Fibrinolytics – (Pharmacology)

FIBRINOLYTIC SYSTEM

• The process of dissolution of a clot is called fibrinolysis.

FIBRINOLYTICS

• Used to lyse the thrombi/clot to re-channelize the occluded blood vessel (mainly coronary artery).
• Work by activating the Fibrinolytic system:

1. STREPTOKINASE
2. UROKINASE
3. RETEPLASE (analogue of alteplase)
4. ALTEPLASE (tissue – Plasminogen Activator [t-PA])
5. TENECTEPLASE

Streptokinase:

• Obtained from – hemolytic streptococci.
• Binds with circulating plasminogen to form plasmin.
• A complex that activates plasminogen to plasmin.
• t½ = 30 − 80 min.
• Antigenic, Pyrogenic.
• Destroyed by circulating antistreptococcal antibodies.
• Hypotension and Arrhythmia can occur.

Uses:

• Acute myocardial infarction, – 7.5 to 15 lac IU; I.V over 1 hr period.
• Deep vein thrombosis, Pulmonary embolism.

Adverse Effects:

• Bleeding, hypotension, allergic reactions, fever, arrhythmias.

Contraindications:

• Recent trauma, surgery, abortion, stroke, severe.
• hypertension, peptic ulcer, bleeding disorders.

Urokinase:

• An enzyme isolated from human urine, now prepared from cultured human kidney cells.
• Direct plasminogen activator.
• t ½ of 10 to 15 min.
• Non-antigenic, Non-allergenic.
• Fever can occur but hypotension rare.
• Indicated in patients in whom streptokinase has been for an earlier episode.

Alteplase:

• Recombinant tissue Plasminogen Activator (rt-PA)
• Selectively activates plasminogen bound to fibrin
• Non-antigenic, not destroyed by antibodies
• Rapid acting, more potent
• Superior in dissolving old clots
• Short half-life 4-8 min
• Nausea, mild hypotension, fever may occur
• Expensive.

Newer Recombinant Tissue Plasminogen Activators:

Reteplase:

1. Modified rt-PA.
2. Longer half-life 15 -20 min, but less specific for fibrin bound plasminogen.

Tenecteplase:

1. A genetically engineered mutant form of alteplase.
2. Higher fibrin selectivity and longer half-life – 2 hrs. o Single bolus dose of 0.5 mg/kg sufficient.
3. Very expensive.

Uses of Fibrinolytics:

• Acute myocardial infarction.
• Deep vein thrombosis.
• Pulmonary embolism.
• Peripheral arterial occlusion.
• Ischemic Stroke.

Make sure you also check our other amazing Article on : Anticoagulation