GI Pharmacology and Disorders

Gastro-Intestinal (GI) Pharmacology

• GI Pharmacology encompasses the actions of drugs affecting GI system function.
• These drugs normalize impaired function in the GI tract.
• The GI tract is the passageway of the digestive system, leading from the mouth to the anus (oral cavity, pharynx, esophagus, stomach, small intestine, large intestine, and anal canal).

GI Picture

• Diagram showing the major components of the GI tract: mouth, esophagus, stomach, duodenum, jejunum, ileum, colon/large intestine, rectum, anus, liver, gallbladder, pancreas, ileocecal valve.

Gastroesophageal Reflux Disease (GERD)

• GERD is characterized by the reflux of gastric contents into the esophagus.
• Reflux: The flow back or return; abnormal reflux of gastric contents into the esophagus can cause symptoms or mucosal damage.
• Typical symptom is frequent and persistent heartburn.

Normal Physiology Functions (Esophagus and LES)

• Esophagus: Transports food from the mouth to the stomach via peristaltic contractions.
• Lower Esophageal Sphincter (LES): Relaxes during swallowing to allow food to enter the stomach and then contracts to prevent reflux.

Pathogenesis of GERD

• 3 lines of defense must be impaired for GERD to develop.
• LES barrier impairment
• Relaxation of LES, low resting LES pressure.
• Increased gastric pressure
• Decreased clearance of refluxed materials from the esophagus.
• Decreased esophageal mucosal resistance.

Contributing Factors

• Decreased LES pressure: Chocolate, alcohol, fatty meals, coffee, cola, tea, garlic, onions, smoking.
• Direct irritation of the gastric mucosa: Tomato-based products, coffee, spicy foods, citrus juices, NSAIDs, aspirin, iron, potassium chloride, alendronate.
• Stimulate acid secretions: Soda, beer, smoking.

Lines of Defense

• Clearance of refluxed materials from the esophagus.
• Primary peristalsis from swallowing – increases salivary flow.
• Secondary peristalsis from esophageal distension.
• Gravitational effects.
• Esophageal mucosal resistance: Mucus production in the esophagus and bicarbonate movement from blood to mucosa.

Factors Determining Extent of Esophageal Damage

• Amount of esophageal damage is dependent on:
• Composition of refluxed material (acid or alkaline).
• Volume of refluxed material.
• Length of contact time of reflux material.
• Natural sensitivity of esophageal mucosa
• Rate of gastric emptying.

Typical Symptoms

• Common symptoms experienced when pH < 4: Heartburn, belching, regurgitation, hypersalivation.
• Symptoms may be aggravated by meals and reclining position.

Atypical Symptoms

• Chronic cough, hoarseness, and chest pain (mimics angina)
• Possible only symptoms – “omeprazole test.”

Complications

• Esophagitis, esophageal strictures and ulcers, hemorrhage, perforation, aspiration, precipitation of an asthma attack.

Warning Signs

• Requires endoscopy if present: Dysphagia, odynophagia, bleeding, unexplained weight loss, choking, and chest pain.

Diagnosis

• Clinical symptoms and history; Presenting symptoms and associated risk factors, Give empiric therapy and look for improvement.
• Endoscopy if warning signs are present.

When to Refer for Further Care

• Chest pain, heartburn while taking PPIs, or heartburn that continues after 2 weeks of treatment.
• Nocturnal heartburn symptoms, frequent heartburn for >3 months, GI bleeding and other warning signs, concurrent use of NSAIDs.
• Pregnant or nursing patients, children <12 years old.

Therapy Goals

• Alleviate or eliminate symptoms.
• Diminish frequency and duration of esophageal reflux.
• Promote healing if the mucosa is injured.
• Prevent complications.

Therapy

• Directed at: Increasing LES pressure, enhancing esophageal acid clearance, improving gastric emptying, protecting esophageal mucosa, decreasing acidity of reflux, decreasing gastric volume available to be refluxed.

Treatment

• Three phases:
• Phase I: Lifestyle changes (2 weeks), lifestyle modifications, patient-directed therapy with OTC medications.
• Phase II: Pharmacologic intervention (standard/high-dose antisecretory therapy).
• Phase III: Surgical intervention.
• Severe GERD complications, patients who fail pharmacologic treatment.
• LES positioned within the abdomen where it's under positive pressure.

Treatment Selection

• Mild intermittent heartburn (Phase I): Lifestyle changes plus antacids.
• Symptomatic relief of mild to moderate GERD (Phase II): Lifestyle changes plus standard doses of proton pump inhibitors (PPIs) for 4-8 weeks.
• Healing of erosive esophagitis or treatment of moderate to severe GERD (Phase II): Lifestyle modifications plus PPIs for 8-16 weeks.
  • PPIs are the preferred initial choice due to more rapid symptom relief and higher rate of healing.
• May also add a prokinetic agent in selected patients.

Examples of Prokinetic Agents

• Metoclopramide, Domperidone.

Lifestyle Modifications

• Elevate the head of the bed 6-8 inches, decrease fat intake, smoking cessation, avoid recumbency for at least 3 hours post-prandial, weight loss, limit alcohol intake, wear loose-fitting clothing, avoid aggravating foods.

Drug Therapy - Antacids

• Antacids with or without alginic acid: Increase LES pressure and do not promote esophageal healing.
• Neutralize gastric acid, causing alkalinization.
• Alginic acid forms a highly viscous solution that floats on top of gastric contents.
• Dose as needed; typical action is 1-3 hours.
• Products: Magnesium salts, aluminum salts, calcium carbonate, sodium bicarbonate.
• Examples: Maalox/Mylanta, Maalox TC/Mylanta II, Gaviscon, Tums, Nugel tabs or suspension.

Drug Therapy - PPIs

• Proton Pump Inhibitors (PPIs) treat moderate to severe GERD.
• All agents are effective.
• Omeprazole released OTC.
• Use for heartburn that occurs ≥2 days/week.
• Standard dosing: Esomeprazole 20-40 mg daily (approved for adolescents 12-17 years), Lansoprazole 15-30 mg daily, Omeprazole 20-40 mg daily, Pantoprazole 40 mg daily, and Rabeprazole 20 mg daily.
• Timing: Best taken 30-60 minutes prior to meals.
• May give higher doses BID for patients with a partial response.
• Patients with breakthrough symptoms; patients with severe esophageal dysmotility.
• Always give a second dose 30-60 min prior to evening meal.

Drug Therapy - Prokinetics

• Prokinetic agents enhance motility of smooth muscle, accelerating gastric emptying.

• Results of therapy: Improved gastric emptying, enhanced tone of the lower esophageal sphincter, stimulated esophageal peristalsis.

• Prokinetic Agents - Products: Metoclopramide (only use if motility dysfunction is documented, administer at least 30 minutes prior to meals, dose 10-15 mg before meals and at bedtime).

Special Populations

• Pregnancy: Common due to decreased LES pressure and increased abdominal pressure.
• Nearly half of all pregnant women experience GERD.
• Antacids generally considered safe, but avoid chronic high doses.

Counseling Questions

• Before recommending a therapy, ask about the duration and frequency of symptoms, quality and timing of symptoms, use of alcohol and tobacco, dietary choices, medications already tried to treat symptoms, and other disease states present and medications being used.

Case Study

• AA, a 45-year-old male postal worker, complains of heartburn 3-4 times per month, typically after meals.
  • Has tried Tums with some success and wants something more effective.
• Questions to ask: What questions should you ask AA first? What would cause you to refer AA to a physician? What type of GERD does AA have? What treatment should you recommend?