Management of gastroesophageal reflux disease

OVERVIEW ㅡ Gastroesophageal reflux disease (GERD) is a common chronic, relapsing condition that is associated with a risk of significant morbidity and the possibility of mortality from complications. Patients have heartburn, the hallmark of acid regurgitation, at least once a month. Many patients self-diagnose and self-treat, and do not seek medical attention for their symptoms, while others have more severe disease, including erosive esophagitis. Patients who have GERD generally report decreased quality of life, reduced productivity, and decreased well-being. In many of these patients, reported quality of life is lower than in patients who have untreated angina pectoris or chronic heart failure.

CAUSES AND RISK FACTORS

CAUSES ㅡ Incompetent or hypotonic lower esophageal sphincter, transient lower esophageal sphincter relaxations, hiatal hernia. Medications that reduce lower esophageal sphincter tone such as calcium channel blockers, anticholinergics, sedatives, prostaglandins, theophylline, nitrates and α-Adrenergic antagonists. Foods and beverages that may reduce lower esophageal sphincter tone (onions, chocolate, peppermint, alcohol and coffee). Also tobacco use and pregnancy.

RISK FACTORS AND/OR ASSOCIATIONS ㅡ Sex affects men and women equally. Males are more commonly affected by erosive esophagitis and Barrett esophagus. Other risk factors/associations include obesity and NSAIDs.

DIAGNOSIS

Table (1). Assessment of gastroesophageal reflux disease
	COMMENTS
History	Heartburn is reported by most patients May occur only after meals and not at night (upright reflux due to transient relaxation of the lower esophageal sphincter) May be aggravated by bending over or lying down  Nocturnal heartburn, with cough and regurgitation, may awaken patients Often relieved by antacids  Acid regurgitation (regurgitation of gastric contents into mouth) Other gastrointestinal symptoms Indigestion and dyspepsia Intermittent dysphagia Bitter taste in mouth Epigastric and chest pain Early satiety, abdominal fullness, and abdominal bloating Belching Globus pharyngeus (feeling of a lump in the throat) Hypersalivation Pain when swallowing (usually associated with ulcerated esophagus) Nausea and/or vomiting Halitosis Gastrointestinal bleeding due to esophageal erosions or ulcerations Nongastrointestinal symptoms  Wheezing (due to bronchospasm) Asthma exacerbation Nocturnal cough Nocturnal choking or aspiration of gastroesophageal contents Hoarseness and laryngitis (atypical features, but may indicate laryngopharyngeal reflux)
Physical examination	Physical examination findings are typically normal Signs of anemia (pallor) may be present if the patient has iron deficiency anemia caused by significant, long-term blood loss from esophageal ulcerations or erosions Pharyngitis Enamel erosion and dental decay Halitosis
See, algorithm of diagnosis and treatment of GERD

MANAGEMENT

LIFESTYLE MODIFICATIONS ㅡ Based on expert opinion, lifestyle modifications should be initiated and continued throughout the course of therapy in patients with a history that is typical of uncomplicated GERD (Table 2). Although there is little supporting evidence, it is considered reasonable to educate patients about various factors that may precipitate reflux.

Table (2). Suggested Lifestyle Modifications for Patients with GERD
Avoid large meals.
Avoid acidic foods (citrus- and tomato-based products), alcohol, caffeinated beverages, chocolate, onions, garlic, and peppermint.
Decrease dietary fat intake.
Avoid lying down within three to four hours after a meal.
Avoid medications that may potentiate GERD symptoms, including calcium channel blockers, beta agonists, alpha-adrenergic agonists, theophylline, nitrates, and some sedatives.
Elevate the head of the bed 10 to 20 cm (4 to 8 inches).
Avoid wearing clothing that is tight around the waist.
Lose weight.
Stop smoking.

PHARMACOTHERAPY ㅡ For the empiric trial, treatment may be initiated with a standard dosage of a histamine H2-receptor antagonist (H2RA) taken twice daily on demand or a standard dosage of a proton pump inhibitor (PPI) taken 30 to 60 minutes before the first meal of the day. The preferred empiric approach is step-up or step-down therapy. Step-up therapy begins with an eight-week trial of an H2RA and progresses to use of a PPI if symptoms of heartburn and regurgitation are not relieved. Step-down therapy starts with a PPI for eight weeks; treatment is then “downgraded” to the lowest effective dosage and type of medication that provide symptom relief. Drug selection should be based on the frequency or severity of symptoms at presentation, with a treatment goal of complete, cost-effective symptom relief (Figure 1 and Table 3). Diagnostic testing should be reserved for patients who present with warning signs and symptoms, have not responded to PPI therapy, or have disease duration of five to 10 years.

