For over 80 years, the treatment of heartburn in the setting of gastroesophageal reflux disease (GERD) has been predicated on the premise that regurgitated stomach acid causes a chemical burn in the esophageal lining. However, this long-standing hypothesis has been recently challenged by clinical and basic science. The successful treatment of heartburn involves a personalized approach to patient-centered care. Each patient who presents to the doctor with heartburn has a unique set of symptoms and triggers, which require careful consideration when formulating a comprehensive treatment protocol.
Heartburn research is a fluid and dynamic field, as science continually provides new information that often challenges the status quo. For instance, a group of doctors at Southwestern Medical Center and the Dallas VA Medical Center reported that when 11 of 12 GERD patients discontinued proton pump inhibitors (PPIs) they experienced an immune reaction in the esophageal lining and not an “acid burn” as expected.
Another example is the long-held observation that many individuals with GERD had a low-grade increase in the infiltration of allergy cells (eosinophils) (<15 per high power field) that cleared up with a powerful acid blockade. However, over time, a growing epidemic of patients presented with GERD symptomatology and the infiltration of many eosinophils (>15 per high power field) that was not responsive to an acid blockade called eosinophilic esophagitis (EoE). The first-line treatment of EoE is the dietary elimination of highly allergic foods. Not all patients experiencing heartburn have the same root causation or response to intervention. The disease is highly heterogeneous and requires a personalized approach.
This article will address the conventional medical treatment of GERD while the next blog will discuss alternative options.
Medical Treatment of Heartburn.
Over-the-Counter Antacids: Since the 1930s, on-demand therapy for heartburn either neutralizes or blocks the production of stomach acid and is the treatment of choice (TOC) for mild-to-
intermittent heartburn that is episodic and not chronic. Remember the good old days when heartburn commercials marketed the miracles of on-demand over-the-counter (OTC) immediate relief antacid agents? There are several antacids on the market that act to buffer stomach acid that regurgitates into the lower esophagus. Antacids are known to be fast acting for those whose heartburn is provoked by acid. Tums® is a calcium carbonate-based antacid that may provide an advantage by inducing production of protective factors such as bicarbonate and mucus.
Magnesium and aluminum salts are acid-neutralizing forms of OTC antacids. Magnesium salts are known to cause diarrhea as a side effect, and aluminum salts, which can cause constipation. In patients who have kidney failure, all of these agents would require careful monitoring and restricted use.
Dual-Acting Coating Antacid Agents: Act by coating the esophageal lining and defend against invasion by harmful agents such as acid, bile, enzymes, and others. Gaviscon® is an antacid that contains alginic acid from algae (also known as alginate) that coats the esophagus, and it also sits in the stomach and neutralizes the “acid pocket “and is also known as a “raft-forming agent.” The alginic acid forms a thick, viscous gel that temporarily adheres to the esophageal lining and in the stomach provides an additional barrier to prevent regurgitation of harmful chemicals. Acid-neutralizing bicarbonate is combined with alginic acid to provide additional acid-buffering of stomach acid, but it also expands the matrix in the stomach into a floating foam that forms a barrier of protection. Alginate has been shown to decrease the frequency and intensity of GERD with efficacy comparable to antacids. Figure 1. Alginate in Gaviscon® (shown in white) floats above the collection of digestive juices (gastric acid, bile and enzymes shown in green) in the proximal stomach, physically suppressing reflux.
Figure 2. Scintigraphic images of 99mTc-pertechnetate–labeled acid pocket (A) and 111mIn-labeled alginate-antacid (B) and the two scintigraphic recordings superimposed (C). After a meal, 99mTc-pertechnetate is excreted by the parietal cells of the stomach, and this visualizes the acid pocket near the esophageal-gastric junction (EGJ) (A). After intake, 111mIn-labeled alginate-antacid (B) is present in the proximal stomach. Superimposed, it is demonstrated that the 111mIn-labeled alginate-antacid is present on top and co-localizes with the acid pocket in the proximal stomach. In the Supplementary Video, the superimposed dynamic images demonstrate that the alginate-antacid remains in this position during the entire study period. Reproduced from Roof WO1, Bennink RJ, Smout AJ, Thomas E, Boeckxstaens GE. Clin Gastroenterol Hepatol. 2013 Dec;11(12):1585–91
Alginate preparations are highly effective at reducing both the intensity and the frequency of reflux attacks. Several studies show that the use of raft-forming agents are highly beneficial for chronic GERD. A study in 2012 demonstrated that the use of alginate agents was equivalent to Prilosec, a very potent acid blocker. In many individuals, a gaseous pressure build-up after meals promotes GERD. Simethicone helps break down gas bubbles and reduces heartburn. Maalox Anti-Gas and Mylanta Gas contain simethicone for this additional benefit.
