Anticoagulants Flashcards
Anticoagulants
In general, they are used to prevent venousthrombosis.
Vitamin K Epoxide Reductase Inhibitor
Warfarin
MOA: inhibits vit. K reductase, this interferes with hepatic synthesis of vitamin K-dependent coagulation factors (II, VII, IX, X), with the end result of inhibiting the conversion of prothrombin to thrombin.
Adverse effect: bleeding (narrow therapeutic index, highly bound to proteins but with a relatively low affinity leading to a lot of drug interactions that potentiates the effect of warfarin).
Indirect Thrombin Inhibitors - Heparin
Heparin: (unfractionated MW 5K-40K Daltons)
MOA: Indirect thrombin inhibition, heparin binds to antithrombin III and this inhibits thrombin, thus no fibrin forms.
Heparin is the anticoagulant of choice during pregnancy.
Labs: aPTT, platelet count (For UFH)
Side effects: bleeding, and Heparin-induced thrombocytopenia (HIT): has 2 types:
Type1 HIT: non-immune, transient low platelet count 2 days after starting heparin
Type2 HIT (HITT): immune-mediated, occurs 4-10 days after starting heparin. Presents with low platelets together with venous thromboembolism (DVT& PE)
Direct Thrombin Inhibitors (Oral)
Dabigatran (Pradaxa®): the first approved oral anticoagulant in over 50 years which works by directly inhibiting thrombin.
Indication: stroke prevention in patients with non-valvular AF, DVT/PE.
Compared to Warfarin: Dabigatran has much faster onset (on day one), more predictable response, limited drug interactions, wider therapeutic window, no dosage adjustment, no lab monitoring, no CYP implications.
Adverse effects: bleeding.
*The newly introduce antidote for Dabigatran, Idarucizumab rapidly reverses the effects of dabigatran in bleeding patients.
Direct Factor Xa Inhibitors (Oral)
Rivaroxaban (Xarelto®), Apixaban (Eliquis®), Betrixaban (Bevyxxa®), Endoxaban (Lixiana®): All are orally active direct factor Xa inhibitors, which work on day one, NO monitoring required.
Indications: stroke prevention in non-valvular AF, DVT/PE
Adverse effects: internal bleeding.
The FDA recently (May 2018) approved Andexanet alfa (AndexXa®) as the first and only antidote for the oral direct factor Xa inhibitors when reversal of anticoagulation is needed.
Indirect Thrombin Inhibitors - LMWH
LMWH: (fractionated, MW less than 8K Daltons). Longer half-life than heparin.
1) Enoxaparin (Lovenox®)
MOA: Indirect inhibition of factor Xa. When LMWH binds to antithrombin III this accelerates the inactivation of factor Xa
Advantage over heparin: does not need to be routinely monitored by aPTT, and can be given at home (BID)
Side effects: bleeding, thrombocytopenia
2) Fondaparinux (Arixtra®)
Advantage over heparin: It does NOT cause HIT, therefore it is the best alternative of heparin in patients with HIT Used for same indications namely PE/DVT.
Side effects: bleeding
Warfarin VS DOAC
Warfarin: Takes days to initiate effect, unpredictable efficacy, requires INR monitoring, a lot of interactions, more incidence of bleeding side effects.
The only advantage over DOAC:
Metal heart valves
Stroke prophylaxis in valvular AF (mitral stenosis)
Myeloproliferative disorders (Polycythemia Vera (PV)).
DOAC: Include the oral direct thrombin inhibitor: Dabigatran, and the oral direct factor Xa inhibitors: Rivaroxaban, Apixaban, …etc.
Major advantages over warfarin: work on day one, no monitoring required, less bleeding side effects, less drug interactions.
Replaced warfarin in:
DVT/PE
Stroke prophylaxis in nonvalvular AF
Warfarin vs Heparin
Warfarin: Oral, Liver, Slow (days), Impairs synthesis of vitamin K-dependent clotting factors (II, VII, X, and X) as well as anticlotting proteins C and S, Reversal: vit K & FFP, PT/INR (extrinsic pathway), teratogenic.
Heparin: IV/SC, Blood, Rapid (seconds), Activates antithrombin III, which inhibits the actions of factor IIa (thrombin) and factor Xa, reversal: protamine sulfate, PTT (intrinsic pathway), doesnt cross placenta (can use heparin in 1st trimester).
