Hematologic Agents

Question 1

Define thrombosis and describe differences between venous and arterial thrombosis

Answer 1

It is the inappropriate clot formation
Arterial: Ruptured atherosclerotic plaques, revealing Platelet rich center (White Thrombus)
Venous: Platelet poor plugs (Red thrombus), occur at valve plugs where there is stasis, DVT

Question 2

What are common causes of thrombosis?

Answer 2

Heriditary factors: antithrombin def, Prot C def, Prot S def, Factor V, Prothrombin gene mutation
Acquired factors: Age, Previous VTE, Cancer, Obesity
Triggering factors: sx, immobilization, pregnancy, estrogen, plaque rupture, mechanical heart valve

Question 3

MOA: 
Argatroban
Lepirudin
Bivalirudin
Dabigatran

Answer 3

Direct thrombin Inhibitors

all are parenteral administration except Dabigatran, which is oral

Question 4

MOA: Fondaparinux

Answer 4

Indirect inhibitor of thrombin/factor Xa

its the synthetic analog of pentasaccharide sequence of heparin

Question 5

MOA: Heparin

Answer 5

Indirect inhibitor of thrombin via antithrombin

binds AT and increases affinity for factor Xa and also for Thrombin

Question 6

MOA: Vorapaxar

*****

Answer 6

PAR antagonst. Prevents thrombotic events in pnts with a hx of MI

Question 7

MOA:
Rivaroxaban
Apixaban

Answer 7

Direct factor Xa inhibitors

Question 8

MOA: Warfarin

Answer 8

Vitamin K antagonist. competes for Vit K receptor

Question 9

MOA: Enoxaparin (Low molecular weight Heparin)

Answer 9

Indirect inhibitor of factor Xa

Question 10

MOA:
Abciximab
Eptifibatide
Tirofiban

Answer 10

Glycoprotein IIb/IIIa antagonists
Abciximab: antigen binding segment of Monoclonal AB
Eptifibatide: Peptide that binds
Tirofiban: Small molecule that binds
All prevent platelet aggregation by preventing fibrinogen cross bridges from forming

Question 11

MOA: Vorapaxar

Answer 11

Protease Activated Receptor (PAR) antagonist

Question 12

Compare and contrast the metabolism of P2Y12 antagonists.
Clopidogrel
Prasugrel
Ticagrelor
Cangrelor
*****

Answer 12

Clopidogrel and prasugrel are irreversible P2Y12 inhibitors that have prodrugs that must be activated by livver.
Ticagrelorr and Cangrelor are reversible inhibitors and do not need to be metabolized. more rapid

Question 13

Describe warfarin...
Pharmacokinetics
adverse effects
MOA: 
Route of administration

Answer 13

Pharmacokinetics: close to 100% bioavailability. highly bound to albumin - :takes 3-5 days for effects,
Adverse Effects: Hemorrhage, Placental transfer (NEVER USE DURING PREG), Necrosis
MOA: competes with Vitamin K for binding to Vit K Red
Route of Administration: Oral

Question 14

What drugs can disrupt the anticoagulation effect of warfarin?
How do they do it?

Answer 14

Vitamin K - competes with warfarin

Fresh plasma

Question 15

MOA:
Alteplase
Reteplase
Tenecteplase

Answer 15

Tissue PLasminogen activator

acute MI with ST elevation within 12 hours of onset

Question 16

MOA: Streptokinase

Answer 16

thrombolytic drug. activates plasminogen into plasmin. for emergency MI or PE

Question 17

MOA:
Aminocaproic acid
Tranexaminic acid

Answer 17

block interaction of plasmin with fibrin

Inhibits fibrinolysis

Question 18

MOA: Protamine

Answer 18

Inhibits heparin

Question 19

MOA: Vitamin K

Answer 19

competes with warfarin for vitamin K reductase

Question 20

MOA: Idarucizumab

Answer 20

Binds to dabigatrin and completely inactivates

Question 21

What is the general use of Anticoagulants?

Answer 21

keeps coagulation system in check

Question 22

What is the general use of antiplatelets?

Answer 22

to reduce clotting

Question 23

What is the general use of fibrinolytics?

Answer 23

to break up clots that are already there

Question 24

What are the contraindications of using Fibrinolytics?

Answer 24

if it is a NSTEMI, pnt is over 75
>24 hours since onset
Stroke in past year
bleeding
Significant trauma to head in past 3 mo
pregnant

Question 25

Heparin
Pharmacokinetics
AE
MOA
ROA

Answer 25

Pharmacokinetics: cleared by Kidney/Liver and also taken up by endothelial cells. CL decreases as dose increases, which inc half life
AE: bleeding, osteoporosis
MOA: binds AT and brings factor Xa and thrombin into contact.
ROA: parenterally

Question 26

Mechanism of HIT

Answer 26

Heparin binds to Platelet factor 4, antibodies are made agains that, macrophages eat

Question 27

Enoxaparin
Pharmacokinetics
AE
MOA
Contraindications
antidotes

Answer 27

Pharmacokinetics: safer, easier, but similar
AE: Protamine only partially reverses
MOA: binds AT and brings in factor Xa
Contraindications: Renal failure
antidotes: Protamine only partially reverses

Question 28

Fondaparinux
Pharmacokinetics
AE
MOA
Contraindications
antidotes

Answer 28

Pharmacokinetics: main clearance is by the kidney
AE: only for establishe TE, only does factor Xa
MOA: Binds to AT and causes AT to go after Xa
Contraindications: Renal failure
antidotes: Protamine doesnt work

Question 29

Direct Thrombin Inhibitors
Pharmacokinetics
MOA
Contraindications

Answer 29

Pharmacokinetics: Only one that can inhibit thrombin AFTER it is bound to fibrin
MOA: binds to thrombin on fibrin
Contraindications: Does not cause HIT

Question 30

Factor Xa inhibitors
Pharmacokinetics
MOA
Contraindications
antidotes

Answer 30

Pharmacokinetics: Oral,
MOA:, Thrombin inhibitor. prevent stroke in a fib pnts. prevent dvt pe
Contraindications: mechanical heart valve
antidotes: Idarucizumab

Question 31

Route of administration
DTI’s
Factor Xa inhibitors

Answer 31

Factor Xa: Oral

DTI: all are Parenteral except Dabigatran, which is oral

Question 32

Assays for 
Warfarin
Heparin
Dabigitran
Fibrinolytics

Answer 32

Warfarin: PT
Heparin: PTT
Dabigitran: Factor Xa assay
Fibrinolytics: ?

Question 33

Uses for fibrinolytics

Answer 33

Break down a clot alerady there