Anticoag drugs 0504 Flashcards
heparin moa
cofactor for activation of ANTITHROMBIN.
antithrombin inactivates thrombin and Xa, which converts prothrombin to thrombin
(decrease thrombin and Xa)
heparin use
short half life.
duration of action is only hours.
IMMEDIATE anticoag for PE, stroke, acute coronary syndrome, MI, DVT
can heparin be used in pregos?
yes - does not cross placenta
how should heparin tx be monitored?
follow PTT - intrinsic pathway
(three letters long, like “Hep”)
also causes increased thrombin time
heparin tox
bleeding
thrombocytopenia (HIT)
osteoporosis
drug-drug interaction
heparin antidote
protamine sulfate - positively charged molecule that binds negatively charged Hep
heparin-induced thrombocytopenia (HIT)
Hep binds factor IV, causing Ab production that binds to and activates plts - lead to plt clearance.
thrombocytopenic, hypercoagulable state.
LMWH (enoxaparin) moa
binds antithrombin III ONLY.
acts more to inhibit Xa.
enoxaparin pharmacodynamics
better bioavailability. 2-4 times longer half life. admin SQ. no lab monitoring. not easily reversible.
fondaparinux
smallest heparin form.
synthetic pentasaccharide inhibitor of Xa.
no activity with antithrombin.
causes increased PT and aPTT.
no effect on thrombin time.
hirudin derivatives
lepirudin
bivalirudin
argatroban
dabigatran
hirudin derivatives moa
DIRECT thrombin inhibition. prevent new clot formation.
does not require ATIII.
prolongs thrombin time.
hirudin derivatives use
alternative to Hep in pts with HIT.
warfarin (Coumadin) moa
interferes with normal synthesis and gamma-carboxylation of vit K-dependent factors II, VII, IX, X, prot C and S.
warfarin metabolism
cyto P450
warfarin lab results
increase PT (affects extrinsic pathway)
warfarin use
long half life.
duration of action for days.
CHRONIC anticoag - post STEMI, prophylaxis for venous thromboembolism.
how is warfarin use monitored?
follow PT/INR values
can warfarin be used in pregos?
NO! can cross placenta
what other drug must be administered when warfarin is initiated?
Hep/enoxaparin - anticoag prot C and S are quickly depleted (shortest half lives); can result in paradoxical PROcoagulant state if Hep not given
warfarin tox
bleeding
teratogenic
skin/tissue necrosis**
drug-drug interactions
warfarin antidote
reverse OD: IV vit K
rapidly reverse SEVERE OD: fresh frozen plasma
why is the onset of therapeutic action for warfarin delayed for a few days?
vit K-dependent factors have long half lives
route of admin for Hep
parenteral (IV, SC)
site of action for Hep
blood
Hep structure
large, anionic acidic polymer
warfarin structure
small lipid soluble molecule
route of admin for warfarin
oral
site of action for warfarin
liver
can Hep or warfarin inhibit coag in vitro?
Hep does, warfarin does not
thrombolytics
streptokinase
urokinase
tPA (alteplase)
APSAC (anistreplase)
thrombolytics moa
directly or indirectly aid conversion of PLASMINOGEN to PLASMIN, which cleaves thrombin and fibrin clots
thrombolytics lab changes
increase PT
increase PTT
no change in plt count
thrombolytics use
early MI
early ischemic stroke
thrombolytics tox
bleeding
thrombolytics contraindications
pts with: active bleeding history of intracranial bleeding recent surg known bleeding diatheses severe HTN
thrombolytics antidote
aminocaproic acid - inhibits fibrinolysis
aspirin moa
acetylates and IRREVERSIBLY inhibits cyclooxygenase (COX1 and COX2) to prevent conversion of arachidonic acid to thromboxane A2
aspirin lab changes
increase bleeding time
no effect on PT, PTT
aspirin uses
antipyretic
analgesic
anti-inflamm
anti-platelet
aspirin tox
gastric ulceration bleeding hyperventilation Reye's syndrome tinnitus (CN VIII)
clopidogrel, ticlodipine moa
inhibit plt aggregation by irreversibly blocking ADP receptors - block GpIIbIIIa expression, which is needed to bind fibrinogen
clopidogrel, ticlodipine use
acute coronary syndrome.
coronary steal syndrome.
decrease incidence or recurrence of thrombotic stroke.
ticlodipine tox
neutropenia
cilastazol, dipyridamole moa
phosphodiesterase III inhibitor - increase cAMP in plts to inhibit plt aggregation.
also vasodilator.
cilastazol, dipyridamole use
intermittent claudication.
coronary vasodilation.
prevention of stroke or TIAs (combined with aspirin).
angina prophylaxis.
cilastazol, dipyridamole tox
nausea headache facial flushing hypOtension abd pain
abciximab moa
monoclonal Ab that binds to GpIIbIIIa on activated plts, preventing aggregation
abciximab use
acute coronary syndrome.
percutaneous transluminal coronary angioplasty
abciximab tox
bleeding
thrombocytopenia
