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Fall 2020: Therapeutics 2 > Dyslipidemia > Flashcards

Dyslipidemia Flashcards

1
Q

What are the 4 lipid classes?

A
  • Cholesterol
  • Cholesterol esters
  • Triglycerides
  • Phospholipids
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2
Q

What are the three types of lipoproteins?

A
  • LDL
  • HDL
  • VLDL
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3
Q

What are the three types of apolipoproteins?

A
  • Apo-B
  • Apo-A1
  • Apo-CIII
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4
Q

List the six steps in the pathogenesis of atherosclerosis.

A
  1. Endothelial injury
  2. Inflammatory response
  3. Macrophage infiltration
  4. Platelet adhesion
  5. Smooth muscle cell proliferation
  6. Extracellular matrix accumulation
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5
Q

Although dyslipidemia is largely asymptomatic, what symptoms may present depending on disease severity and duration?

A
  • Chest pain
  • Palpitations
  • Sweating
  • Anxiety
  • SOB
  • Loss of consciousness
  • Difficulty with speech or movement
  • Abdominal pain
  • Sudden death
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6
Q

What are the six signs of dyslipidemia?

A
  • Pancreatitis
  • Eruptive xanthomas
  • Peripheral polyneuropathy
  • Increased BP
  • Waist size (>40 inches in men, >35 in women)
  • BMI >30
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7
Q

What lab parameters are increased in dyslipidemia?

A
  • Non-HDL-C
  • TC
  • LDL-C
  • TG
  • Apo-B
  • CRP
  • LDL-P
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8
Q

What lab parameter is decreased in dyslipidemia?

A

HDL

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9
Q

What is LDL-C?

A

The amount of cholesterol in LDL particles

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10
Q

What is LDL-P?

A

The number of LDL particles (not routinely ordered)

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11
Q

What is non-HDL-C?

A

The amount of cholesterol in atherogenic particles (not routinely reported)

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12
Q

How do you calculate non-HDL-C?

A

TC - HDL-C

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13
Q

What is Apo-B?

A

Number of atherogenic particles (not routinely ordered)

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14
Q

What three lab parameters are all valid in non-fasting sample with elevated TG and are all more predictive of future CVD risk than LDL-C alone?

A
  • ApoB
  • LDL-P
  • Non-HDL-C
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15
Q

What four parameters are included in an FLP?

A
  • TC
  • TG
  • HDL-C
  • LDL-C
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16
Q

What is the Friedewald Equation used for?

A

Calculating LDL from FLP

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17
Q

When is the Friedewald Equation not valid?

A

When TG >400 mg/dl

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18
Q

What parameters are included in a non-fasting sample?

A
  • TC
  • HDL
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19
Q

What is goal TC/HDL?

A

≤5:1 (optimal 3-3.5:1)

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20
Q

List the four lifestyle management options that can be used to help treat dyslipidemia.

A
  • DASH, USDA, or AHA diet
  • Reduce percent of calories from saturated and trans fats (5-6% calories from saturated fats)
  • Lower sodium intake (<2400 mg daily)
  • Moderate-vigorous aerobic physical activity 3-4 sessions/week for 40 minutes/session
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21
Q

How many calories are there per 1 gram of fat?

A

9 calories

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22
Q

What is Olestra?

A

A non-digestable, non-absorbable, non-caloric fat substitute with GI adverse effects and notable drug interactions

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23
Q

What are some examples of soluble fibers that can decrease LDL?

A
  • Oat bran
  • Pectins or gums
  • Psyllium products
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24
Q

How do psyllium products decrease LDL?

A

Bind cholesterol in gut and reduce hepatic production and clearance

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25
Q

What dose of psyllium seed can decrease TC and LDL by 20%?

A

10-15 grams daily

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26
Q

What dose of stanols/sterols is recommended for lowering LDL?

A

2-3 grams daily

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27
Q

If a dyslipidemia patient is overweight, how much weight loss is recommended?

A

10%

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28
Q

How do fish oils/omega-3 fatty acids affect TG and LDL?

A
  • Reduces TG
  • May increase LDL 4-49%
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29
Q

What is the usual dose of Lovaza (RX omega-3)?

A

2-4 grams daily or divided BID

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30
Q

What is the usual dose of Vascepa (RX omega-3)?

A

2 grams PO BID with food

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31
Q

What drugs/classes are most effective in lowering serum LDL?

A
  • Statins
  • BARs
  • Ezetimibe
  • PCSK9 inhibitors
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32
Q

What drug classes are most effective in lowering serum TG?

A
  • Fibrates
  • Omega-3 fatty acids
  • Niacin
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33
Q

What drug is mot effective at increasing serum HDL?

