Dyslipidemia Drugs: Statins Flashcards
What is the site of free fatty acid and cholesterol absorption
lumen of small intestine
Cholesterol esters are packaged into the interior of chylomicrons in
intestinal cells
_______ make up most of the chylomicron
triglycerides
Chylomicrons contain
surface apolipoproteins A, B, C, and E
Chylomicrons deliver triglycerides from the
intestine to peripheral tissues
Triglycerides in chylomicrons and VLDLs are hydrolyzed by
LPL, releasing free fatty acids
Free fatty acids can be
- used for energy by heart and skeletal muscle
2. converted back into triglycerides and stored in adipose tissue
Chylomicron remnants return to the
liver
The LDL receptor binds to
ApoE and transports chylomicron remnant into liver via endocytosis
Cholesterol from chylomicron remnants are used by
the liver
HMG CoA reductase synthesizes
cholesterol in the liver
The first intermediate in cholesterol synthesis is
mevalonic acid
_______ make up most (~60%) of the VLDL
triglycerides
Cholesterol esters are packaged into the interior of VLDLs in
hepatocytes
Apolipoprotein B100 is found on
“bad cholesterol” (LDL and VLDL)
VLDLs deliver triglycerides from the liver to
peripheral tissues
Low density lipoprotein (LDL) is formed as
VLDLs lose triglycerides via LPL and hepatic lipase
LDLs contain a core of
cholesterol esters
LDLs deliver cholesterol to
peripheral tissues expressing LDL receptors
LDL receptor binds
ApoB and transports LDL particle into liver via endocytosis
Nascent HDL is secreted by the
liver and intestine
HDL extracts cholesterol from
peripheral tissues
Lecithin:cholesterol acyltransferase (LCAT)
converts free cholesterol into cholesterol esters for transport by HDL
Mature HDL particle contains
LCAT-generated cholesterol esters
HDL transfers
cholesterol esters to LDLs and VLDLs to be transported back to the liver
HDL delivers cholesterol esters
directly to the liver via scavenger 1 receptor
Statins include
- simvastatin
- atorvastatin
- rosuvastatin
Statins inhibit
HMG CoA reductase
Statins cause
increased LDL receptor expression on hepatocytes, clearing LDLs from circulation
Statins are the most effective drugs for lowering
LDLs (30-60%)
Statins can
- Decrease LDL
- Decrease Triglycerides
- Increase HDL
Statins have a mild effect on
- triglycerides
2. HDL
Hypercholesterolemia (LDL) is treated with
lifestyle modification and statins (first-line agent)
Statins improve
survival
Statins are the most effective lipid lowering drug for preventing
future cardiac events
Statins are the only lipid-lowering drug consistently proven to
reduce risk of atherosclerotic heart disease
Statin therapy is initiated in setting of
MI and other acute coronary syndromes (ACS)
statins reduce risk of cardiovascular events and mortality in
- high-risk diabetics
2. Peripheral artery disease
Statins reduce risk of future vascular events in patients with
a history of a TIA or stroke
Statins may be
teratogenic
Statins can cause
- myopathy weeks to months after starting therapy (muscle weakness/soreness)
- elevations in serum CK (myopathy)
What effect do statins have on liver function tests
mild elevations in liver function tests (LTFs) are common (reversible with discontinuation of statin)
All statins except for pravastatin are metabolized by
cytochrome p450 (CYP-450) in the liver