Table (3). Acute and Maintenance Therapy for GERD
AGENT		EQUIVALENT DOSAGES	DOSAGE
Histamine H2-receptor antagonists
Cimetidine (Tagamet)		400 mg twice daily	400 to 800 mg twice daily
Famotidine (Antodine)		20 mg twice daily	20 to 40 mg twice daily
Nizatidine (Nizatect)		150 mg twice daily	150 mg twice daily
Ranitidine (Zantac)		150 mg twice daily	150 mg twice daily
Proton pump inhibitors
Esomeprazole (Nexium)		40 mg per day	20 to 40 mg per day
Lansoprazole (Zoton fast)		30 mg per day	15 to 30 mg per day
Omeprazole (Losec)		20 mg per day	20 mg per day
Pantoprazole (Controloc)		40 mg per day	40 mg per day
Rabeprazole (Pariet)		20 mg per day	20 mg per day

Antacids. Over-the-counter acid suppressants and antacids are considered appropriate initial therapy for GERD. Antacids (e.g. Maalox) and combined antacid–alginic acid preparations (Gaviscon) have been shown to be more effective than placebo in relieving GERD symptoms, based on measures such as lower global symptom scores, less acid regurgitation, and fewer days and nights with heartburn. Sucralfate (Gastrofait), a prescription drug, increases the barrier to acid penetration in the esophagus. However, clinical studies have shown limited or no clinical efficacy for this agent in patients with GERD.

Histamine H2-receptor antagonists. Higher dosages and more frequent dosing than standard doses appear to increase the effectiveness of these agents in treating reflux symptoms and healing esophagitis. Disadvantages of using maximal dosages of H2RAs may include cost (possibly equal to or higher than the cost of PPI therapy) and poor compliance with the medication regimen.

          The U.S. Food and Drug Administration has approved the use of cimetidine (Tagamet), famotidine (Antodine), nizatidine (Nizatect), and ranitidine (Zantac) as over-the-counter preparations, with the dosage for each medication uniformly one half of the standard lowest prescription dosage. The four agents have similar clinical efficacy. Some patients with GERD may be able to predict when they will have reflux symptoms. These patients may benefit from premedication with an over-the-counter H2RA. Alternatively, patients may elect to take the medication when symptoms occur (on-demand therapy). The over-the-counter H2RAs are believed to be more effective than antacids, alginic acid. Patients may develop tolerance to H2RAs, with some decrease in efficacy occurring after 30 days of therapy. Dosages of H2RAs may need to be decreased in the elderly and in patients with renal insufficiency. In some case reports, these agents have been associated with rare cytopenias, gynecomastia, liver function test abnormalities, and hypersensitivity reactions.

Protonpump inhibitors. If a patient who was initially started on twice-daily H2RA therapy does not respond after two weeks, appropriate step-up therapy is to switch to once-daily PPI therapy (Figure 1). Better control of reflux disease symptoms was achieved over a four-to eight-week period in patients treated with PPIs than in those given H2RAs. In the treatment of erosive esophagitis, faster healing rates were achieved in patients who received PPI therapy for four to eight weeks than in patients who were given H2RAs for the same period. At one year, patients treated daily with a PPI were significantly less likely to relapse than those who received an H2RA.

          PPIs include lansoprazole (Zoton Fast), omeprazole (Losec), pantoprazole (Controloc), and rabeprazole (Pariet). For these agents, no significant differences have been demonstrated in the symptomatic treatment of GERD or the healing of erosive esophagitis. Esomeprazole (Nexium) is the S-isomer of omeprazole. Compared with omeprazole, esomeprazole is associated with higher rates of healing and symptom resolution in patients with GERD and reflux esophagitis. In patients with chronic or complicated GERD, the potential benefit of long-term PPI therapy generally outweighs the risk of adverse events. The most common side effects include headache and diarrhea. Rarely, cobalamin absorption is decreased, but a clinically significant decrease in serum vitamin B₁₂ levels is unusual. The profound decrease in gastric acid secretion induced by PPIs leads to increased gastrin production from antral G cells. PPIs have not been linked to gastric cancer or carcinoid since their release more than 16 years ago.

REFERENCES

• Heidelbaugh, J.J., Nostrant, T.T., Kim, C. and Richard Van Harrison (2014). Management of Gastroesophageal Reflux Disease. American Family Physician, [online] 68(7), pp.1311–1318. Available at: https://www.aafp.org/afp/2003/1001/p1311.html
  
  Virginia, Y.Z. Standards of Care for GERD. [online] www.uspharmacist.com. Available at: https://www.uspharmacist.com/article/standards-of-care-for-gerd