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warfarin MOA
- interferes with hepatic synthesis of vitamin K dependent clotting factors
- 7,C,9,10,S,2 - shortest to longest T1/2
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warfarin's onset of action, full therapeutic effect and duration of action
- 24-72 hrs
- 5-7 days
- 2-5 days
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warfarin's absorption and distribution
- F = .9
- Vd = 0.1-0.2
- 90% bound to albumin
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warfarin's metabolism
- S - CYP2C9
- R - 1A1, 1A2, 2C19, 3A4
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drugs that can have an increase risk of bleeding but don't affect INR
- NSAID's
- ASA
- clopidogrel
- SSRI's
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a food that will increase INR
cranberry
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risk factors that can affect INR
- fever
- N/V
- diarrhea
- hyper & hypothyroidism
- hepatic failure
- CHF
- cancer
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5 pt factors to consider when deciding to initiate on warfarin
- age
- comorbidities
- diet
- medications
- nutritional status
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rules of thumb for starting doses
- > 65 - start with < 5mg
- < 65 and healthy 5-10 mg
- AFib - 3mg
- DVT 10mg x 2 days then check INR
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when do we monitor warfarin upon initiation and maintenance
- initiation - day 3 (checking for antithrombotic effect) and day 5 (possible full therapeutic affect)
- maintenance - 1-2 weeks after dose change
- q4 week once stable
- q12 wks stable & reliable
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Coumadin indication and INR levels not 2-3
- pulmonary hypertension 1.5-2.2
- mechanical mitral valve 2.5-3.5
- multiple indication (AFib & valve) - 2.5-3.5
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coumadin indications with and INR goal of 2-3
- AFib
- DVT/PE
- biologic mitral valve/aortic valve or mechanical aortic valve
- post MI
- post stroke
- prophylaxis of DVT
- cardioversion
- nephrototic syndrome
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length of warfarin tx for AFib, DVT and PE
- lifelong
- 3 months 1st episode, multiple lifelong
- 3-6 months
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absolute CI of warfarin
- major bleeding
- major surgeries
- pregnancy
- blood dyscrasias
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relative CI of warfarin
- alcoholic
- noncompliance
- liver disease
- fall risk
- uncontrolled HTN
- malnutrition
- some surgeries
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rules for dose adjustment of warfarin
- based on weekly doses
- typically 10-20%
- 5% in sensitive pts
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hereditary effects on warfarin
- VKOR
- Asians = more senstive
- African & European = more resistant
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pradaxa MOA
direct thrombin inhibitor
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when is the maximum effect of pradaxa and the T1/2
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pradoxa's indication and dose
- nonvalvular AFib
- 150 mg BID
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what is the dose of pradaxa if the CrCl is 30-50 ml/min
75 mg BID
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what is the dose of pradaxa if the CrCl is < 30 ml/min
avoid use
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xarelto indication and dose
- nonvalvular AFib - 20 mg QD
- postoperative thromboprophylaxis after knee or hip surgery - 10 mg QD
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xarelto MOA
factor Xa inhibitor
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heparin MOA
- converts antithrombin from a slow clotting enzyme to a fast one
- inactivates thrombin and factor Xa 1:1
- prevents conversion of fibrinogen to fibrin
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heparin dosing for DVT
80 unit/kg bolus then18 unit/kg/hr
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heparin dosing for STEMI & nonSTEMI
60 unit/kg bolus then 12 unit/kg/hr
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aPTT time when no change in heparin is needed
55-75
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LMWH's
- lovenox - enoxaparin
- fragmin - dalteparin
- innohep - tinzaparin
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lovenox MOA
strong inhibitor of factor Xa
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lovenox T1/2 and duration of action
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enoxaparin dosing
1mg/kg BID - actual body weight
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therapeutic range of lovenox given BID SQ
0.6-1 iu/mL
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therapeutic range of lovenox given QD SQ
>1 iu/mL
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heparin Vd & T1/2
- 0.07 L - use actual body weight
- 1.6 hrs
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relationship between IV & SQ doses of heparin
SQ should be 10% higher
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difference between heparin metabolisms
- depolymerizations - saturable/rapid
- renal - non-saturable/slower
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arixtra MOA
selective Xa inhibitor
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arixtra contraindication
CrCl < 30 ml/min
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two anticoags CI if CrCl is < 30 ml/min
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arixtra prophylaxis dosing
2.5 mg SQ QD
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arixtra tx weight based dosing
- < 50 kg = 5 mg SQ QD
- 50-100 kg = 7.5 mg SQ QD
- >100kg = 10 mg SQ QD
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