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