Drug Therapy for Suppressing Secretion of Gastric Acid

Understanding the mechanisms involved in secretion of acid from the parietal cell led to development of several drugs capable of inhibiting acid secretion. These drugs are widely used in humans for treatment of acid reflux disorders such as heartburn and gastroesophageal reflux disease. The most effective inhibitors fall into two classes.

H₂ Receptor Antagonists

Histamine is clearly one of the primary regulators of acid secretion, and the parietal cell receptor for histamine is of the H2 type. Evidence of histamine's role in acid secretion is strongly supported by finding that H2 receptor antagonists are quite effective in inhibiting acid secretion. Examples of H2 antagonists commonly used to suppress gastric acid secretion include cimetidine (Tagamet HB), ranitidine (Zantac 75), famotidine (Pepcid AC) and nizatidine (Axid AR).

These drugs, particularly cimetidine, are among the most widely prescribed drugs in man. They are also useful for management of certain gastric diseases in dogs and horses. Antihistamines that engage H1 receptors (e.g. those used to treat colds) have no effect on acid secretion.

Proton Pump Inhibitors

Acid secretion is absolutely dependent on function of the H+/K+ ATPase or proton pump located in the cannilicular membrane of the parietal cell. Several drugs have been developed that non-competively bind and inactivate the ATPase, resulting in strong inhibition of acid secretion. Omeprazole (Prilosec) is an acid-activated prodrug that binds covalently to two cysteines on the ATPase, resulting in its irreversible inactivation. Other inhibitors, including lansoprazole (Prevacid), esomeprazole (Nexium), rabeprazole (Aciphex) and pantoprazole (Protonix) have similar modes of action.

References and Reviews

• Hellstrom PM, Vitols S: The choice of proton pump inhibitor: does it matter? Basic Clin Pharmacol Toxicol 94:105, 2004.
• Sachs G, Prinz C, Loo D, etc: Gastric acid secretion: activation and inhibition. Yale J Biol Med 67:81-95, 1994.
• Shamburek RD, Schubert ML: Control of gastric acid secretion. Histamine H2-receptor antagonists and H+K(+)-ATPase inhibitors. Gastroenterology Clinics of North America. 21:527-550, 1992.
• Welage LS: Pharmacologic properties of proton pump inhibitors. Pharmacotherapy 23:74S-80S, 2003.

Send comments to Richard.Bowen@colostate.edu