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Endocrinology Exam 2 > Antihyperlipidemics > Flashcards

Antihyperlipidemics Flashcards

1
Q

Dyslipidemic states

A

Hypercholesterolemia
Hypertriglyceridemia
Familial combined (mixed) hyperlipidemia
Familial hypercholesterolemia
Elevated Lp(a)
Familial chylomicronemia syndrome (FCS)
Other rare genetic conditions

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2
Q

LDL-C treatment goal for extreme risk category

A

<55

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3
Q

LDL-C treatment goal for very high risk category

A

<70

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4
Q

LDL-C treatment goal for high risk category

A

<100

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5
Q

LDL-C treatment goal for moderate risk category

A

<100

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6
Q

LDL-C treatment goal for low risk category

A

<130

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7
Q

How often should lipids be checked when treating LDL-C to Goal?

A

every 3 months or more frequently where necessary

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8
Q

TG goal for all ASCVD risk categories is

A

<150

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9
Q

Five general recommendation categories for Lifestyle recomendations in CV risk patients

A

Nutrition
Physical activity
Sleep
Mental health
Smoking

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10
Q

If someone is determined to be low risk for ASCVD, what is the first step?

A

No risk factors
Lifestyle change

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11
Q

If someone is determined to be moderate risk for ASCVD, what does this mean and what is the first step?

A

<2 risk factors and 10-year risk <10%
Lifestyle + moderate intensity statin

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12
Q

If someone is determined to be high risk for ASCVD, what does this mean and what is the first step?

A

> 2 risk factors and ASCVD risk 10-20%
Diabetes or CKD >3 with no orther risk factors

Start lifestyle + moderate intensity statin

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13
Q

If someone is determined to be very high risk for ASCVD, what does this mean and what is the first step?

A

Established ASCVD or recent hospitalization for ACS, or 10 year risk >20%
Diabetes with >1 risk factors
CKD >3 with albuminuria
HeFH

Start Lifestyle + High intensity statin

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14
Q

If someone is determined to be extreme risk for ASCVD, what does this mean and what is the first step?

A

Progressive ASCVD including unstable angina
established ASCVD plus diabetes or CKD >3 or HeFH
History of premature ASCVD (<55 years male or <65 years female)

Start Lifestyle + High intensity statin

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15
Q

Measure Lp(a) in patient sin the following settings

A

Family history of previous ASCVD risk
All patients with premature or recurrent ASCVD despite LDL-C lowering

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16
Q

CAC scoring

A

Coronary Artery Calcium scoring:
Type of heart CT (not the same as a regular CT, must order CAC scan)
Can predict ASCVD risk (in conjunction with other risk scoring)

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17
Q

Who do we scan with CAC scoring?

A

Selected asymptomatic, nondiabetic adults 40+ w/ 10-year ASCVD risk intermediate to high (7.5-20%)
Sometimes borderline risk (5-7.4%)

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18
Q

CAC score ≥ 100 or >75 percentile for age, sex, and race

A

Use statin if LDL-C between 100-190 mg/dL
Daily aspirin too if CAC ≥100

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19
Q

CAC score 1 to 99 or <75th percentile for age, sex, and race

A

Consider statin if LDL-C between 100-190 mg/dL

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20
Q

CAC of zero

A

No statin unless major risk factors (eg, diabetes, active smoking, hypertension, family history of premature coronary artery disease, etc.)

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21
Q

STATINS

A

Simvastatin (Zocor)
Atorvastatin (Lipitor)
Rosuvastatin (Crestor)
Lovastatin (Altoprev, Mevacor)
Pravastatin (Pravachol)

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22
Q

Statins MOA

A

HMG CoA Reductase is an enzyme that mediates the first step in cholesterol synthesis
Statins inhibit this enzyme, thereby reducing biosynthesis of cholesterol.
Leads to increased number of hepatic LDL receptors (decreasing LDL-C in circulation), small increase in HDL and decrease in TGs.

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23
Q

Statins are associated with _____

A

plaque stabilization and decreased inflammation in the arterial walls

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24
Q

Statins effect on LDL-C, HDL-C and TGs

A

Can decrease LDL-C by 18-50%!
Can increase HDL-C by 5-15%.
Can decrease plasma Triglycerides by 10-25%.

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25
Q

First line agents in the management of hyperlipidemia

A

Statins

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26
Q

Contraindications for Statins

A

Pregnancy! Statins cause birth defects.
Liver disease - this is NOT absolute.
Muscle disease - case by case (myopathy).
Caution with concomitant Coumadin (may increase INR).

