The introduction of proton pump inhibitors (PPIs) in the late 1980s optimized the medical treatment of acid-related disorders. In addition, PPIs have allowed clinicians to evaluate the role of gastric acid in several extraesophageal manifestations of gastroesophageal reflux disease, including noncardiac chest pain and tracheopulmonary diseases [1-4].
This topic review will provide an overview of the pharmacology and clinical efficacy of the proton pump inhibitors for a variety of acid-related disorders and address issues related to the comparison of these agents. It will also discuss issues related to stopping these medications. The pharmacology of other drugs used in the treatment of acid-related diseases is presented separately. (See "Pharmacology of antiulcer medications".)
PHYSIOLOGY OF ACID SECRETION
The normal human stomach contains approximately one billion parietal cells that secrete 0.16 M hydrochloric acid (HCl) into the gastric lumen in response to three principal physiological stimuli: acetylcholine, histamine, and gastrin (figure 1). (See "Physiology of gastric acid secretion".)
●Acetylcholine is the chief neurocrine transmitter, which is released by vagal postganglionic neurons and appears to stimulate hydrogen ion generation directly via a parietal cell muscarinic M3 receptor.
●Histamine is the primary paracrine transmitter that binds to H2-specific receptors on the parietal cell basolateral membrane, while gastrin, secreted from antral G-cells, comprises the primary endocrine pathway.