Specific Characteristics of Different Groups of Heartburn Medications
According to epidemiological data, half of all people experience heartburn—the main symptom of gastroesophageal reflux disease (GERD)—at least once a month, approximately one-fifth experience it once a week, and about one in ten experience it every day [1]. Both the course of the disease and its treatment can vary; therefore, it is important to understand the characteristics of different groups of medications and to consider the frequency and intensity of symptoms when recommending treatment to a patient.
Heartburn, or gastroesophageal reflux disease (GERD), is a condition in which contractions of the lower part of the esophagus are impaired, causing the contents of the stomach (and, less commonly, the duodenum) to repeatedly enter the esophagus—a phenomenon known as reflux. The main cause of GERD is the regurgitation of acidic gastric contents, i.e., reflux, while the main cause of reflux is an inadequate antireflux barrier. If the sphincter muscle ring separating the esophagus from the stomach functions properly, acidic gastric contents do not move upward.
Symptoms of gastroesophageal reflux disease may be triggered by certain foods, including coffee, chocolate, spicy, fatty and fried foods, garlic, onions, tomato sauce, oranges, apples, and alcohol. Symptoms may also be triggered by large meals, lying down shortly after eating, and certain medications—calcium channel blockers, theophylline, nitrates, and antihistamines. GERD occurs more frequently in patients with hiatal hernia, diabetes mellitus (due to slowed esophageal peristalsis), pregnancy, and obesity. Pregnancy and obesity increase pressure within the abdominal cavity and stomach.
Treatment may reduce or completely eliminate symptoms; however, changes in diet or lifestyle and, in some cases, stress may cause gastroesophageal reflux symptoms to recur. As the disease progresses, the risk of complications increases, and esophageal adenocarcinoma may even develop.
Groups of Medications Used to Treat GERD
The medications most commonly used to treat GERD can be divided into three groups: antacids, histamine H2 receptor blockers, and proton pump inhibitors. Their most important characteristics are presented in Table 1.
Table 1. Comparison of Different Groups of Medications Used to Treat GERD
| Drug Group | Mechanism of Action | Onset and Duration of Action |
|---|---|---|
| Antacids | Neutralize existing gastric acid | Begin acting very rapidly; effect lasts 30–60 min |
| Histamine H2 receptor blockers | Block histamine-stimulated gastric acid secretion | Begin acting within 30–45 min; effect lasts 4–10 hours (after which tolerance develops) |
| Proton pump inhibitors | Inhibit gastric acid secretion by participating in the final stage of gastric acid formation | Effect begins within 2–3 hours; lasts 12–24 hours (maximum effect is achieved after 3–5 days of use) |
Gastric acid-neutralizing preparations—antacids—relieve symptoms of gastroesophageal reflux, including heartburn and indigestion. They are recommended when GERD symptoms are mild or occur infrequently. Because of their particularly rapid onset of action, they are also used as an adjunct to treatment with medications from other groups. These medications are inexpensive, accessible, and safe to use. Antacids usually contain magnesium hydroxide, aluminum hydroxide, or calcium carbonate, which neutralize gastric pH and thereby reduce exposure of the esophageal mucosa to gastric acid during an episode of GERD.
These medications were developed as early as the 1970s and continue to be used today. Their onset of action is rapid, but compared with other groups of medications, their effect is relatively short, lasting up to 60 minutes. The effect may be prolonged for up to 3 hours when the medications are taken with food. Antacids are recommended with each meal and before bedtime.
Another major group of medications used to treat GERD is histamine H2 receptor blockers. This group includes medications such as ranitidine, cimetidine, famotidine, and nizatidine. Histamine is released in the body under various conditions and, when released in the gastrointestinal tract, stimulates gastric acid secretion. By binding to histamine H2 receptors located on gastric parietal cells, these medications block the receptors and thereby reduce gastric acid production.
Histamine H2 receptor blockers are more commonly recommended for intermittent use as needed. They are used to treat grade I–II esophagitis and patients with mild to moderate GERD symptoms. Histamine primarily regulates basal gastric acid secretion between meals, making it rational to take these medications in the evening. They are generally taken once in the evening to suppress nocturnal acid secretion. One disadvantage of these medications is that their acid-suppressing effect diminishes over time.
The effect of histamine H2 receptor blockers usually begins to diminish after 2–6 weeks of use. This is thought to result from the development of receptor tolerance (tachyphylaxis). In addition, histamine H2 receptor blockers reduce the degradation of H2 receptors, which may clinically manifest as increased acid secretion after the medication is discontinued [4]. Although histamine H2 receptor blockers have a slower onset of action than antacids, their duration of action is longer, remaining effective for 4–10 hours after administration.
The third group of medications prescribed and used for GERD treatment is proton pump inhibitors (PPIs). These medications are prescribed to patients in whom treatment with histamine H2 receptor blockers twice daily at maximum doses is ineffective, those diagnosed with erosive esophagitis, and/or those with severe GERD symptoms affecting quality of life [1, 6].
Proton pumps are ion transport systems located in the canalicular membrane of gastric parietal cells. In the resting state, the pumps are located in the cytoplasm; once activated, they move into the lumen and exchange one hydrogen (H) ion for one potassium (K) ion. At the same time, chloride (Cl) is released, which is required for the formation of gastric acid (HCl).
