Week 5 Pharmacology

Review of haemostatic and fibrinolytic systems.

Heparin (unfractionated).

  • Bind to antithrombin –> conformational change –> expose active site –>  enhance its inactivation of IXa, Xa and thrombin 1000 fold
  • Needs APTT monitoring of levels in therapeutic levels.
  • Surgeons prefer due to reversibility
  • Toxicity – bleeding, allergy, alopecia, osteoporosis
  • Heparin induced thrombocytopenia
  • Systemic hypercoagulable state
  • 1-4% of people treated for a minimum of 7d. Esp surgical patients.
  • Usually venous thrombosis, sometimes arterial occlusions.
  • Platelet count should be performed regularly when giving heparin
  • Rx – stop heparin give direct thrombin inhibitor (hirudin, agatroban)


LMW Heparin.

  • Bind to antithrombin and enhance its inactivation of Xa and also to a lesser extent inactivation of thrombin
  • Equal efficacy to heparin, better bioavail from S/C injection, less freq dosing required, less risk of HIT
  • Measured with anti Xa levels



  • Reverses heparin (heparin antagonist)
  • 100mg per 10000units heparin


Oral direct thrombin inhibitors

  • Dabigatran
  • Rivaroxiban (Xa inhibitor)
  • Used for prev of venous thromboembolism and non vavlular AF
  • No monitoring
  • No reversal agent



  • PD – Vitamin K inhibitor,  inhibit Protein C and S first then partially inhibit synthesis of factor II, VII, IX, X(with normal degradation so coag levels fall).
  • PK – 100% bioavailability, 99% albumin bound, Small Vd, T1/2 36hrs
  • Toxicity – can cross placenta and cause fetal haemorrhage, birth defects. Initial procoagulant then anticoagulant –> bleeding
  • Lot of diet and drug interactions. Narrow therapeutic window therefore needs lots of INR monitoring.
  • Reversed with Vit K
Increase INR Decrease INR









Hepatic disease


Barbiturates&  rifampicin(induce enzymes in liver to increase bd of warfarin),

Cholestyramine(reduce absorption),

Diuretics(increase cloting factor concentration),

Vit K,



No significant effect – etOH, benzos, phenothiazides, acetaminophen, opioids, indomethacin



  • Increase formation of plasmin from plasminogen
  • Made by streptocci



  • Endogenous plasminogen activator
  • These preferentially activate plasminogen bound to fibrin so is a bit more selective to the thrombus formed
  • Recombinant DNA tech has allowed us to make manufactured t-PA (alteplase/tenecteplase(longer half life))
  • Indications – PE with haemodynamic compromise, STEMI, severe DVT, stroke within 4hrs of onset.


Aspirin (antithrombotic effects)

  • Irreversibly inhibit cyclo-oxygenase in platelets (inhibit thromboxane production–> inhibit platelet activation and aggregation).


  • Irreversibly block ADP receptor on platelets
  • Duration of effect 7-10d.


G2b/3a inhibitors

  • Used in ACS
  • GP2b and 3a Receptor on platelets bind to fibrinogen and vWF. Activation of these receptors is the final common pathway for platelet aggregation.
  • ABCiximab, tirofiban/ eptifibatide


Vitamin K.

  • Reverses warfarin


Blood products:

  • FFP.
    • Coag factors + plasma proteins + fibrinolytics + complement
    • Indications: Replacement of factors that aren’t available individually, warfarin reversal, massive transfusion protocol, antithrombin 3 deficiency, TTP
  • Cryoprecipitate.
    • Precipitate of FFP when thawed and centrifuged
    • Fibrinogen + Factor 8, Factor 13, vWF
    • Indications – haemphilia, vWF disease, low fibrinogen levels, qualitative problems with fibrin, bleeding from excessive anticoagulation, DIC
  • Factor VIII.
    • Haemophilia A
  • Factor IX.
    • Haemophilia B
  • Desmopressin can release more vWF.


Viva questions:

  • Tell me about Heparin.
  • What are the differences between unfractionated Heparin and LMW Heparin ?
  • How can you reverse the actions of Heparin ?

Protamine sulfate 1mg IV per 100units heparin

  • Tell me about warfarin
  • Tell me about the PK/PD/interactions of Warfarin.
  • How can you reverse the action of Warfarin ?
  • Tell me about the antithrombotic efects of Asprin
  • Tell me about STK / t-PA.
  • What pharmacological agents could be used to treat a patient with a major haemorrhagic complication following administration of STK ?

Aprotinin – inhibits fibrinolysis by plasmin and inhibits plasmin-streptokinase complex.

  • Tell me about clopidogrel

Tell me about Abciximab/Tirofiban/Eptifibatide