Pharmacology - DRUGS FOR HYPERLIPIDEMIA (MADE EASY)
Summary
TLDRThis lecture delves into hyperlipidemia, a condition marked by elevated blood lipids, which can lead to heart attack and stroke. It explains the role of cholesterol, triglycerides, and phospholipids, and their transport via lipoproteins. The video outlines various lipid-lowering drugs, including statins, niacin, fibrates, bile acid sequestrants, cholesterol absorption inhibitors, PCSK9 inhibitors, and omega-3 fatty acids, detailing their mechanisms and potential side effects, providing a comprehensive overview of managing hyperlipidemia.
Takeaways
- 𧬠Hyperlipidemia is a condition where there's an abnormal elevation of lipids in the blood, posing a risk for heart attack and stroke.
- π The three main lipids in the blood are cholesterol, triglycerides, and phospholipids, which serve various functions in the body.
- π Lipoproteins are protein capsules that transport lipids through the body, and they come in four main types: chylomicrons, VLDL, LDL, and HDL.
- π LDL is often called 'bad cholesterol' because high levels can lead to atherosclerosis, while HDL is known as 'good cholesterol' for its protective role.
- π Statins are HMG-CoA reductase inhibitors that lower cholesterol levels by inhibiting cholesterol production in the liver.
- π₯ Statins can have side effects such as elevated liver enzymes and muscle-related problems, including rhabdomyolysis.
- π Niacin, also known as Nicotinic Acid, reduces triglyceride levels and increases HDL by inhibiting hormone-sensitive lipase in adipose tissue.
- π Fibrates work by activating PPAR-alpha, leading to increased removal of triglycerides and higher HDL levels.
- π± Bile acid sequestrants bind bile acids in the intestine, reducing their reabsorption and leading to increased LDL receptor production in the liver.
- π« Cholesterol absorption inhibitors, like Ezetimibe, block cholesterol uptake in the intestine by inhibiting NPC1L1, thus lowering LDL cholesterol levels.
- π€ PCSK9 inhibitors are monoclonal antibodies that reduce LDL cholesterol levels by preventing the degradation of LDL receptors on liver cells.
- π Omega-3 fatty acids primarily lower triglyceride levels by inhibiting their synthesis in the liver and are associated with mild side effects.
Q & A
What is hyperlipidemia?
-Hyperlipidemia is a disorder characterized by abnormally elevated levels of fat particles, known as lipids, in the blood. These lipids can adhere to the walls of the arteries, restricting blood flow and creating a significant risk of heart attack and stroke.
What are the three major lipids found in the blood?
-The three major lipids in the blood are cholesterol, triglycerides, and phospholipids.
What is the role of cholesterol in the body?
-Cholesterol is necessary for the synthesis of bile acids, steroid hormones, and to maintain the integrity of cell membranes.
What are lipoproteins and why are they important for lipid transport?
-Lipoproteins are protein capsules that transport lipids throughout the body. They are important because lipids are insoluble in blood plasma and need to be carried in these protein packages.
How do chylomicrons and VLDL contribute to energy delivery in the body?
-Chylomicrons and VLDL deliver energy-rich triglycerides to cells throughout the body. They are composed primarily of triglycerides and some cholesterol, and they are broken down by lipoprotein lipase into fatty acids that are taken up by tissues.
Why is LDL cholesterol often referred to as 'bad cholesterol'?
-LDL cholesterol is often called 'bad cholesterol' because abnormally high levels of it can accumulate in the innermost layer of the artery wall, leading to the formation of atherosclerotic lesions.
What is the primary function of HDL cholesterol?
-HDL cholesterol, often referred to as 'good cholesterol,' prevents the formation of atherosclerotic lesions by removing cholesterol and suppressing LDL oxidation and vascular inflammation.
How do statins work to reduce cholesterol levels?
-Statins work by inhibiting the HMG-CoA reductase enzyme in the liver, which is responsible for converting HMG-CoA into mevalonic acid, a cholesterol precursor. This reduction in cholesterol production leads to an increase in LDL receptor synthesis, which in turn increases the clearance of LDL cholesterol from the blood.
What is the mechanism of action of Niacin as a lipid-lowering drug?
-Niacin works in adipose tissue by inhibiting the hormone-sensitive lipase enzyme, which is responsible for breaking down triglycerides into free fatty acids. By reducing the levels of free fatty acids available for transport to the liver, Niacin decreases hepatic VLDL synthesis and increases HDL levels.
How do fibrates affect lipid metabolism in the body?
-Fibrates work by activating the PPAR-alpha receptor, which induces the activation or inhibition of certain genes involved in lipid metabolism. This leads to increased expression of lipoprotein lipase, decreased expression of Apo-CIII, and increased expression of Apo-AI and Apo-AII, resulting in lower triglyceride levels and higher HDL levels.
What is the role of bile acid sequestrants in lowering LDL cholesterol?
-Bile acid sequestrants bind to bile acids in the small intestine, preventing their reabsorption and leading to their excretion. This increases the demand for bile acid production by the liver, which in turn increases the number of LDL receptors to bring in more LDL cholesterol, resulting in decreased circulating LDL levels.
How do cholesterol absorption inhibitors like Ezetimibe work?
-Cholesterol absorption inhibitors, such as Ezetimibe, work by binding to the NPC1L1 protein in the intestinal wall, inhibiting its interaction with the clathrin AP2 complex necessary for endocytosis. This leads to decreased delivery of intestinal cholesterol to the liver, reduced hepatic cholesterol levels, and increased clearance of LDL cholesterol from the circulation.
What are PCSK9 inhibitors and how do they lower LDL cholesterol levels?
-PCSK9 inhibitors are monoclonal antibodies that bind to and inactivate PCSK9 enzyme, which promotes the degradation of LDL receptors on liver cells. In the absence of PCSK9, more LDL receptors are available to clear LDL from the circulation, leading to decreased levels of LDL cholesterol.
What are the primary effects of omega-3 fatty acids on lipid levels?
-Omega-3 fatty acids are primarily used for their triglyceride-lowering effects, which are thought to be caused by the inhibition of VLDL and triglyceride synthesis in the liver.
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