Dyslipidemia Flashcards
1
Q
Chylomicrons carry fats absorbed in the ____
A
Diet
2
Q
VLDL carries fats from the ____
A
Liver
3
Q
LDL is “___” cholesterol
A
Bad
4
Q
HDL is the “____” cholesterol
A
Good
5
Q
Lipoproteins are spherical particles that transport ____ molecules, principally cholesterol and triglycerides
A
Hydrophobic
6
Q
The surface of chylomicrons is composed of a monolayer of ____ and unesterified cholesterol molecules
A
Phospholipid
7
Q
Apolipoprotein B-100 carries ____ to tissues
A
Cholesterol
8
Q
The goal for apolipoprotein B-100 is < ____ mg/dl for high-risk individuals
A
80
9
Q
Apolipoprotein B-100 levels may be a better indicator of ____ ____ risk than total cholesterol or LDL
A
Cardiac disease
10
Q
Exogenous cholesterol and triglycerides are simultaneously absorbed from the ____ ____ by different mechanisms
A
Intestinal lumen
11
Q
Cholesterol is taken up from micelles across a regulatory channel named ____
A
NPC1L1
12
Q
A fraction of the cholesterol is pumped back into the lumen by ____, a heterodimeric ATP-dependent plasma membrane protein
A
ABCG5/G8
13
Q
The remainder of cholesterol is converted to cholesteryl esters by ____
A
ACAT
14
Q
Triglycerides are taken up as ___ ___ and ____, which are re-esterified by DGAT
A
Fatty acids, monoglycerides
15
Q
Formation of ____ occurs when IDL particles interact with hepatic lipase to become denser and cholesteryl ester-enriched
A
LDL
16
Q
When LDL is formed, both ___ and ____ lose affinity for the particle and are transferred to HDL, leaving only apoB1000
A
apoE and apoCII
17
Q
The binding of apolipoprotein B100 to LDL receptors on hepatocytes or other cell types promotes LDL internalization into endocytic vesicles and fusion of the vesicles with ____
A
Lysosomes
18
Q
LDL receptors are recycled to the cell surface, whereas lipoprotein particles are hydrolyzed into amino acids, releasing free _____
A
Cholesterol
19
Q
Intracellular cholesterol has what 3 regulator effects on the cell?
A
-Cholesterol decreases the activity of HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis
-Cholesterol activates acetyl CoA: cholesterol acyltransferase (ACAT), an enzyme that esterifies free cholesterol into cholesteryl esters for intracellular storage or export
-Cholesterol inhibits the transcription of the gene encoding the LDL receptor, and, thereby, decreases further uptake of cholesterol by the cell
20
Q
Elevated LDL is a major risk factor for the development of _____
A
Atheroscleorosis
21
Q
Native LDL that migrates into the subendothelial space can under chemical transformation to oxidized LDL via lipid peroxidation and fragmentation of _____
A
apoB100
22
Q
Oxidized LDL has a number of deleterious effects on _____ function
A
Vascular
23
Q
Oxidized LDL promotes monocytes chemotaxis to the ____ space and inhibits monocyte egress from that space
A
Subendothelial
24
Q
Resident monocyte:macrophages bind to oxidized LDL via a scavenger receptor, resulting in the formation of lipid-laden ___ ___
A
Foam cells
25
Oxidized LDL can directly injure endothelial cells and cause endothelial _____
Dysfunction
26
Oxidized LDL can also cause foam cell ____, with a release of numerous proteolytic enzymes
Necrosis
27
Within a hepatocyte, a portion of cholesterol is concerted to ____ ____
Bile acids
28
The process of converting cholesterol to bile acids is rate-limited by ____ _____, which is expressed only in hepatocytes
Cholesterol 7a-hydroxylase
29
____ is the most abundant bile salt synthesized by the human liver
Cholate
30
What are some non-pharmacological treatments of dyslipidemia?
-Lifestyle and diet habits
-Low cholesterol, low-fat diet (12 weeks before starting drug treatment and continued thereafter)
-Weight loss program
-Exercising
-Evaluate for alcoholism (may be the cause of hyperlipidemia)
31
Options for the pharmacological treatment of dyslipidemia:
Inhibitors of HGM-CoA Reductase (statins):
-Lovastatin
-Simvastatin
-Fluvastatin
-Atorvastatin
-Pravastatin
-Rosuvastatin
-Pitavastatin
32
Adjuncts to hypertension treatment with dyslipidemia are based on patient cardiovascular risk:
-High-intensity statin
-Moderate-intensity statin
-Move away from LDL goals
-Move away from non-statins if patient can't tolerate statin
33
What are high-intensity statins?
