Hyperlipidemics Flashcards
What breaks down triglycerides into free fatty acids?
Lipoprotein lipase
Endogenous route of getting FFA to tissues?
Liver produces VLDL which takes triglycerides to tissues which are broken down by LPL
What happens to VLDL after dropping off triglycerides?
Converted to IDL and taken up by liver.
Or IDL can be converted to LDL which is taken up by liver or extrahepatic tissues through LDL receptor
LDL and HDL are higher in density because they have less what and more what?
LDL and HDL have less triglycerides and more cholesterol
Which lipoproteins are present on chylomicrons? 4
A, B-48, C-2, and E
Which lipoproteins are present on VLDL? 3
B-100, C-2, and E
Which lipoproteins are present on LDL? 1
B-100
Which lipoproteins are present on HDL? 5
A-1, A-2, C-2, D, and E
What 2 enzymes re-esterify cholesterol and monoglycerides?
- ACAT (acetyl-CoA acyltransferase)
2. DGAT (diglyceride acyltransferase)
Which transporter transporter cholesterol from the lumen of the SI into the SI?
Which drug inhibits this transporter?
NPC1L1
Ezitemibe (Zetia)
What is the lipoprotein that chylomicrons acquire in the SI?
What lipoproteins (2) do they acquire from HDL?
What lipoprotein/cofactor allows chylomicrons to bind to LPL?
Once triglycerides have left, which lipoprotein is released back to HDL?
Which lipoproteins are necessary for reuptake by the liver? 2
Apo-B48 Apo-C2 and Apo E Apo-C2 does the LPL thing Apo-C2 is released back to HDL Apo B48 and Apo E allow remnants to be taken up by liver but it is mostly Apo E
VLDL particles receive which lipoprotein in the liver?
Which 2 lipoproteins do VLDL receive from HDL?
What lipoprotein/cofactor allows VLDL to bind to LPL?
Which lipoprotein is an important ligand for LDL receptors?
Apo-B100
Apo-C2 and Apo E
Apo C2 does the LPL thing again
Apo B100 allows LDL to be taken up into the liver or extra-hepatic tissues
HDL is transported to the liver where it binds to (what) though which lipoprotein? What is transferred to hepatocytes?
HDL binds to SR-B1 through Apo A-1
Cholesterol esters are selectively delivered to hepatocytes
Cause of primary chylomicronemia?
Deficient LPL activity
Cause of familial hypertriglycerideemia?
Deficient removal of VLDL or chylomicrons
Cause of familial combined hyperlipidemia/hypercholesterolemia?
Increased VLDL production
Cause of familial dysbetalipoproteinemia?
Deficient clearance of VLDL, IDL, and chylomicron remnants due to dysfunction or absence of Apo E
Cause of familial hyper-cholesterolemia
LDL-R impairment
Cause of familiar ligand-defective apoB?
Mutation in apo-B100 resulting in impaired endocytosis of LDL
Fibric acid derivatives (2(
Gemfibrozil and fenofibrate
How do the fibric acid meds work? 3
- Increase plasma HDL
- Increases reverse cholesterol transport
- Increased fatty acid oxidation
Gemfibrozil and fenofibrate upregulate which transcription factor?
Activate/upregulate the PPAr receptor
Which lipoproteins are upregulated with gemfibrozil and fenofibrate?
Apo A1 and Apo A2
Why should gemfibrozil and fenofibrate not be combined with statins?
Increased risk of myopathy
How do cholestyramine. colesevelam, colestipol work?
Bind bile acids and bile salts in the intestines and shat them out. Liver has to increase synthesis of bile acid to replaces what was lost
How do the bile binders remove LDL?
Liver requires LDL to replace lost bile acids so there is an upregulation of LDL-R in the liver
Bile binders would help treat which disorder?
Familiar hypercholesterolemia (LDL-R issues)
Which population should not be taking bile-binders?
Anyone with high triglycerides
Bile binders are drug of choice for which 2 populations?
- Children
2. Pregnant or lactating women
Niacin is used to lower (2) and raise (1)?
Lower VLDL and LDL, raise HDL
How does niacin work exactly?
Niacin decreases lipase activity in adipose tissue. This decreases FFA in the blood which means the liver cannot produce triglycerides as much.
This causes less VLDL and LDL delivery to peripheral cells. The liver needs cholesterol so there is an upregulation of cholesterol removal by HDL.
This cholesterol is brought to liver to be used for bile acids and other stuff
How effective is niacin?
Not very effective which is why it is used in combination therapy
4 common side effects of niacin?
- Flushing/itching (niacin flush)
- Hyperuricemia
- Hyperglycemia
- Hepatotoxicity
Safest niacin + statin combination?
Least safest combination?
Niacin plus fluvastatin is good.
Niacin plus lovastatin is bad
Ezetimibe blocks intestinal absorption of cholesterol and bile acids through which transporter?
Niemann-Pick C1 like 1 protein
Statin adverse effects (2)
- Liver toxicity in low percentage of patients
2. Never use in pregnancy
