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)
and two of the following:
Amoxicillin, Bismuth, Clarithromycin, Metronidazole, Tetracycline

7. Inflammatory Bowel Disease
Chronic Inflammatory disease:
Crohn's Disease (CD)  - full thickness inflammation anywhere in gastrointestinal tract
Ulcerative Colitis (UC) - inflammation of superficial layers, continuous from rectum
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  
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)      
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)
TNFa 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 (TNFa) 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

21. Review of drugs for GI Disorders
DRUGS THAT REDUCE GASTRIC ACIDITY
Histamine 2 receptor antagonists
• Cimetidine, famotidine, and ranitidine
Proton pump inhibitors
Lansoprazole and omeprazole
Muscarinic receptor antagonists
• 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
DRUGS FOR INFLAMMATORY BOWEL DISEASES
• .Azathioprine, infliximab, mercaptopurine, mesalamine, metronidazole, prednisolone, and sulfasalazine

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