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Pharmacology > Week 11 Dyslipidemia > Flashcards

Week 11 Dyslipidemia Flashcards

1
Q

Where does cholesterol come from?

A

synthesized by the liver
additional from diet
membrane structure

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2
Q

What is the precursor to steroid hormones?

A

cholesterol

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3
Q

What is included in total cholesterol?

A

LDL-C
HDL-C
VLDL-C

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4
Q

What is the “bad” cholesterol? why?

A

LDL-C (low density lipoproteins)

promotes plaque development

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5
Q

What is the “good” cholesterol? why?

A

HDL-C (high density lipoproteins)

protective against plaque development

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6
Q

What the the category of triglycerides?

A

VLDL-C

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7
Q

What is the optimal level of LDL-C?

A

<100 mg/dL

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8
Q

What is “high” LDL-C?

A

160-189

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9
Q

What is the ACC/AHA recombination for pts with LDL-C >190?

A

high intensity statin to the goal of <100

+ or - ezetimibe and PCSK9 inhibitor

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10
Q

What are common causes of secondary dyslipidemia? (5)

A 
diabetes
hypothyroidism
obstructive liver disease
chronic renal failure
drugs that raise LDL and lower HDL (progestins, anabolic steroids and corticosteroids)
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11
Q

What are the therapeutic lifestyle changes in LDL-C lowering therapy? (3)

A

TLC diet
weight reduction
increased physical activity

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12
Q

What are the 2 criteria of TLC diet?

A

restrict intake of cholesterol raising nutrients (sat fats <7% of total) and dietary cholesterol
LDL lowering therapeutic options (plant stannous/sterols 2g daily) and viscous fiber (10-25g/day)

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13
Q

What is the lipid lowering drug of choice for tc of hyperlipidemia and for prevention in most pts?

A

statins

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14
Q

Why are statins the #1 for hyperlipidemia?

A

reduced the risk of first cardiovascular event and death in pts at increased risk for atherosclerotic cardiovascular disease (ACSVD)
decrease the risk of major coronary events and death in pts with ACSVD

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15
Q

Addition of what can reduce the risk of secondary cardiovascular events?

A

ezetimibe

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16
Q

What can be added to a statin to reduce LDL-C levels much more than a statin alone and can reduce the risk of CV events?

A

PCSK9 inhibitor

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17
Q

What else besides ezetimibe and PCSK9 shows limited evidence that it may reduce the risk of CV events when added to a statin?

A

bile acid sequestrants

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18
Q

What is the only fibrate has demonstrated beneficial events on CV outcomes but its use with statins can increase the risk of myopathy and NOT recommended?

A

gembribrozil

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19
Q

Is there convincing evidence that adding an extended-release niacin to a statin to increase CV outcomes?

A

NO

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20
Q

What reduced the risk of ischemic CV event in patients with hypertiglyceridemia and CV risk factors in one random controlled trial?

A

Icosapent ethyl, an omega 3 polyunsaturated fatty acid

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21
Q

What are statins?

A

HMG CoA Reductase Inhibitors

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22
Q

How much do statins lower LDL-C?

A

18-55%

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23
Q

How much do statins lower TG levels?

A

7-30%

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24
Q

How much do statins raise HDL-C levels?

A

5-15%

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25
Q

What are the major side effects of statins?

A

myopathy (increased CK)

Increased liver enzymes (AST/ALT)

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26
Q

What are contraindications to statins?

A

absolute: liver disease
relative: certain drugs

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27
Q

What are the demonstrated therapeutic benefits of statins? (5)

A 
reduce major coronary events
reduce CHD mortality
reduce procedures (PCTA/CABG)
reduce stroke
reduce total mortality
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28
Q

What is the MOA of statins?

A

block rate-limiting step in cholesterol synthesis

(HMG-CoA to Mevalonic acid Blocked) decreases hepatic cholesterol

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29
Q

What indicates statin induced myopathy?

A

Serum CK >10 x the upper limit of normal with UNEXPLAINED muscle pain or weakness

30
Q

What indicates statin induced rhabdomyolysis?

A

Serum CK >40 times the upper limit with UNEXPLAINED muscle pain or weakness

31
Q

What statin has the highest risk of stain-induced myopathy?

A

high dose simvastatin (Zocor)

32
Q

What causes the statin induced myopathy?

A

metabolism of CYP3A4

33
Q

What should be done if pts experience SE of statin medication?

A

try a different statin

34
Q

What are 2 examples of HMG CoA Reductase Inhibitors (Statins)?

A

atorvastatin (Lipitor)

Rosuvastatin (Crestor)

35
Q

What statin is not available generically as of 2/11/19?

A

Pitavastatin (Livalo)

36
Q

What 3 statins have the highest efficacy by percentage of LDL lowering?

