Hyperlipidemia Q2L Flashcards
What % of annual deaths does CHD account for?
50%
What is incidence of CHD correlated with?
positively associated with high total cholesterol and elevated LDL in the blood
Clinical artherosclerotic disease confers high risk for CHD: Clinical CHD, Symptomatic carotid artery disease, symptomatic carotid artery disease, peripheral arterial disease, abdominal aortic aneurysm
What are the risk factors for CHD?
smoking, HTN, low HDL, family Hx of premature CHD, age (>45yrs men, >55 women)
HDL >60mg/dl is a negative risk factor (good cholesterol)
How much reduction in mortality due to CHD can clinical management provide?
30-40% (clinical management = lifestyle changes + drug therapy)
What are the different types of familial hyperlipidemias?
Type I, IIA, IIB, III, IV, V
What is Type I hyperlipidemia?
(Familial hyperchylomicronemia)
◦ Massive fasting hyperchylomicronemia
◦ Deficiency of lipoprotein lipase
◦ NOT associated with an increase in coronary heart disease
What is Type IIA hyperlipidemia?
(Familial hypercholesterolemia)
◦ Elevated LDL with normal VLDL caused by a block in LDL degradation
◦ Characterized by an increased serum cholesterol level but normal TG levels
◦ Correlated to ischemic heart disease
◦ Treated with cholestyramine, niacin, or a statin
What is Type IV hyperlipidemia?
(familial hypertriglyceridemia)
◦ Increased VLDL levels with normal or decreased LDL levels resulting in normal to increased cholesterol and GREATLY elevated TG
◦ Overproduction and / or decreased removal of VLDL and TG in serum
◦ Common
◦ Treated with niacin and / or fenofibrate
What are the important apolipoproteins and their functions?
Apoliproprotein B-48 + PL, TG, CE = Chylomicrons.
B-100 binds to LDL receptor
C-II cofactor for activating lipoprotein lipase
E mediates remnant uptake
What are the important apolipoprotein functions?
Apolipoproteins bind lipids to form lipoproteins.
What is the primary goal of hyperlipidemia treatment?
reduction of the LDL level
What are the desirable levels of cholesterols?
LDL: < 200
TG <150
What is xanthalasma?
fat deposits in the skin (can be anywhere, but we will likely see them in the eyelids)
What is arcus?
cholesterol deposits in the corneal stroma. Common in the elderly, but can occur earlier in life due to hypercholesterolemia.
What are treatment options for hypertriacylglycerolemia?
- diet and exercise are the primary modes
2. niacin and fibric acid derivatives (fibrates)
How do ‘-statins’ class of drugs work?
Note: HMG is the precursor of cholesterol
- inhibits the first step of cholesterol synthesis –> decreases amount of cholesterol in the cell
- decreased cholesterol in cell stimulates synthesis of LDL receptors-> increase amount of LDL receptors promotes uptake of LDL in blood
- decreased cholesterol also decreases VLDL secretion from cell - improves coronary endothelial function
- inhibits platelet thrombus formation
- anti-inflammatory
Statin SEs
SE: liver failure, myopathy, CI in pregnancy
What is niacin used for?
Most effective agent for increasing HDL*
Niacin Side effects
SE: intense cutaneous flush and pruritus, inhibits tubular secretion of uric acid
What are the fibrates?
Fibrates increase lipoprotein lipase therefore lowering serum triacylgycerols and increasing HDL levels-> use to treat hypertriacylglycerolemias
Fibrate SEs
SE: gallstones (more cholesterol into gall bladder), myositis
Fibrate MoA
Fenofibrate and Gemfibrol binds to PPAR-alpha
What are the bile acid sequestrants?
Colesevelam, colestipol, cholestyramine
-prevent reabsorption of bile acids and salt, therefore liver uses more cholesterol to replace the bile
Bile Acid sequesterant SEs
SE: constipation, nausea, flatulence, impair the absorption of fat soluble vitamins (DAKE)
An example of cholesterol absorption inhibitor?
Ezetimibe
Which drug to start if a patient has high cholesterol?
Statins
Which drug to start if a patient has high TG?
Fibrates
Which drug to start if a patient has low HDL?
Niacin
What is the advantage of combo cholesterol drugs?
Synergistic effect and better compliance.
What is the disadvantage of combo cholesterol drugs?
Liver and muscle toxicity occurs more frequently, cost
