Pharmacology - VTE anticoagulants Flashcards
briefly explain the mechanism of clot formation
vasoconstriction
platelet plug formation – platelets aggregate and stick together
clot formation - FIBRIN proteins stick together to form a CLOT
briefly explain what is happening in deep vein thrombosis
clot forms in the legs
this can potentially form an embolus which travels to other areas of the body and can cause major issues
ie - pulmonary embolism
3 risk factors for venous thromboembolism
-stasis (not moving)
-endothelial injury (ie - surgery, trauma)
-hypercoagulability
____ use can potentially cause thromboembolism
estrogen
there are intrinsic and extrinsic coagulation pathways.
which factor is common to both???
Xa
therefore, Xa inhibitors are very common anticoagulants!
what causes coagulation factors to initiate coagulation?
when they come in contact with the endothelium — ie bc of injury
name 3 things that can be blocked to treat deep vein thrombosis
fibrinogen
Xa
prothrombin
unfractionated heparin is also called…
high MW heparin
name 4 LMWH’s
enoxaparin
dalteparin
tinzaparin
fondaparinux
name 4 oral Xa inhibitors
rivaroxaban
apixaban
edoxaban
betrixaban
name a thrombolytic
alteplase
low molecular weight heparins are ____ ____ antagonists
parenteral Xa
name 2 direct thrombin inhibitors
bivalirudin
argatroban
name a vitamin K antagonist
warfarin
explain the MOA of unfractionated heparin (high MW heparin)
it accelerates the formation of antithrombin III (our natural anticoagulant)-thrombin complex
this inactivates thrombin (IIa) (and inhibits its formation), as well as Xa, and prevents the conversion of fibrinogen to fibrin, and PREVENTS clot formation overall
true or false
unfractionated heparin cannot be given in pregnancy
FALSE
it does not cross the placenta
it’s ok in pregnancy
**major AE of high MW heparin (unfractionated)
THROMBOCYTOPENIA (low platelets)
called HIT (heparin-induced thrombocytopenia)
what does heparin do to aPTT time
increases it
name 2 monitoring parameters for heparin (unfractionated)
bleeding
APTT
heparin (unfractionated) contraindication
any bleeding issue
ie - another anticoagulant
name 4 types of drugs that antagonize anticoagulation and thus can cause a clot when administered with heparin
nicotine
cardiac glycosides
antihistamines
tetracyclines
thrombosis meaning
clot
3 major advantages of high MW heparin
continuous IV drip - accurate dosing
rapid onset and short duration
monitoring APTT can help to determine if it’s working as it should
low molecular weight heparins are said to have higher ___ activity than ____
higher inhibition of Xa than IIa (THROMBIN)
like a 4:1 ratio
true or false
low molecular weight heparins have a lower incidence of thrombocytopenia than unfractionated heparin
true
true or false
LMWH has focused action against IIa
FALSE - against Xa
not as much to thrombin
prototype for low MW heparins
enoxaparin
how is enoxaparin administered
subq injection
2 AE of enoxaparin
hemorrhage, thrombocytopenia
name some drugs that have a DDI concern with enoxaparin and have a bleeding concern
other anticoagulants, antiplatelets, NSAIDS
how often is enoxaparin administered**
Q12 for DVT treatment
and QD for prophylaxis
***do labs need to be monitored for LMWH’s like enoxaparin
NO
*****true or false
low molecular weight heparins have a lower incidence of HAT
true
this is the non-immune-mediated thrombocytopenia
*****LMWH’s are administered subq
how is this an advantage?
dont need a hospital IV - reduced expenses
can administer at home to prevent DVT during the 9 months of pregnancy
what is the QD dosing for LMWH’s
1mg/kg
**what is the name of the heparin antagonist?
what is it used for?
protamine sulfate
to back titrate an over dose of heparin (high MW)
what is a big caution when giving protamine sulfate
it releases histamine!
this can lower BP potentially too much and cause shock
therefore, infuse SLOWLY over 10 mins
**big problem with high molecular weight IV heparin
HIT - heparin induced thrombocytopenia
what are the findings when a patient gets HIT
is it immune mediated?
