New pharmacological treatments for gastroesophageal reflux: Potassium-competitive acid blockers and bile acid sequestrants

(doi:10.24875/NGL.18000007)

Hidekazu Suzuki, Fellowship Training Center and Medical Education Center, Keio University School of Medicine, Tokyo, Japan

ABSTRACT

Gastroesophageal reflux disease (GERD) is a representative disorder of acid-related diseases.

Antisecretory agents such as proton-pump inhibitors (PPIs) are mainly used to treat

these disorders. Recently, in addition to conventional PPIs, potassium-competitive acid

blockers (P-CABs) have been developed as a new class of agents for acid suppression that

acts by inhibiting the gastric H+/K+-ATPase in a K+-competitive manner. On the other hand,

duodenogastroesophageal reflux of bile acid is another promoter of GERD and their associated

complications, such as Barrett’s esophagus and lower esophageal adenocarcinoma.

Therefore, bile acid sequestrants may play a role in this type of reflux. Herein, the roles of

PCABs and bile acid sequestrants in the treatment of GERD are reviewed. There are three

types of P-CABs, one of which is vonoprazan (VPZ), which has a potent and long-lasting

antisecretory effect on H+/K+-ATPase due to its high accumulation and slow clearance from

the stomach. VPZ is now used in Japan for the treatment of reflux esophagitis, inducing

high mucosal healing rate in patients with PPI-resistant refractory reflux esophagitis and

in protecting esophageal epithelia. Bile acid sequestrants, such as cholestyramine, bind to

bile acids and may be physiologically effective in reducing the exposure of bile acid to the

esophageal epithelial surface. While currently, three available P-CABs have different degrees

of effectiveness in the therapy of GERD, that of bile acid sequestrants has not been fully

proven.

Keywords: Key words: Vonoprazan. Tegoprazan. Revaprazan. Cholestyramine.