L1 - GORD

Introduction to Gastrointestinal Pharmacology

• Topic Overview: GORD (Gastroesophageal Reflux Disease) and Diarrhea.

• Instructor: Greg Smith.

• Secondary Instructor: Amy (mid-trimester).

• Recommended Resource: Chapter 30 of Rang & Dale’s Tenth Edition.

Learning Outcomes

• Pathophysiology: Describe basic pathophysiology of GORD and diarrhea.

• Pharmacological Mechanisms: Explain drug mechanisms for treating GORD and diarrhea.

• Adverse Reactions: Predict common adverse drug reactions and interactions.

• Communication Skills: Effectively communicate pharmacological concepts related to GI conditions.

Gastric Acid Overview

• Secretion: The stomach produces 2-2.5 liters of gastric juice daily.

• Composition:

  • Hydrochloric acid (HCl) is the primary component.

  • Pepsinogen converts to pepsin for protein digestion upon activation by acid.

  • Intrinsic factors are essential for vitamin B12 absorption.

• Protective Mechanisms: Mucus and bicarbonate form a protective barrier against gastric acid.

• Role of Gastric Acid:

  • Denatures proteins, activates digestive enzymes, facilitates absorption (Fe, Ca, B12).

  • Regulates food movement through the digestive tract.

  • Acts as a defense mechanism against pathogens.

Regulation of Gastric Acid Secretion

• Key Receptors:

  • H2 Receptors: Activated by histamine from ECL cells. Triggers acid secretion via ATPase proton pump.

  • Gastrin Receptors: Activated by gastrin from G cells upon food intake.

  • M3 Muscarinic Receptors: Stimulated by acetylcholine from the vagus nerve, increases calcium levels to stimulate acid secretion.

• Protective Mechanisms: Mucus and bicarbonate secretion protect gastric lining integrity.

GORD (Gastroesophageal Reflux Disease)

• Definition: A condition where stomach acid/bile refluxes into the esophagus.

• Prevalence: About 22-23% in Western countries; globally rising.

• Symptoms: Heartburn, chest discomfort, difficulty swallowing.

• Primary Cause: Dysfunction of the Lower Esophageal Sphincter (LES).

• Contributing Factors: Increased gastric acid production, delayed gastric emptying, and increased intra-abdominal pressure.

• Risks: Chronic exposure can lead to complications like esophageal ulcers and cancer.

• Risk Factors:

  • Obesity, dietary triggers (saturated fats, caffeine), smoking, certain medications (like calcium channel blockers).

Pathophysiology of GORD

• LES Dysfunction: Weakened or relaxed LES allows acid to escape into the esophagus.

• Complications: Chronic symptoms can cause ulcers and increase cancer risk.

• Management: Lifestyle changes, medications, and possibly surgery.

Pharmacological Treatment of GORD

• Drug Classes:

  • H2 Receptor Antagonists: E.g., ranitidine. Competitive inhibition at H2 receptors decreases acid secretion.

  • Proton Pump Inhibitors (PPIs): E.g., omeprazole, lansoprazole. Irreversibly bind to the proton pump, blocking all acid secretion.

  • Antacids: Neutralize existing gastric acid for symptom relief.

H2 Receptor Antagonists

• Mechanism of Action: Competitively inhibit H2 receptors, leading to decreased cyclic AMP levels and reduced acid secretion.

• Indications: Mild to moderate acid-related disorders (GORD, peptic ulcers).

• Side Effects: Rare; may inhibit CYP450 metabolism affecting drug interactions.

Proton Pump Inhibitors

• Mechanism of Action: Irreversibly inhibit the ATPase proton pump; binding is permanent until new pumps are synthesized.

• Indications: Severe reflux cases and peptic ulcers.

• Side Effects: Headaches, rash, risk of Clostridium difficile infection in high-risk patients.

Antacid Overview

• Types: Non-systemic (not absorbed) and systemic (absorbed into circulation).

• Mechanism: Neutralizes gastric acid, increases pH, protects mucosa.

Diarrhea Overview

• Definition: Passage of loose/watery stools more than three times a day.

• Causes: Infections, medications (antibiotics, laxatives), malabsorption (IBS).

• Treatment: Antidiarrheal agents, hydration therapy, address underlying causes.

Antidiarrheal Agents

• Loperamide: Opioid receptor agonist; reduces intestinal motility, allowed water/electrolyte absorption.

  • Side Effects: Constipation, nausea, risk of bowel obstruction.

• Cholestyramine: Binds bile acids; used for bile acid-induced diarrhea.

  • Side Effects: Constipation, flatulence, can affect absorption of fat-soluble vitamins.

• Hyoscine Butylbromide: Antimuscarinic agent; reduces spasms and discomfort.

  • Side Effects: Dry mouth, blurred vision.

• Rifaximin: Non-absorbable antibiotic; treats traveler’s diarrhea and IBS-D.

  • Side Effects: Risk of pseudomembranous colitis.

Summary of GORD and Diarrhea

• GORD: Chronic acid reflux; symptoms managed through lifestyle and medication.

• Diarrhea: Different causes treated symptomatically; need to address underlying issues.

• Clinical Role: Pharmacists must recommend treatments, educate patients, and manage drug interactions.

• Study Tips: Create tables for medications, mechanisms, indications, and side effects. Use active recall for reinforcement.