A

Niacin

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34
Q

List the seven statins on the market.

A
  • Lovastatin (Altoprev, Mevacor)
  • Pravastatin (Pravachol)
  • Pitavastatin (Livalo)
  • Simvastatin (Zocor)
  • Fluvastatin (Lescol)
  • Atorvastatin (Lipitor)
  • Rosuvastatin (Crestor
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35
Q

List the two high-intensity statins.

A
  • Rosuvastatin 20-40 mg
  • Atorvastatin 40-80 mg
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36
Q

List the four low-intensity statins.

A
  • Simvastatin 10 mg
  • Pravastatin 10-20 mg
  • Lovastatin 20 mg
  • Fluvastatin 20-40 mg
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37
Q

What are the two hydrophilic statins?

A

Pravastatin and rosuvastatin

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38
Q

What are the five lipophilic statins?

A
  • Fluvastatin
  • Pitavastatin
  • Lovastatin
  • Simvastatin
  • Atorvastatin
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39
Q

What three statins have interactions with CYP3A4?

A
  • Lovastatin
  • Simvastatin
  • Atorvastatin
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40
Q

What statin has a CYP3A5 interaction?

A

Simvastatin

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41
Q

The WOSCOPS study demonstrated that ___ years of a statin has a lifetime of CV benefit.

A

5

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42
Q

What statin (name and dose) has notably increased ADRs when compared to lower doses?

A

Simvastatin 80 mg; sjould only be used in patients who have been taking this dose for 1 year+ without evidence of myopathy

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43
Q

When should a statin be discontinued relative to LFTs?

A

When LFT is 3x the upper limit of normal

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44
Q

What are the two indicators that a patient taking a statin may be developing myopathy or rhabdomyolysis?

A

Unusual muscle pain and darkened urine

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45
Q

What food/drink should be avoided when taking statins?

A

Large quantities of grapefruit juice (>1 quart daily)

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46
Q

What groups are statins contraindicated in?

A

Pregnancy or women who may become pregnant

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47
Q

What characteristics can predispose a patient to statin adverse effects?

A
  • Impaired renal/hepatic function
  • Prior statin intolerance/muscle disorders
  • Unexplained ALT elevations >3x upper limit of normal
  • Other drugs that affect statin metabolism
  • >75 years
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48
Q

At what CK value should statins be discontinued?

A

CK >10 times the upper limit of normal

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49
Q

Which statins are preferred when concurrent therapy with a strong CYP3A4 inhibitor cannot be avoided?

A
  • Pravastatin
  • Fluvastatin
  • Rosuvastatin
  • Pitavastatin
50
Q

How much trial CoQ 10 can help prevent adverse muscle side effects from statins?

A

150-200 mg daily prior to statin rechallenge and during the course of statin therapy

51
Q

Although not really recommended by Dr. Gonzalvo, what alternative dosing strategy can be used to improve statin utilization/tolerability and decrease cost?

A

Every other day or once weekly dosing

52
Q

Which statins may require double the daily dose necessary for every other day dosing in order to achieve comparable LDL lowering?

A
  • Atorvastatin
  • Fluvastatin
  • Rosuvastatin
53
Q

What medications are contraindicated with simvastatin?

A
  • Itraconazole
  • Ketoconazole
  • Posaconazole
  • Erythromycin
  • Clarithromycin
  • Telithromycin
  • HIV protease inhibitors
  • Nefazodone
  • Gemfibrozil
  • Cyclosporine
  • Danazol
54
Q

You should not exceed 10 mg simvastatin daily with which two drugs?

A
  • Verapamil
  • Diltiazem
55
Q

You should not exceed 20 mg simvastatin daily with what three drugs?

A
  • Amiodarone
  • Amlodipine
  • Ranolazine
56
Q

Generally speaking, how do statins impact glycemic control?

A

They worsen glycemic control/increase risk of diabetes

57
Q

What’s the verdict on statins and cognitive decline?

A

Case reports and observational studies have demonstrated varied degrees of cognitive decline; PROSPER study shows that pravastatin did not affect cognitive decline over a 3-year follow-up period

58
Q

How soon following statin initiation should a FLP be taken?

A

4-12 weeks

59
Q

What are the three Bile Acid Resins (BARs)?

A
  • Cholestyramine (Questran, Prevalite)
  • Colestipol (Colestid)
  • Colesevelam (WelChol)
60
Q

What are the major advantages of BARs?

A

They decrease LDL and cholesterol

61
Q

What are the disadvantages of BARs?

A
  • May increase TGs
  • Must take other medications 1 hour before or 4 hours after BAR
62
Q

What side effects are associated with BARs?

