Anticoagulant Drugs Flashcards
Heparin MOA
- binds to antithrombin and inactivates factor IIa and Xa
- prevents fibrinogen–> fibrin
Unfractioned Heparin prophylaxis
SQ: 5000U q8 or q12
Unfractioned heparin VTE Tx
IV: 80u/kg IV bolus then 18u/kg/hr infusion
unfractioned heparin ACS/STEMI Tx
IV: 60u/kg bolus then 12u/kg/hr infusion
SE UFH
HIT, Hyperkalemia, osteoporosis
UFH antidote
protamine-completely reverses
UFH monitoring
caution with pork allergy
aPTT (goal 1.5-2x control) or heparin assay (goal 0.3-0.7) q6h til therapeutic then q24h
half life=1-2hr
low molecular weight heparin examples
Enoxaparin (Lovenox), Dalteparin (Fragmin)
lovenox prophylaxis
30mg SQ q12 or 40mg SQ qd
CrCl <30: 30mg qd
lovenox treatment
1mg/kg q12 (to nearest 10mg)
CrCl<30: 1mg/kg q24
LMWH SE
anemia, elevated LFTs, HIT, hyperkalemia, thrombocytopenia, osteoporosis, injection site bruising
LMWH antidote
protamine- incompletely reverses
preferred pregnancy agents
UFH and LMWH
LMWH monitoring
Anti-Xa level-obesity, pregnancy, renal failure
Warfarin (Coumadin, Jantoven) class
Vit K antagonist
Warfarin MOA
decreases Factors II, IV, IX, X and Protein C and S through competitive inhibition of subunit 1 of VKOR complex
Warfarin initial dosing
10mg qd x2d then 5mg qd
may start <5mg qd if old, malnourished, hepatic impairment, CHF, high risk of bleeding
Warfarin dose adjustments
based on INR
target INR 2-3 except mechanic heart valve (2.5-3.5)
Warfarin SE
purple-toe syndrome, skin necrosis
many drug interactions (CYP3A4), NTI
warfarin in pregnancy
AVOID
Warfarin antidote
Vitamin K +/- Kcentra or FFP
Factor Xa inhibitors
Rivaroxaban (Xarelto), Apixaban (Eliquis), Edoxaban (Savaysa), Fondaparinux (Arixtra)
FXa inhibitor MOA
- Xarelto and Eliquis directly inhibit factor Xa
- Fondaparinux indirectly inhibits factor Xa
Xarelto non-valvular AFib dosing
20mg qd
Xarelto DVT prophylaxis dosing
10mg qd
if hip/knee replacement, duration for 35 days for hip and 12 days for knee
Xarelto DVT/PE Tx
15mg BID for 21d then 20mg qd
Xarelto BBW
premature discontinuation increases risk of thrombotic events
TAKE WITH FOOD
Xarelto SE
anemia, more bleeding than warfarin
FXa inhibitor conversion
d/c warfarin and start:
Xarelto when INR <3
Edoxaban when INR <2.5
Apixaban when INR <2
Eliquis, Xarelto, off-use Edoxaban antidote
Andexxa
FXa inhibitor warnings
no use in pregnancy
avoid interacting agents (P-gp inhibitors/inducers for all DOACs and CYP3A4 inhib/inducers for apixiban/rivaroxaban)
Eliquis/Xarelto increase INR
concern w/ all DOACs in patients <50kg or >120kg
Arixtra route
SQ
Arixtra SE
anemia, thrombocytopenia, hypokalemia
CrCl <30: AVOID USE
Direct Thrombin Inhbitors (DTIs)
Argatroban (IV), Dabigatran (Pradaxa) oral
DTI MOA
- directly inhibit thrombin (Factor IIa)
- binds to and inhibits the active site of free and fibrin bound thrombin
Argatroban HIT dosing
2mcg/kg/min
Max: 10mcg/kg/min
HIT
heparin-induced thrombocytopenia
Argatroban PCI dosing
350mg/kg (bolus) then 25mcg/kg/min
PCI
percutaneous coronary intervention
Argatroban SE
anemia, chest pain, GI hemorrhage
Argatroban monitoring
aPTT
raises INR
Pradaxa non-valvular AFib dosing
150mg bid
Pradaxa DVT/PE Px and Tx dosing
150mg bid
Pradaxa DVT Px knee/hip replacement dosing
110mg on day of surgery and 220mg qd for min of 10-14 days up to 35 days
Pradaxa BBW
thrombotic events
Pradaxa SE
dyspepsia, gastritis-like symptoms, bleeding, hemorrhage
Pradaxa antidote
Idarucizumab (Praxbind)
Pradaxa inititation
requires at least 5 days parenteral anticoag before initiation in Tx of DVT/PE
do not open/chew caps and keep in original container
D/C Warfarin and start Pradaxa when INR<2
use w/ EXTREME caution in patients >75yo
Protamine reverses
completely: UFH
incompletely: LMWH, lovenox, fragmin
Protamine MOA
Protamine (alkaline protein molecule, large + charge) and Heparin (acidic, - charge) when combined form a stable salt diminishing the anticoag activity
Protamine considerations
IV only
rapidly reverses UFH
BBW: hypersensitivity (fish)
Praxbind (Idarucizumab) reverses
Pradaxa (Dabigatran)
Praxbind MOA
humanized MAb fragment that has an affinity for dabigatran that is ~350 times greater than that of thrombin
Praxbind considerations
neutralized anticoag effect w/in minutes
lasts 24hrs, if pradaxa not cleared after 24hr, give another dose of Praxbind (ex. renal failure)
most common SE: headache
Monitor: re-elevation of coag parameters
KCentra reverses
VitK Antag: Warfarin
off label: FXa drugs
Kcentra MOA
Prothrombin Complex Concentrate (PCC): (II, VII, IX, X and Protein C and S)
Kcentra considerations
BBW: arterial and venous thromboembolic complications
advantages to FFP (fresh frozen plasma): lower infusion volume, lower infection rate, less complications, rapid reversal
NovoSeven reverses
warfarin-related intracerebral hemorrhage
NovoSeven MOA
Factor VIIA (recombinant)
VKA-dependent glycoprotein that promotes hemostasis by activating the extrinsic pathway of the coag cascasde
NovoSeven considerations
BBW: thrombosis
high cost
Fresh frozen plasma reverses
Warfarin
FFP considerations
high volumes of FFP may be problematic in all pts esp those sensitive to rapid fluid shifts (HF)
Vitamin K reverses
Warfarin
Vitamin K MOA
promotes liver synthesis of clotting factors II, IV, IX, X
Vitamin K considerations
Formulations:
oral: 2.5-5mg when INR>10 (no bleeding) or minor bleeding w/ any INR
IV: 5-10mg infused slowly due to anaphylaxis indicated in emergency situations or major bleeding (in addition to PCC)
Hemodialysis reverses
removes 57-68% of Pradaxa w/in 4hrs
removes 20% of Edoxaban
Andexxa reverses
Eliquis and Xarelto
Andexxa MOA
inactive recombinant modified Human Factor Xa Protein
Andexxa considerations
BBW: thrombosis, ischemic events, cardiac arrest, sudden death
off-label reversal of Edoxaban
Bleeding symptoms
tachycardia, SOB, blood-loss, blood in stool, urine, blowing nose, brushing teeth
Bleeding signs
increased RR, increased HR, decreased BP
