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Fall 2020: Therapeutics 2 > Dyslipidemia > Flashcards

Dyslipidemia Flashcards

(120 cards)

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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
What dose of psyllium seed can decrease TC and LDL by 20%?
10-15 grams daily
26
What dose of stanols/sterols is recommended for lowering LDL?
2-3 grams daily
27
If a dyslipidemia patient is overweight, how much weight loss is recommended?
10%
28
How do fish oils/omega-3 fatty acids affect TG and LDL?
* Reduces TG * May increase LDL 4-49%
29
What is the usual dose of Lovaza (RX omega-3)?
2-4 grams daily or divided BID
30
What is the usual dose of Vascepa (RX omega-3)?
2 grams PO BID with food
31
What drugs/classes are most effective in lowering serum LDL?
* Statins * BARs * Ezetimibe * PCSK9 inhibitors
32
What drug classes are most effective in lowering serum TG?
* Fibrates * Omega-3 fatty acids * Niacin
33
What drug is mot effective at increasing serum HDL?
Niacin
34
List the seven statins on the market.
* **Lovastatin** (Altoprev, Mevacor) * **Pravastatin** (Pravachol) * **Pitavastatin** (Livalo) * **Simvastatin** (Zocor) * **Fluvastatin** (Lescol) * **Atorvastatin** (Lipitor) * **Rosuvastatin** (Crestor
35
List the two high-intensity statins.
* Rosuvastatin 20-40 mg * Atorvastatin 40-80 mg
36
List the four low-intensity statins.
* Simvastatin 10 mg * Pravastatin 10-20 mg * Lovastatin 20 mg * Fluvastatin 20-40 mg
37
What are the two hydrophilic statins?
Pravastatin and rosuvastatin
38
What are the five lipophilic statins?
* Fluvastatin * Pitavastatin * Lovastatin * Simvastatin * Atorvastatin
39
What three statins have interactions with CYP3A4?
* Lovastatin * Simvastatin * Atorvastatin
40
What statin has a CYP3A5 interaction?
Simvastatin
41
The WOSCOPS study demonstrated that ___ years of a statin has a lifetime of CV benefit.
5
42
What statin (name and dose) has notably increased ADRs when compared to lower doses?
Simvastatin 80 mg; sjould only be used in patients who have been taking this dose for 1 year+ without evidence of myopathy
43
When should a statin be discontinued relative to LFTs?
When LFT is 3x the upper limit of normal
44
What are the two indicators that a patient taking a statin may be developing myopathy or rhabdomyolysis?
Unusual muscle pain and darkened urine
45
What food/drink should be avoided when taking statins?
Large quantities of grapefruit juice (\>1 quart daily)
46
What groups are statins contraindicated in?
Pregnancy or women who may become pregnant
47
What characteristics can predispose a patient to statin adverse effects?
* 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
48
At what CK value should statins be discontinued?
CK \>10 times the upper limit of normal
49
Which statins are preferred when concurrent therapy with a strong CYP3A4 inhibitor cannot be avoided?
* Pravastatin * Fluvastatin * Rosuvastatin * Pitavastatin
50
How much trial CoQ 10 can help prevent adverse muscle side effects from statins?
150-200 mg daily prior to statin rechallenge and during the course of statin therapy
51
Although not really recommended by Dr. Gonzalvo, what alternative dosing strategy can be used to improve statin utilization/tolerability and decrease cost?
Every other day or once weekly dosing
52
Which statins may require double the daily dose necessary for every other day dosing in order to achieve comparable LDL lowering?
* Atorvastatin * Fluvastatin * Rosuvastatin
53
What medications are contraindicated with simvastatin?
* Itraconazole * Ketoconazole * Posaconazole * Erythromycin * Clarithromycin * Telithromycin * HIV protease inhibitors * Nefazodone * Gemfibrozil * Cyclosporine * Danazol
54
You should not exceed 10 mg simvastatin daily with which two drugs?
