Lec 17 Antihyperlipidemic Drugs

Question 1

What is major regulator of serum LDL?

Answer 1

hepatocyte LDL receptors

Question 2

What is action of statins?

Answer 2

HMG CoA reductase inhibitors –> block cholesterol production in liver –> stimulates SREBP [sterol regulatory element binding protein] which upregulate LDL receptors on hepatocytes

Question 3

What is comparative efficacy:
atorvastatin
rosuvastatin
lovastatin
simvastatin

Answer 3

rosuvastatin > atorvastatin > simvastatin > lovastatin

double doses to get same efficacy
rosuvastatin 1/2 the dose of atorvastatin

lovastatin needs 4x simvastatin

Question 4

What is rule of 6?

Answer 4

double dose of statin to get another 6% lowering

Question 5

What is atorvastatin basic dose to use to calculate needed dosages?

Answer 5

10 mg atorvastatin = 35% reduction

Question 6

What is HDL in men vs women?

Answer 6

45 in men

55 in women

Question 7

What is goal for HDL?

Answer 7

HDL > 60

Question 8

Which 2 statins are capable of 50% LDL reduction?

Answer 8

• atorvastatin

- rosuvastatin

Question 9

What dietary changes to reduce LDL?

Answer 9

• less saturated fat, cholesterol, trans fatty acids

Question 10

What are side effects of statins?

Answer 10

• myalgias
• rhabdomyalisis
• high AST/ALT

Question 11

Is there still increased benefit from decreasing LDL below 100?

Answer 11

linear increase benefit with lower LDL

Question 12

Whats up with grapefruit and statins?

Answer 12

• statins inhibit CYP450 in gut
• grapefruit inhibits cyp450
• if have lots of grapefruit –> more statin absorbed, higher plasma levels of statin

Question 13

What is action of ezetimibe?

Answer 13

blocks receptor in intestinal brush border to block cholesterol absorption from gut –> decrease hepatocyte intracellular cholesterol conc –> more LDL receptors in liver

Question 14

What happens if give ezetimibe monotherapy?

Answer 14

decrease LDL and triglycerides

Question 15

What happens if you give statin and ezetimibe?

Answer 15

its like doubling the statin dose 3 times = get huge decrease LDL and TG

= greater LDL reduction than atorvastatin 20 or 40 alone

Question 16

What are side effects of ezetimibe?

Answer 16

rare myalgias

Question 17

Does ezetimibe improve outcomes?

Answer 17

decreases LDL but unproven yet to lower ischemic CV events

Question 18

What is effect of statins? [on LDL/HDL/TG/outcomes]

Answer 18

• decrease LDL by a lot
• increase HDL
• decrease TG
• decrease risk of poor outcome [death/MI]

Question 19

What is effect of ezetimibe? [on LDL/HDL/TG/outcomes]

Answer 19

• decrease LDL
• not really affect HDL and TG
• not known whether it decreases risk of poor outcome

Question 20

What is effect of bile acid binders [on LDL/HDL/TG/outcomes]

Answer 20

• 15-20% decrease LDL
• slightly increase HDL and TG
• decrease CHD events within 3 yrs

Question 21

Fibrates [on LDL/HDL/TG/outcomes]

Answer 21

• decrease LDL a little
• increase HDL
• decrease TG a lot
• prevent ischemic CV disease

Question 22

Niacin [on LDL/HDL/TG/outcomes]

Answer 22

• decrease LDL
• increase HDL a lot [#1 choice]
• decrease TG
• decrease CV risk

Question 23

What is difference cholestyramine vs colesevalam?

Answer 23

cholestyramine = first gen; anion binder = lots of drug interactions b/c binds other medications

colesevalam = docking site more specific for bile acid –> less drug interactions

Question 24

What are side effects of bile acid binders [colesevalam and cholestyramine]?

Answer 24

difficult to take = large pills
constipation
decrease absorption other drugs

Question 25

What normal TG level?

Answer 25

normal < 150 | high >200

Question 26

When do chylomicrons appear?

Answer 26

at TG > 1000 --> can lead to pancreatitis

Question 27

What is risk with high TG?

Answer 27

independent risk factor for CHD especially with low HDL < 40

Question 28

Which meds can you use to lower TG?

Answer 28

- statins - fibric acids - niacin - fish oils

Question 29

Which meds can you use to lower LDL?

Answer 29

d

Question 30

Which meds can you use to increase HDL?

Answer 30

- niacin is best - fibrates minor effect: statins, bile acid binders

Question 31

What is mech of action fish oil?

Answer 31

inhibits VLDL formation so less VLDL secreted good for treating high TG

Question 32

What is action of fibrates on HDL/TG/LDL?

Answer 32

HDL: increases Apo A-I/II --> incraese HDL production TG: decrease TG synthesis --> decreased VLDL synthesis; increase LPLipase --> increase VLDL clearance LDL: decrease # of LDL particles

Question 33

Does fish oil decrease CV events?

Answer 33

no

Question 34

Does niacin added to statins bring extra benefit?

Answer 34

nope