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27
Q

Side Effects of Statins

A

Typically well tolerated
Headache
Arthralgias/Myalgias (without CK changes)
Very mild myositis? Occurs in about 10% of patients
Fatigue
Flu-like symptoms

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28
Q

Adverse reactions of statins

A

Hepatotoxicity (very rare)
Myositis and Rhabdomyolysis

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29
Q

Follow Up and Monitoring of statins

A

All are Pregnancy Category X and unsafe in lactation!
Check Creatinine and LFTs at baseline

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30
Q

Statins are also known as

A

HMG CoA Reductase Inhibitors

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31
Q

Fibric Acid Derivatives

A

Gemfibrozil (Lopid)
Fenofibrate (Tricor)

32
Q

Fibric Acid Derivatives MOA

A

These bind to gene promoters which transcriptionally upregulate production of certain proteins.
Increased expression of lipoprotein lipase (which does what again?)
Increased expression of apoproteins found in High Density Lipoproteins

33
Q

Taking a Fibric Acid Derivative Results in decreased plasma triglycerides by about ____%.

A

30

34
Q

Function of Fibric Acid Derivatives

A

Results in decreased plasma triglycerides by about 30%.
Decreases circulating levels of VLDL
Increases circulating levels of HDL ( by ~9%).

35
Q

Fibric Acid Derivatives Indication

A

Essentially used for Hypertriglyceridemia.
Fenofibrate can be added to Statin therapy if there is significantly elevated Triglycerides

36
Q

Contraindications of Fibric Acid Derivatives

A

Gemfibrozil should NOT be used in combination with Statins

37
Q

Side Effects of Fibric Acid Derivatives

A

GI side effects (N/V, dyspepsia) are common
Associated with development of Cholelithiasis

38
Q

Adverse Effects of Fibric Acid Derivatives

A

Myositis and Rhabdomyolysis (rare)
- More common if combined with Statins
- Rosuvastatin + Fenofibrate = Safest combo option
Pancreatitis (MOA is largely unknown)

39
Q

Follow Up and Monitoring of Fibric Acid Derivatives

A

Both are pregnancy category C; contraindicated during breastfeeding.
Creatinine and LFTs at baseline and then periodically.

40
Q

Niacin (Niacor, Niaspan) MOA

A

Decreases rate of HDL break down, resulting in 15-35% increase in HDL.
Prevents lipolysis in adipocytes, decreasing free fatty acid circulation, decreasing VLDL (and LDL) levels.

41
Q

Niacin (Niacor, Niaspan) Indication

A

Most effective agent for increasing HDL levels (NO DATA for benefit though).
Modestly effective at decreasing LDL and serum Triglycerides.
Decent 3rd or 4th line option in patients who do not tolerate Statins and in whom you have tried ezetimibe and/or PCSK9i.
Pellagra (Niacin deficiency).

42
Q

Contraindications of Niacin

A

Hepatic disease
Gout
Peptic Ulcer Disease

43
Q

Side effects of Niacin

A

Flushing and Pruritus- very common
Hyperuricemia and gout attacks
Hyperglycemia due to impaired glucose tolerance

44
Q

Adverse Reactions of Niacin

A

Myositis and Rhabdomyolysis
NOT SEEN when Niacin is used alone!

45
Q

Niacin Follow Up and Monitoring

A
  • You want to start at a low dose and increase gradually to 1500-3000 mg daily over 2-3 months (Or 1g ER dose at night).
  • Check LFTs at baseline, then again after 6-8 weeks, and again after 6-8 weeks on max dose.
  • Fasting glucose and uric acid level at baseline and again after 6-8 wks.
  • Pregnancy category C and lactation safety unknown.
46
Q

Cholesterol Absorption Inhibitor

A

Ezetimibe (Zetia)

47
Q

Cholesterol Absorption Inhibitor MOA

A

Selectively inhibits absorption of dietary and biliary cholesterol in the small intestine.
Decreases circulating LDL cholesterol by about 15-20%.
Very small increase in HDL levels.

48
Q

Indication for Cholesterol Absorption Inhibitor

A

Hypercholesterolemia - Consider Ezetimibe 2nd line therapy.

49
Q

Contraindications of Cholesterol Absorption Inhibitor (Ezetimibe)

A

Hepatic dysfunction

50
Q

Side Effects of Cholesterol Absorption Inhibitor

A

URI and Flu-like symptoms are common
Myalgias (without increasing CK)
Diarrhea is common

51
Q

Adverse Reactions of Cholesterol Absorption Inhibitor

A

Myositis and Rhabdomyolysis (rare, highest risk when combined with statin – ARE YOU SEEING A PATTERN HERE?)
Drug-induced hepatitis
Acute Pancreatitis
Thrombocytopenia

52
Q

Follow Up and Monitoring of Cholesterol Absorption Inhibitor

A

Pregnancy category C and unknown safety with lactation.
Check LFTs at baseline and periodically

53
Q

Bile Acid Sequestrants

A

Cholestyramine (Questran, Prevalite)
Colestipol (Colestid)
Colesevelam (Welchol)

54
Q

Bile Acid Sequestrants MOA

A
  • These Resins bind negatively charged Bile Acids in the small intestine.
  • The Resin-bound Bile Acids cannot be reabsorbed.
  • Because bound Bile Acids are not reabsorbed, the liver is forced to make more Bile Acid than normal by metabolizing LDL-C
55
Q

Indication of Bile Acid Sequestrants

A

Hyperlipidemia
Interesting off-label uses for Colestipol and Colesevelam:

56
Q

Contraindications of Bile Acid Sequestrants

A

GI obstruction

57
Q

Side effects of Bile Acid Sequestrants

A

GI symptoms- Nausea, bloating, constipation, flatulence.