Proton pump inhibitors (PPIs) inhibit the activity of the gastric acid pump (H,K-ATPase), which is involved in the final stage of gastric acid formation. PPIs bind covalently to proton pumps, and gastric acid production recovers after PPI treatment only when the proteins are replaced and pump inhibition ceases. Therefore, despite their short plasma half-life, PPIs can be administered once daily.
These medications are most effective when taken 30–60 minutes before the first meal of the day because, at that time, the canalicular membranes of the parietal cells contain the greatest number of H,K-ATPase pumps following the overnight fasting period. These medications should be taken continuously rather than only when symptoms occur, because even with continuous use during the first five days, steady-state acid secretion is reduced by only 66%. The inhibitory effect of PPIs on gastric acid secretion increases during the first days of treatment and stabilizes by the third to fifth day.
Difficulties in GERD Treatment – The Rebound Effect (Acid Rebound)
Rebound acid hypersecretion is defined as gastric acid secretion greater than that present before treatment, occurring within a few weeks after discontinuation of antisecretory medications. This phenomenon may cause the symptoms experienced before treatment, such as heartburn and acid regurgitation, to recur, further encouraging patients to resume treatment with antacids, PPIs, or other medications [10].
Rebound acid secretion has also been observed after the use of calcium carbonate. The rebound effect, including its development and underlying mechanisms, has been studied most extensively with PPIs. One theory proposes that long-term PPI use blocks proton pumps and increases gastric pH, thereby stimulating compensatory gastrin secretion. This causes hypertrophy and hypersecretion of other gastric wall cells—enterochromaffin-like cells—and an increase in chromogranin A (CgA) levels. As a result, the gastric mucosa has an increased capacity to secrete gastrin after PPI treatment is discontinued. It has not yet been established what level of secretion produces clinical symptoms of hypersecretion and increased acidity [2].
Dennis and colleagues conducted a study to determine whether antacids could promote rebound hypersecretion. Gastric pH was measured, after which participants consumed foods that provoke acidity—a chocolate milkshake, a fatty hamburger, and potatoes fried in oil. One hour after eating these foods, participants chewed aluminum- and magnesium-based or calcium-based antacid tablets. Throughout the study, including during eating, gastric and esophageal pH was measured using a sensor inserted through a nasogastric tube.
The maximum pH effect of medications containing aluminum and magnesium hydroxides (Al(OH)₃ and Mg(OH)₂) was greater: within 10 minutes, they increased pH to 7.3, whereas medications containing calcium carbonate (CaCO₃) increased pH to 6.9. In the control group, pH increased to 6.4. Gastric and esophageal pH was measured for another 120 minutes after administration of the medications. Medications containing Al(OH)₃ and Mg(OH)₂ maintained both gastric and esophageal pH at higher levels for longer than medications containing CaCO₃ (Table 2). This is associated with the fact that calcium-containing preparations also promote the rebound phenomenon, i.e., increased gastric acid production after administration [9].
Table 2. Gastric and Esophageal pH Measurements After Administration of Different Antacids [9]
| pH Measurement | Medication | Time Point I | Time Point II | 0–30 min | 30–60 min | 60–90 min | 90–120 min |
|---|---|---|---|---|---|---|---|
| Esophageal pH | Al(OH)₃ / Mg(OH)₂ | 5.5 | 5.5 | 3.2 | 6.2 | 9.1 | 12.1 |
| CaCO₃ | 5.6 | 5.4 | 3.0 | 5.9 | 8.7 | 11.6 | |
| Placebo | 5.4 | 5.5 | 2.8 | 5.5 | 8.1 | 10.9 | |
| Gastric pH | Al(OH)₃ / Mg(OH)₂ | 1.4 | 2.9 | 1.2 | 2.4 | 3.4 | 4.4 |
| CaCO₃ | 1.4 | 2.8 | 1.0 | 2.0 | 2.9 | 3.8 | |
| Placebo | 1.4 | 2.9 | 1.1 | 2.1 | 3.1 | 3.9 |
Time Point I: acidity before 5–60 min of intubation. Time Point II: acidity 60 min after intubation, before administration of the study medication.
GERD Can Also Be Prevented and Managed With Non-Pharmacological Measures
The risk of gastric acid reflux into the esophagus and GERD can be reduced through various measures:
- reduce body weight if overweight;
- avoid overeating and eating within 3 hours before bedtime;
- avoid drinking large amounts of fluids with meals and chew food thoroughly;
- limit fatty foods, chocolate, coffee, alcohol, and other foods that increase acidity;
- do not smoke;
- avoid working in a bent-over position after eating;
- sleep with the head slightly elevated;
- avoid tight, constricting clothing.
If GERD symptoms cannot be prevented, it may be worth trying non-pharmacological measures before taking medication, for example:
- frequently drink small sips of non-carbonated water at room temperature;
- eat buckwheat or millet porridge every morning;
- snack on a few nuts or seeds, such as sunflower or pumpkin seeds, between meals, particularly when meals are irregular and separated by long intervals.
Certain medicinal plants may also help reduce gastric acidity, improve digestion, suppress inflammatory processes, and thereby relieve heartburn, including marsh cudweed, wild angelica, St. John’s wort, yarrow, and calamus root.
Prepared by Dr. S. Stankevičiūtė
Source: Farmacija ir laikas, 2016
