Anion exchange resins

Mechanism of Action

1.       Cholestyarmine is an oral anion-exchange resin which binds bile acids in the intestines.

2.    Bile acids are formed from cholesterol in the liver, pass into the gut in the bile and are reabsorbed at the terminal ileum.

3.    Bile acids bound to cholestyramine are lost in the faeces and the depletion of the bile acid pool stimulates conversion of cholesterol to bile acid.

4.       Results in:

a.    A fall in intracellular cholesterol in hepatocytes.

b.    An increase in both LDL receptors and cholesterol synthesis.

c.    Fall in plasma LDL cholesterol by 20 – 25%.

5.    In many patients there is some compensatory increase in hepatic triglyceride and cholesterol output.

6.    The only drugs that eliminate cholesterol.

Pharmacokinetics

1.       Polymeric basic anion-exchange resins, insoluble and not absorbed.

Clinical use

1.    Drug of choice for treatment of hypercholesterolaemia on the basis of their safety and efficacy.

2.       Effect is enhanced if used in combination with a HMG-CoA reductase inhibitor which reduce plasma cholesterol by 50%.

3.    Not used for triglyceridaemia.

Side effects

1.    GI: constipation, nausea, vomiting, steatorrhoea and a bloating sensation.

Drug interactions

1.       Binds the following drugs:

a.       Warfarin.

b.       Digoxin.

c.       Thiazides.

d.       Phenobarbitone.

e.       Thyroid hormones.

2.       These should be taken 1h before or 6h after cholestyramine to avoid impairment of their absorption.