58
Q

Bile Acid Sequestrants Adverse reactions

A

Decreased absorption of fat soluble vitamins (A, D, E, K)
Drug interactions- Cholestyramine and Colestipol can interfere with absorption of many drugs

59
Q

Bile Acid Sequestrants follow up

A

Cholestyramine and Colestipol are Pregnancy category C.
Colesevelam is Pregnancy category B.
Seem to be safe with lactation.
No routine lab tests recommended.

60
Q

Omega-3 Fatty Acids include

A

EPA: eicosapentaenoic acid (icosapent ethyl, Vascepa)
EPA/DHA: Eicosapentaenoic/Docosahexanoic acid (Lovaza)

61
Q

Omega-3 Fatty Acids MOA

A

Evidence suggests that Omega-3’s decrease TGs by…
- Reducing VLDL production by the liver.
- Accelerating chylomicron and VLDL elimination from blood.
Can result in up to 25-30% reduction in circulating TGs.

62
Q

Omega-3 Fatty Acids Indication

A

Hypertriglyceridemia >500 (prescription strength)

63
Q

Contraindications with Omega-3 Fatty Acids

A

Caution if hepatic impairment
Caution if allergic to fish or shellfish

64
Q

Side Effects of Omega-3 Fatty Acids

A

“Fishy” taste in mouth
Dyspepsia
Nausea, vomiting
Mild AST, ALT increase

65
Q

Adverse Reactions of Omega-3 Fatty Acids

A

Anaphylaxis observed in people with fish or shellfish allergy.

66
Q

T/F Dietary Omega-3 Fatty Acids supplement forms are monitored by FDA

A

F

67
Q

ATP-Citrate Lyase (ACL) Inhibitors

A

Bempedoic acid (Nexletol)
Bempedoic Acid +Ezetimibe (Nexlizet)

68
Q

ATP-Citrate Lyase (ACL) Inhibitors MOA

A

Inhibits cholesterol synthesis
Inhibits ATP-citrate lyase (upstream of HMG-CoA reductase)
Upregulates LDL receptors to reduce LDL-C

69
Q

ATP-Citrate Lyase (ACL) Inhibitors Indications

A

Heterozygous familial hypercholesterolemia
Atherosclerotic cardiovascular disease
Usually used w/ max tolerated statin

70
Q

ATP-Citrate Lyase (ACL) Inhibitors Contraindications

A

Pregnancy or breastfeeding
Caution w/ age >60, renal disease, gout hx, tendon disorder hx

71
Q

Side effects of ATP-Citrate Lyase (ACL) Inhibitors

A

URI
Muscle spasms
*Hyperuricemia/Gout
Back pain or extremity pain
Abdominal pain
Elevated LFTs
BPH

72
Q

Adverse reactions of ATP-Citrate Lyase (ACL) Inhibitors

A

Tendon rupture

73
Q

ATP-Citrate Lyase (ACL) Inhibitors follow up

A

Check lipid panel and LFTs 8-12 weeks after starting
Watch for signs of hyperuricemia and test as needed
Monitor for signs/symptoms of tendinopathy or tendon rupture (eg, joint pain, swelling, inflammation).

74
Q

PCSK9 inhibitors* (PCSK9i)

A

Monoclonal Antibodies (mAB)
- Evolocumab (Repatha)
- Alirocumab (Praluent)
siRNA
- Inclisiran (Leqvio)

75
Q

Mechanism of Action for PCSK9 inhibitors* (PCSK9i)

A

Monoclonal Antibodies (mAB)
Bind circulating PCSK9 and prevent it from degrading LDL receptors.
SQ injection 1-2 x per month
siRNA
Blocks synthesis of PCSK9
SQ injection every 3 months for 2 doses, then every 6 months

76
Q

PCSK9 inhibitors* (PCSK9i) Indications

A

Indications (Evolocumab, Alirocumab):
Primary hyperlipidemia
Heterozygous or homozygous familial hypercholesterolemia
Clinical ASCVD event risk reduction
*Typically used w/ statin

Indications (Inclisiran):
Primary hyperlipidemia
Heterozygous familial hypercholesterolemia
*Typically used w/ statin

77
Q

Side Effects of PCSK9 inhibitors* (PCSK9i)

A
  • > 10% Nasopharyngitis (4-10.5%)
    URI (2.1-9.3%)
    Influenza (1.2-7.5%)
    Back pain (2.3-6.2%)
    Injection site reactions (3.2-5.7%)
    Cough (1.2-4.5%)

Endocrinology Exam 2 (4 decks)

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