Thromboembolic Disorder Drugs - Konorev Flashcards Preview

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Flashcards in Thromboembolic Disorder Drugs - Konorev Deck (65):
1

White thrombus
- Seen where?
- Seen when?

Platelet-endothelium aggregation, little fibrin
- High pressure arteries
- Ischemia via coronary occlusion (MI or unstable angina)

2

Red thrombus
- Seen where?
- Seen when?

Fibrin-rich with trapped RBCs in fibrin tails
- Low pressure veins, and in heart
- Embolic stroke, pain and severe swelling

3

Anticoagulant drugs - function

Used when?

Regulate clotting factors

- Used to prevent red thrombi (veins, heart)

4

Anti-platelet drugs - function

Used when?

Inhibit platelet aggregation

- Used to prevent white thrombi (arteries)

5

Thrombolytics - function

Used when?

Destroy clots

- Used to re-establish flow once clots have formed

6

2 types of anticoagulants

- Parenteral
- Oral

7

2 types of parenteral anticoagulants

- Indirect thrombin/factor Xa inhibitors
- Direct thrombin inhibitors

8

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

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

9

Indirect thrombin/Xa inhibitors - mechanism of action

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

10

Contrast the 3 indirect thrombin/Xa inhibitors

HMW (unfractionated) Heparin - binds/inhibits BOTH

LMW Heparin - binds/inhibits factor Xa mostly

Fondaparinux - inhibits Xa only

11

Using HMW vs. LMW Heparin

LMW - less frequent injections, more predictable dosing

12

Uses for Heparin

Red thrombi prevention
- Protect against embolic stroke/pulmonary emboli
- DVT, atrial arrhythmias
- Emboli prevention during surgery/hospital

13

Monitoring Heparin use

- aPTT should be longer (50-75 sec vs. 30-50 sec)
- Anti-Xa assay

14

Adverse effects of Heparin

- Bleeding
- Thrombocytopenia, thrombosis (platelet/immune complex)

15

Contraindications to Heparin use

- Severe HTN
- Active TB
- GI ulcers
- Recent surgery

16

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

Stop heparin, give DTI

17

How to stop heparin action?

Protamine sulfate

18

Fondaparinux - function

Indications?

Bind/stimulate antithrombin 3 --> inactivate factor Xa

- Prevent DVT
- Treat DVT (w/ warfarin)
- Treat pulmonary embolism

19

How is Fondaparinux unlike Heparin? (3)

- Does not inhibit thrombin
- Does not induce HIT
- NOT reversed by protamine sulfate

20

Direct thrombin inhibitors (parenteral) - MoA

Directly inhibit auto-protease activity of thrombin

21

2 types of direct thrombin inhibitors (and drugs)

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

22

Contrast function of 3 direct thrombin inhibitor drugs

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

23

Clinical uses for direct thrombin inhibitors

- HIT
- Coronary angioplasty (reversible inhibitors)

24

Adverse effect of direct thrombin inhibitors

- Bleeding

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)