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Cardiovascular 2 > Thromboembolic Disorder Drugs - Konorev > Flashcards

Thromboembolic Disorder Drugs - Konorev Flashcards

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1
Q

White thrombus

  • Seen where?
  • Seen when?
A

Platelet-endothelium aggregation, little fibrin

  • High pressure arteries
  • Ischemia via coronary occlusion (MI or unstable angina)
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2
Q

Red thrombus

  • Seen where?
  • Seen when?
A

Fibrin-rich with trapped RBCs in fibrin tails

  • Low pressure veins, and in heart
  • Embolic stroke, pain and severe swelling
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3
Q

Anticoagulant drugs - function

Used when?

A

Regulate clotting factors

  • Used to prevent red thrombi (veins, heart)
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4
Q

Anti-platelet drugs - function

Used when?

A

Inhibit platelet aggregation

  • Used to prevent white thrombi (arteries)
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5
Q

Thrombolytics - function

Used when?

A

Destroy clots

  • Used to re-establish flow once clots have formed
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6
Q

2 types of anticoagulants

A
  • Parenteral

- Oral

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7
Q

2 types of parenteral anticoagulants

A
  • Indirect thrombin/factor Xa inhibitors

- Direct thrombin inhibitors

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8
Q

3 classes of indirect thrombin/Xa inhibitors (w/ members)

A 
Unfractionated heparins
   - Heparin sodium
Low molecular weight heparins
   - ...-aparin (x3)
Synthetic pentasaccharide
   - Fondaparinux
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9
Q

Indirect thrombin/Xa inhibitors - mechanism of action

A

Increase ANTITHROMBIN 3 activity by binding to it and TOGETHER binding/inactivating factor Xa (at least)

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10
Q

Contrast the 3 indirect thrombin/Xa inhibitors

A

HMW (unfractionated) Heparin - binds/inhibits BOTH

LMW Heparin - binds/inhibits factor Xa mostly

Fondaparinux - inhibits Xa only

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11
Q

Using HMW vs. LMW Heparin

A

LMW - less frequent injections, more predictable dosing

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12
Q

Uses for Heparin

A

Red thrombi prevention

  • Protect against embolic stroke/pulmonary emboli
  • DVT, atrial arrhythmias
  • Emboli prevention during surgery/hospital
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13
Q

Monitoring Heparin use

A
  • aPTT should be longer (50-75 sec vs. 30-50 sec)

- Anti-Xa assay

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14
Q

Adverse effects of Heparin

A
  • Bleeding

- Thrombocytopenia, thrombosis (platelet/immune complex)

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15
Q

Contraindications to Heparin use

A
  • Severe HTN
  • Active TB
  • GI ulcers
  • Recent surgery
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16
Q

A patient on heparin begins developing multiple thrombi. How to treat?

A

Stop heparin, give DTI

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17
Q

How to stop heparin action?

A

Protamine sulfate

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18
Q

Fondaparinux - function

Indications?

A

Bind/stimulate antithrombin 3 –> inactivate factor Xa

  • Prevent DVT
  • Treat DVT (w/ warfarin)
  • Treat pulmonary embolism
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19
Q

How is Fondaparinux unlike Heparin? (3)

A
  • Does not inhibit thrombin
  • Does not induce HIT
  • NOT reversed by protamine sulfate
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20
Q

Direct thrombin inhibitors (parenteral) - MoA

A

Directly inhibit auto-protease activity of thrombin

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21
Q

2 types of direct thrombin inhibitors (and drugs)

A 
Bivalent (bind active site AND substrate site)
   - Lepirudin
   - Bivalirudin
Bind active/catalytic site ONLY
   - Argatroban
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22
Q

Contrast function of 3 direct thrombin inhibitor drugs

A

Lepirudin - irreversible inhibitor
Bivalirudin - reversible inhibitor + platelet inhibitor
Argatroban - short-acting/IV

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23
Q

Clinical uses for direct thrombin inhibitors

A
  • HIT

- Coronary angioplasty (reversible inhibitors)