-Atorvastatin 40-80 mg
-Rosuvastatin 20-40 mg
34
What are examples of moderate-intensity statins?
-Simvastatin 20-40 mg
-Atorvastatin 10-20 mg
-Rosuvastatin 5-10 mg
-Lovastatin 40 mg
-Pravastatin 40-80 mg
-Pitavastatin 2-4 mg
-Fluvastatin 80 mg
35
Mechanism of action of statins:
-Block the rate-limiting step in the synthesis of cholesterol
-Molecular site of action: bind to and inhibit the enzyme HMG Co-A reductase, the rate-limiting enzyme in the synthesis of cholesterol by the hepatocytes
36
Statins competitively inhibit HMG-CoA reductase, the enzyme that catalyzes the rate limiting synthesis in ____ biosynthesis
Cholesterol
37
Decreased cellular cholesterol concentrations lead to _____ activation and cleavage of the sterol regulatory element binding protein, which is a transcription factor that normally resides in the cytoplasm
Protease
38
The cleaved sterol regulatory element binding protein diffuses into the nucleus, where it binds to sterol response elements, leading to up-regulation of ___-____ gene transcription
LDL-receptor
39
Up-regulation of LDL-receptor leads to ____ cellular LDL-receptor expression
Increased
40
The increased LDL receptor expression promotes uptake of LDL particles and results in reduced _____ concentrations in the plasma
LDL-cholesterol
41
The liver compensates for the reduced ability to synthesize cholesterol by ____ ___ cholesterol circulating in the blood in
Taking up
42
The reduction in the cholesterol concentration in the liver leads to an ____ in the number of LDL receptors inserted in the hepatocyte membrane
Increase
43
The goal for treatment of dyslipidemia is to increase the hepatic uptake of ____, which decreases the amount in circulation
LDL
44
Statins reduce LDL by ___-___%
20-55
45
Potency differs between statins; what is the most potent to least potent statin?
Ruvostatin > Atorvastatin > Simvastatin > Pravastatin (in ability to reduce LDL per equal dose)
46
Adverse effects of statins?
-Liver toxicity (low incidence, but would need to d/c drug)
-Myotoxicity
-Rhabdomyolysis
-Abdominal pain
-Nausea
-Headache
-Photosensitivity
47
How is liver toxicity evidenced by statins?
Increase in blood transaminase, an enzyme that is released from the liver when hepatocytes are damaged
48
Myotoxicity results from damage to ____ muscle cells and ranges from symptoms of myalgia (muscle pain) to rhabdomyolysis (deterioration and death of skeletal muscle cells)
Skeletal
49
Myotoxicity can be monitored by measuring blood levels of ____ ____, which is an enzyme that is released from damaged skeletal muscle cells
Creatine phosphokinase
50
____ is a syndrome characterized by muscle necrosis that causes intracellular constituents of the affected skeletal muscle to be released into the circulation
Rhabdomyolysis
51
The severity of rhabdomyolysis ranges from asymptomatic elevations of muscle enzymes in blood to a life-threatening condition that leads to...
-Extreme increases in muscle enzymes in the blood
-Electrolyte imbalances
-Acute renal failure (liver function tests are recommended before start (or increase of dose) and 12 weeks after to monitor for problems)
52
Warnings/precautions for statins:
-Pregnancy category X
-Report unexplained muscle pain to doctor
53
What statins are metabolized by the 2C9 CYP pathway?
-Fluvastatin
-Rosuvastatin (also 2C19)
54
What statin is not metabolized by any CYP450 enzymes?
Pravastatin
55
What 3 statins are metabolized by the 3A4 enzyme of CYP?
-Lovastatin
-Simvastatin
-Atorvastatin
56
What are two statin drugs that are not lipophilic?
-Rosuvastatin
-Pravastatin
57
What two statin drugs have no active metabolites?
-Fluvastatin
-Pravastatin
58
What statin drug has the highest half-life?
Rosuvastatin
59
What drug class is contraindicated for someone on a statin drug?
