Exam 2: Atherosclerosis Flashcards
1
Q
Tunica intima
A
Endothelium
2
Q
Tunica media
A
Elastic fibers and smooth muscle
3
Q
Tunica media is thicker in ____ and thinner in ____
A
Thicker in arteries
Thinner in veins
4
Q
Tunica extern
A
elastic and collagen fibers (connective tissue)
5
Q
Tunica extern is thinner than media in ____- but thickest layer in
A
Thinner than media in arteries, but thickest layer in veins
6
Q
Arteries tend to be ____ than veins
A
Thicker than veins
7
Q
Arteries contain more
A
Elastic fibers that helps them stretch and recoil during the cardiac cycle
8
Q
Veins are not designed to
A
Withstand high pressure, but are distensible enough to adapt to variations in the volume and pressure of blood passing through them
9
Q
Veins have ____ to prevent back flow
A
Valves!
10
Q
Both arteries and veins are innervated by
A
The SNS
11
Q
Is the vascular endothelium a simple, single layer of cells lining the heart and blood vessels?
A
No! it is a lot more than that
12
Q
The vascular endothelium is a
A
- Metabolic interface between the blood and other tissues
-
13
Q
The vascular endothelium forms a unique
A
thromboresistant layer between sub endothelial tissue and blood
14
Q
the vascular endothelium modulates
A
tone, growth, hemostasis, and inflammation throughout the circulatory system
15
Q
What is an initial step in atherosclerosis
A
Endothelial vasodilator dysfunction
16
Q
Endothelial vasodilator dysfunction is caused by **
A
loss of endothelium-derived nitric oxide
17
Q
The body’s endothelial cells account for an area of
A
4,000 - 7,000 sq. miles
18
Q
Vascular endothelium regulates vasodilation by decorating vasoactive substances like
A
Nitric Oxide
Angiotensin-converting enzyme
Receptors for NE on surfaces of endothelial
19
Q
What does nitric oxide cause
A
Vasodilation
20
Q
Angiotensin converting enzyme on the surface of endothelial cells cause
A
Vasoconstriction via RAAS
21
Q
Vascular endothelium prevents thrombus formation b/c
A
Physiologically thromboresistant
Secretes heparin and other substances that inhibit platelet activity
22
Q
Arteriosclerosis is a
A
generic term for “hardening of the arteries” (because they become less elastic)
23
Q
Atherosclerosis is a type of
A
Arteriosclerosis
24
Q
ATHerosclerosis is a
A
pathologic process involving development of fibrofatty lesions in the intimal lining of cerebral, coronary, and peripheral arteries
25
Factors that contribute to the pathogenesis of atherosclerosis
- Endothelial dysfunction
- Dyslipidemia (family history - familial hypercholesterolemia)
- Inflammation
26
Atherosclerosis is associated with
```
Smoking
Hypertension
Diabetes
Gender (male > female premenopausal)
Obesity
```
27
Important risk factors for Atherosclerosis and dyslipidemia
High levels of low density lipoprotein (LDLs)
| Low levels of High density lipoprotein (HDLs)
28
Atherosclerosis begins with
injury to the endothelial cells lining the artery walls
29
The endothelial injury then progresses to
Fatty streak and fibrotic plaque, which leads to complicated lesion
30
Endothelial damage --->
Monocytes and platelets attracted to site
31
Elevated LDLs alter permeability of endothelial lining allowing
Macrophages to migrate under endothelial
32
Inflammation and endothelial cell dysfunction causes
Macrophages release inflammatory cytokines
| Endothelial cells cannot make normal amounts of antithrombin and vasodilation substance
33
Free O2 radicals released by inflammatory process causing
Oxidation of LDL (Toxic to endothelium and further damages it)
34
Macrophages engulf oxidized LDL which causes
Foam cells which causes fatty streaks
35
Macrophages also reales growth factors that stimulate
Smooth muscle proliferation which causes smooth muscle and collagen migrate over the fatty streak which causes fibrous plaque
36
Plaque may
1. calcify and protrude into the lumen or
| 2. lipids realized from necrotic foam cells from an unstable plaque that may rupture
37
Fatty streaks are
Lesions that can be found in the arterial walls of most people.
