GI Pharmacology and GERD Overview

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 from the mouth to the anus (oral cavity, pharynx, esophagus, stomach, small intestine, large intestine, and anal canal).

GI Picture

• Diagrams depicting the following components of the digestive system:
  • Mouth
  • Esophagus
  • Stomach
  • Small intestine (Duodenum, Jejunum, Ileum)
  • Large intestine
  • Colon
  • Rectum
  • Anus
  • Liver
  • Gallbladder
  • Pancreas
  • Ileocecal valve

Gastroesophageal Reflux Disease (GERD)

• GERD is defined as the abnormal reflux of gastric contents into the esophagus.

Overview of GERD

• Symptoms of GERD can include:
  • Reflux
  • Heartburn (frequent and persistent)

Normal Physiology Functions

• Esophagus: Transports food from the mouth to the stomach.
• Lower Esophageal Sphincter (LES): Relaxes when swallowing to allow food to enter the stomach. LES contracts to prevent reflux.

Pathogenesis

• 3 Lines of defense need to 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 esophagus
  • Decreased esophageal mucosal resistance

Contributing Factors

• Contributing factors to GERD include:
  • Decrease LES Pressure: Chocolate, alcohol, fatty meals, coffee, cola, tea, garlic, onions, and smoking.
  • Directly irritate gastric mucosa: Tomato-based products, coffee, spicy foods, citrus juices, NSAIDs, aspirin, iron, potassium chloride, and alendronate.
  • Stimulate acid secretions: Soda, beer, and smoking.

Lines of Defense

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

Factors Determining Extent of Esophageal Damage

• The severity of esophageal damage depends on several factors:
  • Amount of esophageal damage
  • 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

• Typical symptoms of GERD present when pH < 4
  • Heartburn
  • Belching
  • Regurgitation
  • Hypersalivation
• Symptoms can be aggravated by meals and reclining position.

Atypical Symptoms

• Atypical symptoms can include:
  • Chronic cough
  • Hoarseness
  • Chest pain (mimics angina)
  • May be only symptoms – “omeprazole test"

Complications

• Possible complications of GERD include:
  • Esophagitis
  • Esophageal strictures and ulcers
  • Hemorrhage
  • Perforation
  • Aspiration
  • Precipitation of an asthma attack

Warning Signs

• If present, consider an endoscopy for the following:
  • Dysphagia
  • Odynophagia
  • Bleeding
  • Unexplained weight loss
  • Choking
  • Chest pain

Diagnosis

• The diagnosis of GERD involves:
  • Clinical symptoms and history
  • Presenting symptoms and associated risk factors
  • Give empiric therapy and look for improvement
  • Endoscopy if warning signs present

When to Refer for Further Care

• Refer for further care in the following conditions:
  • Chest pain
  • Heartburn while taking PPIs or continuous heartburn after 2 weeks of treatment.
  • Nocturnal heartburn
  • Frequent heartburn (>3 months)
  • GI bleeding
  • Concurrent use of NSAIDs
  • Pregnancy or nursing
  • Children <12

Therapy Goals

• Therapy for GERD aims to:
  • Alleviate or eliminate symptoms
  • Diminish the frequency and duration of esophageal reflux
  • Promote healing (if mucosa is injured)
  • Prevent complications

Therapy

• Therapy is 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

• Treatment for GERD consists of three phases:
  • Phase I: Lifestyle changes (2 weeks) and potentially OTC medications.
  • Phase II: Pharmacologic intervention (standard/high-dose antisecretory therapy).
  • Phase III: Surgical intervention for patients who don't respond to Phase I and II therapies or have severe complications.
  • LES positioned within the abdomen with positive pressure may also be an issue.

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 moderate to severe GERD (Phase II): Lifestyle modifications plus PPIs for 8-16 weeks. PPIs are often preferred due to rapid symptom relief and higher healing rate. A prokinetic agent may also be added in selected cases

Examples of Prokinetic Agents

• Metoclopramide
• Domperidone

Lifestyle Modifications

• Lifestyle modifications for GERD management include:
  • Elevating the head of the bed (6-8 inches)
  • Decreasing fat intake
  • Smoking cessation
  • Avoiding recumbency after meals (at least 3 hours post-prandial)
  • Weight loss
  • Limiting alcohol intake
  • Wearing loose-fitting clothing
  • Avoiding aggravating foods

Drug Therapy - Antacids

• Antacids: Antacids increase LES pressure, do not promote esophageal healing, neutralize gastric acid, and cause alkalinization. Alginic acid forms a 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, and sodium bicarbonate
    • Examples listed: Maalox/Mylanta, Maalox TC/Mylanta II, Gaviscon, Tums, Nugel.

Drug Therapy - PPIs

• Proton Pump Inhibitors (PPIs): Used for moderate to severe GERD. All agents effective, choose based on cost.
• Timing: Best taken 30-60 minutes prior to meals
  • Products:
    • Esomeprazole
    • Lansoprazole
    • Omeprazole
    • Pantoprazole
    • Rabeprazole
• Higher doses may be used for patients with partial response, breakthrough symptoms, or severe esophageal dysmotility. Always give second dose 30-60 min before evening meal.

Drug Therapy - Prokinetics

• Prokinetic Agents: Enhance motility of smooth muscle from esophagus to proximal small bowel; accelerates gastric emptying and transit of intestinal contents.
  • Results: Improved gastric emptying; enhanced tone of the lower esophageal sphincter (LES); and stimulates esophageal peristalsis

Prokinetic Agents-Products

• Metoclopramide: Only if motility dysfunction documented; administer at least 30 minutes prior to meals; dose 10-15mg before meals and at bedtime

Special Populations

• Pregnancy: GERD is common due to decreased LES pressure and increased abdominal pressure. Antacids are generally considered safe; however, avoid chronic high doses.

Counseling Questions

• Before recommending a therapy ask:
  • Duration and frequency of symptoms
  • Quality and timing of symptoms
  • Use of alcohol and tobacco
  • Dietary choices
  • Medications already tried to treat symptoms
  • Other disease states present and medications being used

Case Study

• AA, a 45-year-old male postal worker experiences 3-4 heartburn episodes per month, primarily after meals. He has tried Tums with limited success. He wants a more effective treatment.
• 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 (mild, moderate, or severe)?
  • What treatment should you recommend?