Gastro-Intestinal Pharmacology Overview

Gastro-Intestinal (GI) Pharmacology

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

GI Picture

• A diagram showing the major organs of the digestive system.
• Labels for organs like the mouth, esophagus, stomach, small intestine (duodenum, jejunum, ileum), large intestine (colon, cecum, rectum), liver, gallbladder, pancreas, and anus.

Gastroesophageal Reflux Disease (GERD)

• GERD is characterized by the flow of stomach contents back into the esophagus.
• Typical symptoms include frequent and persistent heartburn.
• Other symptoms, such as belching, regurgitation, and hypersalivation, may also occur when pH is less than 4.
• GERD might have atypical symptoms, like a chronic cough, hoarseness, or chest pain (mimicking angina).
• Possible symptoms may only be noticeable with an "omeprazole test".

Normal Physiology Functions - Esophagus

• The esophagus transports food from the mouth to the stomach via peristaltic contractions.
• The lower esophageal sphincter (LES) relaxes during swallowing, allowing food entry into the stomach, and then contracts to prevent reflux.

Pathogenesis of GERD

• For GERD onset, 3 lines of defense must be compromised:
  • 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 of GERD

• Factors decreasing LES pressure include: chocolate, alcohol, fatty meals, coffee, cola, tea, garlic, onions, and smoking.
• Factors directly irritating the gastric mucosa include tomato-based products, coffee, spicy foods, citrus juices, NSAIDs, aspirin, iron, potassium chloride, and alendronate.
• Substances that stimulate acid secretions are soda, beer, and smoking.

Lines of Defense

• Clearance of refluxed materials from the esophagus, including primary and secondary peristalsis, gravitational effects.
• Esophageal mucosal resistance, including mucus production in the esophagus, and bicarbonate movement from the blood to the mucosa.

Factors Determining Extent of Esophageal Damage

• Factors influencing esophageal damage include the amount of damage, composition of refluxed material, volume of refluxed material, length of contact time of reflux material, natural sensitivity of esophageal mucosa, and rate of gastric emptying.
• A key consideration is whether acid or alkaline refluxed material is worse.

Complications of GERD

• Esophagitis
• Esophageal strictures and ulcers
• Hemorrhage
• Perforation
• Aspiration
• Asthma attack precipitation

Warning Signs Requiring Endoscopy

• Dysphagia
• Odynophagia
• Bleeding
• Unexplained weight loss
• Choking
• Chest pain

Diagnosis of GERD

• Clinical symptoms and history
• Presenting symptoms and associated risk factors
• Empiric therapy and monitoring of improvement
• Endoscopy if warning signs are present

When to Refer for Further Care

• Chest pain
• Heartburn while taking PPIs or persistent heartburn after 2 weeks of treatment
• Nocturnal heartburn symptoms
• Frequent heartburn for more than 3 months
• GI bleeding and other warning signs
• Concurrent use of NSAIDs
• Pregnancy or nursing
• Children under 12 years old

Therapy Goals

• Alleviate or eliminate symptoms
• Diminish reflux frequency and duration
• Promote healing if the mucosa is damaged
• Prevent complications

Therapy

• Therapy targets increasing LES pressure, enhancing esophageal acid clearance, improving gastric emptying, protecting esophageal mucosa, decreasing reflux acidity, and decreasing gastric volume available for reflux.

Treatment Phases

• Phase I: Lifestyle changes (2 weeks) for mild intermittent heartburn, plus antacids.
• Phase II: Pharmacologic intervention (standard/high-dose antisecretory therapy) for symptomatic relief of mild to moderate GERD, involving lifestyle changes plus standard doses of proton pump inhibitors (PPIs) for 4–8 weeks.
• Phase III: Surgical intervention for patients who fail pharmacologic treatment or have severe GERD complications, possibly involving repositioning the LES within the abdomen.

Treatment Selection

• Mild intermittent heartburn: Lifestyle changes and antacids.
• Mild to moderate GERD (Phase II): Lifestyle changes plus standard doses of PPIs (4–8 weeks).
• Moderate to severe GERD (Phase II): Lifestyle changes plus PPIs (8–16 weeks), possibly with prokinetic agents.

Examples of Prokinetic Agents

• Metoclopramide
• Domperidone

Lifestyle Modifications

• Elevate the head of the bed (6–8 inches)
• Decrease fat intake
• Stop smoking
• Avoid recumbency for 3 hours after meals
• Lose weight
• Limit alcohol intake
• Wear loose-fitting clothing
• Avoid aggravating foods

Drug Therapy - Antacids

• Antacids increase LES pressure but do not promote esophageal healing.
• They neutralize gastric acid, causing alkalinization.
• Alginic acid forms a viscous solution that floats on top of stomach contents.
• Use as needed with typical action of 1-3 hours.
• Antacid products include magnesium salts, aluminum salts, calcium carbonate, and sodium bicarbonate. Some brand examples include Maalox/Mylanta, Maalox TC/Mylanta II, Gaviscon, Tums (Calcium Chloride) and Nugel.

Drug Therapy - PPIs

• Used to treat moderate to severe GERD, choosing based on cost.
• Omeprazole was made OTC in 2003.
• Used for heartburn occurring 2+ times per week.
• Standard doses include: esomeprazole (20-40 mg daily), lansoprazole (15-30 mg daily), omeprazole (20-40 mg daily), pantoprazole (40 mg daily), and rabeprazole (20 mg daily).
• Timing is best 30 to 60 minutes before a meal.
• Higher doses may be needed in some patients.

Drug Therapy - Prokinetics

• Enhances smooth muscle motility from the esophagus to the proximal small bowel.
• Accelerates gastric emptying and transit of intestinal contents from the duodenum.
• Results in improved gastric emptying, enhanced tone of the lower esophageal sphincter, and stimulated esophageal peristalsis.
• Prokinetic agent example: Metoclopramide (10-15 mg before meals and at bedtime).

Special Populations - Pregnancy

• GERD is common due to decreased LES pressure and increased abdominal pressure.
• Nearly half of all pregnant women experience GERD.
• Antacids are generally safe but avoid chronic high doses.

Counseling Questions

• Duration and frequency of symptoms
• Quality and timing of symptoms
• Alcohol and tobacco use
• Dietary choices
• Medications already tried
• Other underlying conditions and medications used

Case Study

• A 45 year old male postal worker with heartburn 3-4 times per month, appearing after meals.
• Has tried Tums with partial success.
• Questions to ask AA: history, details of the pain, lifestyle, medications, and medical history.
• Reasons for referral: severe symptoms or potential complications.
• Probable GERD type: mild.
• Recommended treatment: lifestyle modifications and PPIs.

This quiz explores the pharmacology of the gastrointestinal (GI) system, focusing on the actions of drugs that affect GI function. You'll learn about important conditions like GERD and the anatomy of the digestive tract, including its major organs. Test your knowledge of how medications can normalize impaired GI functions and understand chronic diseases associated with the GI system.