Review of Pharmacology - 9E (2015)

Review of Pharmacology
Management of HIT
Pulmonary emboilism (PE) in
treated by anticoagulants. Indicatiions
of thrombolytics in PE
are:
• Massive PE i.e with hemodynamic
instability
• PE without hemodynamic
instability but right ventricular
compromise
Direct thrombin inhibitors
(Lepirudin and Argatroban)
are anticoagulants of
choice for heparin induced
thrombocytopenia.
• Stop all forms of heparins and LMW Heparins.
• Do not give platelet transfusions.
• Direct thrombin inhibitors (Lepirudin and Argatroban) are anticoagulants of choice.
• Lepirudin is safe in liver failure whereas argatroban can be safely administered in
anuria (renal failure).
• Initially, warfarin causes hypercoagulability, therefore should be avoided.
• Lepirudin is continued till platelet count reaches 1,00,000/µL.
• Now, warfarin should be started and direct thrombin inhibitors discontinued.
Warfarin should be given for at least 30 days.
• Fondaparinux can also be used for HIT.
Heparin
1. Route of administration Parenteral (i.v, s.c.) Oral
Oral Anticoagulants
2. Onset of action Rapid Delayed (1-3 days)
3. Activity In vitro and in vivo In vivo only
4. MOA Activates Antithrombin III ↓ Activation of II, VII, IX, X
5. Monitoring by aPTT PT
6. Antagonist Protamine sulphate Vit. K 1
(Phytonadione)
7. Placental barrier Does not cross placenta Fetal warfarin syndrome
8. Use To initiate therapy For maintenance
3. Direct Thrombin Inhibitors
Hematology
N
Rivaroxaban and Apixaban are
new oral anticoagulants that act
by direct inhibition of factor Xa
This group includes hirudin, lepirudin, bivalirudin, argatroban, dabigatran, melagatran
and ximelagatran. Dabigatran and Ximelagatran (a prodrug of melagatran) can be given orally.
All other drugs are used parenterally. These drugs directly inactivate factor IIa (thrombin).
These are the anticoagulant of choice for heparin induced thrombocytopenia. Bleeding is
the major adverse effect of this group of drugs also. All of these drugs (except agratroban) are
excreted by kidney, therefore, should be avoided in renal failure. Argatroban is secreted in bile
and thus is safe in renal failure. Lepirudin can be used in liver disease.
Note:
• All can prolong aPTT whereas argatroban can prolong INR also.
• Bivalirudin has shortest t 1/2
(25 min)
446
Rivarsible
Oral
Xa
Blocker
Rivaroxaban
4. Target Specific Oral Anticoagulants
Target specific (or direct) oral anticoagulants include dabigatran, rivaroxaban, edoxaban and
apixaban. Dabigatran is a direct thrombin inhibitor. Rivaroxaban, edoxaban and apixaban
are new oral anticoagulants that act by inhibiting factor Xa. These are preferred over
warfarin in atrial fibrillation by European guidelines.
Warfarin is preferred in patients with:
– Mechanical prosthetic valves
– Advanced kidney disease [CrCL < 30 mL/min]
– Moderate or severe mitral stenosis
– Cannot afford new drugs
5. Other Anticoagulants
• Danaparoid (mixture of 84% heparan sulfate, 12% dermatan sulfate and 4%
chondrioitin sulfate) is approved for prophylaxis of DVT. It is also effective for HIT
syndrome. It mainly promotes inhibition of factor Xa by antithrombin.
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