Antihyperlipidemic Drugs

Question 1

How do statins work?

Answer 1

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.

Question 2

Why do statins cause myalgias?

Answer 2

Because they block the creation of ubiquinone (CoQ10).

Question 3

Cell bio of LDL receptor synthesis in the setting of statin admin.

Answer 3

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.

Question 4

Strength of statins

Answer 4

Losuvastatin, pravastatin, simvastatin weak ones
Atorvastatin medium
Rosuvastatin strongest. 2x stronger than atorvastatin.

Question 5

Goals of lowering LDL-C?

Answer 5

35% or 50% usually.

Question 6

Rule of 6

Answer 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%

Question 7

Crestor 20mg lowers cholesterol by what %?

Answer 7

50%

Question 8

Crestor 10 lowers cholesterol by what %

Answer 8

about 45.

Question 9

Do statins reduce risk of CV events

Answer 9

Yes

Question 10

Lescol XL 80mg

Answer 10

Weakest statin but fewest muscle aches.

Used in people who can’t tolerate statins.

Question 11

Are statins safe?

Answer 11

Yes absolutely

Question 12

Can you eat grapefruit with statins?

Answer 12

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.

Question 13

Ezetimibe

Answer 13

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.

Question 14

Does ezetimibe cause myalgia?

Answer 14

No

Question 15

Is ezetimibe + atorvastatin more effective than atorvastatin alone?

Answer 15

yes.

Question 16

Does ezetimibe lower CV events?

Answer 16

Maybe, not investigated yet so only approved to lower LDLC

Question 17

Colesevelam

Answer 17

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

Question 18

Problem with colesevelam

Answer 18

May bind anions, so watch TSH or INR if on coumadin.

Question 19

What does colesevelam do to lipids

Answer 19

Decreases LDL-C. Also reduces cardiac events

Question 20

Are elevated triglycerides harmful?

Answer 20

Yes, an independent risk factor for CHD, but even more so with low HDL (<40).

Question 21

How do triglycerides affect other lipids

Answer 21

VLDL filled with triglycerides. Triglycerides cut up HDL and lowers it. Lowering triglycerides raises HDL.

Question 22

What happens with extremely high triglycerides >1000?

Answer 22

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.

Question 23

Normal range of triglycerides?

Answer 23

<150

Question 24

Medications to lower triglycerides

Answer 24

fibric acids, niacin (B3), statins fish oil ** (shown to be ineffective)

Question 25

Do statins lower triglycerides?

Answer 25

Yes, about 20%

Question 26

Which drugs are fibrates

Answer 26

Gemofibrozil, fenofibrate

Question 27

What effects do gemofibrozil and fenofibrate have on lipids?

Answer 27

Increase HDL production

Decrease VLDL synthesis and increase VLDL clearance

Decrease number of LDL particles (kinda).

Question 28

When do fibrates work best?

Answer 28

In patients with low HDL (High ratio of LDL/HDL)

Question 29

Side effect of gemfibrozil

Answer 29

Increases concentration of statins, so careful. May cause rhabdomyolysis.

Question 30

What medication is best to raise HDL?

Answer 30

Niacin is best.

Fibrates are good too.

Question 31

Side effect of niacin (nicotinic acid, B3)

Answer 31

Itching

Question 32

PCSK9

Answer 32

an enzyme that prevents LDL receptor from being recycled, can increase LDLC in blood

Question 33

PCSK9 mAb

Answer 33

Blocks effect of PCSK9, decreases LDLC because allows LDLR to be recycled.

Question 34

Gemfibrozil and Niacin FDA approved to…

Answer 34

Reduce CV events