Lipid Metabolism, Dyslipidemias and Treatment 2 Flashcards
- 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
- 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%)
- 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
- 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
- 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
- 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
- The majority of cholesterol export in extra hepatic tissues is mediated by what transporter.
ABC transporter (ABCA1)
- Exported cholesterol joins with ApoA-1 which is synthesized in the _____ where cholesterol is esterified by ____-______ ______ resulting in mature HDL
intestine
lecithin- cholesterol acyltransferase (LCAT) **important to keep flux of cholesterol from cells to HDL
- Mature HDL can bind to ___ ___-___ which selectively mediates the transfer of cholesterol ester from HDL into the liver.
SR- BI
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
- 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
- List the lipoprotein and associated dyslipideima with the Fredrickson classification I, IIa, IIb, III, IV, and V.
I Chylos FH IIa LDL FCH IIb LDL, VLDL FCH III IDL, familial dysbetalipoproteinemia IV VLDL FCH V Chylos, VLDL, familial hypertryglyceridemia
- 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
- 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
