Anticoagulants Flashcards
What drug classes are used in stable angina?
Aspirin
Thienopyridines
What drug classes are used in UA/NSTEMI?
Aspirin Thienopyridines Glycoprotein IIb/IIIa Unfractionated heparin LMW heparin Factor Xa inhib Direct thrombin inhib
What drug classes are used in STEMI?
Aspirin Thienopyridines Glycoprotein IIb/IIIa Unfractionated heparin LMW heparin Factor Xa inhib Direct thrombin inhib Fibrinolytic therapy
What drug classes are used in atrial fib?
Aspirin
Factor Xa inhibitors
Direct thombin inhibitors
Warfarin
What drug class is used for treatment only of venous thromboembolism?
Fibrinolytics
Between what two parts of the coagulation cascade does the most binding occur?
Between glycoprotein Ib-IX platelet receptor and von Willebrand factor
What two substances are the most potent platelet activators?
Collagen & thrombin
aspirin general indications
Indicated for all CHD patients
81-325mg
Clopidogrel 75mg can be used in pts w/ aspirin hypersensitivity
aspirin indications and dosing for acute management
162-325mg one time, chewed & swallowed non-enteric coated
aspirin indications and dosing for maintenance
81mg PO, enteric coated, indefinitely
Thienopyrdine MOA
Anti-platelet: blocks the ADP receptor thus preventing platelet activation
How are thienopyridines dosed before/during and after the PCI?
All pts receive a loading dose before/during PCI followed by maintenance dose
What is the difference between 300mg clopidogrel and 600mg clopidogrel?
300mg provides adequate antiplatelet activity in 6 hrs, 600mg provides antiplatelet activity in 2 hrs
If CABG is planed, how should thienopyridine meds be managed?
Thienopyridines need to be held for 5 (clopidigrel & ticagrelor) to 7 (prasurgrel) days before surgery.
What is the dosage of prasurgrel in pts weighing less than 60kg?
5mg
ticlopidine (Ticlid) dosing/indications
500mg loading dose
250mg BID maintenance
*can cause neutorpenia
clopidogrel (Plavix) dosing/indications
300-600mg loading dose
75mg QD maintenance
contraindication w/ 2C19 inhibitors (omeprazole) & poor metabolizer id’d as CYP2C192 or CYP2C19*3
prasugrel (Effient) dosing/indications
60mg loading
10mg QD maintenance
- 5mg for pts <60kg
- caution in >75y, stroke/TIA hx
ticagrelor (Brilinta)
180mg loading
90mg maintenance
- can cause hyperuricemia, increased creatinine & ventricular pause
- caution in gout, 3A inducers/inhibitors, aspirin maintenance >100mg & hepatic impairment
Glycoprotein IIb/IIIa inhib MOS
Inhibits the GB IIb/IIIa receptor on platelets preventing the fibrinogen crosslink and platelet aggregation
Glycoprotein IIb/IIIa inhib general indications and dosing
- Reserved for high risk pts w/ ischemic EKG changes or increased cardiac markers
abciximab is preferred for what kind of PCI reperfusion?
immediate
What 2 GP IIb/IIIa inhibitors are preferred for delayed PCI reperfusion?
tirofiban & eptifibatide
What GP IIb/IIIa requires renal dosing?
