Atherosclerosis

Question 1

What is the cholesterol biosynthetic pathway?

Answer 1

acetyl CoA–> HMG CoA–> mavalonic acid via HMG CoA reductase–> geranyl pyrophosphate–> farnesyl pyrophosphate–> cholesterol

Question 2

What are triglycerides?

Answer 2

an ester; glycerol + 3 fatty acids; component of animal fat and vegetable oil; store and circulate fat; important source of energy

Question 3

What are lipoproteins?

Answer 3

complex of lipids & proteins w/ hydrophobic core; enable transport of lipids (triglycerides to periphery)

Question 4

exogenous pathway of lipid metabolism

Answer 4

intestinal absorption of dietary cholesterol & fatty acids; free fatty acids combine w/ glycerol to form triglycerides; cholesterol esterified to cholesterol esters via ACAT; triglycerides & cholesterol assembled into chylomicrons that enter circulation; lipoprotein lipase hydrolyzes (removes) triglycerides in extrahepatic tissues; chylomicron remnants taken up by hepatocytes

Question 5

high density lipoproteins

Answer 5

HDL; small diameter; high density; B-100 apolipoproteins

Question 6

low density lipoproteins

Answer 6

LDL; larger diameter; less dense; B-100 apolipoproteins

Question 7

very low density lipoproteins

Answer 7

VLDL; large diameter; low density; B-100 apolipoproteins

Question 8

chylomicrons

Answer 8

largest diameter; low density; B-48 apolipoproteins

Question 9

endogenous pathway of lipid metabolism

Answer 9

nutrient deficiency; liver packages triglycerides into VLDL; muscle or adipose pick up free fatty acids; remnants (IDL) rich in cholesterol esters can go back to liver for metabolism or have triglyceride further removed to be left w/ LDL; LDL is rich in esters so can be taken back to liver for metabolism or stripped of extra cholesterol & turned into HDL

Question 10

mechanism of action of hypolipidemic agents

Answer 10

prevent intestinal absorption of cholesterol or bile acids; decrease cholesterol synthesis (increase LDL receptors & uptake); inhibit VLDL secretion (decrease LDL production); upregulate lipoprotein lipase (decrease triglycerides)

Question 11

What is CYP7A1?

Answer 11

rate-limiting enzyme of converting cholesterol into bile acids

Question 12

What is the negative feedback loop of cholesterol use in the body?

Answer 12

bile acids activate nuclear hormone receptor FXR in ileocyte; hormone FGF-15/19 goes back to liver via portal circulation to regulate expression of CYP7A1; regulates amt of bile acids generated; prevents body from using too much cholesterol

Question 13

mechanism of action of bile acid sequestrants

Answer 13

target the negative feedback loop; prevent reabsorption of bile acids; bile acids needed to burn up cholesterol

Question 14

mechanism of action of nicotinic acid

Answer 14

impairs production of VLDL to decrease LDL production; decreases triglycerides

Question 15

mechanism of action of HMG CoA reductase inhibitors

Answer 15

competitive inhibition; liver senses low cholesterol levels; decrease cholesterol synthesis & upregulate LDL receptors on hepatocytes (decrease circulating LDL)

Question 16

Why do statins need to be taken in the evening?

Answer 16

They are HMG CoA reductase inhibitors. Cholesterol synthesis takes place at night.

Question 17

drug-drug interactions of CYP3A4 substrate statins

Answer 17

increased drug levels in CYP3A4 inhibitors (fibrates, macrolides, cyclosporine); decreased drug levels in CYP3A4 inducers (phenytoin, barbs)

Question 18

drug-drug interactions of CYP2C9 substrate statins

Answer 18

increased drug levels in CYP2C9 inhibitors (azoles, amiodarone)

Question 19

Which medications are affected by grapefruit juice?

Answer 19

lovastatin, simvastatin, atorvastatin; juice inhibits CYP3A4

Question 20

mechanism of action of fibric acids

Answer 20

ligands for PPAR alpha; upregulate lipoprotein lipase, apo A-I, apo A-II; clears chylomicrons and VLDL; lowers VLDL & raises HDL

Question 21

mechanism of action of exetimibe

Answer 21

impairs intestinal absorption of cholesterol; absorbed & glucuronidated; excreted into bile & feces