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EZETIMIBE (ZETIA). Mechanism of action. Indications. Explained.
00:00 Introduction
00:18 Indications
00:44 Mechanism of action
03:40 Dosage and Side effects
Ezetimibe inhibits intestinal uptake of dietary and biliary cholesterol at the level of the brush border of the intestine by interacting with the Niemann-Pick C1-like protein 1 without affecting the absorption of fat-soluble nutrients.
According to the newest ESC Guidelines for the management of dyslipidemias
Combination with ezetimibe is recommended as additional therapy to statins for pharmacological lowering of low density lipoproteins If the goals are not achieved with the maximum tolerated dose of a statin.
This position has the strongest level of recommendation.
Absorbtion of cholesterol in intestine provided by Niemann–Pick C1-like protein 1 which transport cholesterol inside the enterocyte. Further Cholesterol with triglyceride’s carry from gut in form of chylomicrons and can be up taken by liver for further processing.
Ezetimibe inhibits intestinal cholesterol absorption by selectively blocking the Niemann–Pick C1-like protein 1 in the brush border. As a result cholesterol excretes with the feces.
By inhibiting cholesterol absorption, ezetimibe reduces the amount of cholesterol delivered to the liver by chylomocrons. When the cholesterol levels in the hepatocyte decrease. It cause the activation of LDL receptor transcription on the hepatocyte. It leads to increased clearance of LDL from the blood that therefore to decreasing intraarterial cholesterol accumulation and prevent the atherosclerosis development.
Also low level of cholesterol inside of hepatocyte increase activity of HMG-CoA reductase, which stimuli cholesterol synthesis from acetyl-Coa. This is the reason why ezetimibe is used in combination with the statins which inhibit HMG-Coa reductase therefore cholesterol synthesis.
Sources which was used for preparing:
Introduction to Lipids and Lipoproteins
https://www.ncbi.nlm.nih.gov/books/NBK305896/
Balancing Cholesterol Synthesis and Absorption in the Gastrointestinal Tract
https://www.ncbi.nlm.nih.gov/p....mc/articles/PMC23908
Ezetimibe therapy: mechanism of action and clinical update
https://pubmed.ncbi.nlm.nih.gov/22910633/
2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS)
https://academic.oup.com/eurhe....artj/article/41/1/11
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