Over-the-Counter Prescription Acid Blockade.
H2-Receptor Antagonists: Scientific advances in acid physiology reveal that medications opposing histamine receptors on the stomach’s acid-producing cells diminish GERD. Histamine-2 receptor antagonists (H2RAs) deliver significant improvements in heartburn prevention when they are taken before meals when compared to over-the-counter (OTC) antacids alone.
H2RAs take 30 to 90 minutes to work, so taking them 30 to 60 minutes before meal ingestion is the best strategy. Overall, H2RAs relieve symptoms in about half of GERD patients, and the effect can last for several hours. When used with on-demand, fast-acting antacids for breakthrough heartburn, H2RAs provide sustained benefits for patients with heartburn. H2RAs are usually taken before dinner at night and for some twice daily.
H2RAs inhibit acid secretion for 6 to 24 hours and are very useful for people who need persistent acid suppression. They may also prevent heartburn episodes. In some studies, H2RAs improved asthma symptoms in people with both asthma and GERD. However, one study suggested that they rarely provide complete symptom relief for chronic heartburn and dyspepsia, and they have done little to reduce physician office visits for GERD.
H2RAs have substantial interference with the liver metabolism of drugs and can lead to many drug interactions, making them a less appealing option for those on multiple medications.
Proton Pump Inhibitors (PPIs): The H2RAs were once considered a breakthrough in providing heartburn relief in the 1970s, but as America has become more obese and stressed with late-night heavy-eating patterns, the H2RAs became obsolete. In the 1980s, pharmaceutical companies explored the use of proton pump inhibitors (PPIs) for heartburn as they provide complete acid suppression. PPIs are now the “gold standard” for medical therapy for GERD. PPIs are long-acting, as a single dose lasts 24 hours.
However, they are associated with many potential long-term adverse effects that will be discussed in a subsequent article.
When stomach acid production is completely ablated, heartburn symptomatology will be superior over H2RAs. However, not all heartburn is caused by excessive acid reflux and PPIs do not improve all cases of heartburn. Due to their popularity and efficacy, PPIs have been consistently among the top 10 best-selling drugs sold worldwide. When compared to H2RAs, PPIs provide additional efficacy for GERD management (see above figure). However, PPIs also may have little or no effect on regurgitation or other extra-esophageal manifestations such as asthma.
PPIs are effective in relieving chest pain and the acid reflux that typically occurs during strenuous exercise. Eight-week therapy with standard (once daily) dose PPIs can achieve healing of reflux esophagitis in more than 80% of patients when there are visible erosions present during endoscopy. The more severe the esophageal lesions are, the better the response to PPIs and the healing rate is enhanced doubling the PPI dose. Meta-analyses have shown that when compared to omeprazole, lansoprazole, and pantoprazole, esomeprazole achieves the highest healing rates of reflux esophagitis in the short term.
PPIs have not been shown to be helpful for asthma, chronic cough, and functional heartburn. The debate about whether heartburn should be treated in step-up verses step-down fashion continues; however, there is no scientific evidence that step-down therapy presents an advantage. In fact, once a patient has been on PPIs, it is practically impossible to wean patients off these medications due to a wicked rebound secretion of stomach acid which elicits profound heartburn. Of interest, the Federal Drug Administration (FDA) approved the use of PPIs for GERD for a short-term basis (8 weeks).
Heartburn is a symptom complex resulting from a painful impulse that occurs when noxious agents penetrate the esophageal lining barrier. Most commonly refluxed stomach acid is a trigger, but bile, digestive enzymes, and other chemicals can also elicit painful responses. Some patients are hyper-reactive to physiologic acid reflux and are categorized as having “functional” disease.
Medical therapies are highly effective for visibly erosive disease due to an “acid burn.” In these cases, FDA guidelines are clear that only eight weeks of PPI therapy is indicated. Furthermore, GERD is a heterogeneous disease, and a universal response to PPIs is not achieved. Patients with GERD do not overproduce stomach acid and do not have a PPI deficiency. Rather, a more personalized approached using a step-up approach with diet, lifestyle, over-the-counter medications, and, when necessary, temporizing OTC low-dose PPIs may be needed to control symptoms as root causes are explored by a treating physician.
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