Anticoagulants Flashcards
What is the MOA of the oral anticoagulant warfarin?
inhibits the hepatic synthesis of Vit K dependent clotting factors II, VII, IX, and X via inhibition of vitamin K epoxide reductase
What is the MOA of heparin?
catalyzes the binding of antithrombin III ( a serine protease inhibitor) to factors IIa, IXa, Xa, XIa, and XIIa resulting in their rapid inactivation; therefore inhibiting activity of several activated clotting factors.
What is the purpose of protein C and protein S in the body?
to cause proteolysis of factors Va and VIIIa (endogenous anticoagulants)
Compare and contrast the chemical nature of heparin to warfarin?
Heparin is a large polysaccharide that is water soluble; whereas
warfarin is a small molecule that is lipid soluble
PTT meaning?
partial thromboplastin time
PT meaning?
prothrombin time
Heparin is monitored using PT or PTT? Which pathway extrinsic or intrinsic?
PTT (intrinsic)
What is the antidote for heparin use?
protamine sulfate - chemical antagonism, fast onset
What is the antidote for warfarin?
Vit. K inc. cofactor synthesis (slow onset)
fresh frozen plasma (fast)
What are the uses for heparin?
rapid anticoagulation (intensive) for thromboses,
emboli,
unstable angina
DIC
open-heart surgery
What are the uses for warfarin?
longer-term anticoagulation (controlled) for thromboses,
emboli
post-MI,
heart valve damage,
atrial arrythmias
etc
What are some toxicities associated with heparin use?
bleeding
osteoporosis
heparin-induced thrombocytopenia (HIT),
HSR
What are some toxicities associated with warfarin use?
bleeding
skin necrosis (if low protein C)
drug interactions
teratogenic (bone dysmorphogenesis)
What are some potential advantages of using low-molecular weight heparins?
have longer half-life,
less thrombocytopenia,
possible enhanced activity against factor Xa
What is normal PT time?
10-14 s
What is normal INR range?
0.8 - 1.2 (think around 1)
What is a safe range for the INR (international normalized ratio) to go up to when a patient is on warfarin?
around 2 - 2.5
How can warfarin lead to protein C deficiency and hyper-coagualable states?
Has a short half life so transient deficiency will occur
Vit. C is endogenous anticoagulant so other coagulation factors are in high amounts with unopposed action
What is the MOA of direct thrombin inhibitors?
To directly inhibit thrombin and does not require antithrombin III
Directly inhibits IIa
Name a LMW heparin?
enoxaparin
Name some direct thrombin inhibitors.
Argatroban
Dabigatran
Bivalirudin
Indication for argatroban?
used in HIT
Which direct thrombin inhibitor does not require monitoring of PT or INR?
dabigatran
Indication for dabigatran?
a fib as an alternative to warfarin
What is the antidote for use of dabigatran?
idarucizumab
Bivalirudin Indication.
used with aspirin in unstable angina when undergoing percutaneous transluminal coronary angioplasty (PTCA)
Name the direct factor Xa inhibitors. What is the suffix to remember them?
“-xabans”
(has xa in name)
Rivaroxaban
Do factor Xa inhibitors require monitoring of PT or INR?
no
Indications for the direct factor Xa inhibitors?
Used to prevent DVTs after knee/hip surgery;
prevention of stroke
systemic embolism in non-valvular atrial fibrillation
Antidote for the direct factor Xa inhibitors.
rapidly reversed by andexanet alfa
(also has xa in name) Xa net