38
Fatty streaks produce
Toxic free radicals, recruit T-cells leading to autoimmunity and secrete inflammatory mediators that further damage the vessel walls
39
Cells in the area begin to proliferate in response to endothelial injury, producing
Collagen and cover the fatty streak forming a fibrous plaque
40
Clinical manifestation of atherosclerosis
- Depends on location and extend of obstruction (Coronary, carotid, cerebral, peripheral)
- Stenosis, plaque ulceration, and rupture, aneurysm formation, hemorrhage, ischemia, infarction
41
Lipoproteins are
tiny, spherical structures composed of lipids and proteins
42
Lipoproteins serve as
Carriers for transporting lipids (which are insoluble in plasma) in the blood
43
How do lipoproteins serve as carriers for transporting lipids
They have a hydrophilic shell that makes lipids soluble in plasma
44
lipids are transported to various tissues for
Energy utilization
Lipid disposition
Steroid hormon production
bile acid formation
45
Lipoproteins contain one or more Apolipoproteins that act
as recognition sites for cell-- surface receptors and enzymatic activity
46
Lipoproteins are classified by
their lipid and protein content (density), apolipoprotein content, and transport function
47
Density of lipoprotein is determined by
Protein and lipid content
48
Protein is more
Dense than lipid
49
Lipoproteins that have a high % of protein have a
relatively higher density
50
Very low density lipoproteins (VLDLs)
Mainly carry triglycerides
51
Low density lipoproteins (LDLs)
Less protein, more fat
52
High density lipoproteins (HDLs)
More protein, less fat
53
three classes of lipoproteins relevant to atherosclerosis
- very low density lipoproteins
- low density lipoproteins
- high density lipoproteins
54
Desirable level for total serum concentration
< 200
55
LDL definitely contributes to
Arteriosclerosis
56
LDL cholesterol desirable level
< 130
57
HDL cholesterol protects
Against atherosclerosis
58
Desirable HDL cholesterol level
> or = 40
59
Triglycerides probably contribute
to atherosclerosis
60
Desirable levels or triglycerides
< 150
61
Divide total cholesterol number by the HDL number: goal ratio below ____ (optimal ratio ___)
below 5.1
| Optimal ratio 3.5
62
Drug therapy for dyslipidemia are indicated as
Adjuncts to lifestyle modifications
63
Dyslipidemia is
elevation of plasma cholesterol, triglycerides (TGs), or both, or a low high-density lipoprotein cholesterol level that contributes to the development of atherosclerosis
64
Drug therapy for dyslipidemia are often prescribed
In combination
65
Most widely used and most effective drugs for lowering LDL cholesterol levels are
HMG-CoA reductase inhibitors (statins)
66
Atorvastastin drug class
Antilipemic, HMG-CoA reductase inhibitors (statins)
67
MOA of atorvastatin
Inhibits hepatic enzyme HMG C0-A (enzymes involved with cholesterol synthesis)
68
For atorvastatin, increased synthesis of LDL receptors in hepatocytes causes
Increased LDL catabolism, which causes decreased LDL cholesterol
69
Atorvastatin increases
HDL cholesterol
70
Atorvastatin promotes
Plaque stability
71
When is dosing preferred for statins (HMG-CoA reductase inhibitors?)
Dosing in the evening to preferred, but may take without regard to time of fay
72
What should be avoided when taking Atorvastatin?
Large quantities of grapefruit juice
73
Atorvastatin administration
PO only
74
Adverse affects for atorvastatin
Hepatotoxicity
Myopathy/rhabdomyolysis (Increased risk if concurrent use of protest inhibitors)
Increase risk of diabetes
75
Atorvastatin is contraindicated in
Pregnancy, it is a category X
76
Rhabdomyolysis
Striated muscle breakdown
77
Rhabdomyolysis is associated with
other toxic or chemical damage; excessive muscular stress, prolonged muscle compression, crushing trauma, ischemia
78
Myoglobin
O2 carrying protein important to muscular O2 consumption
79
Release of myoglobin causes
Oxidative stress, initiating the inflammatory response
80
What happens when myocytes break down
their intracellular contents are released into the plasma
81
Clinical manifestations of rhabdomyolysis
- Fatigue, muscle tenderness, weakness
- Dark urine (caused by myoglobin in the urine)
- Renal tubules may eventually be obstructed by myoglobin
82
Labs for rhabdomyolysis
```
renal function (BUN, Creatinine)
Intracellular enzymes (CK, LDH, ALT, AST)
Urinalysis
```
83
Contents of when myocytes break down
```
Myoglobin
Creatine kinase (CK)
