aticoagulation deck 2 Flashcards
Factor Xa Inhibitor Oral Anticoagulants
and Direct Thrombin Inhibitor (DOACs) MOA
Prevent factor Xa from converting prothrombin to thrombin by binding directly to factor Xa*
Direct Thrombin inhibitor: inhibits
thrombus
◦ dabigatran
Factor Xa Inhibitor Oral Anticoagulants
and Direct Thrombin Inhibitor (DOACs) indications
◦ Reduction of risk of stroke and systemic embolism in nonvalvular atrial fibrillation
◦ Prophylaxis of DVT following knee replacement surgery
◦ Treatment of DVT and PE
Factor Xa Inhibitor Oral Anticoagulants
and Direct Thrombin Inhibitor (DOACs) pharmacodynamics
◦ Half life variable by agent: 5-15 hours
◦ Variable renal elimination by agent
◦ Edoxaban, Rivaroxaban renal precautions
◦ Dabigatran renal contraindications
Factor Xa inhibitors and interacting drugs
◦ Betrixaban and P-glycoprotein (P-gp) inhibitors
◦ Edoxaban and P-glycoprotein (P-gp) inhibitors
◦ Apixaban and P-gp or CYP3A4 inhibitors
◦ Rivaroxaban and P-gp/CYP3A4 inducers
◦ Vorapaxar and CYP3A inhibitors
◦ All: platelet inhibitors, anticoagulants, antithrombotics
Direct Thrombin Inhibitors and interacting drugs
◦ Dabigatran and P-glycoprotein (P-gp) inhibitors, Rifampin, Dronedarone
Dabigatran do not use if
GFR is low
Factor Xa/Direct Thrombin Inhibitors:
Drug Interactions and ADRs
◦ Bleeding and Anemia
◦ Variable renal elimination: Dabigatran, edoxaban require renal adjustment
◦ Monitor renal status
◦ GI: Dyspepsia, nausea, upper abdominal pain, GI hemorrhage, diarrhea
◦ Dabigatran: Black Box warning potential for rebound thrombotic event on discontinuation
◦ Dabigatran: Black Box warning
warning potential for rebound thrombotic event on discontinuation
American College of Clinical Pharmacy (ACCP) guidelines for
r DVT or PE after initial
stabilization:
DVT and PE treatment after stabalization
3 months of dabigatron, rivaroxaban, apixaban or endoxaban (fixed doses) for
3 months
Factor Xa Inhibitors/Direct Thrombin Inhibitors
Do not require routine monitoring, if do, aPTT not INR
Factor Xa Inhibitors/Direct Thrombin Inhibitors not used
Not used in pregnancy or if CrCl <15mL/min3
◦ Idarucizumab received FDA approval in 2017 as a reversal agent for
dabigatran
Andexanet alfa is an inactive, decoy
factor Xa (FXa) molecule that binds FXa inhibitors, and ciraparantag is a synthetic molecule designed to bind fractionated and unfractionated heparins, and each of the currently approved DOACs; not FDA approved
risk of inctracranal bleeding was reduced with ___ compared with warfarn
DOACs
DOAC pregnancy
Pregnancy category C*
Unknown whether excreted into breast milk
DOAC peds
Safety and efficacy not established for pediatric patients
DOAC advantages compared to warfarn
Absence of food interactions
Few strong drug interactions
Predictable pharmacokinetic and pharmacodynamic
profiles except renal and obesity
Rapid onset and offset of action
Short half-life
Absence of the need for laboratory monitoring
Wide therapeutic windows
Greater efficacy in AF
Lower risk of intracranial hemorrhage, except for
dabigatran
DOAC disadvantages compared to warfarin
Higher cost Limited specific antidotes Limited experience and dosing NOACs should not be used in patients with patients: ◦ severe renal and hepatic disease, ◦ mechanical heart valves ◦ younger than age 18 years ◦ the elderly
Heparin MOA
Binds to antithrombin III and turns off activating factors that develop clots
Heparin pharmacokinetics
◦ Given intravenously (IV) or subcutaneously (SC)
◦ Variable bioavailability
◦ Extensively protein bound
◦ Metabolized by liver and renally eliminated
Heparin precautions and contraindications
◦ Pregnancy category C
◦ Avoid in advanced hepatic or renal disease