Fibrates (Gemfibrozil)
60
What other drug classes are contraindicated with some statin drugs?
-Azole antifungals
-Macrolide antibiotics
-Calcium channel blockers
-Amiodarone
-Cyclosporine
-Protease inhibitors
-Antidepressants
61
Ezetimibe (ZETIA) is a drug that interferes with the absorption of ____ ____
Dietary cholesterol
62
Ezetimibe inhibits the absorption of dietary cholesterol in the ___ ___
Small intestine
63
Ezetimibe (ZETIA) binds to and inhibits the transport protein that assists the transport of dietary cholesterol through the ____ _____ (NCP1L1) across the cell membrane of the columnar epithelial cells of the brush border of the small intestine
Sterol transporter
64
The net effects of Ezetimibe (ZETIA) is that less cholesterol from the diet is _____ and delivered to the liver
Absorbed
65
Ezetimibe has no effect on cholesterol synthesized by the _____
Liver
66
The amount of cholesterol absorbed from the diet that enters the blood and is delivered to the liver is ____ when on Ezetimibe
Decreased
67
Ezetimibe reduces LDL cholesterol by approximately ____%
18
68
Clinical uses of Ezetimibe:
-With statin to further enhance the lowering of LDL
-To permit a lowering of stain dosage to avoid statin-related complications
-To treat hypercholesterolemia when statin use cannot be tolerated or is contraindicated
69
Adverse effects of Ezetimibe:
-Arthralgia
-Dizziness
-Diarrhea
-Sinusitis
-Increased liver enzymes when added to statins
70
Ezetimibe is pregnancy category ____
C
71
What are four drug-drug interactions with Ezetimibe?
-Cyclosporine (increases the concentration of both drugs)
-Fenobirate (may lead to cholelithiasis)
-Cholestyramine (can decrease ezetimibe concentration by 55%)
-Coumadin (monitor INR)
72
Alirocumab (Praluent) is a monoclonal antibody indicated for ____ ____ and ____ ____ _____, and needs additional decrease in lipids
Familial hypercholesterolemia and coronary artery disease
73
Alirocumab (Praluent) inhibits _____, which normally reduces the number of receptors that remove LDL from the bloodstream
PCSK9
74
Alirocumab (Praluent) causes a significant decrease in ____, but the long-term effects on cardiovascular morbidity and mortality is yet to be determined
LDL
75
_____, a water-soluble B complex vitamin, was first described as a lipid-lowering agent around 1955
Niacin
76
The effectiveness of niacin as a lipid-lowering agent is unrelated to its vitamin effects and requires a much _____ dose
Higher
77
Niacin decreases hepatic production and secretion of _____ and _____
LDL and VLDL
78
The effect niacin has on LDL and VLDL is secondary to the inhibition of _____ is adipose tissue (intracellular lipase system)
Lipolysis
79
Niacin/nicotinic acid acts on the nicotinic acid receptor that is expressed by ____ ____ and present in the cellular membrane of the adipocyte
Adipose tissue
80
Niacin causes less free ____ ____ to be formed, and as a result, there are less in the plasma
Fatty acids
81
Since niacin causes a decrease in the free fatty acid concentration, the liver has less available substrate to form _____
Triglycerides
82
Reduced synthesis of triglycerides in the liver results in a _____ in the formation of VLDL triglycerides and therefore, the circulation triglyceride levels
Decrease
83
With less VLDL produced, there is a drop in the formation of ____
LDL
84
Niacin lowers ____ and ____ levels, which increases HDL levels
LDL and triglycerides
85
Niacin's effects on lipoprotein levels:
-Decrease in VLDL and LDL
-Decrease in triglycerides by 25-30%
-Decrease in LDL by 10-25%
-Increase in HDL by 15-35%
86
Adverse effects of niacin:
-Flushing of the face and upper extremities
-Gastrointestinal effects include dyspepsia, nausea, and vomiting
-May cause ulcers and is therefore contraindicated in individuals with a history of ulcers
87
What are three examples of fibric acid derivatives used for the treatment of dyslipidemia?
