Antiplatelet drugs Dr.V.V.Gouripur

Antiplatelet drug An antiplatelet drug is a member of a class of drugs that decreases platelet aggregation and inhibits thrombus formation.

Antiplatelet drugs Cyclooxygenase inhibitors –Aspirin Adenocine di phosphate(ADP) receptor inhibitors –Clopidogrel (Plavi) –Ticlopidine (Ticlid) Phosphodiesterase inhibitors –Cilostazol (Pletal) Glycoprotein IIB/IIIA inhibitors (intravenous use only) –Abciximab (ReoPro) –Eptifibatide (Integrilin) –Tirofiban (Aggrastat) –Defibrotide Adenocine reuptake inhibitors –Dipyridamole (Persantine)

Mechanism of action of aspirin 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).

Clinical uses of low dose aspirin prophylaxis of MI, prevention of reinfarction, and prevention of stroke

Mechanism of action Dipyridamole inhibits platelet phosphodiesterase, causing an increase in cyclic AMP with potentiation of the action of PGI2 – opposes actions of TXA2 USES of Dipyridamole (Persantine) and Dipyridamole plus aspirin (Aggrenox  ) - Only for prevention of thromboembolism after heart valve replacement surgery and used with warfarin

Glycoprotein IIb/IIIa receptor antagonists block a receptor on the platelet for fibrinogen and von Willebrand factor. They are known as “super aspirins”. They are the most effective antiplatelet drugs marketed. The mechanism of action is reversible blockade of platelet GP IIb/IIIa receptors Used only IV.

Ticlopidine (Ticlid  ) and clopidogrel (Plavix  ) Adenosine Diphosphate Receptor Antagonists Oral antiplatelet drugs whose effects similar to aspirin used for prevention of ischemic stroke and MI Mechanism Irreversible blockade of ADP receptors on platelet surface B. Adverse Effects-Thrombocytopenia

Thrombolytic drugs Used in medicine to dissolve blood clots ( a procedure termed thrombolysis ) The thrombolytic drugs include: Tissue plasminogen activators - t-PA -alteplase(Activase)Activase -reteplase (Retavase)Retavase -tenecteplase (TNKase)TNKase Others streptokinase (, Streptase)Streptase urokinase (Abbokinase)Abbokinase anistreplase

Mechanism of action Bind with plasminogen to form a complex that acts on molecules of plasminogen to convert it to plasmin to digest fibrin meshwork of clot (also affects fibrinogen and other clotting factors which increase risk of hemorrhage) Effective in dissolving thrombus immediately its after formation (up to six hours)

Uses Thrombolysis is used in myocardial infarction, ischemic strokes, deep vein thrombosis and pulmonary embolism to clear a blocked artery and avoid permanent damage to the perfused tissue (e.g. myocardium, brain, leg) and death. A less frequent use is to clear blocked catheters that are used in long-term medical therapy

Side-effects Hemorrhagic stroke is a rare but serious complication of thrombolytic therapy. If a patient has had thrombolysis before, an allergy against the thrombolytic drug may have developed (especially after streptokinase). If the symptoms are mild, the infusion is stopped and the patient is commenced on an antihistamine before infusion is recommenced. Anaphylaxis generally requires immediate cessation of thrombolysis.

Absolute contraindications Active internal bleeding (except menses) Suspected aortic dissection Acute pericarditispericarditis Intracranial neoplasm History of hemorrhagic stroke Cerebrovascular accident within 12 months

Relative contraindications to thrombolysis 1.Severe, uncontrolled hypertension on presentation (i.e., blood pressure >180/110 mm Hg)hypertension 2.Current use of anticoagulants in therapeutic doses 3.Known bleeding problems 4.Recent trauma (i.e., within 2-4 weeks) including head trauma or traumatic or prolonged (i.e., >10 minutes) cardiopulmonary resuscitation (CPR) 5.Recent major surgery (i.e., within 3 weeks)

Relative contraindications 6. Non-compressible vascular puncture 7. Recent internal bleeding (i.e., within 2-4 weeks) 8. Prior exposure to streptokinase, if that agent is to be administered (i.e., 5 days-2 years) 9. Pregnancy 10. Active peptic ulcer 11. History of chronic, severe hypertension 12. Age >75 years

Streptokinase Inexpensive but opens arteries more slowly than the other agents. Produce profound hypotension and carries a risk of allergic reactions, should be avoided in patients who have received it previously.

Tissue plasminogen activators The advantages of tPA, vs. streptokinase include thrombus specificity and faster reperfusion; however, with a slightly increased risk of bleeding and significantly higher price. Intravenous heparin must be administered concomitantly with these agents

Recent studies suggest that alteplase, Tenactaplase, and reteplase with IV heparin are the most effective currently recommended medical therapies for achieving early coronary reperfusion, but they have a slightly greater risk of intracranial hemorrhage and are considerably more expensive than streptokinase. Thus, the cost-benefit ratio with these agents is greatest in patients presenting within 4 hours of symptom onset when the potential for myocardial salvage is highest.

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