Perfusion Part 3 - Atherosclerosis Flashcards
1
Q
Atherosclerosis is an the build up of arterial ____
A
plaque
2
Q
What are 3 causes of damage to the endothelium lining of blood vessels?
A
- Mechanical stress
- Immune response
- Oxidative stress
3
Q
Example of:
Mechanical stress - ____
Immune response - ____ ____
Oxidative stress: ____
A
HTN
Inflammatory sequelae
ROS
4
Q
How do you balance ROSs?
A
Antioxidants
5
Q
All 3 causes of endothelial damage lead to blood ____
A
clotting
6
Q
Increased cholesterol levels lead to endothelial cells producing an adhesion molecule called ___-_
A
VCAM-1
7
Q
Circulating ____ attach to VCAM-1 on the endothelium
A
monocytes
8
Q
What do monocytes do after attaching to VCAM-1? How does this affect permeability?
A
Squeeze between endothelium cells and move into the intima; increases permeability
9
Q
Monocytes differentiate into ____ in the intima and release ____
A
macrophages, ROSs
10
Q
Circulating ____ are phagocytosed by macrophages, turning the macrophage into a ____ cell
A
LDLs, foam
11
Q
Foam cells undergo ____, the lipid residue remaining turning into a ____ ____
A
apoptosis, fatty streak
12
Q
Fatty streaks are commonly first found in the ____ and ____ arteries
A
aorta, coronary
13
Q
What are the 4 components of plaque?
A
- Foam cells
- Collagen
- Fibrin
- Calcium deposits
14
Q
What are 4 examples of clin. manifestations of atherosclerosis?
A
- Narrowing of vessel
- Vessel obstruction
- Thrombosis + emboli formation
- Weakening of vessel wall
15
Q
What is ischemia?
A
Decreased oxygen to tissues
16
Q
What is tamponade?
A
Coronary arteries rupture + bleed into the pericardium
17
Q
State the most common locations these are found:
Ischemia & infarction - ____ + ____ arteries
Thrombus formation - ____
A
Coronary, cerebral
Aorta
18
Q
What are some risk factors for athersclerosis?
A
- HTN
- High cholesterol/lipids
- Male
- Age
- Smoking
- Family history
- Diabetes mellitus
19
Q
What are 2 strategies to lowering amount of lipid in the body?
A
- Lifestyle/diet
- Pharmacotherapy
20
Q
What are the 3 drug classes used during pharmacotherapy of lowering lipids?
A
- Statins
- Niacin
- Fibrates
21
Q
Which drug class is 1st line treatment post MI?
A
Statins
22
Q
Which 2 drug classes are mainly for synergy?
A
Niacin + fibrates
23
Q
Niacin ____ HDLs while fibrates ____ VLDLs
A
increase, decrease
24
Q
Statins inhibit what?
A
HMG-CoA Reductase
25
HMG-CoA Reductase is the primary regulatory site for ____ ____ and is under a ____ feedback system
Cholesterol synthesis, negative
26
Statins lower LDLs by decreasing ____ ____ and increasing ____ ____
Cholesterol synthesis, hepatic circulation
27
What time of day are statins usually given and why?
Night, cholesterol synthesis peaks at night
28
What are 3 examples of statins?
1. Lovastatin (mevacor)
2. Atorvastatin (lipitor)
3. Simvastatin (zocor)
29
All statins are dependent on ____ function
liver
30
Statins are considered pregnancy category ___, meaning:
X, meaning pregnant people should NOT take them (interfere with fetal CNS myelination).
31
What are some side effects of statins?
- Myopathy (muscle weakness)
| - Drug-drug interactions
32
What are 2 types of disorders of CVD?
- Acute
| - Chronic
33
Describe acute CVD
- Unstable angina
- Unstable plaque (--> rupture)
- Risk of MI
34
Describe chronic CVD
- Stable angina
| - Thick fibrous cap over plaque
35
What are the 4 steps from plaque rupture to clotting?
1. Rupture/injury
2. Vascular spasm
3. Platelet plug formation
4. Coagulation
36
What are the 2 steps of platelet plug formation?
1. Platelet activation
| 2. Signaling for aggregation
37
What are released to signal aggregation?
- ADP
- Thromboxane A2
- Thrombin
38
What is glycoprotein IIB/IIIa responsible for?
Makes platelet sticky + stabilizes fibrin through binding
39
Factor _ converts prothrombin into thrombin
X
40
Thrombin activates ____ into fibrin
fibrinogen
41
Thombrin activates factor _, which makes fibrin from a ____ meshwork to a ____ one.
XIII, loose, stable
42
What are 3 drug classes to counter atherosclerosis?
1. Antiplatelet
2. Anticoagulant
3. Thrombolytic
43
Describe at which point in the clotting process the drug classes work on:
Antiplatelet: ____ ____
Anticoagulant: ____ ____
Thrombolytic: ____ --> ____
Platelet aggregation
Coagulation cascade
Post-clot --> lysis
44
What does STEMI mean?
ST wave Elevation MI
45
STEMI is a total ____ artery blockage, which means the heart is unable to ____ and ____ oxygenation
coronary, rest, no
46
Ischemia goes hand in hand with cellular ____
necrosis
47
What are some signs and symptoms of ischemia?
