Therapy Of Dyslipidemias Flashcards
1
Q
___ is associated with the development of acute pancreatitis.
A
Hypertriglyceridemia
2
Q
Initial therapy of lipoprotein disorder is:
A
Life-style modification
3
Q
What lifestyle modifications can be done for lipoprotein disorders?
A
1) Restricted intake of total and saturated fat and cholesterol
2) Modest increase in unsaturated fat intake (specially mono-unsaturated fat)
3) Regular exercise
4) Smoking cessation
5) Weight reduction
4
Q
A __ is the drug of choice for patients with hypercholesterolemia
A
Statin
5
Q
Patients with hypercholesterolemia NOT responding to statin monotherapy may be treated with combination therapy, but should be monitored closely because of:
A
An increased risk for adverse effects and drug interactions
6
Q
Hypertriglyceridemia usually responds well to:
A
1) Niacin
2) Fibrates
7
Q
Which drugs are fibrates?
A
1) Gemfibrozil
2) Fenofibrate
8
Q
How do you treat low HDL-C?
A
1) Life-style modifications
2) Drug therapy with Niacin and Fibrates
9
Q
Lipoprotein A is formed from:
A
1) LDL
2) Apolipoprotein (a)
10
Q
Lipoprotein A is homologous with:
A
Plasminogen
11
Q
Is Lipoprotein A activated by tissue plasminogen activator (TPA)?
A
NO
12
Q
Lipoprotein A may be found in:
A
Atherosclerotic plaques
13
Q
Lipoprotein A may contribute to:
A
Coronary disease
14
Q
How can Lipoprotein A contribute to coronary disease?
A
By inhibiting thrombolysis
15
Q
Lipoprotein A can be secondarily elevated in patients with:
A
1) Severe nephrosis
2) Some inflammatory states
16
Q
__ reduces levels of Lipoprotein A in many patients.
A
Niacin
17
Q
VLDL carries about 10-15% of:
A
1) Serum cholesterol
2) Most fasting triglycerides
18
Q
High VLDL is a risk factor for:
A
Acute pancreatitis
19
Q
What are Chylomicrons?
A
Triglyceride-rich particles formed from dietary fat solubilized by bile salts.
20
Q
What are the secondary causes of Hypercholesterolemia?
A
1) Hypothyroidism
2) Obstructive liver disease
3) Nephrotic syndrome
4) Anorexia nervosa
5) Acute intermittent porphyria
6) Drugs
21
Q
Which drugs can cause Hypercholesterolemia?
A
1) Progestins
2) Thiazide diuretics
3) Glucocorticoids
4) β-blockers
5) Isotretinoin
6) Protease inhibitors
7) Cyclosporine
8) Sirolimus
9) Mirtazapine
22
Q
What are the secondary causes of Hypertriglyceridemia?
A
1) Obesity
2) Diabetes mellitus
3) Lipodystrophy
4) Glycogen storage disease
5) Ileal bypass surgery
6) Sepsis
7) Nephrotic syndrome
8) Chronic renal disease
9) Pregnancy
10) Acute hepatitis
11) SLE
12) Monoclonal gammopathy:
a) Multiple myeloma
b) Lymphoma
13) Drugs
23
Q
Which drugs can cause Hypertriglyceridemia?
A
1) Alcohol
2) Estrogens
3) Isotretinoin
4) Thiazides
5) β-blockers
6) Glucocorticoids
7) Bile-acid binding resins
8) Asparaginase
9) Interferons
10) Azole antifungals
11) Bexarotene
12) Mirtazapine
13) Anabolic steroids
14) Sirolimus
24
Q
What are the secondary causes of Low HDL?
A
1) Malnutrition
2) Obesity
3) Sedentary life-style
4) Drugs
25
Which drugs can cause Low HDL?
1) Non-ISA β-blockers
2) Anabolic steroids
3) Probucol
4) Isotretinoin
5) Progestins
26
What are the ultimate goals of dyslipidemia therapy?