Lactate dehydrogenase (LDH)
Aspartate aminotransferase (AST)
Potassium
```
84
Treatment for rhabdomyolysis
Hydration (normal saline IV)
Correction of electrolyte imbalance
Supportive measures
85
Additional caution with Atorvastatin
Diabetics: high blood glucose levels have been reported with HBM- CoA reductase inhibitors
Consume large amounts of ethanol
Liver disease
High potential for cytochrome P450 (CYP)
86
Bile acid sequestrants increase the use of
Cholesterol
87
Bile acid sequestrants are often used as
Adjuncts to statins to lower LDL cholesterol
88
Bile acide séquestrants are
```
Biologically Inert (does not initiate a response or interact when introduces to a body tissue)
Insoluable in water
No GI absorption
Pass through intestine
Excreted in feces
```
89
Cholestyramine resin drug classification
Antilipemic agent; bile acid sequestrate
90
Cholestyramine resin MOA
Binds to bile acids in the intestinal lumen, which prevent enterohepatic reabsorption of bile salts, which accelerate fecal excretion of LDLs, which in turn LOWERS LDL cholesterol
91
Bile acid sequestrants comes as
Powder which is mixed in water or fruit juice
92
Bile acid sequestrants can form
complexes with other drugs
93
If a drug is bound to a complex with a bile acid sequestrate,
It is not biologically available
94
Drugs known to form complexed with bile acid sequestrants
Digoxin, thiazide diuretics, warfarin, some antibiotics
95
How to avoid bile acid sequestrant complex formation
Administering PO medications 1 hour before or 4 hours after cholestyramine
96
Bile acid sequestrants decrease absorption of
Fat-soluble vitamins
Folic acid
Iron
Calcium
97
Most common adverse effects for bile acid sequestrants
GI disturbances
| Constipation, nausea, dyspepsia, flatulence
98
Pregnancy category for bile acid sequestrants
Risk factor C
99
Enzetimibe drug class
Antilipemic agent; Cholesterol absorption inhibitor
100
Enzetimibe administration
PO only
101
Enzetimibe MoA
Acts on cells of the small intestine (@ brush border) to inhibit cholesterol absorption
102
Enzetimibe decreases
Total cholesterol levels, LDL, triglycerides
103
Enzetimibe produces
Small increase in HDL
104
Enzetimibe may cause
Fatigue, abdominal pain, cholecystitis, myopathy
105
Pregnancy risk factor for ezetimibe
Risk factor C
106
Triglyceride levels over 500 are given
Fibrates
107
Fibrates are derivative of
fabric acid that lower serum triglycerides and increase serum HDL
108
Gemfibrozil drug classifications
Antilipemic, fibric acid, fibrate
109
Gemfibrozil moA
Decrease serum triglycerides via increase of lipoprotein lipase, which decreases hepatic fatty acid uptake, which decreases hepatic secretions of triglycerides
-ALSO increases serum HDL
110
Lipoprotein lipase
Enzyme that breaks down free fatty acids
111
When to administer gemfibrozil
PO ONLY
| 30 minutes prior to breakfast or dinner
112
Adverse effects of gemfibrozil
Dyspepsia, abdominal pain, myopathy, rhabdomyolysis, cholelithiasis
113
Pregnancy risk factor for gemfibrozil
Risk factor C
114
Examples of PCSK9 inhibitors
Alirocumab
| Evolocumab
115
PCSK9 is a
protein that regulates the lifespan of the cholesterol clearing receptors in the liver
116
PCSK inhibitors promote
Modulation of the receptor that clears LDL-C thereby prolonging the receptor activity and promoting the clearance of chloestorl
117
PCSK9 inhibitor significantly lowers
LDL cholesterol levels (by 50%)
118
Adverse effects of PCSK9 inhibitors
Fairly well tolerated
Muscle pain, diarrhea have been reported
Nasopharyngitis
itching
injection site reactions
Serious allergic reactions have been reported
119
Niacin is a
Soluble vitamin, antilipemic agent
120
Niacin decreases ___ and increases _____
decreases LDL and increased HDL
121
Niacin administration
PO only
122
Niacin MoA
Inhibits mobilization of fatty acids from peripheral tissues
123
What happens when there is an inhibition of mobilization of fatty acids from peripheral tissues.
- Causes decrease in hepatic synthesis of triglycerides and VLDL, which leads to a decrease in LDL production.
- ALSO decreases lipid transfer from HDL to VLDL, leading to an increase of HDL
124
Adverse effects of niacin
Flushing (may be decreased by taking NSAID 30-60 minutes before dosing)
Severe cases of hepatotoxicity
125
Niacin begin dose
250 mg/day
126
Niacin is contraindicated in
Active hepatic disease
127
Caution for niacin in patient
who consume substantial amounts of ethanol
