Anticoagulant, Antiplatelet and Thrombolytic Drugs Flashcards Preview

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Flashcards in Anticoagulant, Antiplatelet and Thrombolytic Drugs Deck (40)
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1

spectrum of thromboembolic disease

•myocardial infarction
•stroke
•transient cerebral ischemic attack
•acute coronary syndrome
•atrial fibrillation
•deep venous thrombosis
•pulmonary embolism
•peripheral arterial disease

*DVT and PE are collectively referred to as venous thromboembolism (VTE)

2

venous thrombosis

•most likely in primary hypercoagulable states (defects in coagulation proteins or the fibrinolytic system)
•or secondary hypercoagulable states, where there is vessel injury or blood flow abnormalities

3

arterial thrombosis

•associated with the involvement of vessel wall pathology and platelets
•for example: erosion or rupture of an atherosclerotic plaque in a mildly stenosed coronary artery can result in thrombus formation followed by an acute coronary syndrome

4

three factors that predispose to thrombus

1. endothelial injury
2. abnormal blood flow (stasis)
•hypercoagulable states (inherited or acquired)

5

antiplatelets drugs

•aspirin
•clopidogrel
•abciximab

6

aspirin

•antiplatelet
•COX 1/2 inhibitor, preventing platelet aggregation
•analgesic, antipyretic, antiplatelet, prophylaxis following MI, transient ischemic attacks and stroke
•bleeding. allergic reaction, overdose, respiratory alkalosis and metabolic acidosis

•irreversible block of prostaglandin (thromboxane A2 - platelet aggregation and local vasoconstriction) synthesis
•primary (less well established) and secondary MI prevention/bleeding (well established)
•side effects: dyspepsia, GI bleeding, allergic reactions, overdose: respiratory alkalosis and metabolic acidosis

7

clopidogrel

•antiplatelet
•irreversible inhibition of AP-mediated platelet aggregation
•prevention of ischemic events, dual antiplatelet therapy with ASA for PCI/stents
•bleeding, thrombotic thrombocytopenic purpura

•blocks ADP receptor, P2Y12
-irreversibly blocks one of the platelet ADP receptors (P2Y12 ) responsible for activation of the Gp IIb/IIIa receptor. Recall that fibrinogen binds the Gp IIb/IIa receptors on platelet surfaces to promote platelet aggregation
•for people who can't take aspirin, or in dual therapy with aspirin in ACS bleeding, TTP, stents
•side effects: bleeding, thrombotic thrombocytopenic purpura (TTP)

8

abciximab

•antiplatelet
•binds and inactivates platelet glycoprotein IIb/IIIa receptors for fibrinogen
•antiplatelet, antithrombotic
•bleeding, thrombocytopenia

•monoclonal aty blocks GP iiB/IIIa to block platelet aggregation, mouse/ human
-Gp IIb/IIIa receptor antibody that inhibits the final step of platelet activation: the cross- linking of platelets by fibrinogen binding to Gp IIb/IIIa receptors
•for PCI anticoagulation/bleeding
•side effects: bleeding, thrombocytopenia

9

anticoagulant drugs

•unfractionated heparin
•low molecular weight heparin
•fondaparinux
•bivalirudin
•argatroban

*the onset of pain during anticoagulant therapy signifies the occurrence of bleeding until proven otherwise!

10

heparin (UFH)

•indirect anticoagulant
•binds and activates antithrombin III, leading to inactivation of Factor Xa and thrombin
•parenteral anticoagulant, reversed by protamine sulfate
•bleeding, thrombocytopenia "HIT"

•monitor with aPTT
•facilitates interaction of AT with clotting factors Xa and IIa
•for prevention and treatment of VTE and PE bleeding, HIT
•neutralize with protamine
•does not cross placenta
•side effects: bleeding, thrombocytopenia (HIT)

11

low molecular weight heparin

•enoxaparin
•indirect anticoagulant, monitoring not required
•less effect on thrombin
•binds and activates antithrombin III, leading to inactivation of Factor Xa and thrombin
•parenteral anticoagulant, reversed by protamine sulfate
•bleeding, thrombocytopenia "HIT" (less risk)

