Antiplatelets, Anticoagulants & Thrombolytics 2 Flashcards
EdoXAban should NOT be used with ______ (4).
- Rifampin
- SSRI/SNRI
- Anticoagulants
- Antiplatelets
EdoXAban & Betrixaban contraindications (3)
- lactation
- renal impairment
- liver impairment
BetriXAban dosing must be reduced for patients taking ______ (rx).
P-glycoprotein (P-gp) inhibitors
Dabigatran reduces the risk of _____ & treats ____.
- stroke, PE in nonvalvular a-fib
- DVT & PE recurrence (or following surgery)
(also prevents thromboembolic events in peds pts)
Dabigatran binds ______.
free and clot-bound thrombin
(is not a substrate, inhibitor or inducer of CYP450)
Dabigatran increases risk of _____ if d/c early.
thrombotic events
Dabigatran is contraindication
mechanical prosthetic heart valve
________ gene is associated w/variable warfarin dose requirements
VKORC1 gene
(CYP2C9*2 vs CYP2C9*3 alleles associated w/decreased activity)
Warfarin onset of action:
Peak effect?
- 24 hours
- delayed 72-96 hours
What is the cause of tissue necrosis as a side effect of Warfarin?
Lack of protein C & S
(aka “purple toe syndrome”)
Adverse effects of warfarin include: tissue necrosis, _______ (2).
- calciphylaxis
- acute kidney disease
Warfarin contraindications
- pregnancy (abnormal bone formation)
- malignant hypertension
______ (3) should not be taken with warfarin?
- amiodarone
- cotrimoxazole
- caffeine
How do you decide on a does for warfarin?
genotype
(note: there can be as much as a 10x difference in dosage)
indirect thrombin inhibitor
(heparin & LMW heparins)
enhance activity of antithrombin → inhibits FX & II
(don’t inhibit coagulation factors)
Smaller size _______ (increases/decreases) half-life.
increases
_______ (Heparin/LMW heparin) may be used in renal failure, but ______ (Heparin/LMW heparin) may NOT.
- heparin
- LMW heparin
Heparin vs. LMW heparin route of administration
- Heparin: IV, Sub-Q
- LMW heparin: Sub-Q
LMW heparin contraindications
HIT w/in past 100 days or w/circulating ab
Disadvantage to using heparin
frequent monitoring needed for HIT, HITT
Why is heparin mostly used in the hospital setting?
heparin: IV or SubQ
(warfarin = PO)
Indications of heparin (5)
- venous or arterial thrombosis, PE
- a-fib
- DIC
- surgery
- blood transfusions, extracorporeal circulation & dialysis
(anticoagulant used in hospital setting)
Heparin MOA & half-life
- binds antithrombin III → enhances protease activity
- 0.2-2 hrs
Heparin AE (8)
- osteoporosis
- spontaneous vertebral fx
- hyperkalemia
- hyperlipidemia, rebound hyperlipidemia
- alopecia
- itching
- hyperkalemia
- priapism
HIT (heparin-induced thrombocytopenia)
AB formation with platelet factor 4 → thrombosis risk due to lowered platelet count
HIT can cause serious _____ events
thromboembolic events → amputation or death
(DVT, PE, cerebral vein thrombosis, limb ischemia, stroke, MI, mesenteric, renal artery, skin necrosis, gangrene)
Patients whose platelet count falls below ______ or who develop recurrent thrombosis should discontinue heparin.
100,000/mm3
(HIT or HITT can occur several weeks after medication discontinuation)
HIT is treated with ______ (2).
- Argatroban
- Bivalirudin
List 2 LMW Heparins
- Enoxaparin (Lovenox ®)
- Fondaparinux (Arixtra ®)
What is the difference in the MOA of LWM Heparin or unfractionated (full sized Heparin)?
UFH: binds to antithrombins at a 1:1 complex to enhances the activity of antithrombin (1000x).
Inactivates complexes of factor IIa (thrombin), IX, and X.
