nincs diacím.ppt

Heparinoids Danaparoid mixture of heparan sulfate (84%), dermatan sulfate (12%) and chondroitin sulfates inactivates mainly factor Xa (by accelerating antithrombin III) only parenteral use, s.c. - 100% bioavailability, half-life 25h used in case of HIT type II major toxicity is bleeding; can not be antagonized by protamine Direct thrombin inhibitors Hirudin derived from medicinal leeches (Hirudo medicinalis) recombinat analogue: desirudin binds directly to thrombin and irreversibly inactivates it parenteral use only (s.c. - 100% bioavailability) eliminated by the kidneys, half-life 1-1,5h (renal insuff. ? much longer) indication: anticoagulant action in case of HIT type II. monitoring its action: aPTT (it should be 1,5-3x higher than the control) adverse effects: bleeding no antidote Direct thrombin or Xa inhibitors Bivalirudin synthetic hirudin-like compound (direct thrombin inhibitor) more rapid onset and shorter duration of action than that of hirudin only i.v. use - percutaneous coronary angioplasty elimination is mostly independent from kidney Argatroban synthetic thrombin inhibitor short half-life, elimination is independent from kidney, influenced by liver diseases used i.v. in case of HIT type II. Orally acting factor inhibitors Dabigatran etexilate orally active prodrug of a direct thrombin inhibitor, given 1x daily Rivaroxaban, apixaban, edoxaban orally active direct Xa inhibitor, given 2x daily Anticoagulants inhibiting clotting factor synthesis: cumarins Anticoagulants inhibiting clotting factor synthesis: cumarins History at the end of the XIXth century - sweet clover was planted in North-USA and Canada 1924 - reports on the hemorrhagic disorders of cattles resulted from the ingestion of spoiled sweet clover silage 1939 - haemorrhagic agent was identified: dicoumarol use of cumarins as rodenticides 1948 - warfarin (name: Wisconsin Alumni Research Foundation was the patent holder + cumarin) was introduced as a rode