Lecture 30: Lipid Lowering Medications

Question 1

What is serum LDL related by? By how much?

Answer 1

Hepatocyte LDL receptors; 70%

Question 2

How do statins work?

Answer 2

Irreversibly block HMG CoA reductase and cholesterol production in liver cells –> lower intracellular cholesterol –> activated sterol regulatory element binding proteins (SREBP) –> upregulated LDL receptors

Question 3

What was the first statin?

Answer 3

Lovastatin

Question 4

What is the trend of statins ove time?

Answer 4

Lower dose –> larger increased in LDL-C reduction

Question 5

Atorvastin 10 gets you a…

Answer 5

35% reduction

Question 6

Double dose of a statin reduces LDL-C by…

Answer 6

6%

Question 7

Order the statins by strength

Answer 7

Rosuvastatin –> atorvastatin –> simvastatin –> pravastatin/lovastatin

Question 8

Can all these statins get us to 50% reduction?

Answer 8

Nope! Only rosuvastatin and atorvastatin

Question 9

Statin side effects

Answer 9

Myalgia (5%), rare case of rhabdomyolysis (muscle breakdown), increased AST, myopathy

Question 10

Statins reduce risk of…(3)

Answer 10

Nonfatal MI, CHD death, strokes

Question 11

What does grapefruit do w/ statins?

Answer 11

Inhibits CYP450 in gut –> more statin absorbed, only dangerous if drinking >quart/day

Question 12

How does ezetimibe work?

Answer 12

Blocks receptor in intestinal brush border –> decreased cholesterol absorption in gut –> decreased hepatocyte intracellular cholesterol concentration –> increased LDL receptor synthesis

Question 13

Does ezetimibe work if you’re not eating cholesterol?

Answer 13

Yes, because we make excess cholesterol that we reabsorb, which is blocked by the drug

Question 14

How much does ezetimibe reduce LDL? Affect HDL or TG?

Answer 14

20%; not really

Question 15

Can you stack statins?

Answer 15

Yes, ezetimibe + atorvastatin = results of high dose atorvastatin

Question 16

SEs of ezetimibe (rare)

Answer 16

Mylagias

Question 17

What is ezetimibe approved to do?

Answer 17

Lower statins and ischemic cerebral events

Question 18

What is the root of the bile acid binders? How do they work?

Answer 18

Chole/cole-; bind biles

Question 19

What is today’s bile acid binder? Advantage of this newer drug?

Answer 19

Colesevelam; doesn’t bind other drugs

Question 20

How much does colesevelam lower LDL? What events do they decrease?

Answer 20

15-20%; decrease CHD events

Question 21

Problems with colesevelam

Answer 21

1. Must take 6 large pills; 2. Cause constipation; 3. Decreases absorption of levothyroxine, coumadin

Question 22

How do we deal with the interactions with levothyroxine and coumadin?

Answer 22

Take 4 hours before

Question 23

Triglycerides are an independent risk factor for…especially with…

Answer 23

CHD, especially with a low HDL (

Question 24

What is a high TG? What happens if you’re over 1000?

Answer 24

200+; chylomicrons cause acute pancreatitis

Question 25

What medications lower TGs? (4)

Answer 25

Statins, fibric acids, high doses of niacin, fish oils

Question 26

Strongest –> weakest statin for lowering TG

Answer 26

Rosuvastatin, atorvastatin, simvastatin, pravastatin

Question 27

How do the fibrates work on HDL, TG, LDL?

Answer 27

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

Question 28

What are the fibrate medications? (2)

Answer 28

Gemofibrozil, fenofibrate

Question 29

When does reducing your TG levels work?

Answer 29

When TG are high AND LDL/HDL ratio is greater than 5, medication will reduce incidence rate

Question 30

Fibric acids and severe hypertriglyceridemia

Answer 30

Excellent, prevent pancreatitis

Question 31

What is gemifborzil approved for that fenofibrate is not? Caveat?

Answer 31

Prevent ischemic CV disease; if TG > 200 and HDL-C

Question 32

Gemfibrozil does what to statin concentrations? How about fenofibrate?

Answer 32

Raises them; much less so

Question 33

If you give a statin and gemfibrozil what do you have to watch out for?

Answer 33

Myositis, rhabdomyolysis

Question 34

In high doses, what do fish oil do? How?

Answer 34

Lowers TG (3 gms EPA/DHA/day); increase hepatic pre-secretory VLDL proteloysis –> increased VLDL secretion

Question 35

Does fish oil prevent PRIMARY CV events?

Answer 35

No evidence; old evidence it might decrease CV events in secondary prevention

Question 36

How to raise HDL cholesterol

Answer 36

Niacin, fibric acids by reducing TG; statins (minor effect)

Question 37

Which statin is best at raising HDL-C? (%)

Answer 37

Rosuvastatin (~7-9%)

Question 38

What does niasin do?

Answer 38

HDL-C increases ~30%, TG reduced by ~40%, LDL reduced by ~30%

Question 39

Does niacin reduce events?

Answer 39

Yes: MI, CHD death, stroke

Question 40

What is the PSK9 gene? Why was it found?

Answer 40

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

Question 41

What is the PSK9 medication name and what is it? % LDL-C decrease. Does it decrease event rates?

Answer 41

Evolocumab; PSK9 antibody; 60% lower; waiting on trials

Question 42

Summary: what two drugs discussed given alone can lower TG and CV events?

Answer 42

Gemfibrozil and niacin

Question 43

Summary: what two drugs discussed given alone are only approved to lower TG?

Answer 43

Fenofibrate and fish oil