Saturday, April 2, 2011

Heparin

Introduction:

Presence in the body:

It is present in the body in the form of histamine-macromolecule complex in the mast cells. (Its functional role in the body is not much clear.)

Extraction of heparin:
It is obtained on commercial scale from

1. Porcine intestine
2. Bovine lung

Properties of heparin:
1. Unfractionated heparin is a mixture of straight chain anionic glycosaminoglycans with wide range of molecular weight.
2. Due to the presence of sulfate group and carboxylic acid groups it is strongly acidic.

Enoxaparin is a low molecular weight (LMWH) heparin. LMWH are prepared by either chemical or enzymatic depolymerization of unfractionated heparin.

Mechanism of action:
It causes a decreased formation of fibrin by changing the activity of plasma protease inhibitor antithrombin III.
Where as enoxaparin binds to anti-thrombin and affects more on Factor Xa as compared to thrombin (Factor IIa).


Therapeutic Uses:
Heparin is used mostly in postoperative venous thrombosis and various other thrombotic diseases such as pulmonary embolism and myocardial infarction.

It is also used in extracorporeal devices such as dialysis machine to prevent thrombosis.

Note: Heparin and enoxaparin are drugs of choice in venous thromboembolism in pregnancy as they do not cross placenta.

Administration:
Heparin is administered IV or deep subcutaneously. And enoxaparin is administered subcutaneously.

Pharmacokinetics:
Heparin has rapid onset of action and this action is finished rapidly after the stoppage of treatment with heparin.

Anticoagulant effect of heparin takes place within minutes after IV injection and 1-2 hours after subcutaneous injection. Anticoagulant effect of LMWH takes about 4 hours to take place after subcutaneous injection.

When heparin gets bind to plasma proteins the activity is neutralized.

Although heparin remains in the general circulation but when taken up by monocyte or macrophage system, it undergoes depolymerization and desulfation leading to inactive products.

The drug and its metabolites are excreted through urine.

Half life of LMWH is approximately 4 hours which is nearly double than that of larger species. Renal insufficiency may prolong its half life.

Dosage:
It is given prophylactically in the dose of 5000 units subcutaneously, two or three times in a day.

For diseases which have already been developed, initially 5000-10,000 units will be given intravenously followed by continuous infusion of 900 units per hour.

Adverse effects:
Enoxaparin causes less thromboembolic problems than heparin.

Some of the adverse effects common to them are:

1. Hemorrhage

2. Hypersensitivity reactions such as fever, chills, urticaria and anaphylactic shock.

3. Chronic administration can decrease antithrombin III activity leading to thrombosis.

4. Transient alopecia can also occur.

5. Heparin induced thrombocytopenia (platelet count can decrease up to 50%), which is of two types:

Type-I: which is mild and is for 1st 5 days

Type-II: Which is IgG mediated and is very serious and is with in 5-14 days

Antidote:
Protamine sulfate
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