A

Rosuvastatin (Crestor) 63%
Atorvastatin (Lipitor) 57%
Simvastatin 46%

37
Q

What is the black box warning of simvastatin (zocor)?

A

restricting dose of simvastatin 80mg dose

38
Q

An 80mg dose of simvastatin should be restricted to what pts?

A

patients who have been taking it for >12 months without s/s of toxic effects on muscle

39
Q

According to simvastatin new labeling what should be done with pts that are on 80mg dose without adverse effects but take a contraindicated drug?

A

switch to another statin

40
Q

According to new simvastatin label what should be done with pts whose LDL-C goal cannot be reached on the 40mg dose?

A

switch to a statin with less risk of myopathy

41
Q

What medication is contraindicated with simvastatin?

A

gemfibrozil

42
Q

What is the max dose of simvastatin if someone taking amino, verapamil or diltiazem?

A

do not exceed 10mg simvastatin daily

43
Q

What is the max dose of simvastatin if someone is taking amlodipine or ranolazine?

A

do not exceed 20mg of simvastatin daily

44
Q

What are the limitations of grapefruit juice if taking simvastatin?

A

do not ingest more than 1 quart daily

45
Q

What is the statin pearl on elevated transaminases on statins?

A

not a reason to stop unless 3x normal

46
Q

Statin side effects are often ____specific, not always ____specific

A

agent;class

47
Q

What is the MOA of bile acid sequestrants?

A

bind dietary cholesterol

48
Q

What are the major actions of bile acid sequestrants? (3)

A

reduce LDL-C 20-30%
Raise HDL 3-5%
May increase TG

49
Q

What are side effects of bile acid sequestrants? (2)

A

GI distress/constipation, diarrhea and bloating

decreased absorption of other drugs

50
Q

What are the contraindications of bile acid sequestrants? (2)

A 
severe hepatic impariment
raised TG (>400 mg/dL)
51
Q

What are examples of bile acid sequestrants? (3)

A

cholestyramine (Questran)
Colestipol (Colestid)
Colesevelam (Welchol)

52
Q

When are bile acid sequestrants usually given?

A

typically add on therapy to max dose statins

53
Q

What are the major actions of Niacin (Nicotinic acid; Vitamin B3)?

A

lowers LDL 5-25%
Raises HDL 15-35%
Lowers TG 10-15%

54
Q

What is a side effect of Niacin?

A

flushing

55
Q

How can flushing be minimized when taking Niacin?

A

pretreatment with aspirin or NSADIS 30-60 minutes prior to ingestion

56
Q

When is Niacin used?

A

as an add on therapy NOT mono therapy (if used at all)

57
Q

According to study did niacin reduce incidence of primary composite endpoint?

A

NO

58
Q

Why was the Niacin trial stopped early?

A

unexpected increase in stroke

59
Q

What are the major actions of fibric acids?

A

decrease TG & VLDL by 25-50%
lower LDL 5-20% (with normal TG)
may raise LDL with high TG
may raise HDL 10-20%

60
Q

What are examples of fibric acids?

A

Gemfibrozil (Lopid)

Fenofibrate (Tricor)

61
Q

What are cholesterol absorption inhibitors?

A

ezetimibe (Zetia)

Vytorin (ezetimibe + simvastatin)

62
Q

How does ezetimibe affect LDL?

A

lowers LDL by 20-25%

63
Q

What is the result of combining ezetimibe with a statin?

A

increases effects of statin by 10-15% without side effects

64
Q

What dose of ezetimibe is well tolerated?

A

10mg daily

65
Q

What is a new class of agents for cholesterol- monoclonal antibodies?

A

PCSK9 inhibitors

66
Q

What is the MOA of PCSK9 inhibitors?

A

bind to proprotein converts subtilisin/kexin (PCSK9) receptors
prevents it from binding to LDL
thereby increase the number of hepatic LDL receptors
Increasing clearance of LDL

67
Q

How do PCSK9 medications affect LDL levels?

A

addition to statins reduce LDLs by 50-60%

68
Q

How are PCSK9 medications given?

A

SC injection every 2-4 weeks

add on to max dose statins

69
Q

What is the newest lipid lowing agent that is not FDA approved?

A

Bempedoic Acid (BPDA)

70
Q

What is the MOA of Bempedoic Acid (BPDA)?

A

inhibits ATP citrate lyase (key enzyme in cholesterol synthesis)

71
Q

What is the PO dose of Bempedoic Acid (BPDA)?

A

180mg daily

72
Q

According to trials, what is the effect of Bempedoic Acid (BPDA)?

A 
LDL decrease by 12.6%
Non HDL decrease by 10%
TC decrease
Apolipoprotein B decrease
High sensitivity CRP decrease

Pharmacology (17 decks)

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