Reflux of stomach contents into the esophagus is known to produce inflammatory changes in the esophageal lining. There are two components in that content responsible for such a damage. These are the hydrochloric acid and a biologically active substance called pepsin, an enzyme which digests protein. Both of acid and pepsin contribute to esophagitis. Inside the stomach acid is mainly produced to activate pepsin from a precursor known as pepsinogen. That reveals the dual effect of the stomach acid in relation to esophageal damage. The first effect being direct and the second indirect through the activation of pepsin which in turn irritates the esophagus.
It is well evident from the previous facts that reduction of acid production prevents damage of the esophageal lining. Acid is produced by cells lining the stomach known as parietal cells. These cells have chemical pumps called proton pumps which moves hydrogen ion from the inside of the parietal cell into the stomach lumen against a concentration gradient. Before this pumping activity the cell responds to signals initiating the process. These signals are: 1- Acetylcholine, a chemical substance released at the nerve endings supplying stomach glands, 2- Gastrin: a local hormone released from capillaries adjacent to stomach glands, and 3- Histamine: a biologically active chemical produced by specialized local cells in the stomach wall. These signals act upon specific sites in the membrane enclosing each parietal cell called receptors and each receptor is named after the name of stimulus which acts upon. Accordingly there are Aceylcholine, Gastrin and histamine receptors.
Acetylcholine is released through the various neurological mechanisms which follow food intake and its digestion. Gastrin is a local hormone produced by G cells located in the wall of the distal part of the stomach called the antrum in response to the chemical effect of digested proteins. Histamine is released mechanically by distention of the stomach and chemically by products of protein breakdown.
Theoretically speaking, we can block acid production by preventing the stimulatory effect of Acetylcholine, Gastrin and Histamine upon the parietal cells. Acetylcholine has well known antagonists but they have generalized effects as Acetylcholine is a universal neuro-transmitter. So far no Gastrin blocker is yet available. In 1964 the role of histamine as a parietal cell stimulant was discovered, however the use of traditional antihhistamine did not reduce acid secretion. That led scientists to postulate the existence of two histamine receptors, the one acted upon by traditional antihistamines (H1) and the other residing in parietal cell wall (H2).
Examples of H2 receptor blockers include: Cimitedine (Tagamet),Ranitidine (Zantac), Nizatidine (Axid) and Famotidine (Pepcid).
They are equally effective, and the standard dose for mild to moderate acid reflux is: 400mg, 150mg, 150mg and 20mg respectively. This dosage is given twice daily for 6-12 weeks. Approximately 50% of patients with esophagitis heal on this regimen. However a high relapse rate of 50% has been reported within two months. Maintenance treatment is indicated in severe esophagitis associated with complications and if symptoms are relapsing immediately after treatment stops. The dosage may be given three times daily in some cases for proper relief of symptoms and healing of complications.
Generally speaking they are more effective than antacids but less effective than proton pump inhibitors.
Together with other measures for acid reflux relieve such as dietary control and lifestyle modifications, they have proven efficacy in mild to moderate symptoms. They are available as over the counter and prescription forms and have relatively lower cost.