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24
Q

Adverse effect of direct thrombin inhibitors

A
  • Bleeding
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25
Adverse effect of long-term LEPIRUDIN (irreversible inhibitor)
Anaphylactic reaction (allergic)
26
2 types of oral anticoagulants
- Coumarin (Warfarin) | - Novel oral anticoagulants (NOAC)
27
Warfarin - MoA (2)
- Inhibit vitamin K reactivation via vitatmin K epoxide reductase - Inhibit carboxylation/activation of factors via GGCX
28
Which factors are inhibited by warfarin?
Prothrombin, 7, 9, 10
29
Warfarin pharmacokinetics
Oral, 100% bioavailability, delayed onset, long half life, 99% BOUND TO ALBUMIN R-isomer - CYP3A4 metabolism S-isomer - CYP2C9 metabolism
30
Major thing to know about Warfarin
Significant individual variability in dose based on disease state, genetics, etc.
31
Clinical uses of warfarin
- Prevent thrombosis or thromboembolism - A. fib. - Prosthetic heart valves
32
Adverse effects of warfarin
- TERATOGENIC (NOT in PREGNANCY) - Skin necrosis, organ infarction - Osteoporosis - Bleeding
33
How to dose Warfarin?
- Based on PT (prothrombin time) - VKORC1 haplotype - CYP2C9
34
VKORC1 haplotypes
``` High dose (resistant) - more in african americans Low dose - more in asians ```
35
Diseases to be cautious of when giving warfarin
- Liver disease (where clotting factors are made) | - Thyroid status
36
Benefits of warfarin
- Oral, long duration, renal function not important | - CAN REVERSE IT
37
How to reverse Warfarin? (2)
- Administer vitamin K (12-24 hours) | - FFP or prothrombin complex concentrate (rapid)
38
Drawbacks of warfarin
- High dosing variability, hard to maintain concentration - Bleeding complications - Requires INR monitoring
39
NOAC factor Xa inhibitors - suffix
-xaban (x3)
40
Clinical use of NOAC factor Xa inhibitors
- Prevent/treat thromboembolism | - Prevent stroke w/ A. fib.
41
Advantages of NOAC factor Xa inhibitors
- Oral - Fixed doses, no monitoring - Seems equal to Warfarin - RAPID ONSET compared to Warfarin
42
Drawbacks of NOAC factor Xa inhibitors
- No antidotes | - Dose adjustment in renal disease (renal excretion)
43
Dabigatran | - Clinical use
NOAC direct thrombin inhibitor | - Reduce risk of stroke and embolism w/ A. fib
44
Advantages to Dabigatran (compared to Warfarin)
- Predictable pharma and bioavailability - Fixed dosing and action - Rapid onset and offset
45
Disadvantage to Dabigatran
- 80% renal excretion (not good for renal patients)
46
4 classes of anti-platelet drugs
- TxA2 synthesis inhibitors - ADP receptor blockers - Platelet glycoprotein receptor blockers - Phosphodiesterase inhibitors
47
TxA2 synthesis inhibitor MoA? Use? Adverse effects?
Aspirin - COX inhibition - Prevent M.I. and other vascular events - Peptic ulcer, GI bleeding
48
ADP receptor blockers - names (4)
- Clopidogrel - Prasugrel - Ticlopidine - Ticagrelor
49
ADP receptor blockers - MoA
- Inhibit receptor --> ACTIVATES A.C. --> increased cAMP
50
Phosphodiesterase inhibitors - MoA
- Inhibition of cAMP degradation | - Increased platelet cAMP
51
Phosphodiesterase inhibitors - names (2)
- Dipyridamole | - Cilostazol
52
Clinical uses of ADP receptor blockers
- Prevent arterial thrombosis in stroke - Prevent thrombosis w/ ACS and recent MI, stroke, peripheral vascular disease - Patients undergoing PCI and stenting
53
Clinical uses of Dipyridamole (PDE inhibitor) (2)
- In combo w/ aspirin to prevent cerebrovascular ischemia | - In combo w/ warfarin to prevent thromboembolic w/ prosthetic valves
54
Clinical use of Cilostazol (PDE inhibitor)
Intermittent claudication
55
Adverse effects of Ticlopidine (ADP receptor blocker)
- TTP, GI stuff, leukopenia
56
A patient is on Ticlopidine, but has blotching on his skin. What to give instead?
Another ADP receptor blocker (Clopidogrel, Prasugrel, Ticagrelor)
57
Function of platelet glycoprotein (GP) receptor antagonists
Prevent binding of fibrinogen to platelets for aggregation
58
Clinical use of platelet glycoprotein (GP) receptor antagonists
- Prevent thrombosis in unstable angina - Coronary angioplasty - W/ other anti-platelet agents
59
Adverse effects of platelet glycoprotein (GP) receptor antagonists
- Hypotension, myalgia, thrombocytopenia
60
Platelet glycoprotein receptor antagonists - drugs
- Abciximab (Anti-2b/3a monoclonal Ab) - Tirofiban (2b/3a antagonist) - Eptifibatide (2b/3a antagonist)
61
3 types of thrombolytic (fibrinolytic) drugs
- tPA - cleaves plasminogen - Urokinase - cleaves plasminogen - Streptokinase - converts plasminogen to plasmin - Purified from bacteria
62
tPA drugs - suffix
-plase (x3)
63
Clinical uses of fibrinolytic drugs
- Embolic/thrombotic stroke - M.I. - Pulmonary embolism - DVT - Ascending thrombophlebitis
64
When should fibrinolytic drugs be used?
WITHIN 3 HOURS
65
Adverse effects of fibrinolytic drugs
- Bleeding from the fibrinogenolysis | - Allergic reactions (streptokinase)

Cardiovascular 2 (20 decks)

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