Lipid Metabolism, Dyslipidemias and Treatment 2 Flashcards Preview

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Flashcards in Lipid Metabolism, Dyslipidemias and Treatment 2 Deck (22):

8. Name the 3 main classes of drugs used to lower LDL cholesterol.

statins (HMG-CoA reductase inhibitors)
resins (bile acid binding resins)
azetidinomes (ezetimibe)

BONUS: drugs that mainly raise HDL and lower TG: niacin, fib rates and omega-3 fatty acids


8. Describe the major mechanism and efficacy of statins.

MM: inhibition of HMG-CoA reductase which reduces the intrahepatic cholesterol pool (reduce VLDL production from liver) and causes up regulation of hepatic LDL receptors (increase clearance of LDL and IDL)

reduction in LDL-C (20-60%)


8. Describe the additional and adverse effects of statins.

"pleiotropic" effects include inhibition of Rho, Ras and Rac which may contribute to CVD reduction

major side effects are dose-depednent including myalgia/myopathy, abnormal liver function tests, contraindicated with liver disease, or pregnancy; caution with use of fibrates


8. What is the mechanism of the action of Ezetimibe?

selectively inhibits uptake of cholesterol at intestinal brush border by inhibiting NPC1L1 (cholesterol transporter) in intestinal lumen side membrane


8. Give several reasons why bile acid binding resins may not be your first choice in treating hypercholesterolemia.

there is a 15-30% reduction in LDL-C by blocking reabsorption of bile salts, they are prescribed in a powder that is poorly tolerated or capsules which are often expensive, can cause constipation and reduce the absorption of other drugs

compensatory increase in HMGCoA reductase often, works best in combo with statins


8. Describe the mechanism of action as well as the hesitation around prescribing Azethidnones.

there is no evidence for CVD reduction or long term safety although Ezethimibe has been shown to reduce LDL-C 14-20% by blocking Niemann-Pick C1 like 1 protein which blocks absorption from the intestine

although it also can result in a compensatory increase in HMG CoA, it is well-tolerated by most, though contraindicated in severe liver disease


5. The majority of cholesterol export in extra hepatic tissues is mediated by what transporter.

ABC transporter (ABCA1)


5. Exported cholesterol joins with ApoA-1 which is synthesized in the _____ where cholesterol is esterified by ____-______ ______ resulting in mature HDL

lecithin- cholesterol acyltransferase (LCAT) **important to keep flux of cholesterol from cells to HDL


5. Mature HDL can bind to ___ ___-___ which selectively mediates the transfer of cholesterol ester from HDL into the liver.



Random interaction of mature HDL with chylomicrons and VLDL/LDL allows for the exchange of ___ ___ for TG, mediated by ___ ____ ____ _____

cholesterol esters for TG exchange caused by cholesterol ester transfer protein (CETP)- synthesized in the liver


In the presence of chylomicronemia or hypertriglyceridemia, CETP leads to enrichment of LDL and HDL with ___ and ____ and VLDL with ____

LDL and HDL enriched with TG
VLDL with cholesterol

the resulting LDL and HDL particles are small, dense, easily oxidized and poorly metabolized


5. Reverse cholesterol transport is unlikely the sole purpose of HDL, other major functions include (2)

anti-inflammatory effects
host defense and immunity (protection from endotoxin and trypanosomes)
apoproteins can be part of immune complexes as part of their immune function


6. List the lipoprotein and associated dyslipideima with the Fredrickson classification I, IIa, IIb, III, IV, and V.

I Chylos FH
III IDL, familial dysbetalipoproteinemia
V Chylos, VLDL, familial hypertryglyceridemia


6. What are arcus corneas and xanthelasmas

arcs corneas: white or gray halos inside the edge of the iris, caused by cholesterol deposition
xanthelasmas are yellowish deposits of cholesterol around the eyes


6. Describe eruptive xanthomata.

caused by really high levels of chylomiconemia eruptive "pustules" form on anything that come in contact with something else- lot of extensor surfaces


6. What is the mechanism and clinical presentation for familial hypercholesterolemia?

genetic deficient/defective LDL receptors (any step involved in getting the receptors working at the surface)

presents with very high total cholesterol levels
tendon xanthomatas
xanthelasmas and arcs corneus
very common and early cardiac events, homozygotes in 1st decade of life, heterozygotes in 3rd (men) or 4th (women) decade


6. Compare the mechanism and presentation of familial defective Apo B-100 to familial hypercholesterolemia.

mechanism is mutation in gene for apo B-100 (key defect instead of lock defect) causing poor LDL binding to receptors

clinically similar to FH


6. What happens to someone with familial combined hyperlipidemia?

is a complex disease either acquired or due to genes which causes an over production of apo B-100, leading to too much LDL, VLDL and many small, dense LDL/VLDL and low levels of HDL

1 in 50 Americans, can present with xanthelasmas, arcs corneus and often associated with HTN, type II DM and obesity in families


6. What causes familial hypoalphalipoporteinemia?

defects in ABCA1 causing very low HDL-C (increased risk of cataracts, arcus corneus and CHD)


6. Name secondary hyperlipidemias related to hypertriglyceridemia.

alcohol use **one of the strongest stimulants of cholesterol
estrogen use
chronic renal disease
etc. (others we didn't discuss)


6. Name secondary hyperlipidemias related to hypercholesterolemia.

chronic renal disease
obstructive liver disease


6. Name secondary hyperlipidemias due to low HDL cholesterol.

chonic renal disease
progestin use