02b: Pharmacology (MI and antithrombotics) Flashcards
1
Q
Myocardial oxygen demand/supply: (increased/decreased) oxygen (demand/supply) in pneumonia.
A
Decreased supply
2
Q
Myocardial oxygen demand/supply: (increased/decreased) oxygen (demand/supply) in sympathomimetic toxicity (i.e. cocaine).
A
Both increased demand and decreased supply
3
Q
Myocardial oxygen demand/supply: (increased/decreased) oxygen (demand/supply) in aortic stenosis.
A
Increased demand
4
Q
T/F: B-blockers, nitrates, and CCBs are disease-modifying agents used for MI.
A
False - non-disease modifying agents used for MI
5
Q
List the B-blocker prototype used for MI.
A
Metroprolol
6
Q
List the Ca channel blockers (CCBs) prototypes used for MI.
A
Diltiazem, verapamil, amlodipine
7
Q
List the nitrate prototypes used for MI. What’s the difference between them?
A
- Nitroglycerin (short-acting)
2. Isosorbide dinitrate (intermediate-acting) and mononitrate (long-acting)
8
Q
First-line therapy in symptom control for patients with exertional angina.
A
B-blockers
9
Q
T/F: B-blockers have been shown to decrease mortality following acute MI.
A
True
10
Q
List the three main disease states that B-blockers are used/indicated for.
A
- Angina/post-MI
- HT
- CHF
11
Q
Metroprolol has (weak/moderate) lipid solubility and is mainly excreted via (bile/renal).
A
Moderate;
renal (95%)
12
Q
Atenolol is (selective/non-selective) antagonist with (moderate/weak) lipid solubility and mainly excreted via (bile/renal).
A
Beta-1 selective;
Weak; renal
13
Q
Propranolol is (selective/non-selective) antagonist with (moderate/weak) lipid solubility and mainly excreted via (bile/renal).
A
Non-selective;
HIGH lipid solubility;
50% bile, 50% renal
14
Q
Labetolol is (selective/non-selective) antagonist with (moderate/weak) lipid solubility and mainly excreted via (bile/renal).
A
Non-selective (like Carvedilol);
Weak;
renal
15
Q
(X) beta-antagonist is ONLY given by IV. Why?
A
X = esmolol
Relative potency is very low (not given for maintenance)
16
Q
List some important side effects to consider with beta-blockers.
A
- Bradycardia and bronchoconstriction
- Fatigue/CNS stuff (depression, nightmares, insomnia)
- Erectile dysfunction
- Worsen PVD (ex: Raynaud’s)
17
Q
β-antagonists should be used with caution in combination with (X) drugs. Both types can (increase/decrease) myocardial contractility and AV nodal conduction, possibly causing (Y).
A
X = nondihydropyridine CCBs (ex: Diltiazem/verapamil)
Decrease;
Y = heart failure or AV conduction block
18
Q
CCBs block (inward/outward) Ca current through which specific cardiac channels?
A
Inward;
L-type Ca channel (responsible for maintaining plateau phase)
19
Q
T/F: CCBs dilate all coronary and peripheral vessels.
A
False not veins
20
Q
Which CCB prototype would you choose for vasodilation?
A
Amlodipine - specific target tissue is vascular SM cell
second choice: diltiazem
21
Q
Which CCB prototype would you choose for slowing HR?
A
Verapamil - target nodal tissue
second choice: diltiazem
22
Q
Which CCB prototype would you choose for reducing wall tension?
A
Verapamil - target cardiac myocyte
second choice: diltiazem
23
Q
T/F: Verapamil, Diltiazem, and amlodipine are all eliminated via renal mechanisms.
A
False - all hepatic
24
Q
T/F: Most common side effects of CCBs include nausea, HA, constipation, hypotension.
A
True
25
(Beta-blockers/CCBs/nitrates) are contraindicated for patients with heart failure.
Nondihydropyridine CCBs (i.e. Diltiazem, verapamil)
26
Which side effects of CCBs are potentially most worrisome?
