Antihyperlipidemic Drugs Flashcards
How do statins work?
They’re HMG-CoA reductase inhibitors that lower the synthesis of cholesterol in all cells. Because hepatocytes are exquisitely tuned to cholesterol concentration, reduction in cholesterol causes them to upregulate LDL receptors to pull LDL-C out of the blood.
Why do statins cause myalgias?
Because they block the creation of ubiquinone (CoQ10).
Cell bio of LDL receptor synthesis in the setting of statin admin.
Normally, cholesterol binds to Scap and SREBP. If low intracellular cholesterol, SREBP and Scap cleaved from ER, moves to golgi, where SREBP is modified. Then moves into nucleus where SRE (sterol regulatory element) activates target genes for LDL receptor synthesis.
Strength of statins
Losuvastatin, pravastatin, simvastatin weak ones
Atorvastatin medium
Rosuvastatin strongest. 2x stronger than atorvastatin.
Goals of lowering LDL-C?
35% or 50% usually.
Rule of 6
Doubling the dose of a statin reduces LDL C by 6%.
So, if trying to get cholesterol from 180 to 130. Need 33% reduction. Crestor 5, lipitor 10, zocor 20, pravastatin 80%
Crestor 20mg lowers cholesterol by what %?
50%
Crestor 10 lowers cholesterol by what %
about 45.
Do statins reduce risk of CV events
Yes
Lescol XL 80mg
Weakest statin but fewest muscle aches.
Used in people who can’t tolerate statins.
Are statins safe?
Yes absolutely
Can you eat grapefruit with statins?
Grapefruit is a CYP3A4 inhibitor so can increase level of statins by preventing breakdown. However this effect happens with 1 quart of grapefruit juice. 1 half grapefruit is fine.
Ezetimibe
Blocks the Niemann-Pick receptor in intestinal brush border which blocks cholesterol absorption in gut. This decreases hepatocyte cholesterol concentration so increases LDL. Very effective, but expensive.
Does ezetimibe cause myalgia?
No
Is ezetimibe + atorvastatin more effective than atorvastatin alone?
yes.
Does ezetimibe lower CV events?
Maybe, not investigated yet so only approved to lower LDLC
Colesevelam
Bile acid sequestrant that works by because bile acids are made of cholesterol. Depleting bile acids causes hepatocytes to need more cholesterol and will then upregulate LDL receptor
Problem with colesevelam
May bind anions, so watch TSH or INR if on coumadin.
What does colesevelam do to lipids
Decreases LDL-C. Also reduces cardiac events
Are elevated triglycerides harmful?
Yes, an independent risk factor for CHD, but even more so with low HDL (<40).
How do triglycerides affect other lipids
VLDL filled with triglycerides. Triglycerides cut up HDL and lowers it. Lowering triglycerides raises HDL.
What happens with extremely high triglycerides >1000?
Chylomicrons appear and can get into pancreas and cause huge inflammatory reaction. Pancreatitis is goal of therapy, can’t get into vascular wall because too big so not a problem.
Normal range of triglycerides?
<150
Medications to lower triglycerides
fibric acids, niacin (B3), statins fish oil ** (shown to be ineffective)
Do statins lower triglycerides?
Yes, about 20%
Which drugs are fibrates
Gemofibrozil, fenofibrate
What effects do gemofibrozil and fenofibrate have on lipids?
Increase HDL production
Decrease VLDL synthesis and increase VLDL clearance
Decrease number of LDL particles (kinda).
When do fibrates work best?
In patients with low HDL (High ratio of LDL/HDL)
Side effect of gemfibrozil
Increases concentration of statins, so careful. May cause rhabdomyolysis.
What medication is best to raise HDL?
Niacin is best.
Fibrates are good too.
Side effect of niacin (nicotinic acid, B3)
Itching
PCSK9
an enzyme that prevents LDL receptor from being recycled, can increase LDLC in blood
PCSK9 mAb
Blocks effect of PCSK9, decreases LDLC because allows LDLR to be recycled.
Gemfibrozil and Niacin FDA approved to…
Reduce CV events
