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GI Drugs PHC 5409B Dr. T.C. Peterson. Drugs for GI Tract disorders  DRUGS THAT REDUCE GASTRIC ACIDITY  CYTOPROTECTIVE DRUGS  DRUGS FOR HELICOBACTER.

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Presentation on theme: "GI Drugs PHC 5409B Dr. T.C. Peterson. Drugs for GI Tract disorders  DRUGS THAT REDUCE GASTRIC ACIDITY  CYTOPROTECTIVE DRUGS  DRUGS FOR HELICOBACTER."— Presentation transcript:

1 GI Drugs PHC 5409B Dr. T.C. Peterson

2 Drugs for GI Tract disorders  DRUGS THAT REDUCE GASTRIC ACIDITY  CYTOPROTECTIVE DRUGS  DRUGS FOR HELICOBACTER PYLORI INFECTION  DRUGS FOR INFLAMMATORY BOWEL DISEASES  PROKINETIC DRUGS  LAXATIVES  ANTIDIARRHEAL AGENTS  ANTIEMETICS

3 Peptic Ulcer disease  Characterized by inflamed lesions and ulcers  Causes:  Excessive acid production  Bile acid reflux  Advancing age  Ischemia  Inhibition of PG synthesis  Infection with Helicobacter pylori

4 Drugs that reduce gastric acidity  H2 receptor antagonists  Proton pump inhibitors  Muscarinic antagonists  Prostaglandins  Antacids  Sucralfate

5 Cytoprotective Drugs  Sucralfate  Misoprostol

6 Drugs for H.pylori infection  Multi-drug therapy is usually used  Common combination: Gastric acid secretion inhibitor (PPI or H2 blocker) (PPI or H2 blocker) and two of the following: and two of the following: Amoxicillin, Bismuth, Clarithromycin, Metronidazole, Tetracycline Amoxicillin, Bismuth, Clarithromycin, Metronidazole, Tetracycline

7 Inflammatory Bowel Disease Chronic Inflammatory disease:  Crohn's Disease (CD) - full thickness inflammation anywhere in gastrointestinal tract Crohn's Disease (CD) Crohn's Disease (CD)  Ulcerative Colitis (UC) - inflammation of superficial layers, continuous from rectum Ulcerative Colitis (UC) Ulcerative Colitis (UC)  Lymphocytic Colitis - collections of lymphocytes without granulomas  Collagenous Colitis - collagenous deposition in subepithelial zone, rectum and colon Diagnosis is clinical but requires tissue biopsy for confirmation and classification

8 IBD - Treatment IBD - Treatment  Acute Moderate to Severe Exacerbation - Usually in patients with known disease, now active –Glucocorticoids –Broad spectrum antibiotics (including metronidazole) –Intravenous cyclosporine may be used after 7-10 days if responses are poor  Chronic Therapy (Remission Maintenance)  Chronic Therapy (Remission Maintenance) –5-aminosalicylate (5-ASA) –Azathioprine, 6-mercaptopurine (6-MP) and methotrexate

9 IBD drugs  Sulfasalazine –First line therapy in most patients with acute or chronic IBD –Congener of sulfapyridine and 5-aminosalicylic acid linked by an azo bond –Attenuates inflammation in the large bowel only –Compound is cleaved to composite groups by colonic bacteria (azoreductase) –Requires 5-28 days for efficacy –Contradindicated in patients with sulfa allergy; 15% of patients will discontinue drug –Side effects: cytopenias, pancreatitis, hepatitis, rash, diarrhea, male infertility

10 IBD drugs  Olsalazine –Dimer of 5-ASA linked by azo bond which is split by colonic bacteria –Contraindicated in patients with salicylate allergy; no sulfa moiety –Main side effect is diarrhea (~25% of patients) –Main use is in patients who cannot tolerate sulfasalazine  Appears to be as effective as sulfasalazine for mild to moderate IBD

11 IBD drugs  Mesalamine –Delayed release 5-ASA (ie. coated with acrylic-based resin) dissolves at pH 6 –Mainly released in distal ileum and colon;

