Blood Coagulation/Anticoagulants Flashcards
what is the role of thromboxane A2 in platelet aggregation
stimulates aggregation
what is the role of prostacyclin in platelet aggregation
inhibition of aggregation
heparin and warfarin mainly target factors __ and __
II
X
what is the function of proteins C and S
act as anticoagulants
antithrombin inactivates what clotting factors
IIa, IXa, Xa, XIa, and XIIa
protein C and S inhibit coagulation by inactivation of what clotting factors
Va and VIIIa
parenteral anticoagulants can either be indirect or direct acting. indirect acting include what 2 main classes
unfractionated (high molecular weight) heparin
low molecular weight heparin
what is the mechanism of action of unfractionated (high molecular weight) heparin
activates antithrombin III which inactivates factors IIa, IXa, and Xa
thrombin is clotting factor __
IIa
what is the mechanism of action of low molecular weight heparin
inhibits factor Xa by activation of antithrombin III
heparin shouldn’t be administered by what route
IM injection
why shouldn’t heparin be administered by IM injection
it causes hematoma in muscles
what is the preferred method of delivery of heparin
IV
unfractionated heparin is preferred over low molecular weight heparins in patients with compromised __ function
renal
in a rapid onset emergency condition, is warfarin or heparin used
heparin
is high or low molecular weight heparin preferred to prevent DVT and PE during prolonged bed rest/surgery
low
if severe bleeding occurs after discontinuing heparin, what can be used to neutralize heparin anticoagulant activity
protamine sulfate
what occurs in heparin induced thrombocytopenia (HIT)
heparin, platelet factor, and Ab immune complex and destroy platelets leading to ischemia of limbs, MI, stroke, and skin necrosis
what is used for treatment of heparin induced thrombocytopenia (HIT)
direct thrombin inhibitor such as Argatroban
what are some adverse reactions of heparin usage
osteoporosis
aldosterone synthesis inhibition
hypersensitivity/allergic reactions
increased hair loss
can heparin be used in pregnancy
yes- doesn’t cross BBB
is heparin safe to use in those with kidney disease
yes, it is metabolized in the liver and excreted in bile
what are some contraindications for heparin usage
heparin induced thrombocytopenia
hemophilia
ulcer lesions in GIT
dissecting aortic aneurysm
recent surgery (eye, brain, or spinal cord)
what is the mechanism of action of the synthetic heparin derivative fondaparinux
inhibition of factor Xa by antithrombin III
what is the preferred substitute to heparin in heparin induced thrombocytopenia
argatroban
what is the mechanism of action of warfarin
inhibition of synthesis of vitamin K dependent clotting factors
inhibition of vitamin K epoxide reductase
inhibition of anticoagulant proteins C and S
what are the 4 vitamin K dependent clotting factors
II, VII, IX, X
(2, 7, 9, 10)
why is warfarin not used for emergency situations
effect is not observed until after 3-5 days
since warfarin effect isn’t observed until 3-5 days after administration, what is given in the meantime
low molecular weight heparin
warfarin is metabolized by what enzyme
CYP450
what is the international normalized ratio for warfarin monitoring
prothrombin time observed/normal prothrombin time
what is recommended for the international normalized ratio for warfarin monitoring
2-3
> 3= bleeding complications
<2= no effect
what is the effect of fetal warfarin syndrome
fetal hemorrhage
IUD
teratogenicity
what is used instead of warfarin in the pregnant
heparin
prolonged use of warfarin suppresses the synthesis of __ and __
protein C and S
skin necrosis is a common effect of __ usage
warfarin
what is the effect of cephalosporins on warfarin activity
cephalosporins destroy vitamin K producing bacteria–>
increased inhibition of vitamin K epoxide reductase by warfarin
what is the affect of aspirin usage with warfarin
increased warfarin activity
is warfarin or heparin preferred in atrial flutter and fibrillation and patients on prosthetic heart valves
warfarin
what is the mechanism of action of direct acting oral anticoagulants
direct factor Xa inhibitor