eptifibatide - administer 1 bolus & decrease infusion by 50%
GP IIb/IIIa inhib adverse effects
- Thrombocytopenia
- Occult bleeding
abciximab description
GP IIb/IIIa inhibitor
Fab fragment of a humanized monoclonial antibody against GP IIb/IIIa receptor
tirofiban description
GP IIb/IIIa inhibitor
Nonpeptide, competitive inhibitor of the GP IIb/IIIa receptor
eptifibatide description
GP IIb/IIIa inhibitor
Cyclic peptide, competitive inhibitor of GP IIb/IIIa receptor
Unfractionated heparin MOA
Inhibits clotting factors IIa, IXa, Xa and XIIa (mostly IIa & Xa)
Unfractionated heparin general indications/dosing
UA/NSTEMI & STEMI treatment
DVT/PE prevention & treatment
Unfractionated heparin dosing in UA/NSTEMI w/o GPI
70 units/kg IV bolus followed by 15 units/kg/hr infusion
Unfractionated heparin dosing in UA/NSTEMI w/ GPI
60 units/kg IV bolus followed by 12 units/kg/hr infusion
Unfractionated heparin dosing in STEMI w/ GPI or fibrinolytic co-administered
60 units/kg IV bolus followed by 12 units/kg/hr infusion
Unfractionated heparin dosing in VTE prevention
5000 units SQ BID/TID
Unfractionated heparin in VTE treatment
80 units/kg IV bolus followed by 18 units/kg/hr infusion
What parts of the CBC should you monitor when using Unfractionated heparin?
Hemoglobin, hematocrit & platelets
What is the aPTT therapeutic goal in Unfractionated heparin therapy and how is it monitored?
- aPTT therapeutic goal: 1.5-2.5x control
- monitor every 6hrs until 2 measurements are w/i therapeutic range, the every 24 while on therapy
Dose adjustment for aPTT of <35 sec (1.2x control) in Unfractionated heparin therapy
Rebolus w/ 80 units/kg IV & increase infusion rate by 4 units/kg/hr
Dose adjustment for aPTT 35-45 sec (1.2-1.5x control) in Unfractionated heparin therapy
Rebolus w/ 40 units/kg IV & increase infusion rate by 2 units/kg/hr
Dose adjustment for aPTT of 46-70 sec (1.5-2.5x control) in Unfractionated heparin therapy
None
Dose adjustment in aPTT of 71-90 sec (2.5-3.0x control) in Unfractionated heparin therapy
Decrease infusion rate by 2 units/kg/hr
Dose adjustment for aPTT of >90 sec (>3.0x control) in Unfractionated heparin therapy
Stop infusion for 1 hr, then decrease rate by 3 units/kg/hr
What is the reversal agent for UFH & what is the neutralization ratio?
IV protamine
1mg protamine neutralizes 100 units of UFH
Thrombocytopenia is defined as a reduction in platelets below _____ or _____% from baseline.
<100,000 cells/uL or 50% fall from baseline
How do you manage thrombocytopenia from UFH?
Change to non-heparin anticoagulant or hold all anticoags if under <50,000
UFH cautions & contraindications
- Hemorrhage (duh)
- Malignant hypertension (stage III)
- Thrombocytopenia (platelets <20,000)
- Severel liver dz
Low molecular weight heparin MOA
Inhibits factors Xa & IIA in a 4:1 ratio
What is monitored in LMWH therapy?
CBC: H & H
Why is anti-Xa level not monitored in LMWH therapy?
Anticoagulant response is very predictable
Vitamin K antagonist MOA
Inhibits production of vitamin K dependent clotting factors II, VII, IX & X along with anticoagulant proteins C & S
Why is there a delay in anticoagulant response to vitamin K antagonists?
Warfarin has NO impact on existing clotting factors and anticoagulant response is dependent on half-life of clotting factors
How long does it take Warfarin to change coagulation properties? To become therapeutic?
2-4 days to change coagulation properties & > 1 wk to become therapeutic
What is the usual starting dose of Vitamin K antagonists?
5-10mg PO QD
What pts should have a reduced starting dose of vitamin K antagonists?
-Debilitated
-Malnourished
-CHF
- Liver dz
>60y
How are vitamin K antagoinists abosrbed & metabolized?
Orally absorbed, 95% bound to albumin, metabolized in liver
Which vitamin K antagonist isomer, R or S, is more active? What metabolizes them?
S is 5x more active than R & is metabolized by P450 2C; R is metabolized by P450 1A2/3A4
What adverse effects are caused by vit K antagonists?
