List:
· PC
· PK
· PD
|
Structure |
· Basic cationic polypeptides · Derived from salmon sperm |
|
Presentation |
· Aqueous solution · 50mg in 5mL protamine sulfate |
|
Incompatibilities |
· With some antibiotics: penicillins and cephalosporins |
|
Administration |
· 1mL (10mg) protamine per 1mL (1,000 units) heparin |
|
Time course |
· Onset: within 5 minutes · Duration: 2-3 hours |
|
Distribution |
· VD <0.1L/kg |
|
Metabolism |
· Heparin-protamine complex broken down in the reticulo-endothelial system · Cl 20mL/kg/min · t1/2β 60 mins (cf. heparin 90 mins) |
|
Excretion |
· Urine |
|
Mechanism |
· Protamine (basic cationic) + heparin (acidic anionic) -> stable salt complex · Neutralises high MW but not low MW heparins o UFH ~100% o LMWH ~60% o Fondaparinux 0% · Indirectly restores activity of antifactors IIa, Xa (also VIIa/TF, IXa, XIa) |
|
Haemostatic side effects |
· Inconsistent reversal of Xa inhibition o Doesn’t neutralize low MW heparins present in UFH · Re-heparinisation o Shorter half life than heparin · Anticoagulation if excessive o Interactions with platelets, fibrinogen |
|
Other side effects |
· Systemic hypotension o If rapid infusion · Pulmonary hypertension +/- RV failure o TXA2 release, complement activation o Especially if rapid infusion · Non-cardiogenic pulmonary oedema o Cause: ? TXA2 ? complement ? histamine · Anaphylaxis: o IgE mediated o Sensitisation: Ag on APC -> T cell -> B cell -> IgE -> fix on mast cells o Repeat exposure: mast cell degranulation -> histamine etc o Vasodilatation, capillary leak, hypotension o Bronchospasm o Risk factors: allergy to protaphane insulin or fish; PHx vasectomy |
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