Atherosclerosis and lipoprotein metabolism: Lipid-lowering drugs Flashcards
What is an Atheroma?
Atheroma is a focal disease of the intima of large and medium-sized arteries. Lesions evolve over decades, during most of which time they are clinically silent, the occurrence of symptoms signalling advanced disease. Presymptomatic lesions are often difficult to detect non- invasively, although ultrasound is useful in accessible arteries (e.g. the carotids), and associated changes such as reduced aortic compliance and arterial calcification can be detected by measuring, respectively, aortic pulse wave velocity and coronary artery calcification.
List 11 modifiable risk factors for atheromatous disease?
What does the process of Atherogenesis involve? (8 steps) - eg. How does a fatty plaque form?
How are lipids and cholesterol transported in the bloodstream? What do they consist of?
Lipids and cholesterol are transported in the bloodstream as complexes of lipid and protein known as lipoproteins. These consist of a central core of hydrophobic lipid (including triglycerides and cholesteryl esters) encased in a hydrophilic coat of polar phospholipid, free cholesterol and apoprotein.
What are the 4 main classes of lipoprotein, differing in the relative proportion of the core lipids and in the type of apoprotein?
What are the 4 main classes of lipoprotein, differing in the relative proportion of the core lipids and in the type of apoprotein?
Describe the Endogenous and Exogenous pathways of lipoprotein formation and where Statins, fibrates and Ezetimibe works in each of the pathways?
Describe the rederickson/World Health Organization classification of hyperlipoproteinaemia.
List 5 types of lipid lowering drugs?
The main agents used clinically are:
1. Statins: 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors
2. Fibrates
3. Inhibitors of cholesterol absorption
4. Nicotinic acid or its derivatives
5. Fish oil derivatives.
Give 5 examples of Statins and explain their MOA?
Adverse effects of Statins?
5 Examples of fibrates and their MOA as a lipid-lowering drug?
- bezafibrate
- ciprofibrate
- gemfibrozill
- fenofibrate
- clofibrate
MOA of fibrate as a lipid-lowering agent?
These markedly reduce circulating VLDL, and hence triglyceride, with a modest reduction in LDL and an approximately 10% increase in HDL. They are agonists at PPARα nuclear receptors; in humans, the main effects are to increase transcription of the genes for lipoprotein lipase, apoA1 and apoA5. They increase hepatic LDL uptake. In addition to effects on lipoproteins, fibrates reduce plasma CRP and fibrinogen, improve glucose tolerance and inhibit vascular smooth muscle inflammation by inhibiting the expression of the transcription factor nuclear factor κB.
What is EZETIMIBE? MOA?
Ezetimibe is one of a group of azetidinone cholesterol absorption inhibitors, and is used as an adjunct to diet and statins in hypercholesterolaemia. It inhibits absorption of cholesterol (and of plant stanols) from the duodenum by blocking a transport protein (NPC1L1) in the brush border of enterocytes, without affecting the absorption of fat- soluble vitamins, triglycerides or bile acids.
What is NICOTINIC ACID? How can it be used as a lipid-lowering agent? MOA? Adverse effects?
Nicotinic acid is a vitamin, and as such is essential for many important metabolic processes. Quite separately from this, it has been used in gram quantities as a lipid-lowering agent.
