Statins

Question 1

what are 2 main approaches for treating dyslipidemia

Answer 1

diet/lifestyle

drugs

Question 2

what are 3 lifestyle things to treat dyslipidemia

Answer 2

• avoid high fat/cholesterol foods
• consume agents that increase HDL
• exercise

Question 3

what are 3 main pharmacological lipid lowering approaches

Answer 3

• prevent cholesterol synthesis
• inhibit bile reabsorption from GI
• inhibit cholesterol absorption from GI

Question 4

what is a main way to prevent cholesterol synthesis

Answer 4

inhibit HMG-CoA reductase

Question 5

how do you inhibit HMG-CoA reductase

Answer 5

statins

Question 6

why does inhibiting HMG-CoA reductase help with cholesterol

Answer 6

low cholesterol stimulates increase in LDL receptors, the more LDL will be removed from blood

Question 7

why does inhibiting bile reabsorption from GI help with cholesterol

Answer 7

because it increases bile synthesis which then decreases liver cholesterol levels

Question 8

why does inhibiting cholesterol absorption from GI help with cholesterol

Answer 8

because less from diet so then less overall

Question 9

what do statins do generally

Answer 9

inhibit cholesterol biosynthesis

Question 10

what is an example of a statin

Answer 10

simvastatin

Question 11

what do fibrates do generally

Answer 11

activate PPARalpha receptor (in many tissues) to alter expression of enzymes involved in lipid metabolism

Question 12

what is an example of a fibrate

Answer 12

gemfibrozil

Question 13

what do resins do generally

Answer 13

binda and sequester bile acids

Question 14

what does nicotinic acid do generally

Answer 14

inhibit VLDL secretion

Question 15

what is ezetimibe

Answer 15

inhibits cholesterol absorption

Question 16

what are 5 risk factors for atherosclerosis

Answer 16

smoking, hypertension, diabetes, obesity, low HDL

Question 17

what are the most effective and well tolerated drugs for dyslipidemia

Answer 17

statins

Question 18

what is the mechanism of action of simvastatin

Answer 18

reversible competitive inhibitors of HMGCoA reductase

Question 19

what is the role of HMGCoA reductase (general)

Answer 19

early rate limiting step in cholesterol synthesis in the liver

Question 20

what % of cholesterol is made in liver

Answer 20

80%

Question 21

what % of cholesterol is from your diet

Answer 21

20%

Question 22

what is the top selling drug in the world

Answer 22

simvastatin

Question 23

what is lovastatin

Answer 23

the first statin for human use

Question 24

where did lovastatin come from

Answer 24

mould

Question 25

what is the reaction that HMGCoA reductase catalysis

Answer 25

HMG-CoA --> mevalonate

Question 26

how are statins able to inhibit HMGCoA reductase

Answer 26

they are structural analogues of HMG-CoA

Question 27

are statins reversible or irreversible inhibitors

Answer 27

reversible

Question 28

are statins competitive or non competitive inhibitors

Answer 28

competitive

Question 29

what is the affinity for statins compared to natural substrate

Answer 29

1000-10000X greater for statins!

Question 30

what are 2 main/important LDL effects when HMG-CoA reductase is inhibited

Answer 30

increased LDL receptor synthesis, increased LDL uptake

Question 31

how much can statins reduces plasma cholesterol

Answer 31

by up to 40%

Question 32

what do statins do to VLDL

Answer 32

reduce it

Question 33

what do statins do to plasma TGs

Answer 33

reduce

Question 34

what do statins do to LDL

Answer 34

reduce

Question 35

what do statins do to plasma cholesterol

Answer 35

reduce

Question 36

what do statins do to LDL receptor expression

Answer 36

increase

Question 37

what do statins do to LDL uptake

Answer 37

increae

Question 38

what are 2 main ways statins reduce plasma cholesterol

Answer 38

- reduce VLDL: reduce TGs and LDL | - increase LDL receptor expression: increase LDL uptake

Question 39

how do statins decrease VLDL

Answer 39

decreased intracellular cholesterol (inhibit synthesis) decreases VLDL secretion

Question 40

why does the liver make more LDL receptors

Answer 40

because there is decreased delivery of cholesterol to tissues

Question 41

what 2 things contribute to decreased plasma LDL

Answer 41

increased LDL uptake and decreased plasma VLDL

Question 42

what do statins do to HDL levels

Answer 42

increase

Question 43

what do statins do to endothelial function

Answer 43

improve

Question 44

what do statins do to platelet aggregation

Answer 44

decrease

Question 45

what do statins do to ischemic tissue

Answer 45

increase neovascularization (new vessels in ischemic tissue)

Question 46

what do statins do to inflammation

Answer 46

anti

Question 47

what do statins do to plaque stability

Answer 47

increase

Question 48

what do statins do to LDL oxidation

Answer 48

inhibit

Question 49

what do statins do to endothelial progenitor cells

Answer 49

increase (so a healthier endothelial layer)

Question 50

what are 2 main patient groups that we give statins to

Answer 50

``` primary prevention (risk factors but no CHD) secondary prevention (people with CHD) ```

Question 51

what is the benefit of statins for people with risk factors and no CHD

Answer 51

reduces risk of CV event

Question 52

what is the benefit of statins for people with CHD

Answer 52

reduce cardiac events (MI), stroke and morality even if LDL is normal

Question 53

what did the ASTEOID trial in 2006 conclude

Answer 53

high dose of statin may cause CHD regression

Question 54

what are 2 side effect of statins

Answer 54

myositis and rhabdomyolysis and type 2 diabetes

Question 55

what is myositis and rhabdomyolysis

Answer 55

breakdown of skeletal muscle

Question 56

how can myositis and rhabdomyolysis cause renal damage

Answer 56

accumulation of iron from myoglobin

Question 57

how can statins cause myositis and rhabdomyolysis

Answer 57

due to lack of cholesterol derived mediators required for muscle structure

Question 58

which kind of people taking statins get myositis and rhabdomyolysis

Answer 58

high doses or drugs that interfere with statin breakdown

Question 59

how many people die cause of myositis and rhabdomyolysis statins

Answer 59

1 per million

Question 60

besides myositis and rhabdomyolysis, what else can statins cause

Answer 60

increase risk of type 2 diabetes

Question 61

what is increase risk of type 2 diabetes with statins associated with

Answer 61

impaired insulin sensitivity and insulin secretion

Question 62

what increases risk for increase risk of type 2 diabetes in statins

Answer 62

dose dependent

Question 63

how can statins increase risk of type 2 diabetes

Answer 63

decrease both insulin production and insulin sensitivity of tissues (reduce glucose uptake)