1. Lecture -10 Gastrointestinal Disorders Gastroesophageal Reflex Disease
University of Nizwa
College of Pharmacy and Nursing
School of Pharmacy
PHARMACOTHERAPY II
PHCY 410
Lecture -10 Gastrointestinal Disorders Gastroesophageal Reflex Disease
Dr. Sabin Thomas, M. Pharm. Ph. D. Assistant Professor in Pharmacy Practice School of Pharmacy University of Nizwa

2. Course Outcomes
Upon completion of this lecture the students will be able to
Describe etiology, clinical manifestations and diagnosis of gastroesophageal reflux disorder.
Develop skills for monitoring drug therapy and patient education in patients with gastroesophageal reflux disorder.
Explain drug related problems and develop pharmaceutical care plan in patients with gastroesophageal reflux disorder.

3. Gastroesophageal reflux disease (GERD) refers to symptoms or mucosal damage resulting from the abnormal retrograde movement of gastric contents from the stomach into the esophagus.
When the esophagus is repeatedly exposed to refluxed material for prolonged periods, inflammation of the esophagus (reflux esophagitis).
Some cases it progresses
to erosion of the squamous
epithelium (erosive esophagitis).

4. PATHOPHYSIOLOGY
The key factor in the development of GERD is the abnormal reflux of gastric contents from the stomach into the esophagus.
In some cases, gastroesophageal reflux is associated with defective lower esophageal sphincter (LES) pressure or function.
Patients may have decreased LES pressures related to spontaneous transient LES relaxations, transient increases in intraabdominal pressure, or an atonic LES.
A variety of foods and medications may decrease LES pressure

6. Other factors are
prolonged acid clearance time from the esophagus,
delayed gastric emptying,
and reduced mucosal resistance.
Aggressive factors that may promote esophageal damage upon reflux into the esophagus include gastric acid, pepsin, bile acids, and pancreatic enzymes.
The composition and volume of the refluxate and the duration of exposure are the most important aggressive factors.

7. CLINICAL PRESENTATION
The hallmark symptom of gastroesophageal reflux and esophagitis is heartburn, or pyrosis.
It is a substernal sensation of warmth or burning that may radiate to the neck often aggravated by activities that worsen gastroesophageal reflux (e.g., recumbent position, bending over, eating a high-fat meal).
Other symptoms include water brash (hypersalivation), belching, and regurgitation.

8. Atypical symptoms include nonallergic asthma, chronic cough, hoarseness, pharyngitis, dental erosions, and chest pain that mimics angina.
Inadequately treated GERD may lead to complications from long-term acid exposure such as continual pain, dysphagia, and odynophagia.
Other severe complications include esophageal strictures, hemorrhage, Barrett’s esophagus, and esophageal adenocarcinoma.

9. DIAGNOSIS
The most useful tool in the diagnosis of gastroesophageal reflux is the clinical history, including both presenting symptoms and associated risk factors.
Further diagnostic evaluation should be performed in those who do not respond to therapy, who present with alarm symptoms (e.g., dysphagia, weight loss), or who have long-standing GERD symptoms.
Endoscopy is the preferred technique for assessing the mucosa for esophagitis and complications such as Barrett’s esophagus.
Barium radiography is less expensive than endoscopy but lacks the sensitivity and specificity.
Omeprazole given empirically in standard or double doses as a “therapeutic trial” for diagnosing GERD may be beneficial

10. TREATMENT
Nonpharmacologic Treatment of Gastroesophageal Reflux Disease with Lifestyle Modifications
Elevate the head of the bed (increases esophageal clearance). Use 6- to 8-inch blocks under the head of the bed. Sleep on a foam wedge.
Dietary changes:
Avoid foods that may decrease lower esophageal sphincter pressure (fats, chocolate, alcohol,
peppermint, and spearmint).
Avoid foods that have a direct irritant effect on the esophageal mucosa (spicy foods, orange juice,
tomato juice, and coffee).
Include protein-rich meals in diet (augments lower esophageal sphincter pressure).

11. Eat small meals and avoid eating immediately prior to sleeping (within 3 hours if possible) (decreases gastric volume).
Weight reduction (reduces symptoms).
Stop smoking (decreases spontaneous esophageal sphincter relaxation).
Avoid alcohol (increases amplitude of the lower esophageal sphincter, peristaltic waves, and frequency of contraction).
Avoid tight-fitting clothes.
Discontinue, if possible, drugs that may promote reflux (calcium channel blockers, β-blockers, nitrates, theophylline).

