Pharmacology
Mechanism of action
Rabeprazoles mechanism of action first involves getting absorbed into the parietal cells of the stomach, which are the cells that are responsible for secreting hydrochloric acid (HCl). At this point, rabeprazole is inactive. However, rabeprazole is then secreted into the secretory canaliculus of the parietal cells, which is the space from which acid secretion occurs. Here, acid secretion is mediated by the energy-dependent acid pumps, called hydrogen potassium adenosine triphosphatase (H+/K+ ATPase) pumps. These enzymatic pumps have cysteine amino acid residues. After being activated by gastric (stomach) acid to a reactive sulfenamide intermediate, rabeprazole permanently binds the cysteine residues, forming covalent, disulfide bonds. This action fundamentally alters the configuration of the acid pump, thereby inhibiting its activity. Thus, acid can no longer be secreted into the gastric lumen (the empty space of the stomach), and the pH of the stomach increases (decrease in the concentration of hydrogen ions, H+). Due to the permanent inhibition of the individual proton pump that each molecule of rabeprazole has bound to, acid secretion is effectively suppressed until new proton pumps are produced by the parietal cells.Rabeprazole, like other medications in the same class, cannot inhibit the H+/K+ ATPase pumps found in lysosomes, a cellular organelle that degrades biological molecules, because the pumps found in these organelles lack the cysteine residues involved in rabeprazoles mechanism of action.A unique feature of rabeprazoles mechanism of action in inhibiting acid secretion involves its activation.
Rabeprazole, sold under the brand name Aciphex, among others, is a medication that decreases stomach acid. It is used to treat peptic ulcer disease, gastroesophageal reflux disease, and excess stomach acid production such as in Zollinger–Ellison syndrome. It may also be used in combination with other medications to treat Helicobacter pylori. Effectiveness is similar to other proton pump inhibitors (PPIs). It is taken by mouth.Common side effects include constipation, feeling weak, and throat inflammation. Serious side effects may include osteoporosis, low blood magnesium, Clostridium difficile infection, and pneumonia. Use in pregnancy and breastfeeding is of unclear safety. It works by blocking H+/K+-ATPase in the parietal cells of the stomach.Rabeprazole was patented in 1986, and approved for medical use in 1997. It is available as a generic medication. In 2017, it was the 279th most commonly prescribed medication in the United States, with more than one million prescriptions. Medical uses
Rabeprazole, like other proton pump inhibitors such as omeprazole, is used for the purposes of gastric acid suppression. This effect is beneficial for the treatment and prevention of conditions in which gastric acid directly worsens symptoms, such as duodenal and gastric ulcers. In the setting of gastroesophageal reflux disease (GERD), whose pathophysiology is characterized by prolonged exposure to gastric acid in the esophagus (often due to changes in stomach and/or esophagus anatomy, such as those induced by abdominal obesity), acid suppression can provide symptomatic relief.