Dyslipidemia Flashcards
statin-indicated conditions
- clinical atherosclerosis (MI, stroke, TIA, stable angina, ACS, PAD)
- abdominal aortic aneurysm (aorta > 3 cm or past aneurysm surgery)
- DM - > 40 y/o or > 15 years of DM + > 30 yo, or microvascular complications
- CKD (ACR > 3, or eGFR <60)
- LDL > 5 mmol/L (w/ familial hypercholesterolemia)
treatment targets for LDL
Primary prevention - when to start with statin
Non-statin drugs to treat cholesterol
ezetimibe
fibrates
bile acid sequestrants (cholestyramine)
PCSK9 inhibitors
omega3 fatty acids
Most common cholesterol-transporting lipoproteins
LDL
HDL
Triglycerides
LDL-Lowering drugs
statins
bile acid seq.
cholesterol absorption inhibitors
PCSK9 inhibitors
Triglyceride lowering drugs
omega 3
fibrates
Combined LDL + TG lowering drugs
niacin
Statin MoA
HMG-CoA reductase inhibitor
HmgCoA red. is involved in converting Hmg-CoA to cholesterol in hepatocytes
Drug interactions with statins
reduce dose if patient is also taking: cyclosporine, antifungals (cyp3a4 inhibitors), macrolide antibiotics, danazol
how are statins excreted?
1/5 - urine
rest - bile
Which drugs interact with cyp3a4 inhibitors like grapefruit?
simvastatin, atorvastatin, lovastatin
statin toxicity can lead to?
myopathy due to high concentrations
rhabdomyolysis - medical emergency
What is the best drug to enhance HDL levels and reducing TG?
niacin (vitamin b3)
MoA of fibrates
Activates PPAR-Alpha (peroxisome) –> increases fatty acid oxidation = reduces amount of substrates that can form TGs and VLDL
AEs of fibrates
GI upset
gemfibrozil- +eczema and headache
which fibrate should be completely avoided in combo with a statin?
gemfibrozil = reduces efficacy of statin, increases risk of myopathy due to statin
MoA of cholestryramine
bile acid binding resin - large, water insoluble, binds to negatively charged bile acids. reduces LDL levels. drug not absorbed in intestines. they get flushed away after binding.
Side effects of cholestyramine
GI: bloating, constipation, diarrhea
heartburn
-malabsorption of fat-soluble vitamins (like vit D)
Cholesterol absorption inhibitor (Ezetimibe) MoA
inhibits cholesterol transport protein in intestine
-no effect on TG
-if added to statin, slight improvement in reducing CV risk
why should ezetimibe be avoided with cholestyramine?
cholestyramine (a bile acid binding resin) will reduce ezetimibe absorption
PCSK9 inhibitor examples and MoA
ex. evolocumab, alirocumab
-normally, PCSK9 binds to LDL receptor and promotes its degradation.
WE WANT more receptors on hepatocytes for LDL absorption into cells (from plasma).
-this drug will stop the degradation of ldl receptors
indication for icosapent ethyl (omega3 FA)
severe hypertriglyceridemia
who should be SCREENED for dyslipidemia? (lipid profile)
- children with family history of CVD or dyslipidemia
- men 40+ y/o
- women 40+ y/o and postmenopausal
- South Asian, First Nations, recent immigrants
