Antiaggregants

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Prevention and treatment of arterial thrombosis

Treatment of established arterial thrombosis includes the use of Antiplatelet drugs and thrombolytic therapy.

Antiplatelet drugs

Alter the platelet activation at the site of vascular damage crucial to the development of arterial thrombosis.

Aspirin irreversibly inhibits the enzyme COX, resulting in reduced platelet production of TXA₂ (thromboxane - powerful vasoconstrictor which lowers cyclic AMP and initiates the platelet release reaction).

Dipyridamole inhibits platelet phosphodiesterase, causing an increase in cyclic AMP with potentiation of the action of PGI₂ – opposes actions of TXA₂

Clopidogrel affects the ADP-dependent activation of IIb/IIIa complex

Glycoprotein IIb/IIIa receptor antagonists block a receptor on the platelet for fibrinogen and von Willebrand factor. 3 classes:

• Murine-human chimeric antibodies (e.g. abciximab)

• Synthetic peptides (e.g. eptifibatide)

• Synthetic non-peptides (e.g. tirofiban)

Epoprostenol is a prostacyclin which is used to inhibit platelet aggregation during renal dialysis (with or without heparin) and is also used in primary pulmonary hypertension.

Thrombolytic therapy

Used in myocardial infarction, cerebral infarction and occasionally in massive pulmonary embolism. The main risk is bleeding. Treatment should not be given to patients who have had recent bleeding, uncontrolled hypertension or a hemorrhagic stroke, or surgery or other invasive procedures within the previous 10 days.

Streptokinase forms a complex with plasminogen, resulting in a conformational change which activates other plasminogen molecules to form plasmin.

Plasminogen activators (PA) Tissue-type plasminogen activators (alteplase, tenecteplase) are produced by recombinant technology.