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Home » , » Direct thrombin inhibitors
Direct thrombin inhibitors
Wednesday, April 6, 2011 Posted by Piscean


Direct thrombin inhibitors
Thrombin inhibitors, including argatroban, bivalirudin, and lepirudin, help prevent the formation of blood clots.
Pharmacokinetics
Direct thrombin inhibitors are typically administered by continuous I.V. infusion. They may also be given as an intra-coronary bolus during cardiac catheterization. In that case, the drug begins acting in 2 minutes, with a peak response of 15 minutes and a duration of 2 hours. After subQ injection, plasma levels peak in 2 hours; after I.V. administration, levels peak in less than 1 hour.
Effects on PTT become apparent within 4 to 5 hours of administration. In patients with heparin-induced thrombocytopenia, platelet count recovery becomes apparent within 3 days.
Argatroban is metabolized by the liver and excreted primarily in stool. Bivalirudin and lepirudin are metabolized by the liver and kidneys and excreted in urine
Pharmacodynamics
Direct thrombin inhibitors interfere with blood clotting by directly blocking all thrombin activity. These drugs offer several advantages over heparin: direct thrombin inhibitors act against soluble as well as clot-bound thrombin (thrombin in clots that have already formed); their anticoagulant effects are more predictable than those of heparin; and their actions aren’t inhibited by the platelet release reaction.The binding of the drug to thrombin is reversible.
Pharmacotherapeutics
Administered by I.V. infusion, argatroban and lepirudin are used to treat heparin-induced thrombocytopenia (HIT). Argatroban may also be given with aspirin to patients with HIT who are undergoing a cardiac procedure, such as PTCA, coronary stent placement, or atherectomy.

Bivalirudin has been approved for use in patients with unstable angina undergoing PTCA, and should be used in conjunction with aspirin therapy.
Patients with liver dysfunction may require a reduced dose of argatroban. Also, the dosage of bivalirudin and lepirudin may need to be reduced in patients with impaired renal function.
Use caution when administering a direct thrombin inhibitor to a patient who has an increased risk of bleeding. Patients at greatest risk for hemorrhage are those with severe hypertension, gastric ulcers, or hematologic disorders associated with increased bleeding. Patients receiving spinal anesthesia or those undergoing a lumbar puncture or having major surgery (especially surgery of the brain, spinal cord, or the eye) also have an increased risk for bleeding.
Drug interactions
  • Hemorrhage can occur as an adverse reaction to direct thrombin inhibitors, so avoid giving these drugs with another drug that may also increase the risk of bleeding.
  • Discontinue all parenteral anticoagulants before administering argatroban.
  • Administration of argatroban along with warfarin increases the INR.
  • If the patient has received heparin, allow time for heparin’s effect on PTT to decrease before administering argatroban.

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