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

• 1. Cimetidine
• 2. Famotidine
• 3. Nizantidine
• 4. Ranitidine

• 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

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

• 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

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

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

• 1. Omeprazole (R-S)
• 2. Esomeprazole (R)
• 3. Lansoprazole
• 4. Rabeprazole
• 5. Pantoprazole

• 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

• 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

• 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

• 1. Hyoscamine
• 2. Dicyclomine
• 3. Glyopyrrolate
• 4. Methscopalamine

works as a non-specific antagonist of muscarinic receptors where it inhibits secretion of gastric acid, inhibits gastric motility, and relieve abdominal pain/discomfort

• 1. Dry mouth
• 2. visual disturbances
• 3. urinary retention
• 4. constipation

• 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

Coats ulcers to create a physical barrier, stimulates prostaglandin release, simulates bicarb secretion, and reduces stool frequency

• 1. Ondasetron
• 2. Granisetron
• 3. Dolesetron
• 4. Palonosetron
• 5. Proisetron
• 6. Alosetron (HIGH POTENCY)

vagal signaling of nausea and produce colonic motility

Reduction of GI contractility and motility, increased fluid absorption...used in WOMEN with severe IBS w/diarrhea

• 1. Cisapride
• 2. Zacopride
• 3. Renzapride
• 4. Tegaserod

On presynaptic receptors increase the release of Ach with facilitates cholinergic NT in the gut which increases colonic motor activity

USES: stimulant laxatives

USED IN SEVERE IBS W/CONSTIPATION IN WOMEN BUT REMOVED FROM THE MARKET DUE TO CARDIOVASCULAR DEATHS

• 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)

• 1. Sulfasalzine
• 2. Olsalazine
• 3. Balsalazide
• 4. Mesalamine

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

• Side effects: nausea, GI upset, headaches, arthralgias, bone marrow suppression
• Impairs folate absorption
• Slow acetylators have INCREASED side effects

• 1. Azathiprine
• 2. 6-mercaptopurine

Immunosuppressive properties

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

Uses: IBD, induce and maintain remission in UC & CD

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

• 1. Infliximab
• 2. Adalimumab
• 3. Certolizumab

• 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