Term | Definition |
Low-molecular-weight heparin : | # Enoxaparin, Daltaparin & Tinzaparin
# isolated from UFH |
Mechanism of action of LMWHs: | #greater ability than UFH to inactivate factor Xa
# lesser incidence to cause bleeding
# lesser incidence to cause thrombocytopenia |
Advantages of LMWHs: | 1- LMWH have low affinity for plasma proteins
90% bioavailability > 30% bioavailability
higher SC bioavailability
2-LMWH effect is more predictable than UFH
3-have longer duration of action
4-lab. monitoring unnecessary
5-a lower incidenc |
Therapeutic uses of LMWH: | - Prevention of DVT following surgery
- Prevention of ischemic complications
- Treatment of established DVT |
Side effects of LMWH: | # Bleeding < than UFH
# Immune-mediated thrombocytopenia < than UFH
# Cost > UFH |
Fondaparinux: | - (SC) route
- pentasaccharide structure of fondaparinux
- selective inhibition of Xa as LMWH |
Pharmacokinetics: as LMWH
Fondaparinux | - Fondaparinux has a predictable PH. profile
- Fondaparinux requires less monitoring than heparin
-Fondaparinux is eliminated in urine mainly as unchanged → contraindicated in patients with severe renal impairment |
Therapeutic uses of fondaparinux : | - Prevention of DVT
- Treatment of acute DVT & acute PE (with Warfarin)
- “As alternative” for the treatment of ACS
SE--Bleeding |
Direct Thrombin Inhibitors (DTIs): | Parenteral: as Lepirudin, Bivalirudin
Oral : as Argatroban, Dabigatran
all bind to & block thrombin(IIa) directly at its “active site" |
univalent” thrombin inhibitors: | as argatroban & dabigatran &bivalirudin
only bind at the “active site”→ bind thrombin reversibly |
bivalent” thrombin inhibitors | bind at 2 binding sites “active site & exosite 1
bind thrombin irreversibly
//DTIs effect on soluble thrombin (IIa) & fibrin-bound thrombin |
Lepirudin: | -independent of AT III & no effects on factor Xa
-directly& irreversibly inactivates IIa
-Administered IV & cleared by the kidneys
-Argatoban alternative in renal dysfunction
-aPTT monitoring -anticoagulants in HIT
-bleeding → no antidote is avail |
Bivalirudin | -administered IV & has rapid onset&offset
-alternative to heparin in HIT in coronary angioplasty or cardiopulmonary bypass surgery |
Dabigatran : | -1st oral anticoagulant
-does not require routine monitoring
- few drug-drug interactions compared to warfarin
- prevention of thromboembolism in patients with AF |
Oral anticoagulants: Warfarine | -Active in vivo only
-Vitamin K antagonists
- |
Clotting factors → II, VII, IX , X & protein C &S | are dependent upon vitamin K for their synthesis
in the liver |
vitamin K to a newborn | why newborns get a Vit K shot → to avoid ”hemorrhagic disease of the newborn” |
Oral anticoagulants: Warfarine | -Active in vivo only
-Vitamin K antagonists
- |
Clotting factors → II, VII, IX , X & protein C &S | are dependent upon vitamin K for their synthesis
in the liver |
vitamin K to a newborn | why newborns get a Vit K shot → to avoid ”hemorrhagic disease of the newborn” |
Mechanism of action of warfarin: | Warfarin is structurally similar to vitamin K & competitively inhibit epoxide reductase
-inhibits the synthesis but not the actions of these 4 clotting factors |
Onset of action of warfarin: | -There is a delay in the onset & duration of anti-coagulant effect
-Usually 48-72 hours to achieve its full effects
- the onset of action of warfarin depends on the limination half-lives of the already formed
- |
Pharmacokinetics of Warfarin: | -Absorption: completely absorbed by the GIT
-Food interferes with the absorption of Warfarin
- Distribution: highly protein bound (98-99%)
- Metabolism & excretion: cytochrome P450 enzymes of the liver |
Therapeutic uses of Warfarin: | - Prophylaxis:in atrial fibrillation (AF), post-prosthetic heart valve replacement , previous DVT , repeated PE
-Treatment of established DVT , PE
-used for long-term anticoagulation |
Side effects of Warfarin : | 1- Bleeding (especially in GIT) is the most common side effect
2- Cutaneous reactions: Warfarin-induced purple toe syndrome & skin necrosis
3-Fetal hemorrhage & teratogenenic . |
Target INR when use Warfarin in: | Prophylaxis of DVT )INR 2-2.5)
Treatment of DVT&PE, AF , mural thrombus following MI ( INR 2.5)
Recurrent DVT & PE, mechanical prosthetic heart valve (INR 3.5) |
Warfarin antidote: | -1st step to stop Warfarin administration
- Reversal of Warfarin effects by:
→ Vitamin K1 (phytonadione) oral, IV → several hours to act
→ emergency or urgent cases → to replace the deficient clotting factors→blood replacement ,PCC ,FFP |
large number of pharmacokinetic & pharmacodynamic drug-drug interactions with warfarin activity | |