- Purple toe syndrome
- Warfarin induced skin necrosis
Vit K antagonist cautions
- Hx of GI bleeding
- recent neurosurgery
- liver dz
- heavy ETOH consumption
- Non-compliant pts
- high-risk fall pts
Vit K contraindications
- active bleeding (duh)
- hemorrhagic tendicies (duh)
- Pregnancy
- hx of warfarin-induced skin necrosis
How is warfarin monitored?
prothrombin time (PT)
What does the PT measure?
The amount of time required for clot formation after Ca & thromboplastin are added to citrated plasma
What is the INR?
International Normalized Ratio: attempts to standardize PT measurements using an international sensitivity index (ISI)
What is the ISI and how does it fit into the INR equation?
ISI is a measure of thrompolastins responisiveness using a WHO reference:
(PT patient/PT control) ^ISI
The INR goal and target range is 2.5 (2.0-3.0) except for:
Secondary prevention of AMI, prosthetic mechanical heart valve & pt w/ (+) ASA.
INR goal/range = 3.0 (2.5-3.5)
How often do you monitor INR in hospitalized pts?
On 2nd day, then daily until in therapeutic range for 2 consecutive days
How often do you monitor INR in outpatients?
2x in first week (day 3-4 & 5-7)
Once dose estab: INR every 1-2 weeks unit stabilized
Once stabilized: INR every 4-6 wks
Dose change: INR 1st wk, then every 1-2 wks, then every 4-6 wks
Indirect factor Xa inhibitor MOA
Binds to antithrombin & selectively inhibits factor Xa using specific pentasaccharide sequence. Inhibits growth of formed thrombus and allows natural fibrinolytic system to degrade clot
Direct factor Xa inhibitor MOA
Ribaroxaban selectively inhibits the active site of factor Xa, inhibits growth of formed thrombus & allows natural fibrinolytic system to degrade clot
Indirect factor Xa inhibitor
fondaparinux (Arixtra)
Direct factor Xa inhibitor
rivaroxaban (Xarelto)
fondaparinux & rivaroxaban uses
VTE prevention after ortho surgery & treatment of DVT/PE
What type of factor Xa inhibitors are indicated for afib?
direct
Which 2 factor Xa inhibitors are cautioned in pts w/ renal insufficiency?
fondaparinux (Arixtra) & rivaroxaban (Xarelto)
Which 2 factor Xa inhibitors are strong CYP 3A4 inhibitors/inducers?
rivaroxaban (Xarelto)
apixiban (Eliquis)
*don’t use rivaroxaban in severe hepatic failure
What is unique about fondaparinux (Arixtra) administration compared to other factor Xa inhibitors?
It is administered SQ, whereas the others are all PO
Direct thrombin inhibitor MOA
Binds directly and inhibits clotting factor IIa - does NOT require antithrombin. Can also inhibit clot-bound factor IIa
What is the only direct thrombin inhibitor used for management of HIT?
argatroban
What is bivalrudin commonly used for?
ACS w/ or w/o HIT
What is dabigatran NOT used for and what are its only indications?
Not used for ACS
Only indicated for VTE treatment & afib
Which direct thrombin inhibitor is monitored by aPTT?
argatroban
Monitor 2 hrs after start & 2 hrs after dose change
Goal: 1.5-2.5x control
Which 2 direct thrombin inhibitors require renal function monitoring?
bivalirudin & dabigatran
Which direct thrombin inhibitor requires hepatic enzyme monitoring?
argatroban
Thrombolytic therapy MOA
Promotes conversion of plasminogen to plasmin resulting in thrombus breakdown
Door-to-needle time must be _____ for thrombolytic therapy.
<30 mins
Thrombolytics are indicated for a patient with:
ST segment elevation (>0.1 mV in 2 or more leads) presenting w/i 12 hr of symptom onset (ideal <3hr) & <75yo
PE leading to hemodynamic instability
DVT causing gangrene despite anticoagulation therapy