Warfarin cholestyramine binding

Barbiturates and rifampin cause a marked decrease of the anticoagulant effect by induction of the hepatic enzymes that transform racemic warfarin. Cholestyramine binds warfarin in the intestine and reduces its absorption and bioavailability. 

The answer is c. (Hardman, pp 887, 889.) Bile acid-binding resins bind more than just bile acids, and binding of simvastatin to cholestyramine is the most likely mechanism for decreased Gl absorption. Cholestyramine may also bind to several other drugs, including digoxin, benzothiadiazides (thiazides), warfarin, vancomycin, thyroxine (T4), and aspirin. Medications should be given one hour before or four hours after cholestyramine. 

The principal precaution with use of the bile acid resins is the possibility of impaired absorption of other drugs given orally at the same time. Cholestyramine and colestipol can bind many other drugs, such as digitoxin, phenobarbital, chlorothiazide, and warfarin, and delay or prevent their absorption. For this reason, other drugs should always be taken at least 1 hour before or 4 to 6 hours after the resin. The resins can also decease absorption of fat-soluble vitamins. 

Other oral adsorbents have specific uses. Fuller s earth and bentonite (both natural forms of aluminium silicate) bind and inactivate the herbicides, paraquat (activated charcoal is superior) and diquat cholestyramine and colestipol will adsorb warfarin. 

Cholestyramine and Colestipol. Other interactions involving complexation might be anticipated when cholestyramine (e.g., Questran) and colestipol (Coles-tid) are used. These resinous materials, which are not absorbed from the GI tract, bind with bile acids and prevent their reabsorption. In addition, cholestyramine and colestipol can bind with drugs (e.g., digoxin and warfarin) that are present in the GI tract. To minimize the possibility of an interaction, the interval between the administration of cholestyramine or colestipol and another drug should be as long as possible. 

Few systemic effects (not absorbed across Gl). Gl upset and bloating may occur. Reduces absorption of fat soluble vitamins (A,D and E). PO. Not absorbed from Gl tract. Excreted in feces. Binds to (inactivates) diuretics, antibiotics, barbiturates, digitalis, warfarin, digitalis and others. Administer other drugs or vitamins at least an hour before or after administering cholestyramine. 

In vitro experiments demonstrated significant binding of warfarin to cholestyramine at a pH above its pK of 5.5."... 

---