To reduce the risk of MI, angina, heart failure...etc.
27
What should be implemented in all patients prior to considering drug therapy for dyslipidemias?
Therapeutic life-style modification
28
What are the therapeutic life-style modifications followed for dyslipidemia?
1) Reduced intakes of saturated fats, cholesterol, and total fat
2) Use of dietary options to reduce LDL-C
3) Physical activity of moderate intensity 30 minutes per day for most days of the week
4) Restriction of alcohol drinking
5) Weight reduction in overweight
6) Stop smoking
7) Control hypertension
29
What dietary options can reduce LDL-C?
1) Plant phytosterols
2) Increased soluble fiber intake
3) Weight reduction
4) Increased physical activity
30
___ are structurally similar to cholesterol, and compete for its intestinal absorption.
Plant phytosterols
31
How do Plant phytosterols decrease LDL-C?
1) Competing for cholesterol absorption
2) Reduce bile acid absorption = Cholesterol is degraded into bile acids
32
What are some food sources of phytosterols?
1) Cereals (oat, wheat, brown rice)
2) Legumes (peas, beans, lentils)
3) Nuts and Seeds (peanuts, almonds, sunflower seeds, pumpkin seeds, sesame seeds)
4) Fruits and vegetables (broccoli, cauliflower, apples, avocados, tomato, blueberries)
33
___ + ___ raises HDL and reduces non-HDL cholesterol.
Weight control + Increased physical activity
34
______ can result in useful adjunctive reductions in total and LDL cholesterol.
Increased intake of soluble fiber
35
What are some examples of soluble fibers?
1) Oat bran
2) Pectins
3) Psyllium products
36
Which supplement can be used in hyperlipidemia?
Omega-3 fatty acids
37
How do Omega-3 fatty acids work?
1) Activate peroxisome proliferator-activated receptor-alpha (PPAR-α)
2) Alters synthesis of prostanoids = synthesis of vasodilator prostaglandins and inhibitors of platelet aggregation
38
What do Omega-3 fatty acids do?
1) Reduce triglycerides in VLDL
2) Increase both HDL and LDL
39
Adverse reactions of Omega-3 fatty acids?
1) Thrombocytopenia
2) Bleeding disorders
40
What are the Omega-3 fatty acids?
1) Eicosapentaenoic acid
2) Docosahexaenoic acid
41
Other effects of omega-3 fatty acids include:
1) Changes in immune function and cellular proliferation
2) Antioxidant actions
3) Anti-inflammatory actions
4) Antiarrhythmic activities
42
Which lipid lowering drug is useful for ALL lipoprotein disorders?
NONE
43
What is Type 1 Hyperlipoproteinemia?
Elevated Chylomicrons
44
What is Type 2a Hyperlipoproteinemia?
Elevated LDL
45
What is Type 2b Hyperlipoproteinemia?
Elevated LDL + VLDL
46
What is Type 3 Hyperlipoproteinemia?
Elevated IDL
47
What is Type 4 Hyperlipoproteinemia?
Elevated VLDL
48
What is Type 5 Hyperlipoproteinemia?
Elevated VLDL + Chylomicrons
49
What is the drug of choice for Type 1 Hyperlipoproteinemia?
None
50
What is the drug of choice for Type 2a Hyperlipoproteinemia?
1) Statins!!!!!
2) Bile acid binding resins
3) Niacin
51
What is the drug of choice for Type 2b Hyperlipoproteinemia?
1) Statins!!!!!
2) Fibrates
3) Niacin
52
What is the drug of choice for Type 3 Hyperlipoproteinemia?
1) Fibrates
2) Niacin
53
What is the drug of choice for Type 4 Hyperlipoproteinemia?
1) Fibrates
2) Niacin
54
What is the drug of choice for Type 5 Hyperlipoproteinemia?
