howMed Know Yourself
Fondaparinux
Chemistry – synthetic pentasacchride
Mechanism of Action
Acts by inhibiting factor X.
Pharmacokinetics
Long half life of 17-21 hours.
Given parentally.
Uses
Used instead of heparin in cases where heparin induced thrombocytopenia occurs, as no HIT is seen with this.
Advantage – HIT
Disadvantage – antagonism
No antagonist acts, as protamine sulphate is ineffective.
Idraparinux – a sulfated derivative of Fondaparinux, having an even longer half life.
Heparinoids
These are related with heparin.
Heparan Sulfate
Natural –in mast cells
Commercially prepared as well.
The difference is that polymers of heparin sulphate are less modified than heparin.
Danaparoid is an example.
Advantage -HIT
Direct Thrombin Inhibitors
Mechanism of Action
Hirudin, Lepirudin and Bivalirudin are bivalent and bind to two sites on thrombin directly:
i. Active catalytic site
ii. Substrate recognition site
Argatroban and Melagatran are small molecules and bind only one site; the active catalytic site.
Source
Hirudin occurs naturally in leeches.
Rest are synthesized by recombinant DNA technology.
Monitoring & Pharmacokinetics
All are administered parentally. Therapeutic efficacy is measured by APTT.
Lepirudin
40% of the patients form antibody complex with lepirudin and these complexes are unable to be excreted through kidneys. They are given with caution in renally impaired patients.
Argatroban
It is metabolized by the liver, which is its main eliminating organ.
Thus patients with renal insufficiency are administered Argatroban, while those with hepatic insufficiency, Lepirudin.
Uses
- In surgery for Reattachment of digits (even leeches were used)
- HIT
- Coronary angioplasty
Adverse effects
- Renal
- Anaphylactic reaction –with Lepirudin
Ximelagatran
It is given orally and is a prodrug. It is changed into Melagatran.
Advantage –HIT
