PROTAMINE

1) Action

• Specific Heparin antagonist

2) Mechanism

• Highly basic peptide that combines with heparin as an ion pair to form a stable complex devoid of anticoagulant activity

• The anticoagulant heparin (an acid) is reversed by protamine (an alkali)

• Organic base opposite in action & charge to heparin

• When bound to heparin, protamine prevents heparin from enhancing the anticoagulant effect of AT-III

3) Indications

• Heparin anticoagulant reversal

4) Effects on organs—side effects

5) Toxic effects/ precautions with administration

• Sudden fall in BP

• Bronchospasm

• Bradycardia

• Excess protamine has an anticoagulant effect

• Rate of infusion should not exceed 50 mg in any 10 minute period

• Syndrome of decreased SVR, increased PVR ?due to activation of complement

6) Contraindications

• Not suitable for reversing the action of indirect anticoagulants eg warfarin

7) Reversal, antagonism or antidote

8) Loading dose, maintenance dose, frequency & method of administration

• 1%/5ml; 1%/10ml

• For every 100 units of heparin remaining in the patient, administer 1 mg of protamine sulphate IV; as time elapses after heparin injection, so proportionally less protamine is required

• Give as a slow bolus over 10 minutes

9) Drug’s metabolism—Drug’s excretion—Half life (pharmacokinetics)

• Shorter half life than heparin: the concept of heparin rebound with heparin being released from tissues back into the circulation has led to the adoption in some centres for a 1.3:1 protamine to heparin reversal ratio