A

GI side effects

  • Constipation
  • Bloating
  • Nausea
  • Flatulence
63
Q

What adverse effects are associated with BARs?

A
  • Impaired absorption of fat-soluble vitamins (A, D, E, K)
  • Hypernatremia
  • Hyperchloremia
  • GI obstruction
64
Q

When is cholestyramine contraindicated?

A

Complete biliary obstruction

65
Q

When is colesevelam contraindicated?

A
  • History of bowel obstruction
  • Serum TG >500
  • History of hypertriglyceridemia-induced pancreatitis
66
Q

BARs may decrease the effect of what medications?

A
  • Acetaminophen
  • TzDs
  • OCs
  • Corticosteroids
  • Ezetimibe
  • Fibrates
  • Thiazide diuretics
  • Warfarin
  • Digoxin
67
Q

What is the main side effect associated with niacin?

A

Prostaglandin-mediated flushing and itching

68
Q

What pharmacologic intervention can help reduce niacin-related flushing and itching?

A

ASA 325 mg 30 minutes before taking niacin

69
Q

What is niacin contraindicated for?

A
  • Active hepatic disease
  • Signficant/unexplained persistent liver transaminase elevations
  • Active peptic ulcer
  • Arterial hemorrhage
70
Q

What drug is a cholesterol absorption inhibitor?

A

Ezetimibe (Zetia)

71
Q

What is Vytorin?

A

Ezetimibe and simvastatin combo drug

72
Q

What adverse effects are associated with ezetimibe?

A
  • Fatigue
  • Diarrhea
  • GI upset
73
Q

What is ezetimibe contraindicated for?

A
  • Concomitant use with a statin and active hepatic disease/unexplained persistent serum transaminase elevations
  • Pregnancy and breastfeeding (when used concomitantly with a statin)
74
Q

What are the most common side effects of fibrates?

A
  • GI disturbances
  • Rash
  • Myalgia
  • Dizziness
75
Q

What are fibrates contraindicated for?

A
  • History of gallbladder disease
  • ESRD or dialysis
  • Persistent liver disease
76
Q

Fibrates increase the levels of what four medications?

A
  • Statins
  • Ezetimibe
  • Sulfonylureas
  • Warfarin
77
Q

What are the two PCSK9 inhibitors?

A
  • Alirocumab (Praluent)
  • Evolocumab (Repatha)
78
Q

What are PCSK9 inhibitors indicated for?

A

As an adjunct to diet and statin to reduce LDL in familial heterozygous hypercholesterolemia or atherosclerotic CVD

79
Q

What are PCSK9 inhibitors’ mechanism of action?

A

Subcutaneous injection to Inhibit the binding of PCSK9 to LDL receptors and upregulate the recycling of LDL receptors, resulting in a drastic decrease in LDL – C

80
Q

What are some common adverse effects of PCSK9 inhibitors?

A
  • GI upset
  • Increased LFTs
  • Injection site reaction
  • Myalgia
  • Influenza
81
Q

What is bempedoic acid indicated for?

A

Adjunct to diet and statin to reduce LDL in familial heterozygous hypercholesterolemia or atherosclerotic CVD

82
Q

What are some common adverse reactions to bempedoic acid?

A
  • URTI
  • Muscle spasms
  • Hyperuricemia
  • Back pain
  • Abdominal pain/discomfort
  • Bronchitis
  • Pain in extremities
  • Anemia
  • Elevated liver enzymes
83
Q

List the warnings/precautions associated with bempedoic acid.

A
  • May increase blood uric acid = gout
  • Tendon rupture risk
  • Avoid concomitant use with simvastatin >20 mg and pravastatin >40 mg (myopathy)
84
Q

What is the active ingredient in red yeast rice?

A

Lovastatin

85
Q

What are the benefits of red yeast rice?

A
  • Lowers TC, LDL-C, and TG
  • Lowers risk of CV events and total mortality
  • Increases HDL-C
86
Q

What is mipomerson (Kynamro)?

A

Oligonucleotide inhibitor of apolipoprotein B-100 synthesis indicated as an adjunct to lipid-lowering medications and diet to reduce LDL-C, apo B, TC, and non-HDL-C) in patients with homozygous familial hypercholesterolemia (HoFH)

87
Q

What is the typicaly dose of mipomerson (Kynamro)?

A

200 mg SQ once weekly

88
Q

What is the boxed warning for mipomerson?

A

Hepatotoxicity

89
Q

Mipomerson is only available through what program?

90
Q

What is mipomerson’s mechanism of action?

A
  • Uses antisense technology to inhibit the synthesis of apo B-100 by targeting a specific 20-base sequence on apo B-100 mRNA
  • Binds with the mRNA sequence and prevents the translation and formation of apo B-100 in the hepatocyte
  • Inhibits the synthesis of apo B-100
  • Designed to reduce the formation of VLDL and LDL
91
Q

What is lomitapide (Juxtapid)?

