Anticoagulants Flashcards Preview

Pharmacology > Anticoagulants > Flashcards

Flashcards in Anticoagulants Deck (36)

what are the 4 phases of hemostasis

- vascular spasm
- platelet plug formation (primary hemostasis)
- blood coagulation (2ndary hemostasis)
- dissolution of fibrin clot (tertiary hemostasis)


what is Virchow's triad and what is its importance

endothelial injury, abnormal flow of blood, and hypercoagulability

they predispose one to formation of a thrombus


classes of drugs that are used to reduce clotting

- platelet aggregation inhibitors
- anticoagulants
- thrombolytics


classes of drugs that are used to treat bleeding

- plasminogen activation inhibitors
- protamine sulfate
- vitamin K
- plasma fractions


platelet aggregation inhibitor are useful in the prevention and treatment of

cardiovascular diseases
maintenance of vascular grafts and arterial patency
adjuncts in treatment of MI


what are the platelet aggregation inhibitors

- GP IIb/IIIa inhibitors: abciximab, eptifibatide, tirofiban
- Aspirin
- ADP receptor inhibitors: Clopidogrel, ticlopidine
- Phosphodiesterase inhibitor: Cilostazol, Dipyridamole


mechanism of aspirin

it inhibits thromboxane synthesis by irreversible acetylation of enzyme COX hence it is a COX inhibitor


why is aspirin better than other NSAIDs

it can acetylate COX and is irreversible hence its action lasts longer than the reversible action of other NSAIDs


what is aspirin used for

- prophylactic tx of transient cerebral ischemia
- reduce incident of recurrent MI
- reduce mortality in post MI patient


name the ADP receptor blockers and their mechanism

clopidogrel and ticlopidine

inhibit P2Y12 irreversibly (ADP receptor on platelet surface) --> reduced platelet aggregation


adverse effects of ADP receptor blockers (name the drugs again)

clopidogrel and ticlopidine

thrombocytopenia pupura

but ticlopidine can cause neutropenia


how is clopidogrel activated and what are conditions that can cause it not to be activated

- it is a prodrug that is activated by CYP2C19

- if someone is a poor metabolizer of CYP2C19 or takes omeprazole (CYP2C19 inhibitor), then they would have less of the active metabolite in their plasma


uses of clopidogrel and ticlopidine (more clopidogrel though)

reduce the rate of stroke, MI, death in pts with recent MI or stroke, established peripheral artery disease, or acute coronary syndrome


mechanism of dipyridamole

inhibits phosphodiesterase and/or blocks adenosine uptake --> increase in cAMP --> activates adenylyl cyclase --> coronary vasodilation


uses of dipyridamole

- little to no benefit if taken alone
- with warfarin it prevents post op thromboembolic complication of cardiac valve replacement
- with aspirin it's a prophylaxis for cerebrovascular disease


mechanism of cilostazol

inhibits phosphodiesterase --> vasodilation and inhibition of platelet aggregation


what is cilostazol used for

intermittent claudication


uses of platelet GP IIb/IIIa receptor blocker (name drugs agin)

tirofiban, eptifibatide, abciximab,

- reduce the rate of thrombotic cardiovascular event in non-ST elevation acute coronary syndrome (NSTE-ACS)
- adjunct to percutaneous coronary intervention (PCI) for the prevention of cardiac ischemic complications


how does the IIb/IIIa complex function

- receptor for fibrinogen and vitronectin but also for fibronectin and von willebrand factor

- activation of this complex is the final common pathway for platelet aggregation


condition called in those lacking the IIb/IIIa receptor

bleeding disorder called Glanzmann's thrombasthenia


direct mechanism of the IIb/IIIa drugs

- tirofiban: nonpeptide tyrosine analogue that is a reversible antagonist of the complex

- eptifibatide: cyclic peptide reversible antagonist of the receptor

- abciximab: chimeric mouse human monoclonal antibody against the receptor


anticoagulants can be classified into what four groups

- indirect thrombin and factor X inhibitor: unfractioned standard heparin, low molecular weight heparin (Enoxaparin, Dalteparin, Tinzaparin) and fondaparinux

- direct thrombin inhibitors: lepirudin, bivalirudin, argatroban, dabigatran

- direct factor Xa inhibitor: apixaban and rivaroxaban

- couramin anticoagulants: warfarin


why are low molecular weight heparin (name them) the replacement for unfractioned heparin

Enoxaparin, Dalteparin, Tinzaparin

they have fewer drawback than UFH, have equal efficacy, superior bioavailability, longer half lives, less frequent dosing requirements


mechanism of action of heparin

binds to anti thrombin III --> inhibits clotting factor proteases especially thrombin, IXa, Xa


difference in mechanism of UFH and LMWH

- to most efficiently inactivate thrombin by antithrombin III, heparin has to bind to both antithrombin and thrombin simultaneously

- to inactivate factor Xa by antithrombin III, heparin only needs to bind to antithrombin III

-LMWH inhibits Xa but not long enough to form ternary complex so no effect on thrombin but UFH efficiently inactivates Xa and thrombin


what test is used to monitor heparin levels and prevent bleeding and what does the test check

test for the integrity of the intrinsic and common pathway of coagulation


when taking LMWH why is it not necessary to monitor blood level

it's weight dosing causes predictable plasma levels with normal renal function


when do you have to monitor LMWH

in those with renal insufficiency, pregnancy, and obesity


uses of heparin

- initiate tx of venous thrombosis and pulmonary embolism (warfarin started at same time then heparin discontinued after 5 days when warfarin reaches its full therapeutic effect)

-initial management of pts with unstable angina of acute MI

-coronary balloon angioplasty to prevent thrombosis

- drug of choice for preggos because does not cross the placenta


adverse effects of heparin

-hypersensitivity reactions
-heparin induced thrombocytopenia (two types)
-elevation of liver transaminases


how is type II heparin induced thrombocytopenia work (mechanism)

-seen more commonly in UFH
- antibodies recognize heparin and a platelet protein, platelet factor 4
-IgG binds both heparin and PF4 forming an immune complex then binds to Fc receptor on platelets
- Fc activation lead to platelet degranulation and aggregation
- activated platelets release more PF4 and more immune complexes form
- leads to thrombocytopenia and thrombosis
- hence leading to DVT, heart attack, stroke, PE


what is next step if excessive anticoagulant action with heparin

stop heparin and give direct thrombin inhibitor or fondaparinux

if bleeding give protamine sulfate though it does not reverse action of fondaparinux


mechanism of fondaparinux and what it is mainly used for

selective, indirect, inhibitor of factor Xa with negligible antithrombin activity

mainly used for DVTs


what are the direct thrombin inhibitors and how do they work

which ones are parenteral and which oral

how are they monitored

Bivalirudin, Argatroban, Lepirudin, Dabigatran

they directly bind to the active site of thrombin

all parenteral except for dabigatran

monitored by aPTT


what types of patients should lepirudin be given cautiously to and why

those with renal insufficiency because no antidote exists


what are the direct factor Xa inhibitors and how are they monitored

apixaban and rivaroxaban

like dabigatran, they do not require monitoring

Decks in Pharmacology Class (79):