Gastrointestinal Pharmacology Roy Krishna, Ph.D. FCP.
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Transcript of Gastrointestinal Pharmacology Roy Krishna, Ph.D. FCP.
Gastrointestinal Pharmacology
Roy Krishna, Ph.D. FCP.
Gastrointestinal Pharmacology
• Emesis• Diarrhea• Inflammatory Bowel Disease• Irritable Bowel Syndrome• Gastroesophageal Reflux Disease (GERD)• Peptic Ulcer Disease (PUD)
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
Antiemetics
Prevention and treatment of vomiting
Treatment of chemotherapy-induced vomiting– Phenothiazines. (Prochlorperazine)
– 5HT3 inhibitors (Ondansetron)
– Metoclopramide– Butyrophenones (Droperidol)
– H1-antihistamines (Meclizine, Loratidine)
– Dronabinol
Laxatives
Bulk-forming • 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)
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
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®)
Gastroesophageal Reflux Disease
Retrograde movement of gastric contents from stomach into esophagus:
• Heartburn• Gastroesophageal regurgitation• Esophageal inflammation• Erosive Esophagitis
Gastroesophageal Reflux Disease
• Lifestyle Changes• Antacids
• H2 – antagonists
• Proton pump inhibitors (PPI’s)
Inflammatory Bowel Disease
– Ulcerative Colitis and Crohn’s disease– Ongoing inflammation of the GI
mucosa– Inflammation by an antigen driven
response?
Inflammatory Bowel DiseaseTherapeutic Approach
• Suppression of inflammation and alleviation of signs and symptoms:
Corticosteroids
Immunosuppressive antimetabolites,
Monoclonal antibodies
Aminosalicylates
Pharmacological Management of Peptic Ulcer
Disease
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
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.
Peptic UlcerPathogenesis
1) Causative factors- NSAID use, alcohol, smoking, stress
2) Acid hypersecretion ( Zollinger Ellison Syndrome)
3) Helicobacter pylori (H.pylori) infection
Peptic UlcerClinical Manifestations
– Epigastric pain (“burning sensation”)– Dyspepsia– Perforation and bleeding.– Abdominal/nocturnal pain– Nausea, vomitting– Anorexia
Increased AttackIncreased Attack HyperacidityHyperacidity
Weak defenseWeak defense Helicobacter pyloriHelicobacter pylori Stress, drugs, smoking Stress, drugs, smoking
NormalNormal
Peptic UlcerHelicobacter Pylori
Peptic UlcerTherapeutic Objectives
1) Elimination of H. pylori
2) Reduction of gastric acid secretion or acid neutralization
3) Protection of gastric mucosa from further damage
Peptic UlcerTherapeutic 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)
Peptic UlcerTherapeutic Approach
Proton Pump Inhibitors (PPI): Omeprazole (Prilosec) Lansoprazole (Prevacid) Esomeprazole (Nexium) Pantoprazole (Protonix) Rabeprazole (AcipHex)
Peptic Ulcer DiseaseEradication 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.
Peptic Ulcer DiseaseH.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
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.