## Ezetimibe Mechanism **Key Point:** Ezetimibe selectively inhibits the NPC1L1 cholesterol transporter located on the apical membrane of intestinal enterocytes, reducing dietary and biliary cholesterol absorption. ### Site of Action Ezetimibe acts at the intestinal epithelium, not the liver. It binds to and inhibits the Niemann–Pick C1-like 1 (NPC1L1) transporter protein, which is responsible for the uptake of cholesterol from the intestinal lumen into enterocytes. ### Pharmacological Consequences 1. **Reduced intestinal cholesterol absorption** (by ~50%) 2. **Decreased chylomicron cholesterol content** 3. **Compensatory increase in hepatic LDL receptors** (due to lower hepatic cholesterol from reduced absorption) 4. **Net LDL-C reduction of 15–20%** when used as monotherapy 5. **Additive effect with statins** (up to 25% additional reduction when combined) ### Clinical Use - Often combined with statins for enhanced LDL-C lowering - Used in statin-intolerant patients as monotherapy - Part of combination therapy in familial hypercholesterolemia **High-Yield:** Ezetimibe is the only selective cholesterol absorption inhibitor in clinical use. Its mechanism is fundamentally different from statins — it reduces cholesterol *entry* rather than *synthesis*. **Mnemonic:** **NPC1L1 = Niemann–Pick Cholesterol transporter** — remember it's on the intestinal membrane, not hepatic.
Sign up free to access AI-powered MCQ practice with detailed explanations and adaptive learning.