Anti-Hyperlipidemics Flashcards
1
Q
What should LDL level be lower than?
A
<100
2
Q
What is a desirable total cholesterol level?
A
<200
3
Q
What are the risk equivalents?
A
- Symptomatic carotid artery disease
- Peripheral arterial disease
- Abdominal aortic aneurysm
- Diabetes
4
Q
What are the hyperlipidemia risk factors? (5)
A
- Age
- Family history of premature CHD
- Cigarette smoking
- Hypertension
- Low HDL (< 40 mg/dL)
5
Q
What should a patient with CHD try to maintain as far as their LDL goal?
A
Under 100
6
Q
If a patient has two risk factors for hyperlipidemia than what should their LDL goal be?
A
under 130
7
Q
What are the nonpharmacologic treatment options?
A
- Therapeutic lifestyle change (TLC)
- Diet
- Exercise
- Smoking cessation
8
Q
What are the pharmacologic treatment options for hyperlipidemia?
A
- HMG-CoA Reductase Inhibitors (Statins)
- Nicotinic Acid, Vitamin B3 (Niacin)
- Fibric Acid Derivatives (Fibrates)
- Bile Acid Sequestrants (Resins)
- Cholesterol Absorption Inhibitors
9
Q
What are the benefits of therapeutic lifestyle changes?
A
- May obviate need for drug therapy
- Augment LDL lowering agents
- Allow for lower doses
10
Q
When should you not solely employ therapeutic lifestyle changes?
A
- Severe hypercholesterolemia
- Known CHD
- CHD risk equivalents
- PVD
11
Q
What are the major Anti-hyperlipidemic groups?
A
- HMG-CoA Reductase Inhibitors (Statins)
- Niacin (Nicotinic Acid, Vitamin B3
- Fibric Acid Derivatives (Fibrates)
- Bile Acid Sequestrants (Resins)
- Cholesterol Absorption Inhibitors
12
Q
What is the big drug combination that was listed in the drug list?
A
Simvastatin and Ezetimibe
13
Q
What were the drugs that should be employed for homozygous familial hypercholesterolemia?
A
- Lomitapide (Juxtapid)
- Mipomersen (Kynamro)
14
Q
What drug was presented as a good choice for those suffering from heterozygous familial hypercholesterolemia?
A
Alirocumab (Paluent)
15
Q
Lipids are essential for what three things?
A
- Cell Membrane Formation
- Hormone Synthesis
- Source of free fatty acids (FFA’s)
16
Q
What are the LDL levels associated with the following classifications?
Optimal
Near Optimal/Above optimal
Borderline High
High
Very High
A
Optimal: <100
Near Optimal/Above optimal: 100-129
Borderline High: 130 - 159
High: 160 - 189
Very High: over 190
17
Q
What are the Total cholesterol levels associated with…
Desirable
Borderline High
High
A
Desirable: <200
Borderline High: 200-239
High: >240
18
Q
What are the HDL levels associated with…
Low
High
A
Low: <40
High: >60
19
Q
What are the HMG-CoA Reductase Inhibitors (Statins)?
(7)
A
- •Atorvastatin (Lipitor)
- •Fluvastatin (Lescol)
- •Lovastatin (Mevacor)
- •Pitavastatin (Livalo)
- •Pravastatin (Pravachol)
- •Rosuvastatin (Crestor)
- •Simvastatin (Zocor)
20
Q
What are the fibric acid derivatives (fibrates)? 2
A
- Fenofibrate (Tricor)
- Gemfibrozil (Lopid)
21
Q
What are the bile acid sequestrants we are responsible for?
A
- •Cholestyramine (Questran)
- •Colesevelam (Welchol)
- •Colestipol (Colestid)
22
Q
What cholesterol absorption inhibitor do we need to know?
A
Ezemitibe (zetia)
23
Q
In the presence of CYP inhibitors such as cyclosporine, ketoconazole and fibrates, what happens to Statin concentrations?
A
Increase
24
Q
In the presence of cyp inducers such as pheytoin and ketoconazole, what happens to statin concentrations?
A
They decrease
25
What are the meds we use for niacin therapies?
Nicotinic acid and vitamin B3
26
What is the mechanism of action for statins?
Inhibit HMG-CoA reductase, which is the rate limiting step in cholesterol synthesis
Also, cause upregulation of cholesterol receptors
27
What is the oral absorption fraction for statins?
40-75%
28
To what extent are statins hit by first pass metabolism?
Extensively
29
The half lives for most statins are 1-3 hours, knowing this, and another key piece of information I am withholding to be a jerk... when should you instruct a patient to take this medication?
The other piece of info is that our peak cholesterol synthesis occurs not long after onset of sleep. Thus, patients should take the medication before bed.
30
Which statins have the 14 and 19 hour half lives?
14 hrs - atorvastatin
19 hrs - rosuvastatin
31
Which statin drug is not metabolized by CYP's?
Pravastatin
32
Name four adverse drug reactions associated with statins.
* LFT elevation
* CK elevation
* Rhabdomyolysis
* Myopathy
33
In what situation(s) are statin drugs contraindicated?
Pregnancy
34
What is the mechanism of action of the Niacin agents?
Inhibit triglyceride lipolysis in adipose tissue, and reduces circulating FFA's
35
Name four ADR's for Niacin drugs
* Cutaneous flush (prostaglandin-mediated)
* Pruritus
* Acanthosis nigricans
* Hepatotoxicity
36
What are three CI's (one is relative) associated with Niacin drugs?
1. Hepatic Disease
2. Active PUD
3. Caution DM
37
What is the MOA of gemfibrozil and fenofibrate?
