Medical Pharmacology Topics
| Preliminary Outline |
Anticoagulants Direct Acting Heparin Lepirudin (hirudin) LMW Heparins Enoxaparine Dalteparin Ardeparin Heparinoids Danaparoid Indirect Acting Vit K InhibitorsWarfarinDicoumarolAnisindione |
Anticoagulants are used to prevent cloting during surgery. The can be direct acting, like heparin, low molecular weight (LMW) heparins and heparinoids, or indirect acting, like warfarin.
Heparin is a large polysacharide tha activates antithrombin III. Thrombin and Factor Xa of the cloting cascade are inactivated by antithrombin III (irreversible binding), preventing the formation of clots. Heparin is normally found in mast cells, although its fisiological function is unknown. Therapeutic heparin is obtained from swine or xattle and standarized to USP units. A USP unit is the amount of heparin that prevents 1 ml of citrated sheep plasma from cloting one hour after adding 0.2 ml of 1% CaCl2. The half-life of heparin is concentration dependent. The main side effect is bleeding.
The LMW heparins include enoxaparine, dalteparin, and ardeparin. They are depolymerided heparin derivatives: while the molecular weight of heparin is 12K-15K, LMW heparins are 4K-6K. They have limited FDA approval for use during abdominal, knee and hip replacement surgeries. LMW heparins are more effective than heparin, have a greater bioavailability after subcutaneous injection, and a longer half-life, a lower incidence of thrombocytopenia and generally do not require monitoring. They have a similar incidence of bleeding than heparin. Protamine is the antidote for both heparin and LMW heparins.
Danaparoid, a heparinoid, is a partially depolymerized mixture of heparan sulfate, dermatan sulfate and chondroitin sulfate obtained from porcine intestinal mucosa. Heparinoids are more effective than heparine and LMW heparins, have a longer half-life, and do not require monitoring.
Lepirudin is a recombinant derivative of hirudim, a thrombin inhibitor from the saliva of leeches. It is apprved for use in treating heparin-induced thrombocytopenia. It has a long half-time (1.3 hrs) and antibodies may develop. There is no known antidote.
Indirect-acting anticoagulants like warfarin, dicoumarol and anisindione are competitive inhibitors of vitamin K regeneration. They are effective orally but have a delayed affect. Side effects include bleeding, teratogenicity, and interactions with a variety of drugs and other agents. Vitamin K is the antidote for indirect-acting anticoagulants.
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