Anticoagulants Flashcards
aspirin
indications: Primary and secondary prevention of arterial thrombosis
Inferior to anticoagulants for stroke prevention in atrial
fibrillation, mechanical heart valves
Reduces disorders associated with placental insufficiency
(e.g., preeclampsia)
Efficacious for prevention of venous thromboembolism in
limited situations (e.g., hip fracture surgery)
Rapid absorption, peak platelet effect at 1 hour (3-4 hours
for enteric coated)
Oral bioavailability 40-50%
Half-life is 15-20 minutes BUT effect on platelets is
irreversible
Lasts for entire 7-10 day lifespan of platelets
10-15% of circulating platelets are replaced every 24 hours
Must discontinue the drug 10 days in advance of invasive
procedures for complete restoration of normal platelet function
No effect on platelet adhesion
40 - 160 mg sufficient to inhibit function of most platelets
ADRs:
Major side effects are gastrointestinal and are dose-related
GI upset, ulcer, bleed
Not associated with major bleeding in patients with normal
baseline hemostasis
Bleeding is increased with concurrent use of
anticoagulants, some supplements
Exacerbates bleeding tendency in patient with bleeding
disorders
Elderly are more susceptible
heparin (UF)
mechanism: Accelerates inhibition coagulation factors by antithrombin
indication: Primary prevention of venous and arterial thrombosis
PK/PD
Bioavailability by route of administration
Intravenous: 100% bioavailable; anticoagulant effect is immediate
♪ Much individual variation in bioavailability
♪ Binds widely to plasma proteins
♥ Ineffectiveness of fixed dose
♥ Heparin resistance
Subcutaneous
♪ Poor bioavailability
♪ Acceptable anticoagulant effect 1-3 hours after injection
♪ Must use higher doses than IV
♪ Less frequent dosing
Oral: NO; Zero bioavailability
Intramuscular: NO; Risk for hematoma
Does not cross the placenta and is anticoagulant of choice
in pregnancy
heparin clearance Two phases Initial - rapid ♪ Binds to receptors on endothelial cells and macrophages where it is internalized and metabolized to smaller forms ♪ Binds to plasma proteins Second - slow ♪ Renal Half life is dose-dependent
dosing “Mini” dose Subcutaneous Generally used for thromboprophylaxis 5000 units, two to three times per day No lab monitoring
Therapeutic, adjusted “full” dose
Intravenous
♪ Bolus dose followed by
♪ Continuous infusion; dose adjusted according to effect on
aPTT (goal 80 – 114 sec)
Generally used for treatment of acute thrombosis
Dose adjustments made after 4 to 6 hours at steady state
ADRs: bleeding, osteoporosis, skin lesions, hypoaldosteronism, heparin induced thrombocytopenia
warfarin
mechanism: Warfarin is a vitamin K antagonist. Vitamin K is required as a cofactor in the pathway that effects
gamma carboxylation on coagulation factors II, VII, IX and X. Gamma carboxylation is required for coagulation factor
binding to phospholipid surfaces
indications: primary/secondary prevention of VTE or arterial thrombosis (Stroke prevention in atrial fibrillation, mechanical heart valves
Failure of antiplatelet therapy
In addition to antiplatelet therapy in high risk patients)
Oral dose is rapidly and extensively absorbed from the GI tract
Peak levels reached in 90 minutes after ingestion
Food slows absorption, but does not alter bioavailability
Extensively protein-bound in plasma, especially to albumin
Crosses the placenta; active form does not enter breast milk
Metabolized in liver by cytochrome P450 enzyme pathways
Metabolites excreted in urine
2% of warfarin excreted unchanged in urine
Warfarin clearance declines with age
Clearance of active drug not affected by renal dysfunction, but clearance
is increased in patients on dialysis
Genetic polymorphisms affect warfarin metabolism and dosing
Half-life is approximately 33 hours
Steady state anticoagulation is reached in 7-10 days
Slow onset of action usually demands that warfarin be
started concurrently with a fast-acting anticoagulant (e.g.,
heparin, LMWH)
Important to overlap heparin and warfarin by two days
once therapeutic INR achieved
ADRs: bleeding, skin necrosis, teratogenic during early fetal development
dabigatran
mechanism: inhibit thrombin
prodrug- converted by liver
indication: a fib, acute VTE w/ LMWH
time to max effect: 2 hrs half life- 12-14 hours elimination: 80% renal dosing: bid antidote: yes dialyzable: yes
rivaroxaban
mechanism: inhibit Xa
indication: a fib, prophylaxis ortho surg, VTE tx
time to max effect: 2-4 hrs half life- 7-13 hours elimination: 33% renal, CYP3a4 dosing: qd, bid antidote: in progress dialyzable: no
apixaban
mechanism: inhibit Xa
indication: a fib, prophylaxis ortho surg, VTE tx
time to max effect: 3 hrs half life- 8-13 hours elimination: 27% renal, CYP dosing: bid antidote: in progress dialyzable: yes