_Fibric acid derivatives_
•PPARα agonists, regulates expression of proteins involved in lipoprotein structure and function, increased expression of LPL
38
What is the most important ADR to know about Niacin drugs?
cutaneous flush - mediated by prostaglandins, will be aggravated by warmth, including showers, tea, coffee, etc. Often resolves after a couple of days
39
Why are niacin's to be used with caution in DM?
Increased insulin resistance
40
What is a unique accolade of Niacin drugs?
They are the most potent upregulator of HDL synthesis
41
Fibric acid drugs are well absorbed, but bind to something in plasma, what?
Protein, thus they can end up competing with other protein bound drugs if used in combination.
42
What are the ADR's associated with Fibric acid derivatives?
* Gastrointestinal
* Lithiasis
* Myositis
* Myopathy
43
Fibric acid derivatives are contraindicated in what settings?
1. Hepatic dysfunction
2. renal dysfunction
3. Pregnancy
44
What DDI's do we need to be aware of when considering Fibric acid derivative therapy?
2
1. Potentiates action of warfarin
2. Increased risk of rhabdomyolysis when combined with statin drugs.
45
What is the mechanism of action of resins?
•bind bile acids increasing excretion 10x, enhanced conversion of cholesterol to BA’s, increased LDL clearance
46
What are the ADR's to know for Resins?
* GI (constipation, nausea)
* Impaired ADEK absorption (vitamins)
47
What are the contraindications for Bile acid sequestrants (resins)?
Diverticulitis
Bowel Disease
Cholestasis
48
What DDI is important to keep in mind for Bile acid sequestrants?
They impair drug absorption. Make sure to administer at seperate times.
49
What is the MOA of ezetimibe?
•inhibits NPC1L1; inhibits absorption of cholesterol and plant sterols
50
What ADR is associated with Cholesterol absorption inhibitos?
diarrhea
51
What DDI's are associated with Cholesterol absorption inhibitors?
Note to be administered with bile acid sequestrants
52
Based on the attached image, what drug fits the effects shown?
Statins
53
What drugs fits the profile shown here?
Fibrates
54
What drug matches the effects shown here?
Niacin
55
What drug matches the effects shown here?
Bile acid sequestrants
56
What drug matches the effects shown?
Cholesterol absorption inhibitor
57
Ok, what are the effects of the following on LDL, HDL and TG's?
1. Statins
2. Fibrates
3. Niacin
4. Bile Acid Sequestrants
5. Cholesterol Absorption Inhibitors
58
What are five things to be associated with atherosclerotic cardiovascular disease (ASCVD)?
* History of MI
* Stable or unstable angina
* Coronary or other revascularization
* Stroke or TIA
* Peripheral vascular disease
59
Doing what reduces ASCVD events?
Maximizing statin intensity
60
What are the four statin benefit groups?
* Clinical ASCVD
* Primary elevation of LDL-C ≥ 190 mg/dL
* Age 40-75 years with diabetes and LDL-C 70-189 mg/dL
* No clinical ASCVD or diabetes who are 40-75 years and LDL-C 70-189 mg/dL with ASCVD risk of ≥ 7.5%
61
Adults over 21 y/o who are candidates for statin therapy with clinical ASCVD should recieve what level statin therapy if they are...
1. Aged more than 75 years
2. aged under 75
1. over 75 y/o or if not a candidate for the high intensity statins should recieve moderate intensity statins.
2. Age less than 75 years gets High-intensity statin therapy (barring some good reason to shift to moderate intensity)
62
DM I or II age 40-70 years should get moderate intensity statins, unless...
Estimated 10yr ASCVD risk is greater than 7.5%, in which case use High intensity statin therapy
63
What are the high intensity statins?
MUST KNOW
Atorvastatin 40-80 mg
Rosuvastatin 20-40 mg
64
What is the average LDL-C reduction from high intensity statins?
more than 50%
65
Moderate intensity statins have an average LDL-C reduction of 30-49%. What are the ones we learned?
Atorvastatin 10 mg
rosuvastatin 10 mg
Simvastatin 20-40 mg
Pravastatin 40 mg
Lovastatin 40 mg
66
Low intensity statins have an average LDL-C reduction of up to 30%. What are the examples we were given?
Simvastatin 10 mg
Pravastatin 10-20 mg
Lovastatin 20 mg
67
What are the two drugs we should use for homozygous familial hypercholesterolemia?
Mipomersen (Kynamro)
Lomitapide (Juxtapid)
68
Mipomersen (kynamro) is administered as a once weekly injection as adjunct to diet and other lipid therapy. What is its MOA?
Inhibits apo B-100 synthesis by binding to the mRNA of apoB reducing formation
69
What ADRs are we to know for mipomersen?
**Injection site reactions**
- erythema
- pain
**Flu-like symptoms**
**headache**
**elevation of liver transaminases**
70
What are the contraindications of mipomersen?
Moderate or severe hepatic impairment
Active liver disease
71
Lomitapide (Juxtapid) is a once daily oral dose adjunct to diet and other lipid therapies, meant for tx of homozygoua familial hypercholesterolemia. What is the mechanism of action for this drug?
•binds and inhibits microsomal triglyceride transfer protein (located in lumen of endoplasmic reticulum); prevents assembly of apoB)
72
What are the ADRs we should be aware of with regard to Lomitapide (Juxtapid)?
**GI**
- diarrhea
- nausea
**Increased liver transaminases**
**Hepatic fat accumulation**
73
What is the contraindication of lomitapide?
pregnancy, is category X
74
Alirocumab (praluent) is used in the tx of heterozygous familial hypercholesterolemia, once every two weeks by subcutaneous injection as adjuct to diet and maximally tolerated statin therapy.
What is its mechanism of action?
Human monoclonal antibody against PCSK9, which normally degrades LDL receptors on hepatocyte surfaces.
