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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
Created by: ahmad445



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