◦ Avoid in bleeding disorders or active bleeding
Heparin is highly
protein bound so it can be desttroid in GI tract. Reason it isn’t oral
Indications for heparin
DVT, PE, Acute coronary, anticoagulation
heparin needs to be dosed
multiple times. due to short half life
Heparin ADR
◦ May cause thrombocytopenia
◦ Life-threatening bleeding
◦ Pain at injection site (SC)
Heparin antidote
◦ May cause thrombocytopenia
◦ Life-threatening bleeding
◦ Pain at injection site (SC)
◦ Antidote is protamine sulfate
Heparin monitoring
◦ aPTT
◦ CBC with platelets
Heparin interacions
Cephalosporins and penicillins
◦ Warfarin, antiplatelets, and thrombolytics
◦ Valproic acid
◦ Protamine sulfate is antagonist
LMWH definition
Fragments of unfractionated heparin; smaller molecules than unfractionated heparin
LMWH MOA
◦ Some effects on antithrombin III which complexes to thrombin and inactivates it
◦ Preferentially inhibits the activation of Factor Xa
◦ Minimal effects on thrombin (factor II) because of small size
◦ Less action on platelets than heparin
LMWH Kinetics
◦ Volume of distribution varies between agents
◦ t1/2 is about 4h for all products, NOT protein bound
◦ Inconsistent bioavailability but Improved from heparin
◦ more predictable, dose-independent clearance
◦ Liver disease and renal disease may affect metabolism and elimination
Indications for LMWH
DVT prophylaxis in medium and high-risk groups (surgical, orthopedic and medical patients)
Treatment of venous thromboembolism in pregnancy
Treatment of DVT and PE in nonpregnant women (those with both high and low risk of recurrence)
Treatment of STEMI (in both those undergoing percutaneous coronary intervention and those not)
Unstable angina
Prevention of clotting in extracorporeal circuits
LMWH precautions
◦ Low body weight (<50kg), HTN, liver disease, PUD, malignancy
LMWH contraindictions
◦ Known hypersensitivity to heparin or pork products
◦ Active bleeding or blood dyscrasias
◦ Suggested: trauma, epidural half-life, hemorrhagic disorders, peptic ulcer disease, recent cerebral
hemorrhage, severe hypertension, and recent surgery to the eye or nervous system
LMWH dosing
◦ Each LMWH has its own unique dosing regimen because of relative proportions of anti-Xa to anti-IIa
activity
◦ There are differences in manufacturing, half-life, ratio of anti-Xa to anti-IIa activity, and dose
◦ they CANNOT be used interchangeably
LMWH Monitoring
◦ Patient should monitor for side effects (no blood monitoring necessary, although periodic CBC, platelet,
hemocult stool sometimes recommended)
◦ Chromogenic anti-factor Xa assay is currently the gold standard for monitoring LMWH and fondaparinux
therapy
LMWH Interactions
◦ Other drugs affecting anticoagulation
◦ PCNs, cephalosporins
LMHW Adverse reactions
Bleeding, thrombocytopenia, elevated liver function tests
LMWH first line
First line drug if antithrombotic therapy required during pregnancy
LMWH is safe for
Safe for breast feeding
LMWH betware of
Beware of spinal puncture with LMWHs because it can lead to paralysis
LMWH risk for
Risks of osteoporosis and thrombocytopenia are less than with heparin
LMWH not for
Not for thromboprophylaxis with mechanical heart valve
Heparain Fast Facts (for comparason with LMWH)
Usually used in-patient Requires monitoring via aPTT Dosed IV, SC Marked variability in anticoagulant response Short half life Highly protein bound Risk of osteoporosis
no spinal injections when on a DOAC due to
bleeding
LMWH Fast Facts (for comparason with Heparin)
Can be used in or outpatient Do not require blood monitoring Dosed SC More predictable anticoagulant response Half life is 2-4 times that of heparin Not protein bound Less risk of osteoporosis