* Verapamil * Diltiazem
55
You should not exceed 20 mg simvastatin daily with what three drugs?
* Amiodarone * Amlodipine * Ranolazine
56
Generally speaking, how do statins impact glycemic control?
They worsen glycemic control/increase risk of diabetes
57
What's the verdict on statins and cognitive decline?
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
How soon following statin initiation should a FLP be taken?
4-12 weeks
59
What are the three Bile Acid Resins (BARs)?
* **Cholestyramine** (Questran, Prevalite) * **Colestipol** (Colestid) * **Colesevelam** (WelChol)
60
What are the major advantages of BARs?
They decrease LDL and cholesterol
61
What are the disadvantages of BARs?
* May increase TGs * Must take other medications 1 hour before or 4 hours after BAR
62
What side effects are associated with BARs?
**GI side effects** * Constipation * Bloating * Nausea * Flatulence
63
What adverse effects are associated with BARs?
* Impaired absorption of fat-soluble vitamins (A, D, E, K) * Hypernatremia * Hyperchloremia * GI obstruction
64
When is cholestyramine contraindicated?
Complete biliary obstruction
65
When is colesevelam contraindicated?
* History of bowel obstruction * Serum TG \>500 * History of hypertriglyceridemia-induced pancreatitis
66
BARs may decrease the effect of what medications?
* Acetaminophen * TzDs * OCs * Corticosteroids * Ezetimibe * Fibrates * Thiazide diuretics * Warfarin * Digoxin
67
What is the main side effect associated with niacin?
Prostaglandin-mediated flushing and itching
68
What pharmacologic intervention can help reduce niacin-related flushing and itching?
ASA 325 mg 30 minutes before taking niacin
69
What is niacin contraindicated for?
* Active hepatic disease * Signficant/unexplained persistent liver transaminase elevations * Active peptic ulcer * Arterial hemorrhage
70
What drug is a cholesterol absorption inhibitor?
Ezetimibe (Zetia)
71
What is Vytorin?
Ezetimibe and simvastatin combo drug
72
What adverse effects are associated with ezetimibe?
* Fatigue * Diarrhea * GI upset
73
What is ezetimibe contraindicated for?
* Concomitant use with a statin and active hepatic disease/unexplained persistent serum transaminase elevations * Pregnancy and breastfeeding (when used concomitantly with a statin)
74
What are the most common side effects of fibrates?
* GI disturbances * Rash * Myalgia * Dizziness
75
What are fibrates contraindicated for?
* History of gallbladder disease * ESRD or dialysis * Persistent liver disease
76
Fibrates increase the levels of what four medications?
* Statins * Ezetimibe * Sulfonylureas * Warfarin
77
What are the two PCSK9 inhibitors?
* Alirocumab (Praluent) * Evolocumab (Repatha)
78
What are PCSK9 inhibitors indicated for?
As an adjunct to diet and statin to reduce LDL in familial heterozygous hypercholesterolemia or atherosclerotic CVD
79
What are PCSK9 inhibitors' mechanism of action?
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
What are some common adverse effects of PCSK9 inhibitors?
* GI upset * Increased LFTs * Injection site reaction * Myalgia * Influenza
81
What is bempedoic acid indicated for?
Adjunct to diet and statin to reduce LDL in familial heterozygous hypercholesterolemia or atherosclerotic CVD
82
What are some common adverse reactions to bempedoic acid?
* URTI * Muscle spasms * Hyperuricemia * Back pain * Abdominal pain/discomfort * Bronchitis * Pain in extremities * Anemia * Elevated liver enzymes
83
List the warnings/precautions associated with bempedoic acid.
* May increase blood uric acid = gout * Tendon rupture risk * Avoid concomitant use with simvastatin \>20 mg and pravastatin \>40 mg (myopathy)
84
What is the active ingredient in red yeast rice?
Lovastatin
85
What are the benefits of red yeast rice?