1. Erectile dysfunction
| 2. Liver dysfunction (rare)
27
T/F: Nitrates dilate all coronary and peripheral vessels.
True (venodilators, coronary vasodilators, and arteriolar dilators0
28
T/F: CCBs are usually administered orally, once-a-day.
True
29
The main physiologic action of nitrates is (X), particularly targetted to (Y).
```
X = vasodilation
Y = systemic veins (decrease myocardial oxygen demand)
```
30
T/F: Nitrates have a mortality benefit nearly equal to that of beta-blockers.
False - no mortality benefit
31
What's the mechanism of action of nitrates/nitroglycerin?
1. Converted to NO at cell membrane
2. Induces cGMP formation by guanylyl cyclase
3. cGMP decreases intracellular Ca
4. SM relaxation
32
Nitrates are very (hydrophilic/lipophilic) compounds. This is why (X) forms of the drug are used in the treatment of acute angina attacks.
Lipophilic;
| X = sublingual tablets or sprays (rapidly absorbed via oral mucosa!)
33
T/F: Nitroglycerin is effective when taken prophylactically.
True
34
List the main side effects of nitrates.
HA, postural hypotension, flushing, reflex tachycardia
35
T/F: Tolerance has not yet been an issue in chronic nitrate use.
False
36
If administered concurrently with (X) drug, Sildenafil, a(n) (Y) drug, can cause severe hypotension.
```
X = nitrates;
Y = PDE5 inhibitor (used to treat erectile dysfunction)
```
37
Nitrates are contraindicated in which diseases/patients?
1. Severe aortic stenosis
2. Acute RV infarction
3. Hypertrophic cardiomyopathy
4. Sildenafil use (within 24 h)
38
Aspirin used as antithrombotic agent for its (stimulatory/inhibitory) action on (X), thus impacting (Y) step of (primary/secondary) hemostasis.
Inhibitory
X = COX (synthesizes TXA2 from arachidonic acid);
Y = vasoconstriction and platelet activation
Primary hemostasis
39
List the classes of antiplatelet agents used for antithrombotic therapy.
1. COX inhibitors (aspirin)
2. P2Y12 (ADP)-R antagonists (Clopidogrel)
3. Glycoprotein IIb/IIIa inhibitors (abciximab)
40
How does the integrin IIb/IIIa receptor play a role in (primary/secondary) hemostasis?
Primary hemostasis;
| Conformational change causes fibrinogen binding
41
Platelet granule release of (X) is important in (primary/secondary) hemostasis.
X = ADP, TXA2, and Ca
| Primary
42
Final active protease is (X), activated in (primary/secondary) hemostasis.
X = thrombin (cleaves fibrinogen)
| Secondary
43
Oral contraceptives (increase/decrease) thrombosis risk via which mechanism?
Increase;
Increase in hepatic synthesis of clotting factors
44
At present all anti-thrombotic agents have increased (X) as their principle toxicity.
X = bleeding risk (hemorrhage)
45
(X) class of antithrombotic drugs prevent primary hemostastic plug formation.
X = antiplatelet
46
(X) class of antithrombotic drugs inhibit clotting cascade to ultimately prevent (Y) formation.
```
X = anticoagulant
Y = fibrin clot
```
47
(X) class of antithrombotic drugs dissolve an existing clot by digesting (Y).
```
X = thrombolytic
Y = fibrin
```
48
Which antiplatelet drugs are especially beneficial in treatment/prevention of ACS and the prevention of thromboembolic events?
P2Y12 (ADP) receptor antagonists
49
Which antiplatelet drugs are administered IV, are effective during percutaneous coronary intervention (PCI).
Glycoprotein IIb/IIIa antagonists
50
T/F: Patients are given high dose aspirin post-MI to inhibit COX synthesis of TXA2.
False - low dose! (325 mg/day)
51
Higher dose aspirin leads to inhibition of (X) production and reduced clinical efficacy of therapy.
X = prostacyclin
52
T/F: Aspirin inactivation of COX is irreversible.