LMWH: Shorter motif that reduces thrombin inhibition but rapidly inactivates factor X
Which has a longer half life: Enoxaparin (Lovenox ®) or Fondaparinux (Arixtra ®) ?
- Fondaparinux ~ 20 hrs
- Enoxaparin ~ 5 hrs
(both are LMWH)
LMWH Enoxaparin (Lovenox ®) & Fondaparinux (Arixtra ®) both treat DVT (prophylaxis & acute). Which treats MI and which treats PE?
- Enoxaparin (Lovenox ®) : MI
- Fondaparinux (Arixtra ®): PE
Adverse effect of LMWH
thrombocytopenia
List 2 direct thrombin inhibitors
- Argatroban
- Bivalirudin
(used to tx HIT)
Bivalirudin (Angiomax ®) MOA
HIT & HITT
(HITT = heparin-induced thrombocytopenia and thrombosis)
You must used caution in prescribing Bivalirudin to patients w/ ______ (2)
- geriatric → increased bleeding risk
- renal impairment
Which anticoagulant is indicated for thromboprophylaxis after hip arthroplasty?
Desirudin
Desirudin route of admin.
twice-daily Sub-Q
(dosage adjustment for renal impairment)
Argatroban drug interactions (2)
- Heparin (wait for aPTT test)
- oral anticoagulant
Argatroban MOA
- direct thrombin inhibitor
- reversible binding to thrombin active site
(work on free and clot bound thrombin)
Argatroban half life
~ 1 hour
Streptokinase (fibrinolytic Rx) is eliminated via the _______ (2 organs).
- intestines
- kidney
(protein produced by streptococci, used to tx thrombolysis)
Antibodies to ______ (fibrinolytic rx) can last for months to years after administration.
Streptokinase
Urokinase half-life?
~ 12 minutes
Urokinase MOA
plasminogen → plasmin
Urokinase indications
PE
(lysis when unstable hemodynamics - failure to maintain BP w/o support)
Recombinant form of human tPA
Alteplase
Alteplase MOA
selectively binds to fibrin in a thrombus
Alteplase indications (3)
- STEMI (acute MI)
- PE
- Ischemic stroke
Mutant tPA
Tenectaplase
Tenecteplase (mutant tPA) contraindications
severe uncontrolled HTN
Fibrinolytic inhibitors are ______ analogs.
lysine
Fibrinolytic inhibitor contraindication
evidence of active intravascular clotting process
(these rx enhance hemostasis when bleeding continues)
Reteplase & Tenecteplase both treat MI. Which treats PE?
Tenecteplase
(Fibrinolytic rx)
Adverse effects of all 3 fibrinolytic Rx (Alteplase, Reteplase, Tenecteplase)?
major bleeding, including intracranial
Andexxa indication & MOA
- Rivaroxaban & Apixaban overdose
- binds & sequesters them (also inhibits activity of Tissue Factor Pathway Inhibitor - TFPI
Warfarin overdose tx. Indication for use?
- Vitamin K1
- anticoagulant-induced prothrombin deficiency, hemorrhagic disease of newborn, hypoprothrombinemia due ot abx
How soon can hemorrhage be controlled with vitamin K1?
~4 hours
(normal prothrombin levels obtained in ~13 hours)
Heparin overdose tx
Protamine Sulfate
Indication for protamine sulfate
heparin overdose, cardiac surgery
How soon can heparin be neutralized after protamine sulfate is administered?
5 min
2 Adverse effects of protamine sulfate
- sudden drop of BP
- bradycardia
Protamine sulfate drug interactions
abx: cephalosporins & penicillins
Idarucizumab MOA
binds free & thrombin-bound Dabigatran → neutralization
(reverses anticoagulation effects of Dabigatran)
When is Idarucizumab used (2)?
- emergency surgery/urgent procedures
- life-threatening uncontrolled bleeding
(Dabigatran reversal)
Idarucizumab may cause adverse reactions in patients with ______.
fructose intolerance