1. Gastrointestinal Pharmacology
Roy Krishna, Ph.D. FCP.

2. Gastrointestinal Pharmacology
Emesis
Diarrhea
Inflammatory Bowel Disease
Irritable Bowel Syndrome
Gastroesophageal Reflux Disease (GERD)
Peptic Ulcer Disease (PUD)

3. Antiemetics
Emesis is caused by stimulation of chemoreceptor trigger zone (CTZ) and the vomiting center.
Affected by chemical stimuli and afferent input from vestibular system.
Activation of dopamine and serotonin receptors

4. Antiemetics Prevention and treatment of vomiting
Treatment of chemotherapy-induced vomiting
Phenothiazines. (Prochlorperazine)
5HT3 inhibitors (Ondansetron)
Metoclopramide
Butyrophenones (Droperidol)
H1-antihistamines (Meclizine, Loratidine)
Dronabinol

5. Laxatives Bulk-forming Stool softening Stimulants
Act on the stool that causes reflex contraction of the bowel (Psyllium)
Stool softening
Acts on hard or impacted stool (Docusate)
Stimulants
Increase peristalsis (Senna)

6. Antidiarrheal Agents Diarrhea is a result of:
Increased GI tract motility
Reduced fluid absorprtion
Infection.
Antidiarrheal objectives are to reduce peristalsis, act as adsorbents and modify fluid and electrolyte transport

8. Antidiarrheal Agents
Opioids and their derivatives are the most effective antidiarrheal agents
Should be selected for maximal antidiarrheal properties and minimal CNS effects
Diphenoxylate (Lomotil®)
Loperamide (Imodium®)

9. Gastroesophageal Reflux Disease
Retrograde movement of gastric contents from stomach into esophagus:
Heartburn
Gastroesophageal regurgitation
Esophageal inflammation
Erosive Esophagitis

11. Gastroesophageal Reflux Disease
Lifestyle Changes
Antacids
H2 – antagonists
Proton pump inhibitors (PPI’s)

13. Inflammatory Bowel Disease
Ulcerative Colitis and Crohn’s disease
Ongoing inflammation of the GI mucosa
Inflammation by an antigen driven response?

14. Inflammatory Bowel Disease Therapeutic Approach
Suppression of inflammation and alleviation of signs and symptoms:
Corticosteroids
Immunosuppressive antimetabolites,
Monoclonal antibodies
Aminosalicylates

15. Pharmacological Management of Peptic Ulcer Disease

16. Peptic Ulcer
Lesions in stomach or duodenum occurring as a result of excessive pepsin and acid activity.
Zollinger-Ellison Syndrome: Hypersecretion due to gastrin secreting tumor

18. Peptic Ulcer Disease
Balance between aggressive forces (gastric acid and pepsin) and defensive factors (lining) of the mucosa ensures maintenance of integrity of the GI mucosa.

19. Peptic Ulcer Pathogenesis
Causative factors- NSAID use, alcohol, smoking, stress
Acid hypersecretion ( Zollinger Ellison Syndrome)
Helicobacter pylori (H.pylori) infection

20. Peptic Ulcer Clinical Manifestations
Epigastric pain (“burning sensation”)
Dyspepsia
Perforation and bleeding.
Abdominal/nocturnal pain
Nausea, vomitting
Anorexia

21. Increased Attack Hyperacidity
Weak defense
Helicobacter pylori Stress, drugs, smoking
Normal

22. Peptic Ulcer Helicobacter Pylori

23. Peptic Ulcer Therapeutic Objectives
Elimination of H. pylori
Reduction of gastric acid secretion or acid neutralization
Protection of gastric mucosa from further damage

24. Peptic Ulcer Therapeutic Approach
Antacids
H2 –antagonists (Ranitidine, Famotidine)
Cytoprotective Agents (Bismuth Subsalicylate)
Proton Pump Inhibitors (Omeprazole, Esomaprazole)
Antimicrobial Agents (Amoxicillin, Clarithromycin)
Triple Therapy (proton pump inhibitor + 2 antimicrobial agents)

25. Peptic Ulcer Therapeutic Approach
Proton Pump Inhibitors (PPI):
Omeprazole (Prilosec)
Lansoprazole (Prevacid)
Esomeprazole (Nexium)
Pantoprazole (Protonix)
Rabeprazole (AcipHex)

26. Peptic Ulcer Disease Eradication of H.pylori
First-line therapy for patients colonized with H.pylori.
Rapid healing of peptic ulcers
Low recurrence rates
Combination therapy (“triple therapy”)-proton pump inhibitor (PPI) with metronidazole or amoxicillin plus clarithromycin – 7-14 days 
90% eradication rate.

27. Peptic Ulcer Disease H.pylori Eradication Regimens
PPI –based 3 –drug regimens:
First-line therapy
*Omeprazole 20mg b.i.d +
Clarithromycin 500mg b.i.d
Amoxicillin 1g b.i.d/Metronidazole 500mg b.i.d

28. Zollinger-Ellison (ZE) Syndrome
Gastric acid hypersecretion and concurrent peptic ulceration.
PPI’s are the drugs of choice
Omeprazole-60 mg/d effectively controls acid output and relieves symptoms
Gradual reduction in dose over time is recommended.