12 IBD drugs  Azathioprine –Side Effects: Pancreatitis (~5%), Bone marrow suppression (~2%), hepatitis –Mildly effective as single agent, does prevent flares of disease and maintain remissions –Usually permits reduction in glucocorticoid dose required for suppression of disease –Note: this drug is metabolized to 6-MP

13 IBD drugs  6-Mercaptopurine (6-MP) –Effective in prevention of relapses and possibly in active disease –Most patients require >17 weeks to see initial effect –6-MP and AZA are effective in 50-70% of patients with IBD –Side effects include bone marrow suppression and pancreatitis, hepatitis

14 IBD drugs  Methotrexate –20-25mg/week given i.m. in refractory Crohn's disease disease –Extremely well tolerated –Allowing lowering of steroid doses and control of disease –Recommended now in nearly all patients requiring higher dose prednisone

15 IBD drug  Cyclosporine –Good response initially to iv form, usually within 48 hours –Relapses common when drug is stopped –This agent shows most rapid onset of activity in steroid refractory disease –Reduces need for surgical resection in fulminant UC –Dose must be monitored closely

16 Novel Therapies for IBD  Specific Cytokine Blockers –IL-1 receptor antagonist (IL-1RA) –TNF  blockers  Other immunosuppressive agents may be effective –Cyclosporine –Rapamycin –FK506 and other immunosuppressives  Fish Oil (EPA) –May reduce production of inflammatory leukotrienes and thromboxanes –Suppresses IL-1 and TNF production –Reduced CD exacerbations at 1 year

17 IBD drugs  Tumor Necrosis Factor Alpha (TNF  ) Blockade –Activity predicted on the basis of certain animal models –Has good activity in Crohn's Disease, including fistula healing

18 Prokinetic Drugs  Drugs used to increase GI motility  Increase activity of smooth muscle in the esophagus, stomach and intestine  examples: –Cisapride: stimulates 5-HT receptors –Metoclopramide: blocks dopamine D2 receptors

19 Antidiarrheal Agents  Bismuth subsalicylate, diphenoxylate, kaolin-pectin, loperamide, and polycarbophil  Opioid Drugs

20 Antiemetic drugs  Dopamine D2 receptor antagonists  Serotonin 5HT3 receptor antagonists  Other antiemetics Dimenhydrinate and scopolamine Dimenhydrinate and scopolamine

21 Review of drugs for GI Disorders  DRUGS THAT REDUCE GASTRIC ACIDITY Histamine 2 receptor antagonists Cimetidine, famotidine, and ranitidine Cimetidine, famotidine, and ranitidine Proton pump inhibitors Lansoprazole and omeprazole Lansoprazole and omeprazole Muscarinic receptor antagonists Atropine and pirenzepine Atropine and pirenzepine Gastric antacids Aluminum and magnesium hydroxides and calcium carbonate

22 Review of drugs for GI Disorders Cytoprotective drugs Misoprostol and sucralfate Drugs for Helicobacter pylori infection Amoxicillin, bismuth, clarithromycin, metronidazole, and tetracycline Amoxicillin, bismuth, clarithromycin, metronidazole, and tetracycline  DRUGS FOR INFLAMMATORY BOWEL DISEASES.Azathioprine, infliximab, mercaptopurine, mesalamine, metronidazole, prednisolone, and sulfasalazine.Azathioprine, infliximab, mercaptopurine, mesalamine, metronidazole, prednisolone, and sulfasalazine

23 Review of drugs for GI Disorders  PROKINETIC DRUGS Cisapride and metoclopramide Cisapride and metoclopramide  ANTIDIARRHEAL AGENTS Bismuth subsalicylate, diphenoxylate, kaolin-pectin, loperamide, and opiates Bismuth subsalicylate, diphenoxylate, kaolin-pectin, loperamide, and opiates  ANTIEMETICS Serotonin 5-HT3 receptor antagonists Granisetron and ondansetron Granisetron and ondansetron Dopamine D2 receptor antagonists Dopamine D2 receptor antagonists Metoclopramide Metoclopramide


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