3. Gastroesophageal Reflux Disease (GERD) Overview

Gastroesophageal Reflux Disease (GERD)

• GERD is a sensorimotor disorder linked to impaired anti-reflux mechanisms
• It can involve changes in esophageal peristalsis, increased intragastric pressure, increased pressure gradient, or excess gastric acid secretion, though less often

Objectives

• Recall the definition of GERD
• Understand the Los Angeles classification for erosive esophagitis
• Understand the pathophysiology of GERD
• Recognize the structure, pharmacokinetics, and pharmacodynamics of medications for GERD treatment, including antacids, H2R antagonists, PPIs, prostaglandin analogs, cholinemimetics, and dopamine antagonists

Definition

• GERD is a sensorimotor disorder associated with impaired normal antireflux mechanisms of lower esophageal sphincter function, and phrenicoesophageal ligament
• GERD is characterized by changes in normal physiology, such as impaired esophageal peristalsis, increased intragastric pressure, increased abdominothoracic pressure gradient, or, less commonly, excess gastric acid secretion (Zollinger-Ellison syndrome)

Epidemiology

• GERD is common and its prevalence varies geographically
• Prevalence is increasing in many developing countries
• The USA has a prevalence of 18.1-27.8%
• South America has a prevalence of 16.5-23%
• Europe has a prevalence of 8.8-25.9%
• Middle East has a prevalence of 8.7-21.2%
• East Asian countries have a prevalence of less than 10%

Classification

• Erosive GERD: involves mucosal break(s)
• Non-erosive GERD: characterized by symptoms alone without mucosal damage
• Los Angeles classification: Grades A through D based on the extent of esophageal mucosal breaks (in erosive esophagitis)

Symptoms

• Typical: Heartburn (daytime or nighttime), regurgitation (daytime or nighttime), water brash (hypersalivation)
• Atypical: Nausea, eructation (belching), slow digestion, early satiety, epigastric pain, bloating, vomiting, chest pain (precordial), respiratory symptoms(cough, wheeze), chronic rhinosinusitis, ENT symptoms (hoarseness, pharyngeal pain, globus), early awakening, nocturnal awakening, nightmares.
• Symptoms may vary from intermittent (less than two episodes per week) to frequent (two or more episodes per week).

Pathophysiology

• Factors such as acid reflux characteristics, reflux acidity, longitudinal muscle contraction, and mucosal integrity influence the perception of reflux.
• Conditions such as peripheral sensitization (TRPV1, TRPV4, TRPA1, and P2XR) and central sensitization also influence the perception of reflux
• Other factors that promote the occurrence of reflux include obesity, and delayed gastric emptying

Diagnosis

• No gold standard exists
• Recommended approaches prioritize symptom frequency and severity and assess presence of erosive esophagitis or Barrett's esophagus with upper endoscopy if available

Treatment

• Lifestyle Modifications (e.g., dietary avoidance, smoking cessation, weight reduction, avoidance of tight garments, avoidance of eating within 3 hours before bed, elevating head of bed)
• Medications (e.g., antacids, H2R antagonists, PPIs, other drugs)
• Surgical interventions (e.g., Nissen, Toupet, or other fundoplication)

Treatment during pregnancy

• Start with lifestyle modifications
• When lifestyle modifications fail, use first-line agents like antacids (aluminum-, calcium-, or magnesium-containing), alginates, or sucralfate

Proton Pump Inhibitors (PPIs)

• Most effective for typical GERD symptoms
• Associated with complete symptom relief in patients with erosive esophagitis
• Dosage: Omeprazole 20 mg daily for 8-12 weeks

Anti-emetics and Prokinetics

• Cimetidine, metoclopramide, cisapride

Surgical Management

• Indications: Refractory GERD, Barret's esophagus, peptic stricture, and hiatal hernia
• Surgical techniques: Laparoscopic, open, or robotic surgery (total or partial fundoplication)

Other topics

• Antacids: Magnesium Hydroxide
  • Indications: Used as an antacid or laxative, depending on the dose, for temporary relief of heartburn, upset stomach, or acid indigestion
  • Mechanism of Action: Neutralizes stomach acid by combining with H+ ions
  • Absorption: Absorbed slowly in the small intestine
  • Metabolism: Rapidly excreted in the urine; no metabolic changes
  • Toxicity: Drowsiness, flushing, electrolyte disturbances, hypermagnesemia (with high doses), including nausea, vomiting, dehydration, and hypotension
  • Drug interactions: Combining with aluminum-containing antacids, decreases absorption of some drugs (digoxin, dicoumarol, cimetidine), affects absorption of NSAIDs (ex ibuprofen)
• H2R Antagonist: Cimetidine
  • Indications: Acid-reflux disorder (GERD), peptic ulcer disease
  • Mechanism of Action: Blocks histamine receptors on parietal cells, reducing acid production
  • Metabolism: Primarily metabolized by the liver
  • Adverse effects: Nausea, vomiting, diarrhea, excessive saliva, palpitations. Interferes with metabolism of other drugs, vitamin D metabolism and endocrine function, requiring careful consideration for other medication use
• Dopamine Antagonist: Metoclopramide
  • Indications: Used for treating GERD, nausea, vomiting
  • Mechanism of Action: Antagonizes D2 dopamine receptors to accelerate gastric emptying and intestinal transit
  • Pharmacological effects: Promotes gastric emptying through muscle relaxation
  • Metabolism: Hepatic
  • Adverse effects: Dystonic reactions, oculogyric crisis, irritability, drowsiness, emesis, and apnea.
• Cisapride
  • Indications: Treatment of nocturnal heartburn due to GERD
  • Mechanism of Action: 5-HT4, 3A, and 2A agonist; potassium voltage-gated channel subfamily H member 2 antagonist
  • Metabolism: Hepatic, via CYP3A4 enzyme
  • Adverse effects: Withdrawn from market due to life-threatening cardiac arrhythmias (long QT syndrome).

This quiz covers the key aspects of Gastroesophageal Reflux Disease (GERD), including its definition, pathophysiology, and treatment options. Participants will explore the Los Angeles classification for erosive esophagitis and understand various medications used in GERD management. Test your knowledge on this common digestive disorder and its implications.