 5-HT4 Serotonin Receptor Agonists Examples
    • 1. Cisapride
    • 2. Zacopride
    • 3. Renzapride
    • 4. Tegaserod
  20. Pharmacology of 5-HT4 Receptor Agonists
    On presynaptic receptors increase the release of Ach with facilitates cholinergic NT in the gut which increases colonic motor activity

    USES: stimulant laxatives
  21. Tegaserod Pharmacology
  22. Chloride Channel Activator Pharmacology
    • Lubiprostone:
    • Stimulates the type 2 Cl- channel in the small intestines which increases fluid secretion, stimulates intestinal motility

    Uses: chronic constipation, WOMEN with IBS w/constipation (CONTRA: women of childbearing age)
  23. 5-aminosalicylates examples
    • 1. Sulfasalzine
    • 2. Olsalazine
    • 3. Balsalazide
    • 4. Mesalamine
  24. Pharmacology of 5-Aminosalicylates
    MOA: questionable but may stimulate prostaglandin release and inhibit NFkB which would decrease the production of inflammatory cytokines

    Use: IBD, induce and maintain remission in UC
  25. Sulfazalazine Pharmacology (5-aminosalicylate)
    • Side effects: nausea, GI upset, headaches, arthralgias, bone marrow suppression
    • Impairs folate absorption
    • Slow acetylators have INCREASED side effects
  26. Purine Analog Examples
    • 1. Azathiprine
    • 2. 6-mercaptopurine
  27. Pharmacology of Purine Analogs
    Immunosuppressive properties

    Side effects: N&V, bone marrow suppression, hepatic toxicity

    Uses: IBD, induce and maintain remission in UC & CD
  28. Cyclosporine Pharmacology
    DMARD-Disease modifying antirheumatic drug

    • MOA: inhibits interleukin 1 and 2 and inhibits macrophage-Tcell interactions
    • Bioavailabitily: increased by grapefruit juice by 62%
    • Uses: Autoimmune disease, RA, lupus, and IBD
  29. Anti-Tumor Necrosis Factor Examples
    • 1. Infliximab
    • 2. Adalimumab
    • 3. Certolizumab
  30. Pharmacology of Anti-Tumor Necrosis Factor
    • MOA: TNF would normally causes inflammation and activation of NFkB however this drug neutralizes soluble and membrane bound TNF, induces apoptosis of cells bound to TNF, and inhibits cytokine release
    • Side effects: infection due to suppresion of immune system
    • USES: IBD (UC and CD), RA
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GI MTM: Pharmacology of GERD, PUD, IBS, and Pancreatitis
Pharmacology GI