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Antiplatelet Drugs

Aspirin: Aspirin irreversibly inhibit COX (up to the lifetime of the platelets 8-10 days). Both PGI2 and TXA2 synthesis are inhibited. To separate this action aspirin in small dose 75100 mg/day inhibits TXA2 synthesis without significant effect on the endothelial PGI2. This low dose of aspirin may also causes peptic ulcer bleeding in patients > 60 years.

Ticlopidine: Ticlopidine inhibits ADP- dependent platelet aggregation. It is more effective than aspirin, but aspirin is safer and less expensive. It is used to prevent stroke in patient who are intolerant to aspirin. A/E: neutropenia (do WBC count / 2 weeks), GIT upset especially diarrhea.

Clopidogrel: It acts like ticlopidine, but not associated with neutropenia. It is more effective and more expensive than aspirin, but safer than ticlopidine.

Dipyridamole: It inhibits phosphodiesterase enzyme, so increasing intraplatelet cAMP. It may also increase PGI2 in vascular endothelium. It has coronary VD activity. Epoprostenol: It is a prostacyclin. Used during renal dialysis to prevent platelet loss. It is used with or without heparin. It is a potent VD.

Glycoprotein (GP) IIb-IIIa antagonist: e.g. Abciximab: It is a human monoclonal antibody Fab fragment. It binds to GP IIb-IIIa complex on the platelet surface, so inhibiting the final common pathway of platelet aggregation. Also, it has anticoagulant action through inhibition of prothrombine binding to the complex. It produces immediate and profound inhibition of platelet adhesion and the action last for 12-36 h after termination of i.v infusion. The benefit may maintain up to three years. A/E: thrombocytopenia & hemorrhage, but lesser than with small dose of heparin (it is treated by platelet transfusion)

Other antiplatelet drugs


Dazoxiben: it inhibits TXA2, but not PGI2. it is being evaluated in cardiac diseases. Sulphinpyrazone: it is a uricosuric agent and has an antiplatelet effect. It inhibits prostaglandin synthetase. Fish oil (omega 3-marine triglyceride): it may form abnormal thromboxane.

Ketanserine: it is a selective 5HT2 serotonin receptor blocker and alpha bloker. Used in hypertension and PVD. Pentoxifyllin: it is a methylxanthine derivative inhibits phosphodiesterase enzyme, so increasing cAMP. It also decreases fibrinogen concentration, decreases blood viscosity and restores the flexibility of the RBC. It is used in intermittent claudication and PVD. Dextran 70 & 75: they alter platelet function & prolong bleeding time. They are rarely used.

Uses of antiplatele drugs: They are used to protect against stroke, MI or death in patient at high risk e.g. after angina pectoris, MI, atheroma or prothetic valves.

Fibrinolytic Drugs (Thrombolytics)


Mechanism: they activate the conversion of plasminogen to plasmin, which in turn converts fibrin into soluble products. Plasminogen plasmin Fibrin soluble product

Drug

Source (min.)
Beta-hemolytic streptococci

t Adverse Effect Min.


20 Allergy, anaphylactic reaction in patient has antistreptococcal antibodies. Also not reused within 6 months. Rapid injection causes abrupt hypotension.

Streptokinase

Drug

Source

Anistrepla Pro-drug se releases (APSAC) streptokina se slowly

t Min. 70

Adverse Effects As streptokinase

Drug
Urokinase

Source
Human fetal kidney cells in tissue culture

t Min.
< 20

Adverse Effects

Pro-urokinase

Recombinant 7 DNA technology Recombebinan 2-10 t DNA technology

No allergy, but more expensive

Alteplase (rtPA)

NB: Streptokinase, anistreplase and urokinase are non fibrin-selective i.e. they are not absorbed well to fibrin thrombi, so they also convert circulating plasminogen to plasmin and increase the risk of bleeding. Pro-urokinase and altiplase are fibrin-selective i.e. they bind strongly to fibrin thrombi, so their action is more localized on the plasminogen of the thrombi and less likely to produce bleeding.

Uses: Thrombolytic agents are used by i.v infusion in cases of acute MI, pulmonary embolism and deep venous thrombosis. There is also several trials to be used in ischemic stroke (CVA), but with little benefit.

A/E: Bleeding . arrhythmias, hypotension & streptokinase may loses its effect or causes allergy if antibodies was formed against it.