* Lowers TC, LDL-C, and TG * Lowers risk of CV events and total mortality * Increases HDL-C
86
What is mipomerson (Kynamro)?
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
What is the typicaly dose of mipomerson (Kynamro)?
200 mg SQ once weekly
88
What is the boxed warning for mipomerson?
Hepatotoxicity
89
Mipomerson is only available through what program?
REMS
90
What is mipomerson's mechanism of action?
* 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
What is lomitapide (Juxtapid)?
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
Lomitapide is only available through what program?
REMS
93
What is lomitapide's boxed warning for?
Hepatotoxicity
94
What is the dosing range for lomitapide?
5-60 mg PO daily
95
Explain lomitapide's mechanism of action.
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
What is the bare minimum you would give a patient between 40-75 with diabetes?
Moderate-intensity statin
97
What is the bare minimum you would give a patient with an LDL ≥190?
High-intensity statin
98
In patients 40-75 without diabetes and 5-7.4% ASCVD, what could be considered?
Moderate-intensity statin
99
In patients 40-75 without diabetes and 7.5-19.9% ASCVD, what is the bare minimum treatment?
Moderate-intensity statin
100
In patients 40-75 without diabetes and 20+% ASCVD, what is the bare minimum treatment?
High-intensity statin
101
List what are considered "ASCVD events" in the eyes of the guidelines.
* MI * Angina * Revascularization * Stroke/TIA * Peripheral Artery Disease (PAD)
102
After a statin dose has been stabilized, how often should you follow up?
Every 3-12 months
103
What is a Coronary Artery Calcium (CAC) Test?
A CT of the chest to measure calcium building; used rarely to determine initiation of statin
104
What does a CAC of 0 indicate?
Assess other risk factors to determine need
105
What does a CAC between 1 and 99 indicate?
Favors statin therapy, especially in 55+
106
What does a CAC ≥100 indicate?
Initiate a moderate-intensity statin at bare minimum
107
What is the order of preference when prescribing non-statin therapy?
1. Ezetimibe 2. PCSK9 inhibitors 3. BARs
108
What TG range denotes moderate hypertriglyceridemia?
150-499
109
In moderate hypertriglyceridemia, where are excess TGs carried?
In VLDL
110
What TG level denotes severe hypertriglyceridemia?
\>500
111
In severe hypertriglyceridemia, where are excess TGs carried?
In VLDL and chylomicrons
112
Elevated TGs and VLDL impart an increased risk of what condition?
Pancreatitis
113
What secondary disorders could be contributing factors in moderate hypertriglyceridemia?
* Diabetes * Hypothyroidism * Chronic liver disease * Chronic kidney disease and/or nephritic syndrome
114
What hormone-related medications can be secondary factors in moderate hypertriglyceridemia?
* Oral estrogens * Tamoxifen * Raloxifene * Retinoids * Glucocorticoids
115
What immune-related medications could be secondary factors in moderate hypertriglyceridemia?
* Cyclosporine * Tacrolimus * Sirolimus * Cyclophosphamide * Interferon
116
What miscellaneous medications can be secondary factors in moderate hypertriglyceridemia?
* Beta-blockers * Thiazides * Atypical antipsychotics * Rosiglitazone * Bile acid sequestrants * L-asparaginase
117
What lifestyle modifications are recommended for reducing TGs?
* 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
When is statin therapy recommended in moderate hypertriglyceridemia?
40-75 with ASCVD risk ≥7.5%
119
When is statin therapy recommended in severe hypertriglyceridemia?
* 40-75 with ASCVD ≥7.5% * 40-75 with TG ≥1000 (initiate statin + fibrate/omega-3)
120
What medications are the go-to therapies to decrease pancreatitis risk?
Fibrates or omega-3 fatty acids

Fall 2020: Therapeutics 2 (11 decks)

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