Hyperlipidemia

Question 1

Three major lipids in the body?

Answer 1

1. Cholesterol
2. Triglycerides
3. Phospholipids

Question 2

How does the liver make cholesterol? (Rate-limiting step)

Answer 2

HMG-CoA is converted to mavelonate by HMG-CoA reductase (this enzyme is the target of statins)

Question 3

What job does a lipoprotein have? Why?

Answer 3

Taxi cab for cholesterol and triglycerides bc they’re insoluble in water

Question 4

Chylomicrons - characteristics?

Answer 4

First step of packaging digested fats

Transports TG’s, cholesterol, and phospholipids derived from diet from the gut to the liver, adipose tissue, and muscle

Question 5

What is the most abundant component in chylomicrons?

Answer 5

TG’s (90%)

Question 6

As chylomicrons make their way to the liver, what component is dropped off at various sites along the way? How?

Answer 6

TG’s; removed by lipoprotein lipase in various cells

Question 7

VLDL - most abundant component?

Answer 7

TG’s (55%); less than in chylomicrons, a little more cholesterol than in chylomicrons (25%

Question 8

LDL - most abundant component?

Answer 8

Cholesterol (55%)

Question 9

HDL - most abundant component?

Answer 9

Proteins (50%)

Question 10

HDL’s job?

Answer 10

Scoops up cholesterol from peripheral cells and brings it back to the liver

Question 11

VLDL’s serve as a precursor to what?

Answer 11

LDL’s

Question 12

Which lipoprotein is known as “bad cholesterol”?

Answer 12

LDL

Question 13

Which lipoprotein is known as “good cholesterol”?

Answer 13

HDL

Question 14

Desirable total cholesterol number is below…?

Answer 14

200mg/dL

Question 15

Desirable LDL number is less than…

Answer 15

100mg/dL

Question 16

Desirable HDL cholesterol is above…?

Answer 16

60

Question 17

Desirable TG’s is less than…?

Answer 17

150

Question 18

Routine initiation of statin therapy in which patient population is not recommended?

Answer 18

1. Class II through IV HF

2. Maintenance hemodialysis

Question 19

What do we use to determine the statin benefit group?

Answer 19

The ASCVD (athersclerotic cardiovascular disease) risk algorithm

Question 20

What is the first major statin benefit group?

Answer 20

Pt’s with clinical ASCVD (Hx of MI, CVA, unstable angina, etc)

Question 21

What is the second major statin benefit group?

Answer 21

LDL > 190

Question 22

What is the third major statin benefit group?

Answer 22

DM (age 40-75) with LDL 70-189mg/dL

Question 23

What is the fourth major statin benefit group?

Answer 23

1. No clinical ASCVD
2. No DM
3. Age 40-75
4. LDL 70-189mg/dL
5. 10-yr ASCVD > 7.5%

Question 24

Name the two high intensity statins:

Answer 24

1. Atorvastatin (Lipitor) 40-80mg

2. Rosuvastatin (Crestor) 20-40mg

Question 25

Which drug class is best for increasing HDL?

Answer 25

Niacin

Question 26

Which drug class is best for decreasing TG’s?

Answer 26

Fibrates

Question 27

Which drug class is best for decreasing LDL’s?

Answer 27

Statins

Question 28

HMG-CoA Reductase Inhibitors - MOA?

Answer 28

Inhibits the first committed enzymatic step of sterol synthesis by BLOCKING HMG-CoA Reductase Depletes intracellular cholesterol supplies Causes up-regulation of LDL receptors Overall decrease in circulating LDL

Question 29

What time of day are statins taken? Why?

Answer 29

At night, bc your body inherently produces more cholesterol while you sleep (high dose statins can be taken anytime of day)

Question 30

Most common statin SE’s?

