[New treatment option for decreasing blood cholesterol level--clinical significance of inhibition of both, cholesterol absorption and synthesis].
In the development of hypercholesterinaemia two factors play an important role. There is the cholesterol-uptake through the gastrointestinal tract, about 300-700 mg daily depending on the diet, on the other hand gastrointestinal tract plays important role in the reabsorption of cholesterol excreted through the bile by the liver, the amount of which takes 1000 mg. It means that about 1300-1700 mg cholesterol is absorbed in the small intestine daily. Previous major studies have demonstrated that statins, the drugs that have been proved to be the most efficient in decreasing the cholesterol level, can decrease both total and cardiovascular mortality. This effect highly depends on the rate of cholesterol level decrease. Thus, their application in higher doses has been recently suggested to reach the target level, which is performed by dose titration. If the desired effect is not achieved with the starting dose of statins, a doubling of dosage only leads to 6% additional LDL-cholesterol level decrease. During long term administration the so called "escape phenomenon" can be observed, which means that the use of these drugs for a longer period reduces their cholesterol decreasing effect. Higher doses increase the risk of adverse effects, and the "escape phenomenon" decreases the effectiveness. To avoid these effects the combination therapy is recommended for use. In combination therapy drugs with different mechanisms of action should be administered, which increase therapeutic effect, but keep the number of adverse effects decreased or unchanged. Concomitant administration of former known lipid lowering agents--beyond enhancing cholesterol level decrease--has unfortunately increased the frequency of adverse effects as well. In this regard, ezetemibe, the cholesterol absorption inhibitor appears to be promising since it selectively decreases the absorption of cholesterol from intestinal epithelial cell, resulting in an 18-22% LDL-cholesterol decrease. At the same time the decreased uptake from the gastrointestinal tract triggers the endogen cholesterol synthesis in the liver. When this process is inhibited by statin, more impressive cholesterol decreasing effect can be reached. Clinical studies with concurrent use of ezetimibe and statin have confirmed this view. Decreasing cholesterol level at more attack points offers a possibility to reach target values without a significant increase in the risk of adverse effects. So with combination and dual inhibition a more significant cholesterol lowering effect can be obtained beside the decrease of side effects.
Paragh
György
G
Debreceni Egyetem Orvos- és Egészségtudományi Centrum, Altalános Orvostudományi Kar, I. Belgyógyászati Klinika.
Márk
László
L
Czine
Zsigmond
Z
D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D001384:Azetidines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D002784:Cholesterol / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000378:metabolism; D004359:Drug Therapy, Combination; D004361:Drug Tolerance; D000069438:Ezetimibe; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D007408:Intestinal Absorption; D008099:Liver / Q000187:drug effects* / Q000378:metabolism
D000924:Anticholesteremic Agents; D001384:Azetidines; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002784:Cholesterol; D000069438:Ezetimibe