Hyperlipidemia Flashcards
Atherosclerotic plaques constrict vessels and lead to
thrombosis, a blood clot occluding a major artery. Causes strokes and heart attacks (myocardial infarction)
Plaques build up over time. Arterial damage (possibly hypertension related) leads to
an aggregation of platelets, macrophages filled with oxidized lipids (foam cells), including cholesterol. Ruptures can precipitate immediate clotting and infarction
Cholesterol plays an important role in
regulating the lipid microenvironment (fluidity; lipid rafts).
Transporting lipids in blood is a problem since blood is _______ and lipids are _________.
aqueous; hydrophobic
Most lipid transport in blood is via carriers called
lipoproteins
Lipoprotein outer surface
Outer surface is largely a monolayer of triglycerides mixed with an apolipoprotein
Lipoprotein inner surface
Inner layers are mixtures of lipids including cholesteryl esters (nonpolar)
As density of particles increases, fat (triglyceride) content ______ while protein content _______.
declines; increases. Size also changes, with smaller particles being more dense
Fats from GI are packaged into large ________ particles. These distribute to tissues and have fatty acids removed by lipoprotein lipase via interaction with apolipoprotein C. ________ go to liver.
chylomicron; Remnants
VLDL remnants (IDLs) are depleted of ________ and picked up by liver, or converted into ____________.
triglycerides; LDL particles
LDL have primarily Apo
B-100
What percent of cholesterol is reabsorbed and transported back to the liver?
90%
If fasting, _______ and ________ are approximately 0
IDL and Chylos
TC=
LDL+HDL+VLDL+IDL+CHYLOS
VLDL ~
Trig/5 if Trig < 450
Primary goal of drug therapy
lower LDL-cholesterol
Secondary goal of drug therapy
is increase HDL or lower triglycerides
Statins
Remarkably effective. Cause up to 60% reductions in LDL cholesterol, 10% increase HDL, slight declines in triglycerides. Also reduce C-reactive protein.
Ezetimibe
Cholesterol absorption inhibitor.
statins MOA
Block HMG-coA reductase, the rate limiting enzyme in cholesterol synthesis in liver. The decrease in liver intracellular cholesterol leads to increased LDL-R expression and uptake of LDL cholesterol from the circulation
statins adverse effects
- Headache – Myalgia – Fatigue
- GI intolerance – Flu-like symptoms
increases in liver enzymes, liver myopathy,
-interacts with grapefruit juice
- GI intolerance – Flu-like symptoms
30% reduction in cardiovascular disease risk with
statin use in high risk populations
Fibric Acid derivatives MOA
Activate PPAR-alpha leading to increased lipoprotein lipase and reduced circulating triglycerides
Fibric Acid derivatives drugs
Gemfibrozil, fenofibrate
Bile acid sequestrants MOA
Binds bile acids in gut increasing excretion. Leads liver to increase LDL-R to obtain more cholesterol for synthesizing increased amounts of bile acids
Bile acid sequestrants drugs
Cholestyramine, colestipol, colesevelam
Niacin MOA
Reduces VLDL production by liver and Apo-B100 thereby reducing LDL in circulation
Cholesterol Absorption Inhibitors
Ezetimibe
Lomitapide treats
Familial Hypercholestrolemia due to homozygous loss of LDL-R
Lomitapide MOA
Blocks microsomal triglyceride transfer protein. reduces LDL
Absorption inhibitors MOA
Block uptake from GI tract to liver. Increase liver LDL receptors. Reduces circulating LDL
