Pharmacology
Summary
Cholestyramine and ezetimibe are lipid-lowering agents that work in distinct ways to regulate cholesterol levels in the body. Cholestyramine operates within the intestines, where it binds to bile acids and inhibits their reabsorption. This prompts the liver to use its own cholesterol stores to synthesize more bile acids. The interruption of bile acid recycling results in the upregulation LDL receptors on hepatocytes, which increases the clearance of LDL from the bloodstream.
In contrast, ezetimibe targets dietary cholesterol absorption, effectively blocking its uptake within the intestines. This action stimulates HMG CoA reductase to synthesize more cholesterol. Similar to cholestyramine, this leads to an upsurge in LDL receptor activity, increasing the clearance of LDL from the blood. While both these agents adeptly reduce LDL levels, they're often used in combination with statins, which remain the cornerstone therapy for hypercholesterolemia.
Lesson Outline
Don't stop here!
Get access to 133 more Pharmacology lessons & 13 more medical school learning courses with one subscription!
FAQs
Cholestyramine and ezetimibe are lipid-lowering agents used to control elevated LDL cholesterol levels. Cholestyramine is a bile acid-binding resin. It works by attaching to bile acids in the intestine, which are then eliminated in the stool. This reduction in bile acids prompts the liver to draw cholesterol from the blood to synthesize more bile acids, thus reducing LDL cholesterol levels. On the other hand, ezetimibe functions by diminishing the absorption of cholesterol in the small intestine, leading to a decrease in the delivery of intestinal cholesterol to the liver. This results in an increase in the clearance of cholesterol from the bloodstream.
Cholestyramine and ezetimibe lower LDL cholesterol levels through different mechanisms. Cholestyramine binds to bile acids in the gut, preventing their reabsorption. This process nudges the liver to convert more cholesterol into bile acids, thereby reducing blood cholesterol levels. Ezetimibe hinders the absorption of dietary cholesterol in the small intestine, which in turn reduces the amount of cholesterol available to the liver and lowers the total amount in circulation.
Cholestyramine and ezetimibe are pivotal in treating hypercholesterolemia, which refers to elevated levels of cholesterol in the blood. Cholestyramine reduces cholesterol by hindering the reabsorption of bile acids, while ezetimibe works by limiting cholesterol absorption in the intestines. Using these medications together can lead to larger reductions in cholesterol levels than either medication used alone.
The LDL receptor is instrumental in maintaining cholesterol balance in the body. When cholestyramine obstructs bile acid reabsorption, the liver must harness more cholesterol to form new bile acids. This process boosts the expression of LDL receptors on hepatocyte surfaces, which then effectively remove LDL cholesterol from the bloodstream. Likewise, the action of ezetimibe in reducing cholesterol absorption spurs the liver to upregulate LDL receptor expression, leading to a marked reduction in circulating LDL cholesterol levels.
Indeed, cholestyramine and ezetimibe can be combined with statins, another important class of medication targeting cholesterol levels. Statins operate by inhibiting HMG-CoA reductase, an enzyme crucial for cholesterol synthesis in the liver. Using them in tandem can result in a more pronounced reduction in LDL cholesterol than either drug class alone.