1) Fibrates
2) Niacin
55
Treatment of type I hyperlipoproteinemia is directed towards:
Reduction of chylomicrons derived from dietary fat with the subsequent reduction in plasma triglycerides.
56
Niacin is __(oxidized/reduced) in the body to the amide which is incorporated into:
Reduced; NAD = Energy metabolism
57
Pharmacodynamics of Niacin?
1) Inhibits VLDL secretion from the liver and thus LDL production
2) Raises HDL cholesterol
3) Reduces the level of LP(a)
4) Reduces fibrinogen levels
5) Increases tissue plasminogen activator (TPA)
58
How does Niacin raise HDL cholesterol?
By decreasing its catabolism
59
Adverse reactions of Niacin?
1) Acanthosis nigricans
2) Elevation of liver function tests
3) Prostaglandin-mediated cutaneous flushing and itching
4) Hyperuricemia
5) Hyperglycemia
60
Niacin is contraindicated in those with:
Active liver disease
61
How can you prevent the flushing and itching associated with Niacin?
By giving Aspirin 325 mg shortly before Niacin
62
____ may mediate niacin-induced vasodilation.
Prostaglandin D receptor subtype 1 (DP1)
63
What is Laropiprant?
A selective antagonist of Prostaglandin D receptor subtype 1 (DP1)
64
Why might we give Laropiprant with Niacin?
To lower flushing and itching symptoms
65
What should be avoided at the time of ingestion of Niacin?
1) Alcohol
2) Hot drinks
66
Why should alcohol and hot drinks be avoided with Niacin?
They may magnify flushing and pruritus
67
Niacin increases risk of ___ when given with Statins.
Myopathy
68
Niacin increases risk of myopathy when given with ___.
Statins
69
Fibric acid derivatives include:
1) Phenofibate
2) Gemfibrozil
70
What do Fibric acid derivatives do?
Enhance hydrolysis of VLDL and chylomicron triglycerides in the circulation by lipoprotein lipase.
71
Fibric acid derivatives stimulate:
Cellular fatty acid uptake
72
A major effect of Fibric acid derivatives is an increase in:
Oxidation of fatty acids in liver and striated muscle
73
ALL effects of Fibric acid derivatives?
1) Reduction of VLDL
2) Modest decrease in LDL
3) Elevation of HDL
74
Fibric acid derivatives may increase LDL in which patients?
With hypertriglyceridemia, as triglycerides are reduced.
75
How do Fibric acid derivatives increase HDL?
By increasing the production of apo-A1 and apoAII in the liver
76
Adverse effects of Fibric acid derivatives?
1) Gallstones
2) May potentiate the effects of oral anticoagulants
3) Reduce platelet activity
4) Hypokalemia and cardiac arrhythmias
5) Myositis and elevations in creatine phosphokinase
6) Elevation of liver enzymes
7) Reduce WBCs and hematocrit
77
Why might Fibric acid derivatives cause gallstones?
Due to an increase in the lithogenicity of bile
78
What should you monitor in a patient taking both Fibric acid derivatives and oral coagulants?
INR
79
Fibric acid derivatives should be avoided in which patients?
1) Hepatic dysfunction
2) Renal dysfunction
80
Primary hypercholesterolemia may be treated with:
1) Statins! (1st choice!)
2) Bile acid binding resins
3) Niacin
4) Ezetimibe
81
Which drugs are Bile acid binding resins?
1) Colestipol
2) Cholestyramine
3) Colesevelam
82
What are Statins mode of action?
HMG Co-A reductase inhibitors
83
HMG CoA Reductase inhibition leads to reduced cholesterol content of hepatocytes =
Increased LDL receptor synthesis (Breakdown of LDL and its precursors)
84
Other actions of Statins include:
1) Reduce oxidative stress
2) Reduce vascular inflammation
3) Stabilize atherosclerotic lesions
4) Improve the microcirculation
5) Inhibit proliferation of arterial wall smooth muscle
6) Improve endothelial cell function
85
Which drugs are Statins?