True - effect persists for life of
| platelet (7-10d)
53
(X) drug was found superior to clopidogrel and aspirin combination therapy in stroke prevention in (Y) patients.
```
X = warfarin
Y = Atrial Fibrillation
```
54
Clopidogrel (reversibly/irreversibly) (stimulates/inhibits) (X). What is the effect of this?
Irreversibly inhibits;
X = P2Y12 (ADP) receptor
Inhibits activation of GPIIb/IIIa (final common) pathway for platelet aggregation
55
T/F: Clopidogrel action persists for life of platelet.
True
56
(X) antiplatelet drug has black box warning that (Y) patients are at high risk of (Z).
```
X = Clopidogrel
Y = poor CYP metabolizers
Z = treatment failure
```
Since clopidogrel is prodrug that requires CYP metabolism
57
(X) antiplatelet drug is Fab fragment of humanized monoclonal Ab directed against the (Y).
```
X = abciximab
Y = GIIb receptor
```
58
```
Anticoagulant drugs typically reduce global clotting factor
activity by (X)% at therapeutic doses.
```
X = 30-50 (need to strike balance!!)
59
Anticoagulant drug classes act by (stimulating/inhibiting) (pro/anti)-clotting factors.
Simulating anti- and inhibiting pro-
60
Heparin is typically given (orally/IV/subQ) and has (short/long) half-life.
IV or subQ; short (1h)
61
Heparin mechanism of action: greatly enhances (X) activity, thus inhibiting (Y).
```
X = antithrombin
Y = clotting factors (IXa, Xa, thrombin)
```
62
Drug of choice for anticoagulation during pregnancy.
Heparin (doesn't cross placenta)
63
Contraindications for heparin therapy.
1. Hemorrhage (esp intracranial)
2. Thrombocytopenia
3. HT
4. Renal/hepatic disease
64
One of the most dangerous potential side effects of heparin is (X), a systemic (hyper/hypo)-coagulable state.
X = heparin-induced thrombocytopenia (HIT)
| Hypercoagulable
65
T/F: Osteoporosis and bone fractures are adverse effects of heparin therapy.
True
66
(X) is an antagonist to heparin. They form a stable complex, devoid of anticoagulant activity.
X = protamine sulfate
67
Heparin-induced thrombocytopenia (HIT) occurs (X) days after therapy initiated. There is (Y)% (increase/decrease) in platelets. Which patients at most risk?
X = 5-14
Y = 50
decrease;
Women and surgical patients
68
Heparin-induced thrombocytopenia (HIT): what's the mechanism behind this complication?
1. Immune system generates Ab against heparin bound to platelet factor 4
2. IgG-heparin-PF4 complex binds platelet receptor and activates platelet
3. Systemic hypercoagulation
69
T/F: The first thing to do if patient has Heparin-induced thrombocytopenia (HIT) is to give heparin antagonist, protamine sulfate.
False
70
T/F: Patient develops Heparin-induced thrombocytopenia (HIT) so it's crucial to administer/transfuse platelets.
False!!!
71
Heparin-induced thrombocytopenia (HIT): in addition to stopping all heparin, what would you administer to patient?
1. Alternative anticoagulant
| 2. Irreversible thrombin inhibitor (Hirudin)
72
T/F: Only IV, not SubQ, heparin therapy needs to be monitored via aPTT.
True
73
Heparin monitored by measuring (X). Typical reference range is (Y) and therapeutic range is (Z) times (Y).
```
X = activated partial thromboplastin time (aPTT)
Y = 25-39 seconds
Z = 2-2.5
```
74
If long-term anticoagulation therapy needed, (X) drug is used until (Y) drug takes effect.
```
X = heparin
Y = warfarin
```
75
List the prototype drugs for low MW heparin.
1. Enoxaparin
| 2. Fondaparinux
76
T/F: Low MW Heparin works by the same mechanism of action as unfractionated heparin
False - only long enough to bind antithrombin and inhibit Factor Xa (not thrombin)
77
T/F: Neutralization by protamine sulfate is more complete for unfractionated heparin than low MW heparin.
