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Home » , » Anticoagulant drugs
Anticoagulant drugs
Tuesday, April 5, 2011 Posted by Piscean

Anticoagulant drugs
Anticoagulant drugs are used to reduce the ability of the blood to clot. Major categories of anticoagulants include:
  • heparin and its derivatives
  • oral anticoagulants
  • antiplatelet drugs
  • direct thrombin inhibitors
  • factor Xa inhibitor drugs.
Heparin
Heparin, prepared commercially from animal tissue, is an anti-thrombolytic agent used to treat and prevent clot formation. Because it doesn’t affect the synthesis of clotting factors, heparin can’t dissolve already-formed clots.

Weighty words
The two types of heparin are unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH). LMWHs, such as dalteparin, enoxaparin, and tinzaparin, were developed to prevent deep vein thrombosis (DVT) (a blood clot in the deep veins, usually of the legs) in surgical patients.
 
Pharmacokinetics
Because heparin isn’t absorbed well from the GI tract, it must be administered parenterally. UFH is administered I.V. by continuous infusion or by subQ injection. LMWHs, because of their prolonged circulating half-life, can be administered once or twice daily by subQ injection.
After I.V. administration, the distribution of heparin is immediate; however, distribution isn’t as predictable following subQ injection.
I.M. is out
Heparin isn’t given I.M. because of the risk of localized bleeding. Heparin is metabolized in the liver, and its metabolites are excreted in urine.
 
Pharmacodynamics
Heparin prevents the formation of new thrombi. Here’s how it works:
  • Heparin inhibits the formation of thrombin and fibrin by activating antithrombin III.
  • Antithrombin III then inactivates factors IXa, Xa, XIa, and XIIa in the intrinsic and common pathways. The end result is prevention of a stable fibrin clot.
  • In low doses, heparin increases the activity of antithrombin III against factor Xa and thrombin and inhibits clot formation.
  • Much larger doses are necessary to inhibit fibrin formation after a clot has been formed. This relationship between dose and effect is the rationale for using low-dose heparin to prevent clotting.
  • Whole blood clotting time, thrombin time, and partial thromboplastin time (PTT) are prolonged during heparin therapy. However, these times may be only slightly prolonged with low or ultra-low preventive doses.

Pharmacotherapeutics
Heparin may be used in a number of clinical situations to prevent the formation of new clots or the extension of existing clots. These situations include:
  • preventing or treating venous thromboemboli, characterized by inappropriate or excessive intravascular activation of blood clotting

  • treating disseminated intravascular coagulation, a complication of other diseases, resulting in accelerated clotting
  • treating arterial clotting and preventing embolus formation in patients with atrial fibrillation, an arrhythmia in which ineffective atrial contractions cause blood to pool in the atria, increasing the risk of clot formation
  • preventing thrombus formation and promoting cardiac circulation in an acute myocardial infarction (MI) by preventing further clot formation at the site of the already formed clot.
Safe and sound
Monitoring PTT in heparin therapy
A patient receiving unfractionated heparin (UFH) therapy requires close monitoring of his partial thromboplastin time (PTT). Dosage adjustments, based on the test results, are typically necessary to ensure therapeutic effectiveness without increased risk of bleeding.
Low-molecular-weight heparin (LMWH) therapy doesn’t require PTT monitoring. Currently, no laboratory test exists to assess the effectiveness of LMWH therapy.
Heparin-induced thrombocytopenia
 
Platelet counts should be monitored in all patients receiving heparin therapy. A patient who develops heparin-induced thrombocytopenia (HIT) should be switched from anticoagulant therapy to argatroban, bivalirudin, or lepirudin. These drugs are direct thrombin inhibitors indicated for use in the patient who needs anticoagulation therapy but has HIT.
Circulate freely
 
Heparin can be used to prevent clotting whenever the patient’s blood must circulate outside the body through a machine, such as the cardiopulmonary bypass machine or hemodialysis machine, and during blood transfusions. 
You’re the one
Heparin is also useful for preventing clotting during intra-abdominal or orthopedic surgery. (These types of surgeries, in many cases, activate the coagulation mechanisms excessively.) In fact, heparin is the drug of choice for orthopedic surgery.


Warning!
Adverse reactions to heparin
One advantage of heparin is that it produces relatively few adverse reactions. Even so, these reactions can usually be prevented if the patient’s partial thromboplastin time is maintained within the therapeutic range
.
Bleeding, the most common adverse reaction, can be reversed easily by administering protamine sulfate, which binds to heparin to form a stable salt.
Other adverse reactions include bruising, hematoma formation, necrosis of skin or other tissue, and thrombocytopenia.
 

Drug interactions
  • Because heparin acts synergistically with all oral anticoagulants, the risk of bleeding increases when the patient takes both drugs together. The prothrombin time and International Normalized Ratio (INR), used to monitor the effects of oral anticoagulants, may also be prolonged.
  • The risk of bleeding increases when the patient takes nonsteroidal anti-inflammatory drugs (NSAIDs), iron dextran, cilostazol, or an antiplatelet drug, such as aspirin, clopidogrel, ticlopidine, or dipyridamole, while receiving heparin.
Another reason to quit
  • Drugs that antagonize or inactivate heparin include antihistamines, cephalosporins, digoxin, neomycin, nicotine, nitroglycerin, penicillins, phenothiazines, quinidine, and tetracycline.
  • Nicotine may inactivate heparin; nitroglycerin may inhibit the effects of heparin.
  • Administration of protamine sulfate and fresh frozen plasma counteract the effects of heparin. 

Piscean

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