•facilitates interaction of AT with Xa
for prevention and treatment of VTE and PE bleeding, HIT
•response in unpredicatable in renal insufficiency
•protamine does not completely neutralize
•side effects: bleeding, less risk of thrombocytopenia (HIT)

12

fondaparinux

•indirect anticoagulant, monitoring not required
•binds and activates antithrombin III and inactivates Factor Xa
•parenteral anticoagulant, reversed by protamine sulfate
•bleeding

•pentasaccharide portion of heparin, binds to AT to inhibit Xa
•for prevention and treatment of VTE and PE bleeding, HIT
•cannot be used in the presence of renal insufficiency
•side effect: bleeding

13

bivalirudin

•anticoagulant
•direct thrombin inhibitor
•for PCI/bleeding
•side effects: bleeding

14

argatroban

•anticoagulant
•direct thrombin inhibitor - reversible
•for management HIT
•side effects: bleeding

15

oral anticoagulants

•Vitamin K antagonists
•warfarin

16

warfarin

•direct acting anticoagulant
•VKA - blocks synthesis of factors VII, IX, X and II, monitor with PT (INR), Vitamin K to reverse
•prevention of VTE and PE/bleeding, teratogenic (crosses placenta), drug and food may alter the response
•side effects: bleeding, increased risk for thrombosis in early treatment due to decrease in protein C (warfarin skin necrosis)

17

non Vitamin K antagonist oral anticoagulants

•dabigatran
•rivaroxaban
•apixaban
•idarucizumab (dabigatran reversal)

18

dabigatran

•oral, non Vitamin K anticoagulant
•direct thrombin inhibitor, monitoring not required
•stroke prevention in AF/bleeding, VTE prophylaxis
•side effects: bleeding

19

rivaroxaban

•oral, non Vitamin K anticoagulant
-apixaban
-edoxaban
•Xa antagonist
•stroke prevention in AF/bleeding, no antidote, VTE prevention
•side effects: bleeding

20

idarucizumab

•monoclonal antibody to dabigatran and its active metabolite
•used for dabigatran reversal

21

limited use anticoagulants

•bivalirudin
•argatroban

22

bivalirudin

•limited use anticoagulant
•direct thrombin inhibitor
•for PCI/bleeding
•side effects: bleeding

23

argatroban

•limited use anticoagulant
•direct thrombin inhibitor - reversible
•for management of HIT
•side effects: bleeding

24

thrombolytic drugs

•tissue plasminogen activator (tPA)

25

tissue plasminogen activator (tPA)

•thrombolytic, fibrinolytic
•action forms plasmin from plasminogen to lyse thrombi
•ACS (STEMi) when PCI not possible (12 hr window) ischemic stroke (3 hour window), clot dissolution and in selected cases of DVT/bleeding, recent surgery
•side effects: bleeding

26

drug interactions with warfarin

•any substance or condition is potentially dangerous when used with warfarin if it alters:
-the uptake or metabolism of warfarin or Vitamin K
-the synthesis, function or clearance of any clotting factor or cell involved in hemostasis or fibrinolysis
-the integrity of any epithelial surface

•rifampin
•antimicrobials
•alcohol
•metronidazole
•amiodarone
•aspirin and other NSAIDs

27

rifampin - drug interactions with warfarin

-CYP2C9 induction
-loss of anticoagulant action

28

antimicrobials - drug interactions with warfarin

-decrease gut flora that synthesize Vitamin K or CYP inhibition
-increases anticoagulant action

29

alcohol - drug interactions with warfarin

-CYP2E1 inhibition with acute use of alcohol, induction with chronic use of alcohol
-increased anticoagulant effect, decrease of anticoagulant effect after cessation of alcohol use
•metronidazole (antimicrobial)
-decreased metabolic clearance of S isomer of warfarin with increased anticoagulant effect

30

metronidazole - drug interactions with warfarin

-antimicrobial
-decreased metabolic clearance of s isomer of warfarin with increased anticoagulant effect