True
78
T/F: Low MW heparin is contraindicated for pregnancy and obesity.
False - but Xa activity is monitored in these patients (as well as renal pts)
79
(Unfractionated/LMW) Heparin has faster absorption. (Unfractionated/LMW) Heparin has longer half-life.
LMW; LMW (4hrs)
80
T/F: LMW Heparin requires more frequent monitoring than Unfractionated heparin.
False - predictable pharmacokinetic response and no effect on aPTT (so less monitoring)
81
(X) is the most widely used oral anticoagulant with (Y) hour half-life. What is directly (stimulated/inhibited) by this drug?
```
X = warfarin
Y = 36
```
Inhibits vit K epoxide reductase (thus inhibiting the reduction of vit K epoxide into active form)
82
Warfarin prevents activation of (X), thus (stimulating/inhibiting) (Y) of which clotting factors?
X = vit K epoxide
Inhibiting
Y = gamma carboxylation (of glutamate)
Prothrombin, factors VII, IX, X
83
Warfarin onset of action is (X) hours/days and max effect is (Y) hours/days after administration
```
X = 8-12 hours (SLOW)
Y = 3-5 days
```
84
T/F: Like LMW Heparin, Warfarin must be frequently monitored in pregnant and obese patients.
FALSE B/C CANNOT GIVE TO PREGNANT PTS (crosses placenta)
85
Why is patient history extra important when prescribing warfarin?
DRUG INTERACTIONS
86
List some drugs that increase the effects of warfarin (if taken simultaneously).
1. Aspirin
2. Anabolic steroids
3. Oral hypoglycemics
4. Tamoxifen (for breast cancer)
87
Patient with vit K deficiency. Which anticoagulant would you be worried about administering?
Warfarin (effects will be increased since it's a vit K antagonist)
88
List some drugs that decrease the effects of warfarin (if taken simultaneously).
1. Oral contraceptives
2. Corticosteroids
3. Cholestyermine (binds warfarin in intestine and reduces bioavailability)
89
Patient with chronic alcoholism. Which anticoagulant would you be worried about administering?
Warfarin (effects will be decreased)
90
(X) is administered to reverse warfarin-associated bleeding.
Phytonadione (vit K1)
91
T/F: Warfarin is metabolized by CYP enzymes.
True
92
Monitoring warfarin requires calculating (X). What's the formula and the normal value?
X = INR (international normalized ratio)
PT (pt)/PT (normal)
where PT is prothrombin time;
Normal INR = 1.0
93
What's the therapeutic INR for warfarin?
2-3 times normal
94
Patient on warfarin has INR of 5. What do you do?
Lower warfarin dose (therapeutic window is 2-3)
95
Dabigatran is in (X) class of drugs. What's its mechanism of action?
X = direct thrombin inhibitor (anticoagulant)
Binds thrombin and prevents cleavage of fibrinogen to fibrin
96
Dabigatran adverse effects.
1. Hemorrhage
2. Heartburn
3. GI upset
4. Increased MI risk
97
T/F: Unlike heparin and warfarin, Dabigatran doesn't require monitoring.
True
98
What are some key issues with Dabigatran?
1. Costly
| 2. No antagonist
99
Rivaroxaban is in (X) class of drugs. What's its mechanism of action?
X = Direct Xa inhibitors (anticoagulant)
Inhibits factor Xa
100
T/F: Unlike heparin and warfarin, Rivaroxaban doesn't require monitoring.
True
101
T/F: Both direct thrombin and direct Xa inhibitors are given orally with slow onset of action.
False - both given orally but RAPID onset of action
102
Alteplase is in (X) class of drugs. What's its mechanism of action?
X = plasminogen activator (fibrinolytic)
Directly converts plasminogen to plasmin (preferentially activates plasminogen bound to fibrin already)
103
T/F: Fibrinolytics, such as Alteplase/tPA, have long half-life.
False - short (3-8 min)
