Overview of pharmacological options for the control of gastric hyperacidity
 

John Horn PharmD: There are a number of different drugs that can be used to control gastric acid secretion in patients who are having symptoms from excess acidity. Perhaps the simplest and longest in use are the antacids, which simply act by neutralizing acidity in the stomach.

We have moved on from the antacids to the H2 antagonists, which work on the parietal cell. They inhibit acid secretion from the parietal cell, so, unlike the antacids, they're actually blocking the delivery of acid to the stomach. They're pretty effective agents, but now they in turn have been surpassed by the proton pump inhibitors, which are even more effective in their activity on parietal cell acid secretion. PPIs really cause a remarkable reduction in the amount of acid from the parietal cell and therefore markedly increase the pH of the stomach contents.

Prokinetic agents have fallen into disfavor somewhat in the past few years, which is, I think, too bad. There are a lot of patients who will respond to a prokinetic agent. Not everyone's symptoms in the upper gastrointestinal tract are caused by too much acid. Some of these patients have symptoms that are caused by dysmotility, so prokinetic agents or drugs that enhance the motility of the stomach are often helpful for them.

The prokinetic drugs have fallen into disuse mainly because of their side-effects. Metoclopramide or Reglan - which has been around for a very long time and is still being used - causes some neurologic side effects, and sometimes they can be irreversible, so that's a major limitation to its use.

Cisapride, which is still available, though on a very limited basis, has the potential to cause some cardiac arrhythmias, in some patients, particularly when combined with drugs that interfere with its metabolism or in patients who have other reasons to have dysrhythmias. And so for that reason, that drug has also now fallen into some disuse.

The efficacy of the H2 receptor antagonist is pretty good, but it is somewhat limited. There are apparently a couple of reasons for this. One is that the drugs just aren't very potent in preventing acid secretion, because they're only affecting the histamine receptor on the parietal cell, which is only one of mechanisms by which the parietal cell can be stimulated to secrete acid. Since H2 receptor antagonists only affect one of the potential ways that you can stimulate the cell, they don't produce a large magnitude of acid reduction.

The second problem we run into with H2s is that when you give them continuously over weeks or months, there does seem to be some reflex increase in acid production - a resistance, if you will, to their response, so that with time the pH effect is diminished with continued use of the H2s.

What differentiates the mechanism of the proton pump inhibitors from H2 receptor antagonists or antacids is that the proton pump inhibitor works, as the name implies, on the proton pump. The proton pump is what secretes the hydrogen ion - proton in this case - that makes hydrochloric acid in the stomach. Since that's the final pathway for all the acid production from the parietal cell, by blocking that final pathway, you can block a very large percentage of the acid output of the parietal cells.

As I said, the H2 receptor antagonists only block the histamine receptor, which does reduce acid production, but not nearly to the degree that you get with blockade of the proton pump. The antacids, of course, don't affect acid production at all; they simply neutralize whatever acid happens to be present in the stomach. Even then, antacids don't do a very good job of neutralizing it, unless you give an awful lot of antacid, which is fraught with other problems.

John Horn PharmD