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Drugs for Coagulation disorders

Drugs for Coagulation disorders. There are a number of different categories of drugs which modify the coagulation process: I. Anticoagulants II. Antiplatelet agents III. Thrombolytics . I. Anticoagulants A. The coagulation cascade.

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Drugs for Coagulation disorders

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  1. Drugs for Coagulation disorders

  2. There are a number of different categories of drugs which modify the coagulation process: • I. Anticoagulants • II. Antiplatelet agents • III. Thrombolytics

  3. I. AnticoagulantsA. The coagulation cascade • The coagulation cascade begins when injured cells release thromboplastin.

  4. Thromboplastin converts the clotting factor prothrombin to thrombin.

  5. Thrombin then converts the plasma protein fibrinogen to long strands of fibrin and activates several clotting factors (V, VIII, XIII, and protein C)

  6. The fibrin strands form an insoluble web

  7. B. Types of anticoagulants • The mechanism of action of anticoagulant medications involves either the inactivation of various existing coagulation factors, or

  8. preventing the synthesis of coagulation factors (the vitamin K antagonists)

  9. Anticoagulant medications do NOT dissolve clots.

  10. 1. heparins • a. standard heparin • b. low molecular weight (LMW) heparins

  11. Heparins are indicated for the treatment of: • deep vein thrombosis (DVT) • prophylaxis and treatment of venous thrombi, alone • prophylaxis and treatment of venous thrombi in conjunction with pulmonary emboli

  12. Heparins are NOT direct thrombin inhibitors.

  13. Instead, heparins prevent thrombin formation by binding to clotting factors in the circulation.

  14. These clotting factors then bind to and inactivate thrombin, the major enzyme in the clotting pathway.

  15. The main commercial sources of standard heparin are the lungs and intestines of cattle (bovine) and pigs (porcine).

  16. LMW heparins are derived from porcine heparin.

  17. They are smaller in size as they only contain the anticoagulant fraction of heparin, and not the additional saccharide chains that standard heparin has.

  18. a. Standard heparin • Standard heparin has an immediate onset of action if administered IV, it peaks within 5-10 minutes, and its duration is 2-6 hours.

  19. Standard heparin has an onset of action of 20 minute – 1 hour if administeredSC, it peaks within 2 hours, and its duration is 8-12 hours.

  20. Standard heparin IV administration: bolus of 10,000 – 12,000 units followed by 5,000-10,000 units every 4-6 hours

  21. Standard heparin SC administration: bolus of 10,000 – 12,000 units followed by 15,000-20,000 units every 12 hours

  22. b. Low molecular weight (LMW) heparins • LMW heparins are ONLY administered SC, have a rapid onset of action, generally peak within 3-6 hours, and have a duration of 12-24 hours depending on the agent. Specific LMW heparins include:

  23. i. dalteparin (Fragmin): • Indicated for prophylaxis of Deep Vein Thrombosis (DVT) in patients undergoing abdominal surgery or hip replacement surgery.

  24. ii. enoxaprin (Lovenox): • Indicated for prophylaxis of DVT in patients undergoing abdominal, hip, or knee surgery.

  25. iii. fondaparinux (Arixtra): • Indicated for both the treatment of and prophylaxis of DVT and pulmonary embolism (PE).

  26. iv. tinzaparin (Innohep): • Indicated for both the treatment of and prophylaxis of DVT.

  27. LMW heparins have certain advantages over standard heparin: • 90% bioavailability (standard heparin has 30%)

  28. LMW heparin can be dosed based on body size without coagulation test monitoring (if patient has normal kidney function)

  29. Adverse effects of heparins: • hemorrhage • anemia in elderly with Lovenox, due to decreased clearance • fever • hair loss • thrombocytopenia (↓ in no. of platelets)

  30. Black box warning for LMW heparin use in patients concurrently receiving epidural or spinal anesthesia as it increases the risk for epidural or spinal hematomas

  31. 2. thrombin inhibitors • Unlike the heparins, these drugs bind directly to thrombin. They are all administered IV.

  32. a. argatroban (Argatroban) • indicated for patients with, or at risk for thrombocytopenia who are undergoing percutaneous coronary intervention (PCI).

  33. b. bivalirudin (Angiomax): used, along with aspirin, in patients with unstable angina who undergo PCI. This treatment is intended to reduce the risk of acute ischemic complications

  34. c. lepirudin (Refludan): derives from the natural product hirudin, found in leech saliva.

  35. Leeches have been used for bloodletting since the times of the ancient Greeks.

  36. 3. anticoagulants which prevent the synthesis of coagulation factors • This category of anticoagulant is significantly different from the heparins in that it can be administered orally.

  37. This type of anticoagulant has a longer onset because of the time required to clear the normal clotting factors from the circulation before an effect can be observed.

  38. The only drug in this class is warfarin sodium (Coumadin): 2-10 mg

  39. Its onset of activity is about 12-72 hours.

  40. However, its duration of action is longer (2 to 10 days) even after drug administration has been discontinued.

  41. Coumadin is indicated for the treatment of DVT and prevention of myocardial re-infarction

  42. Adverse effects include: • GI disturbances • hypotension • hair loss • headache • hemorrhage (most serious)

  43. A black box warning indicates that there is an ↑ risk of hemorrhage in: • patients over 65 • patients with a history of GI bleeding • INR > 4

  44. INR (international normalized ratio) is a test used to monitor coagulation status.

  45. People not on anticoagulants have an INR of 1 • An INR of 2 – 3 is needed for a therapeutic effect with warfarin

  46. II. Antiplatelet agents • Antiplatelet agents exert an anticoagulant effect by interfering with various aspects of platelet function.

  47. Antiplatelet agents are indicated for the treatment of : • thrombocytopenia • acute coronary syndrome • prevention of myocardial re-infarction • and reducing coronary events

  48. The 2 subclasses of antiplatelet agents are: • A. nonselective COX inhibitors • B. adenosine diphosphate (ADP) receptor blockers

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