A

Microsomal triglyceride transfer protein inhibitor indicated as an adjunct to a low-fat diet and other lipid-lowering treatments, including LDL apheresis where available, to reduce LDL-C,TC, apo B, and non-HDL-C in patients with homozygous familial hypercholesterolemia (HoFH)

92
Q

Lomitapide is only available through what program?

93
Q

What is lomitapide’s boxed warning for?

A

Hepatotoxicity

94
Q

What is the dosing range for lomitapide?

A

5-60 mg PO daily

95
Q

Explain lomitapide’s mechanism of action.

A
  1. Directly binds and inhibits microsomal triglyceride transfer protein (MTP), thereby preventing the assembly of apo B containing lipoproteins in enterocytes and hepatocytes.
  2. Inhibits synthesis of chylomicrons and VLDL
  3. Leads to reduced plasma LDL-C
96
Q

What is the bare minimum you would give a patient between 40-75 with diabetes?

A

Moderate-intensity statin

97
Q

What is the bare minimum you would give a patient with an LDL ≥190?

A

High-intensity statin

98
Q

In patients 40-75 without diabetes and 5-7.4% ASCVD, what could be considered?

A

Moderate-intensity statin

99
Q

In patients 40-75 without diabetes and 7.5-19.9% ASCVD, what is the bare minimum treatment?

A

Moderate-intensity statin

100
Q

In patients 40-75 without diabetes and 20+% ASCVD, what is the bare minimum treatment?

A

High-intensity statin

101
Q

List what are considered “ASCVD events” in the eyes of the guidelines.

A
  • MI
  • Angina
  • Revascularization
  • Stroke/TIA
  • Peripheral Artery Disease (PAD)
102
Q

After a statin dose has been stabilized, how often should you follow up?

A

Every 3-12 months

103
Q

What is a Coronary Artery Calcium (CAC) Test?

A

A CT of the chest to measure calcium building; used rarely to determine initiation of statin

104
Q

What does a CAC of 0 indicate?

A

Assess other risk factors to determine need

105
Q

What does a CAC between 1 and 99 indicate?

A

Favors statin therapy, especially in 55+

106
Q

What does a CAC ≥100 indicate?

A

Initiate a moderate-intensity statin at bare minimum

107
Q

What is the order of preference when prescribing non-statin therapy?

A
  1. Ezetimibe
  2. PCSK9 inhibitors
  3. BARs
108
Q

What TG range denotes moderate hypertriglyceridemia?

109
Q

In moderate hypertriglyceridemia, where are excess TGs carried?

110
Q

What TG level denotes severe hypertriglyceridemia?

111
Q

In severe hypertriglyceridemia, where are excess TGs carried?

A

In VLDL and chylomicrons

112
Q

Elevated TGs and VLDL impart an increased risk of what condition?

A

Pancreatitis

113
Q

What secondary disorders could be contributing factors in moderate hypertriglyceridemia?

A
  • Diabetes
  • Hypothyroidism
  • Chronic liver disease
  • Chronic kidney disease and/or nephritic syndrome
114
Q

What hormone-related medications can be secondary factors in moderate hypertriglyceridemia?

A
  • Oral estrogens
  • Tamoxifen
  • Raloxifene
  • Retinoids
  • Glucocorticoids
115
Q

What immune-related medications could be secondary factors in moderate hypertriglyceridemia?

A
  • Cyclosporine
  • Tacrolimus
  • Sirolimus
  • Cyclophosphamide
  • Interferon
116
Q

What miscellaneous medications can be secondary factors in moderate hypertriglyceridemia?

A
  • Beta-blockers
  • Thiazides
  • Atypical antipsychotics
  • Rosiglitazone
  • Bile acid sequestrants
  • L-asparaginase
117
Q

What lifestyle modifications are recommended for reducing TGs?

A
  • 5-10% weight loss
  • Very low fat diet (10-15%) + less alcohol, sugar, refined carbs
  • Moderate-higher intensity physical activity ≥150 minutes per week
118
Q

When is statin therapy recommended in moderate hypertriglyceridemia?

A

40-75 with ASCVD risk ≥7.5%

119
Q

When is statin therapy recommended in severe hypertriglyceridemia?

A
  • 40-75 with ASCVD ≥7.5%
  • 40-75 with TG ≥1000 (initiate statin + fibrate/omega-3)
120
Q

What medications are the go-to therapies to decrease pancreatitis risk?

A

Fibrates or omega-3 fatty acids

Fall 2020: Therapeutics 2 (11 decks)

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