1) Lovastatin
2) Simvastatin
3) Atorvastatin
4) Rosuvastatin
86
Ezetimibe moa?
Inhibits cholesterol absorption through the gut
87
Adverse effects of Statins?
1) Elevation of serum ALT
2) Serious muscle toxicity (myopathy)
3) Elevated serum CPK
4) Rhabdomyolysis
5) Myoglobinuria
6) Renal shutdown
3) Teratogenicity
88
Can you take Statins during pregnancy & Lactation?
NO
89
Myopathy associated with Statins increases in severity if co-administered with:
1) Nicotinic acid
2) Fibrates
3) Ketoconazole
4) Cyclosporine
5) Erythromycin
6) Verapamil
7) Cimetidine
8) Metronidazole
9) Amiodarone
10) Grapefruit juice
11) Protease inhibitors (anti-HIV)
90
Bile Acid Binding Resins moa?
They exchange Cl- for the negatively charged bile acids = preventing negative feedback = enhancing of cholesterol breakdown = increases LDL receptors
91
Loss of bile acids also reduces __ and ___ absorption from GIT.
Fat and cholesterol
92
When might the VLDL be increased during treatment with Bild Acid Binding Resins?
In patients with combined hyperlipidemia (2b)(hypertriglyceridemia and
hypercholesterolemia)
93
Bile Acid Binding Resins are ONLY useful for:
Isolated increases in LDL
94
Adverse effects of Bile Acid Binding Resins?
1) GI complaints of gritty taste,
constipation, bloating (epigastric fullness), nausea, flatulence, and GIT obstruction.
2) Impaired absorption of fat-soluble vitamins A, D, E, and K.
3) Hypernatremia
4) Hyperchloremic metabolic acidosis
95
Bile Acid Binding Resins can reduce the bioavailability of which drugs?
1) Coumarin anticoagulants
2) Nicotinic acid
3) Thyroxine
4) Acetaminophen
5) Hydrocortisone
6) Hydrochlorothiazide
7) Iron
96
How can you avoid drug interactions when giving Bile Acid Binding Resins?
By spacing administration by 6 hours between the bile acid resin and other drugs.
97
Both the statins and the resins are NOT effective in patients lacking:
LDL receptors
98
Which patients may lack LDL receptors?
Those with Familial Homozygous Hypercholesterolemia
99
Severe forms of hypercholesterolemia may
require:
More intensive combination therapy
100
Ezetimibe moa?
1) Inhibits intestinal cholesterol absorption = reduces LDL
2) Inhibits phytosterol absorption
101
Why is Ezetimibe effective even in the absence of dietary
cholesterol?
Because it inhibits reabsorption of cholesterol excreted in bile
102
Ezetimibe could be used in combination therapy, synergistic with ___.
Statins
103
Ezetimibe could be used in combination therapy in which type?
2b
104
Plasma concentration of Ezetimibe is ___(decreased/increased) when
co-administered with fibrates and ___(increased/decreased) when given with resins.
Increased; Decreased
105
Adverse effects of Ezetimibe?
1) Muscle pain and weakness
2) Hepatitis and jaundice
3) Pancreatitis and elevation of amylase
106
Plasma concentration of Ezetimibe is increased when co-administered with __ and reduced when given with __.
Fibrates; Resins
107
Can combined hyperlipoproteinemia (type IIb)
be treated with statins, niacin, or gemfibrozil combinations to lower LDL cholesterol WITHOUT
elevating VLDL and triglycerides?
YES
108
Fibric acid (gemfibrozil, fenofibrate) monotherapy is effective in reducing __, but
may increase __.
VLDL; LDL
109
Low HDL Cholesterol (<40 mg/dL) may be a consequence of:
1) Insulin resistance
2) Physical inactivity
3) Type 2 diabetes
4) Cigarette smoking
5) Very high carbohydrate intake
6) Certain drugs
110
Drugs of choice for Low HDL Cholesterol (<40 mg/dL)?