Answer 30

``` Muscle pain (myalgias) Rhabdomylosis Liver toxicity ```

Question 31

What is a routine blood panel (other than lipid) you should obtain prior to and after initiating statin therapy? Why?

Answer 31

LFT - liver issues are common to statins (commonly seen increase in ALT)

Question 32

Factors that can increase statin-induced myopathy?

Answer 32

1. Age >75 2. Female 3. Liver dysfunction 4. Renal insufficiency 5. ETOH abuse 6. Grapefruit juice (inhibits CYP enzymes)

Question 33

Absolute CI’s to statins?

Answer 33

1. Pregnancy 2. Nursing 3. Acute liver disease

Question 34

Statin drug interactions?

Answer 34

1. Amio 2. Amlodipine 3. Dig 4. Cardizem 5. Coumadin 6. Niacin

Question 35

All statins (except pravastatin) are highly _______ bound.

Answer 35

Protein /// may displace other highly bound drugs (like warfarin)

Question 36

Which two HGM-CoA Reductase Inhibitors require no dose adjustment in patients with renal insufficiency?

Answer 36

Atorvastatin | Pitavastatin

Question 37

Which drug class is most beneficial in treating high triglycerides?

Answer 37

Fibrates (Fibric Acid Derivatives)

Question 38

Fibrates - MOA?

Answer 38

Stimulates lipoprotein lipase activity - hastens the removal of chylomicrons and VLDL’s from plasma, subsequently decreasing TG’s

Question 39

What is the most effective drug for increasing HDL?

Answer 39

Niacin

Question 40

What side effect may occur when Gemfibrozil is combined with a statin?

Answer 40

Myopathy and rhabdomyolysis

Question 41

Gemfibrozil - Pregnancy category?

Answer 41

C

Question 42

Niacin (aka Nicotinic Acid) - MOA?

Answer 42

Inhibits hepatic synthesis of VLDL by inhibiting lipolysis in adipose tissues, in turn decreasing production of free fatty acids BLUF: lowers VLDL, raises HDL

Question 43

Niacin - major clinical benefit?

Answer 43

Reduces major coronary events

Question 44

Niacin - pregnancy category?

Answer 44

C

Question 45

How to reduce Niacin flushing?

Answer 45

ASA 30 mins prior to Niacin Take Niacin with meals

Question 46

Adverse effects of Niacin - three:

Answer 46

1. Liver tox 2. Hyperglycemia 3. Hyperuricemia

Question 47

Niacin - CI’s?

Answer 47

1. Liver disease 2. Severe gout 3. Uncontrolled DM 4. Active PUD

Question 48

Monitoring with Niacin?

Answer 48

Check LFT’s at baseline and every 2-3 months

Question 49

Bile Acid Sequestrants - MOA?

Answer 49

Binds bile acids and salts in the intestine, causing them to be excreted in feces Decreased levels cause liver to use more existing cholesterol to make bile acids / salts Overall effect, decreased cholesterol

Question 50

Bile acid sequestrants best for which type of patient?

Answer 50

Isolated high LDL (because these drugs can increase TG’s)

Question 51

Bile acid sequestrants can cause impaired absorption of?

Answer 51

Fat-soluble vitamins (A,D,E,K) Statins

Question 52

Which bile acid sequestrants are pregnancy category B?

Answer 52

Colistepol | Colesevelam

Question 53

Which bile acid sequestrant is pregnancy category C?

Answer 53

Cholestyramine

Question 54

Bile acid sequestrants - adverse effects?

Answer 54

Gi distress, bloating, constipation (many patients are noncompliant with medication due to these effects) Decreased absorption of: Warfarin, Thiazides, B-blockers, fat-soluble vitamins (A,D,E,K)

Question 55

Bile acid sequestrants - CI’s?

Answer 55

Pt’s with high TG’s

Question 56

Ezetimibe - MOA?

Answer 56

Inhibits intestinal cholesterol absorption

Question 57

Ezetimibe - clinical use?

Answer 57

Reduce LDL in primary hyperlipidemia Adjunct to statin therapy (synergistic)

Question 58

Ezetimibe - pregnancy cat?

Answer 58

C

Question 59

PCSK9 inhibitor - MOA?

Answer 59

Human monoclonal Ab Inhibits the PCSK9 enzyme No PCSK9 —> no degradation of LDLR’s —> increased LDLR’s expressed on hepatocyte surface —> more clearance of LDL’s from circulation —> decreased plasma LDL

Question 60

What’s so great about PCSK9? What’s so bad?

Answer 60

HIGHLY effective at lowering LDL CRAZY expensive

Question 61

Name two PCSK9 Inhibitors:

Answer 61

Alirocumab | Evolocumab

Question 62

Benefits of Omega-3?

Answer 62

Lowers TG’s, raises HDL

Question 63

Omega-3 can have an adverse impact on?

Answer 63

Bleeding time (platelets)

Question 64

Criteria features of high intensity statin primary prevention?

Answer 64

1. LDL > 190mg/dL | 2. Pt’s w/ LDL 70-190mg/dL AND 10-yr ASCVD > 7.5%

Question 65

Clinical features of moderate intensity statin primary prevention?

Answer 65

1. DM pt’s w/ LDL 70-189mg/dL and 10-yr ASCVD LESS THAN 7.5%

Question 66

Best drug for lowering TG’s?

Answer 66

Fenofibrate

Question 67

What is the most common type of lipid abnormality?

Answer 67

Type IIA - familial hypercholesteremia

Question 68

Type IIA causes increased...?

Answer 68

LDL

Question 69

Which lipid abnormality is NOT associated with coronary heart disease?

Answer 69

Type I (familial hyperchylomicronemia)