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Potassium-competitive acid blockers: Advanced therapeutic option for acid-related diseases
- Source :
- Pharmacology & Therapeutics. :12-22
- Publisher :
- The Authors. Published by Elsevier Inc.
-
Abstract
- Acid-related diseases (ARDs), such as peptic ulcers and gastroesophageal reflux disease, represent a major health-care concern. Some major milestones in our understanding of gastric acid secretion and ARD treatment reached during the last 50years include 1) discovery of histamine H2-receptors and development of H2-receptor antagonists, 2) identification of H+,K+-ATPase as the parietal cell proton pump and development of proton pump inhibitors (PPIs), and 3) identification of Helicobacter pylori (H. pylori) as the major cause of peptic ulcers and development of effective eradication regimens. Although PPI treatments have been effective and successful, there are limitations to their efficacy and usage, i.e. short half-life, insufficient acid suppression, slow onset of action, and large variation in efficacy among patients due to CYP2C19 metabolism. Potassium-competitive acid blockers (P-CABs) inhibit H+,K+-ATPase in a reversible and K+-competitive manner, and exhibit almost complete inhibition of gastric acid secretion from the first dose. Many pharmaceutical companies have tried to develop P-CABs, but most of their clinical development has been discontinued due to safety concerns or a similar efficacy to PPIs. Revaprazan was developed in Korea and was the first P-CAB approved for sale. Vonoprazan, approved in 2014 in Japan, has a completely different chemical structure and higher pKa value compared to other P-CABs, and exhibits rapid onset of action and prolonged control of intragastric acidity. Vonoprazan is an effective treatment for ARDs that is especially effective in healing reflux esophagitis and for H. pylori eradication. P-CABs, such as vonoprazan, promise to further improve the management of ARDs.
- Subjects :
- medicine.medical_specialty
medicine.drug_class
Vonoprazan
Peptic
Proton-pump inhibitor
Revaprazan
Proton pump inhibitor
Gastroenterology
Acid-related diseases
Helicobacter Infections
Potassium-competitive acid blocker
Gastric Acid
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Gastrointestinal Agents
Internal medicine
Animals
Humans
Medicine
Pharmacology (medical)
Reflux esophagitis
Pharmacology
Gastrointestinal agent
Peptic ulcer
Helicobacter pylori
biology
business.industry
Proton Pump Inhibitors
biology.organism_classification
Gastric acid secretion
Histamine H2 Antagonists
chemistry
H2 receptor
Drug Design
030220 oncology & carcinogenesis
Gastroesophageal Reflux
Potassium
Gastric acid
030211 gastroenterology & hepatology
business
Subjects
Details
- Language :
- English
- ISSN :
- 01637258
- Database :
- OpenAIRE
- Journal :
- Pharmacology & Therapeutics
- Accession number :
- edsair.doi.dedup.....dc33193426da86350a4f2099c033dc8f
- Full Text :
- https://doi.org/10.1016/j.pharmthera.2016.08.001