- Pain
- SOB
- Hypoxemia
- No contractility
48
Injury of myocardial cells can lead to the leakage of what 3 enzymes?
- Troponin
- Creatine Kinease
- Myoglobin
49
What is the 1st line acute intervention for stable angina?
Nitroglycerin (Nitro) - nitric oxide
50
Nitroglycerin has ____ coronary circulation efficacy
high
51
Nitroglycerin can be administered ____ by _ tablet(s) q _ min x _
sublingually, 1 tablet q5min x3
52
Angioplasty (PTCA) treats ____ within arterial vessels and ____ ____ within cerebral vessels
obstruction (CAD), thrombic CVA
53
CABG is a ____ common treatment for obstruction
less
54
What are 3 meds that can induce cardiac arrest?
- Calcium channel blockers
- Beta 1 blockers
- Potassium
55
Which 2 substances are blocked by anti-platelets?
1. Thromboxane A2.
| 2. ADP.
56
What is the function of Thromboxane A2 normally?
Calls other platelets to initiate aggregation.
57
What are 2 examples of antiplatelets that block Thromboxane A2?
1. ASA (aspirin/acetasalycilic acid)
| 2. Dipryridamole
58
Which 2 drug classes does ASA belong to?
Anti-platelet & NSAID
59
ASA causes _____ __ inhibition.
COX-1.
60
____ is a combination of ASA and Dipyridamole.
Aggrenox.
61
What is the normal function of ADP in platelet aggregation?
Promotes platelet adhesion.
62
What is an example of an anti-platelet that blocks ADP?
Clopidogrel (Plavix)
63
Which anti-platelet is contraindicated in children? Why?
ASA: dose is too high & will increase intracranial pressure.
64
Which anti-platelet is the drug of choice for children?
Clopidogrel (Plavix).
65
What is the recommended dose (amount of drug q_h) of ASA for pain/inflammation?
325-650 mg, q4h
65
What is the recommended dose (amount of drug q_h) of ASA for pain/inflammation?
325-650 mg, q4h
66
What is the recommended dose of aspirin per kg if it was indicated to be used in children?
10-15mg per kg
67
What is one situation where aspirin would be indicated for treatment in children?
Kawasaki syndrome.
68
What are 3 mechanisms of action for anticoagulants?
1. Inhibit thrombin by targeting Active Factor X (activates thrombin).
2. Block thrombin receptors & Factor IIa (2a).
3. Inhibit hepatic (liver) formation of specific clotting factors (specifically II, VII, IX and X)
All ultimately result in fibrin not being produced so the clot does not stabilize.
69
What is the primary anticoagulant that inhibits thrombin via Factor X?
Heparin
70
What are 2 low-molecular weight heparins (LMWHs)?
1. Enoxaparin (Lovenox)
| 2. Dalteparin (Fragmin)
71
What is the antidote to heparins?
Protamine sulfate
72
Which anticoagulant blocks thrombin receptors & factor IIa (2a)?
Dabigatran (Pradaxa)
73
What is special about Dabigatran (Pradaxa) when it comes to ADME?
It is a prodrug.
74
What are anticoagulants that block thrombin receptors & Factor IIa (2a) used to prevent?
Strokes
75
Which anticoagulant inhibits hepatic formation of clotting factors II, VII, IX and X?
Warfarin (coumadin)
76
What are 3 PD characteristics of Warfarin (coumadin)?
1. Long half-life.
2. Highly PPB.
3. Narrow TI.
77
What is the antidote to Warfarin (Coumadin) overdose?
Vitamin K to ensure that blood doesn't get too think & can still clot if needed (ie: if you had an injury).
Vit K promotes formation of clotting factors.
78
What is heparin-induced thrombocytopenia (HIT)?
Emergency: immune reaction to heparin & platelet Factor IV (4).
79
What lab monitoring test (besides monitoring serum drug levels) should patients taking warfarin undergo?
Prothrombin time (PT/INR - internal normalized ratio): evaluation of blood clotting by measuring the number of seconds taken for a clot to form after clotting reagents are added.
80
Which lab monitoring test (besides measuring serum drug levels) should patients taking unfractioned heparins take?
aPTT (activated partial thromboplastin time): evaluates clotting (same mechanism as PT/INR - number of seconds taken for a clot to form after reagents are added)
81
What lab test should we use to monitor a patient taking LMWHs (low molecular weight heparins)?
Anti Factor Xa levels: measures plasma drug levels
82
What is the mechanism of action of thrombolytics?
Promotes dissolution of the fibrin by converting plasminogen (inactive) to plasmin (active)
83
Which drug is considered a thrombolytic?
tPA (tissue plasminogen activator) - Alteplase, Reteplase
84
Which 2 drug classes do we use for an acute atherosclerosis-related event?
1. Antiplatelets (ASA in adults, Plavix in children)
| 2. Thromolytics (tPA)
85
Which drug class would we use for a patient who is at high risk for clotting (ex: due to dysrhythmias, complex surgeries, or a severe MI)?
Anticoagulants.
86
Which drug class would we use for routine prevention of clotting?
Antiplatelets (specifically baby ASA).
87
Which of the atherosclerosis drugs is also used to treat atrial fibrillation patients?
Warfarin (Coumadin)