12. Pharmacologic Treatment
Treatment is categorized into the following modalities:
Phase I: Lifestyle changes and patient-directed therapy with antacids and/or nonprescription histamine2-receptor antagonists (H2RA) or proton pump inhibitors (PPIs).
Phase II: Pharmacologic interventions with standard or high-dose acidsuppressing agents.
Phase III: Interventional therapies (antireflux surgery or endoluminal therapies).

13. Antacids provide immediate, symptomatic relief for mild GERD and are often used concurrently with other acid-suppressing therapies.
An antacid with alginic acid (Gaviscon) is not a potent acid-neutralizing agent, but it does form a viscous solution that floats on the surface of the gastric contents.
This serves as a protective barrier for the esophagus against reflux of gastric contents and reduces the frequency of reflux episodes.
Typical doses are two tablets or 1 tablespoonful four times daily (after meals and at bedtime).

14. H2-RECEPTOR ANTAGONISTS
RANITIDINE, FAMOTIDINE, AND NIZATIDINE
The H2RAs in divided doses are effective for treating mild to moderate GERD.
For nonerosive disease, H2RAs are given in standard doses twice daily.
For nonresponding patients and those with erosive disease, higher doses and/or four times daily dosing provide better acid control.
The most common adverse effects are headache, somnolence, fatigue, dizziness, and either constipation or diarrhea.

15. PROTON PUMP INHIBITORS:
ESOMEPRAZOLE, LANSOPRAZOLE, OMEPRAZOLE, PANTOPRAZOLE, AND RABEPRAZOLE
PPIs block gastric acid secretion by inhibiting hydrogen potassium adenosine triphosphatase in gastric parietal cells, which results in profound and long-lasting antisecretory effects.
PPIs are superior to H2RAs in patients with moderate to severe GERD, including those with erosive esophagitis, complicated symptoms (Barrett’s esophagus, strictures), and nonerosive GERD with moderate to severe symptoms.
PPIs are also efficacious in patients refractory to H2RAs and are more cost effective than H2RAs in patients with severe disease.

16. Patients should be instructed to take oral PPIs in the morning 15 to 30 minutes before breakfast to maximize efficacy, because these agents inhibit only actively secreting proton pumps.
If dosed twice daily, the second dose should be taken approximately 10 to 12 hours after the morning dose and prior to a meal or snack.
Lansoprazole, esomeprazole, and pantoprazole are available in IV formulations for patients who cannot take oral medications.
Comparable doses of proton pump inhibitors are
Omeprazole 20 mg = Esomeprazole 20 mg = Lansoprazole 30 mg = Rabeprazole 20 mg = Pantoprazole 40 mg per day.
Dexlanzoprazole can be taken without regard to meals.

17. PROMOTILITY AGENTS
Promotility agents may be useful as adjuncts to acid suppression therapy in patients with a known motility defect (e.g., LES incompetence, decreased esophageal clearance, delayed gastric emptying).
Cisapride has comparable efficacy to H2RAs in patients with mild esophagitis.
Metoclopramide, a dopamine antagonist, increases LES pressure in a dose related manner and accelerates gastric emptying.
Unlike cisapride, it does not improve esophageal clearance.

18. MUCOSAL PROTECTANTS
Sucralfate is a nonabsorbable aluminum salt of sucrose octasulfate that has limited value and is not routinely recommended for treatment of GERD.
COMBINATION THERAPY
Combination therapy with an acid-suppressing agent and a prokinetic agent or mucosal protectant seems logical for those who have failed high-dose PPI therapy.

19. MAINTENANCE THERAPY
Long-term maintenance therapy should be considered to prevent complications and worsening of esophageal function in patients who have symptomatic relapse after discontinuation of therapy or dosage reduction, including patients with complications such as Barrett’s esophagus, strictures, or hemorrhage.
Most patients require standard doses to prevent relapses.
The PPIs are the drugs of choice for maintenance treatment of moderate to severe esophagitis.
Usual once-daily doses are omeprazole 20 mg, lansoprazole 30 mg, rabeprazole 20 mg, or esomeprazole 20 mg.
Lower doses of a PPI or alternate-day regimens may be effective in some patients with less severe disease.