rivaroxaban, apixaban, and edoxaban are what kind of anticoagulant drugs
direct acting factor Xa inhibitors
what drugs can be used for both treatment and prophylactic of acute DVT, PE, and venous thromboembolic disease
rivaroxaban
apixaban
edoxaban
(direct acting factor Xa inhibitors)
what is an-dexa-net alfa used for
reversal of anti factor Xa effects (to stop uncontrolled bleeding in those taking factor Xa inhibitors)
what is the mechanism of action of an-dexa-net alfa
it prevents factor Xa inhibiting drugs from binding to and inhibiting factor Xa
what is the mechanism of action of direct thrombin inhibitors
directly bind to active site of thrombin
what is the preferred drug for use in heparin induced thrombocytopenia
argatroban ( a direct thrombin inhibitor
what is the mechanism of action of dabigatran
direct inhibitor of thrombin and fibrinogen (both bound and free forms)
dabigatran is inhibited by what drug
ketoconazole
dabigatran, an oral direct thrombin inhibitor is used to reduce the risk of recurrent __
venous thromboembolic disease
what is the effect of idarucizumab on dabigatran
it irreversibly binds and rapidly reverses the anticoagulant effect
what are the advantaes of dabigatran usage over warfarin
lower bleeding rate
rapid effects
no monitoring required
fewer drug+food interactions
streptokinase and urokinase are enzymes used for what type of drug
fibrinolytic drugs (thrombolytics)
what is the mechanism of action of fibrinolytic drugs
activate plasminogen that is bound to fibrin
what type of drug is alteplase
fibrinolytic (thrombolytic)
what is the advantage of reteplase and tenecteplase over alteplase as a fibrinolytic (thrombolytic) drugs
reteplase and tenecteplase have:
longer half life
a bolus dose is enough
no maintenance dose is required
what is the mechanism of action of fibrinolytic drugs (thrombolytic)
convert plasminogen to plasmin
plasmin then degrades the fibrin and fibrinogen, causing clot dissolution
what drug is used for clot dissolution in acute myocardial infarction
fibrinolytic agents such as streptokinase and urokinase
what is the benefit of using fibrinolytic agents for acute myocardial infarction
more beneficial in ST-segment elevation
what is an adverse effect of streptokinase use as a fibrinolytic (thrombolytic)
it can induce a hypersensitivity reaction
in what situations are fibrinolytics contraindicated
prior intracranial hemorrhage
cerebral vascular lesion
malignant intracranial neoplasm
ischemic stroke within 3 months
suspected aortic dissection
significant closed-head trauma or facial trauma within 3 months
what is the function of fibrinolytic inhibitors
block the activation of plasminogen to plasmin to prevent fibrinolysis (helps blood clot)
what are fibrinolytic inhibitors used for
control post-surgery bleeding
heavy menstrual flow
what is the mechanism of action of aspirin
irreversibly inhibit COX-1 inhibiting thromboxane A2 synthesis and prevents platelet activation
low dose aspirin is recommended for patients age __ with high risk heart issues
40-70
what is the mechanism of action of the antiplatelet drugs Ticlopidine, Clopidogrel, and Prasugrel
inhibition of P2Y12 ADP induced activation of GPIIb/IIIa receptors required for binding with fibrinogen and other platelets
what is the advantage of Clopidogrel over Ticlopidine
more potent
rarely associated with neutropenia, leukopenia, and thrombocytopenia
what antiplatelet drug is used as prophylaxis with warfarin in patients with prosthetic heart valves
dipyridamole
what is the mechanism of action of dipyridamole
increases level of cAMP in platelets
what is the action of abciximab
it’s an antibody against GPIIb/IIIa that prevents the binding of fibrinogen to GPIIa/IIIb
when are GPIIb/IIIa receptor antagonists used
unstable angina
post MI
patients undergoing percutaneous coronary intervention
thrombin activates platelets through _____ receptors
protease activated
what is the mechanism of action of vorapaxar
competitive antagonist of PAR-1 and inhibits thrombin induced platelet aggregation
what is the mechanism of action of cilostazol
phosphodiesterase III inhibitor
what is the main use of cilostazol
treatment of intermittent claudication
