Lecture 30: Lipid Lowering Medications Flashcards
What is serum LDL related by? By how much?
Hepatocyte LDL receptors; 70%
How do statins work?
Irreversibly block HMG CoA reductase and cholesterol production in liver cells –> lower intracellular cholesterol –> activated sterol regulatory element binding proteins (SREBP) –> upregulated LDL receptors
What was the first statin?
Lovastatin
What is the trend of statins ove time?
Lower dose –> larger increased in LDL-C reduction
Atorvastin 10 gets you a…
35% reduction
Double dose of a statin reduces LDL-C by…
6%
Order the statins by strength
Rosuvastatin –> atorvastatin –> simvastatin –> pravastatin/lovastatin
Can all these statins get us to 50% reduction?
Nope! Only rosuvastatin and atorvastatin
Statin side effects
Myalgia (5%), rare case of rhabdomyolysis (muscle breakdown), increased AST, myopathy
Statins reduce risk of…(3)
Nonfatal MI, CHD death, strokes
What does grapefruit do w/ statins?
Inhibits CYP450 in gut –> more statin absorbed, only dangerous if drinking >quart/day
How does ezetimibe work?
Blocks receptor in intestinal brush border –> decreased cholesterol absorption in gut –> decreased hepatocyte intracellular cholesterol concentration –> increased LDL receptor synthesis
Does ezetimibe work if you’re not eating cholesterol?
Yes, because we make excess cholesterol that we reabsorb, which is blocked by the drug
How much does ezetimibe reduce LDL? Affect HDL or TG?
20%; not really
Can you stack statins?
Yes, ezetimibe + atorvastatin = results of high dose atorvastatin
SEs of ezetimibe (rare)
Mylagias
What is ezetimibe approved to do?
Lower statins and ischemic cerebral events
What is the root of the bile acid binders? How do they work?
Chole/cole-; bind biles
What is today’s bile acid binder? Advantage of this newer drug?
Colesevelam; doesn’t bind other drugs
How much does colesevelam lower LDL? What events do they decrease?
15-20%; decrease CHD events
Problems with colesevelam
- Must take 6 large pills; 2. Cause constipation; 3. Decreases absorption of levothyroxine, coumadin
How do we deal with the interactions with levothyroxine and coumadin?
Take 4 hours before
Triglycerides are an independent risk factor for…especially with…
CHD, especially with a low HDL (
What is a high TG? What happens if you’re over 1000?
200+; chylomicrons cause acute pancreatitis
What medications lower TGs? (4)
Statins, fibric acids, high doses of niacin, fish oils
Strongest –> weakest statin for lowering TG
Rosuvastatin, atorvastatin, simvastatin, pravastatin
How do the fibrates work on HDL, TG, LDL?
Increases Apo A1 and A-11 –> increased HDL production; decrease TG synthesis and increased LPLipase / decreased Apo C-III –> decreased VLDL synthesis and increased clearance; decreases LDL particles by making them larger
What are the fibrate medications? (2)
Gemofibrozil, fenofibrate
When does reducing your TG levels work?
When TG are high AND LDL/HDL ratio is greater than 5, medication will reduce incidence rate
Fibric acids and severe hypertriglyceridemia
Excellent, prevent pancreatitis
What is gemifborzil approved for that fenofibrate is not? Caveat?
Prevent ischemic CV disease; if TG > 200 and HDL-C
Gemfibrozil does what to statin concentrations? How about fenofibrate?
Raises them; much less so
If you give a statin and gemfibrozil what do you have to watch out for?
Myositis, rhabdomyolysis
In high doses, what do fish oil do? How?
Lowers TG (3 gms EPA/DHA/day); increase hepatic pre-secretory VLDL proteloysis –> increased VLDL secretion
Does fish oil prevent PRIMARY CV events?
No evidence; old evidence it might decrease CV events in secondary prevention
How to raise HDL cholesterol
Niacin, fibric acids by reducing TG; statins (minor effect)
Which statin is best at raising HDL-C? (%)
Rosuvastatin (~7-9%)
What does niasin do?
HDL-C increases ~30%, TG reduced by ~40%, LDL reduced by ~30%
Does niacin reduce events?
Yes: MI, CHD death, stroke
What is the PSK9 gene? Why was it found?
Binds to cholesterol + LDL receptor and causes degradation (so receptor cannot be used again); Variants in this gene causing decreased function have significantly lower LDL with lower CHD events
What is the PSK9 medication name and what is it? % LDL-C decrease. Does it decrease event rates?
Evolocumab; PSK9 antibody; 60% lower; waiting on trials
Summary: what two drugs discussed given alone can lower TG and CV events?
Gemfibrozil and niacin
Summary: what two drugs discussed given alone are only approved to lower TG?
Fenofibrate and fish oil
