Anatomical Therapeutic Chemical Classification System
Exogenous chenodeoxycholic acid is used as replacement therapy to restore the feedback inhibition lost due to the deficiency/absence of endogenous chenodeoxycholic acid. In CTX, deficiency of chenodeoxycholic acid causes a lack of feedback of cholesterol 7 alpha hydroxylase (CYP7A1) and HMG CoA reductase, causing increased production of atypical bile acids, bile alcohols and cholestanol that lead to the pathological consequences of the condition.
Cholic acid is the predominant primary bile acid in man. In patients with inborn deficiency of 3β-Hydroxy-Δ5−C27-steroid oxidoreductase and Δ4-3-Oxosteroid-5β-reductase, the biosynthesis of primary bile acids is reduced or absent. The rational basis for treatment consists of restoration of the bile aciddependent component of bile flow enabling restoration of biliary secretion and biliary elimination of toxic metabolites; inhibition of the production of the toxic bile acid metabolites by negative feedback on cholesterol 7α-hydroxylase, which is the rate-limiting enzyme in bile acid synthesis; and improvement of the patient’s nutritional status by correcting intestinal malabsorption of fats and fat-soluble vitamins.
Obeticholic acid is a selective and potent agonist for the farnesoid X receptor (FXR), a nuclear receptor expressed at high levels in the liver and intestine. FXR activation decreases the intracellular hepatocyte concentrations of bile acids by suppressing de novo synthesis from cholesterol, as well as, by increasing transport of bile acids out of the hepatocytes.
The ursodeoxycholic acid converts lithogenic bile in non-lithogenic bile and gradually dissolves the cholesterol gallstones.