-Clofibrate (original, not used anymore)
-Gemfibrozil (LOPID)
-Fenofibrate (TRICOR)
88
Fenofibrate and Gemfibrozil bind to and stimulate the ____ ____ ____ ____
Peroxisome proliferator-activated receptor alpha
89
Fenofibrate and Gemfibrozil cause _____ expression of lipoprotein lipase
Increased
90
Thus, Fenofibrate and Gemfibrozil have the capacity to reduce circulating triglyceride levels by ____-____% (they may also lower LDL levels 6-20%, or slightly raise levels)
35-53
91
Fibric acid derivatives like Fenofibrate or Genfibrozil can be used alone or in combination with ____ (used in combination can increase risk of myopathy)
Statins
92
Adverse effects of fibric acid derivates:
-Rash
-N/V/D
-Myalgia
93
Firbic acid derivatives are pregnancy category ____
C
94
Kinetics of Fenofibrate:
-Well absorbed from GI
-Food increases absorption
-Highly protein bound (99%)
-Half-life: 20 hours
-Hepatic metabolism
-Renal excretion
95
When would Fenofibrate be contraindicated?
-Hepatic or severe renal dysfunction
-Gallbladder disease
96
Adverse effects of Fenofibrate:
-Pancreatitis
-Hepatotoxicity
-Rhabdomyolysis
97
Kinetics of Gemfibrozil:
-Well absorbed from the GI tract
-Hepatic metabolism
-Renal excretion
98
When would Gemfibrozil be contraindicated?
-Hepatic or severe renal dysfunction
-Gallbladder disease
99
Adverse effects of Gemfibrozil:
-Rhabdomyolysis
-Hyperglycemic effects (monitor diabetic patients)
100
What are three examples of Bile Acid Binding Resin?
-Cholestyramine (Questran)
-Colestipol (Colestid)
-Colesevelam (Welchol)
101
Ion-exchange resins are not ____
Absorbed
102
Bile acid binding resins bind to bile salts in the intestine in exchange for ____ ____
Chloride ions
103
Under normal circumstances, the liver secretes bile acids and ____% are recycled by being reabsorbed
97
104
However, bile salts that are bound to resin are lost in the ____
Feces
105
The liver compensated by forming more ___ ___ from cholesterol
Bile salts
106
Bile acid binding resins increase the liver's need for _____ as a substrate; there is compensatory increase in LDL receptors inserted into the hepatocyte membranes in order to retrieve cholesterol from the LDL
Cholesterol
107
Bile acid binding resins decrease LDL levels by ___-___%
10-30
108
Adverse effects of all bile acid binding resins:
-Constipation (can be severe and lead to impaction)
-GI bleed
-Belthcing
-Bloating
-Flatulence
-N/V
-Indigestion
-Anorexia
109
Additional adverse effects of Cholestyramine:
-Vitamin K deficiencies (from bleeding)
-Headache
-Impaired absorption of fat-soluble vitamins (A, D, E, K)
-Hyperchloremic acidosis
110
Additional adverse effects of Colestipol:
-Dizziness
-Anxiety
-Vertigo
-Fatigue
111
Lovaza is a prescription ____ _____ _____
Omega-3 fatty acid
112
Lovaza decreases synthesis of ____ in the liver because DHA and EPA are poor substrates for enzymes to convert to triglycerides
Triglycerides
113
Lovaza decreases triglycerides by ____% and increases HDL by ____
45%; 9%
114
Lovaza also decreases other cholesterols by ___%
14
115
Side effects of Lovaza:
-Infection
-Weird taste
-Back pain
116
Omega-3s and fish oils have no _____ effects and better manufacturing decreases exposure to mercury
Antithrombotic
117
Fish oils are not equal to prescription omega-3s (Lovaza) due to...
-Ratio of DHA and EPA
-Products being unregulated
118
Fish oils can be taken with ____ and ____
Niacin and Statin
119
Fish oils have what cardio effects that complement statin?
-Antithrombic effects
-Endothelial relaxation
-Anti-inflammatory effects
120
Soluble fiber decreases LDL by ___%
7
121
Phytosterols and plant sterols decrease LDL by 15% by competing with cholesterol for absorption sites in the ____
Intestine
122
Soy protein can decrease LDL by 3%, but you would need to get ___ grams which is hard to get
25
123
Red yeast rice can decrease LDL by ____ mg/dl by blocking cholesterol production in the liver
35
124
Red yeast rice is a natural form of _____ (you must test LFTs)
Lovastatin
125
Flaxseed can also be used to treat dyslipidemia as it a plant source of _____
Omega-3
126
____ can also lower lipid levels
CoQ10
