GI Drugs

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GI Drugs

• PHC 5409B
• Dr. T.C. Peterson

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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

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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

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Drugs that reduce gastric acidity

• H2 receptor antagonists
• Proton pump inhibitors
• Muscarinic antagonists
• Prostaglandins
• Antacids
• Sucralfate

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Cytoprotective Drugs

• Sucralfate
• Misoprostol

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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

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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

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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

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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

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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

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IBD drugs

• Mesalamine
• Delayed release 5-ASA (ie. coated with
  acrylic-based resin) dissolves at pH 6
• Mainly released in distal ileum and colon

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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

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IBD drugs

• 6-Mercaptopurine (6-MP)
• Effective in prevention of relapses and possibly
  in active disease
• Most patients require gt17 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

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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

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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

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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

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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

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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

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Antidiarrheal Agents

• Bismuth subsalicylate, diphenoxylate,
  kaolin-pectin, loperamide, and polycarbophil
• Opioid Drugs

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Antiemetic drugs

• Dopamine D2 receptor antagonists
• Serotonin 5HT3 receptor antagonists
• Other antiemetics
• Dimenhydrinate and scopolamine

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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

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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

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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