aticoagulation deck 2 Flashcards by Nathan Koranda

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*

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Direct Thrombin inhibitor: inhibits

thrombus

◦ dabigatran

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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

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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

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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

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Direct Thrombin Inhibitors and interacting drugs

◦ Dabigatran and P-glycoprotein (P-gp) inhibitors, Rifampin, Dronedarone

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Dabigatran do not use if

GFR is low

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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

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◦ Dabigatran: Black Box warning

warning potential for rebound thrombotic event on discontinuation

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American College of Clinical Pharmacy (ACCP) guidelines for

r DVT or PE after initial

stabilization:

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DVT and PE treatment after stabalization

3 months of dabigatron, rivaroxaban, apixaban or endoxaban (fixed doses) for
3 months

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Factor Xa Inhibitors/Direct Thrombin Inhibitors

Do not require routine monitoring, if do, aPTT not INR

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Factor Xa Inhibitors/Direct Thrombin Inhibitors not used

Not used in pregnancy or if CrCl <15mL/min3

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◦ Idarucizumab received FDA approval in 2017 as a reversal agent for

dabigatran

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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

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risk of inctracranal bleeding was reduced with ___ compared with warfarn

DOACs

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DOAC pregnancy

Pregnancy category C*

Unknown whether excreted into breast milk

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DOAC peds

Safety and efficacy not established for pediatric patients

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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

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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 ```