yes immune mediated
skin is bruised, red, itchy
platelets reduced to 50%
HAT
heparin ASSOCIATED thrombocytopenia (type 1 )
difference in platelet count between HIT and HAT
HIT - below 100,000
HAT - they rarely even go below 150,000
***which drugs can be used in a patient that needs anticoagulation therapy but HAS HIT????
targeted Xa and IIa inhibitors:
fondaparinux (Xa)
hirudin, Bivalirudin, Argatroban, Melagatran (IIa)
**name 1 subQ Xa inhibitor and 4 PO Xa inhibitors
subq - fondaparinux
PO - rivaraxoban, apixaban, edoxaban, betrixaban
explain the MOA of fondaparinux
selectively inhibits factor Xa
does this indirectly through binding ATIII. this causes ATIII to change shape and this increased affinity for Xa to neutralize it more
this neutralization of Xa interrupts the blood coagulation cascade — inhibits thrombin formation and clot development
common and severe SE of fondaparinux
bleeding, bruising
can LMWHs be used in HIT patients
NO there is cross reactivity with the antibodies
fondaparinux can be used as prophylaxis of DVT?
yes - after major orthopedic and abdominal sirgeries
factor Xa is required in the clotting cascade to do what?
cleave prothrombin into THROMBIN
Is there a DDI concern with eliquis and xarelto?
YES
3a4 and p-glycoprotein inhibitors and inducers
*how to recognize the oral Xa inhibitors
“ban”
what class is edoxaban
an oral Xa inhibitor – a NOAC
what class is betrixaban
an oral XA inhibitor (BAN)
how does betrixaban inhibit Xa
competitive and reversible
***which drugs can be used for the treatment of venous thromboembolism?
any anticoagulant
name 2 targeted IIa (thrombin) inhibitors
how are they each administered
bivalirudin - IV
dabigatran - PO
**what are the 3 classes of thrombin inhibitors?
**name each drug in the class
indirect (univalent), bivalent (direct), univalent (direct)
bivalent means they bind at 2 sites
indirect - heparin
direct bivalent - bivalirudin, lepirudin, desirudin
univalent direct - argatroban, ximelagatran, dabigatran
side effects bivalirudin
as a recap, what class is it?
hemorrhage, hypotension
a direct thrombin inhibitor (bivalent)
true or false
dabigatran is an oral IIa inhibitor
TRUE
what are the advantages of dabigatran over warfain
what’s a disadvantage of it
no dietary, DDI, and monitoring problems (INR)
bleeding
true or false
dabigatran is a prodrug
TRUE
dabigatran is a direct thrombin inhibitor
is it noncompetitive or competitive
competitive
main AEs of dabigatran
bleeding - 17%!!!!
dyspepsia and GI complaints - take with food!! no antacids!
a patient is having an issue with dyspepsia while on dabigatran
how do u counsel
they can try an H2 blocker BUT it may decrease bioavailability bc acidic environment is needed for absorption
true or false
dabigatran has no CYP DDIs
true
BUT does have DDI with p-glycoprotein inducers/inhibitors
name 2 ORAL anticoagulants that permit hospital discharge
warfarin (need monitoring)
dabigatran (do not need monitoring)
MOA warfarin
inhibits vitamin K formation - vitamin K antagonist
does this by inhibiting vitamin K reductase and vitamin K epoxide reductase
this inhibits a lot of things – the functional form of a lot of factos, as well as proteins C,S, and Z
true or false
warfarin does NOT dissolve a preexisting clot
TRU
true or false
warfarin is not very protein bound
FALSE - it is 97-99%
can warfarin be used in pregnancy
NO
crosses BBB
polymorphisms in ___ and ____ affect the response to warfarin
explain how they affect it
CYP2C9 and CKOR (vitamin K epoxide reductase)
CYP2C9 will significantly inactive (s)-warfarin (the most potent form)
warfarin works by inhibiting VKOR
endogenous role of vitamin K
causes clotting
what is the coumadin antagonist and thus the antidote for warfarin overdose
VITAMIN K
what is the antidote for dabigatran
idarucizumab (monoclonal antibody)
what is the name of the factor Xa inhibitor (eliquis, xarelto) reversal agent
annexa-A