1) Niacin
2) Fibric acid derivatives
111
Diabetic dyslipidemia is characterized by:
1) Hypertriglyceridemia
2) Low HDL
3) Minimal elevation of LDL
112
Most patients with Diabetic dyslipidemia will require:
1) Therapeutic life-style modification
2) Drug therapy
113
What should you do when LDL-C is high?
1) Intensify glycemic control
2) Add fibric acid derivatives or Niacin
3) Intensify LDL-C-lowering therapy using statins
114
Which patients are more susceptible to adverse effects of lipid-lowering drugs?
The elderly
115
The elderly are more likely to have which Bile Acid Resin adverse effect?
Constipation
116
The elderly are more likely to have which Niacin adverse effects?
1) Skin and eye changes
2) Gout
117
The elderly are more likely to have which Fibric Acid Derivatives adverse effects?
1) Gallstones
2) Bone/joint disorders
118
The elderly are more likely to have which Statin adverse effect?
Bone/joint disorders
119
How should therapy in the elderly be started?
With lower doses and titrated up slowly to minimize adverse effects.
120
__ may be a more important predictor of disease in women.
HDL
121
___ and ___ levels rise progressively throughout pregnancy.
Cholesterol and triglyceride
122
Which dyslipidemia drugs are given during pregnancy?
NONE!!!
123
How do you treat dyslipidemias in pregnant women?
Dietary therapy, with emphasis on maintaining a nutritionally balanced diet.
124
Which dyslipidemia drug may be considered in pregnant women if there is a VERY high risk?
A Bile Acid Resin
125
___ are Category X and are contraindicated in pregnant women.
Statins
126
___ is a pregnancy Category C drug.
Ezetimibe
127
Statins are Category _ in pregnancy.
X
128
Dyslipidemia drug therapy in children is NOT recommended until the age of _ years or older
8
129
Younger children are generally managed with therapeutic life-style changes until after the age of:
2 years
130
___ may be safe and are effective in children.
Statins
131
What is Mipomersen?
Antisense oligonucleotide
132
Mipomersen moa?
Specifically binds to the apolipoprotein B-100 mRNA = blocks translation of the gene product
133
The reduction in production of apo B-100 results in:
Reduced hepatic production of:
1) VLDL
2) IDL
3) LDL
4) Lipoprotein(a)
134
Mipomersen is indicated in which patients?
Those with homozygous familial hypercholesterolemia as an adjunct to diet and other lipid-lowering medications
135
Why is the use of Mipomersen restricted?
Because it is hepatotoxic
136
How is Mipomersen given?
Subcutaneous injection
137
Lomitapide inhibits:
1) Microsomal triglyceride transfer protein (MTP)
2) CYP3A4
3) P-Glycoprotein
138
What is Microsomal triglyceride transfer protein (MTP) responsible for?
Absorbing dietary lipids and transferring triglycerides onto apolipoprotein B (apo-B) in the assembly of VLDL
139
What happens if Microsomal triglyceride transfer protein (MTP) is inhibited?
Transfer of lipid to apo-B is blocked = ApoB destruction and inhibition of lipoprotein secretion
140
What is Lomitapide given for?
Familial hypercholesterolemia
141
Adverse effects of Lomitapide?
1) Elevation of serum aminotransferase
2) Increased hepatic fat (steatohepatitis) and hepatic fibrosis
142
What does PCSK9 do?
Binds to LDL receptors on hepatocytes = LDLR degradation = Elevates LDL-C blood levels
143
What does Alirocumab do?
Inhibits the binding of PCSK9 to
LDL receptors = Reduces LDL-C levels
144
How is Alirocumab given?
Subcutaneous injection
145
Which drug is similar to Alirocumab?
Evolocumab
146
What is Alirocumab given for?
Heterozygous familial hypercholesterolemia
