antiplatelet drugs (2)

7/29/2019 Antiplatelet Drugs (2)

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Antiplatelet Drugs


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Aspirin:

Aspirin irreversibly inhibit COX (up to the life-time of the platelets 8-10 days).

Both PGI2 and TXA2 synthesis are inhibited.

To separate this action aspirin in small dose 75-

100 mg/day inhibits TXA2 synthesis without

significant effect on the endothelial PGI2.This low dose of aspirin may also causes peptic

ulcerbleeding in patients > 60 years.


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Ticlopidine:

Ticlopidine inhibits ADP- dependent platelet aggregation.It is more effective than aspirin, but aspirin is safer andless expensive.

It is used to prevent stroke in patient who are intolerantto aspirin.

A/E: neutropenia (do WBC count / 2 weeks), GIT upsetespecially diarrhea.

Clopidogrel:It acts like ticlopidine, but not associated withneutropenia.

It is more effective and more expensive than aspirin, but

safer than ticlopidine.


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Dipyridamole:

It inhibits phosphodiesterase enzyme, so increasingintraplatelet 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.


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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 inhibitingthe 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 adhesionand 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)


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Other antiplatelet drugs

Dazoxiben: it inhibits TXA2, but not PGI2. it

is being evaluated in cardiac diseases.

Sulphinpyrazone: it is a uricosuric agentand has an antiplatelet effect. It inhibits

prostaglandin synthetase.

Fish oil (omega 3-marine triglyceride): itmay form abnormal thromboxane.


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Ketanserine: it is a selective 5HT2 serotoninreceptor blocker and alpha bloker. Used inhypertension and PVD.

Pentoxifyllin: it is a methylxanthine derivative

inhibits phosphodiesterase enzyme, soincreasing cAMP. It also decreases fibrinogenconcentration, decreases blood viscosity andrestores the flexibility of the RBC. It is used inintermittent claudication and PVD.

Dextran70 & 75: they alter platelet function &prolong bleeding time. They are rarely used.


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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.


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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


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Adverse Effectt

Min.

Source(min.)

Drug

Allergy, anaphylactic

reaction in patient hasantistreptococcal

antibodies. Also not

reused within 6 months.

Rapid injection causes

abrupt hypotension.

20Beta-hemolytic

streptococci

Streptokinase


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Adverse Effectst

Min.

SourceDrug

As streptokinase70Pro-drug

releasesstreptokina

se slowly

Anistrepla

se(APSAC)


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Adverse

Effects

t

Min.

SourceDrug

No allergy, but

more expensive

< 20Human fetal

kidney cells intissue culture

Urokinase

7Recombinant

DNA technology

Pro-urokinase

2-10Recombebinant DNAtechnology

Alteplase (rt-PA)


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NB:

Streptokinase, anistreplase and urokinase arenon fibrin-selectivei.e. they are not absorbed

well to fibrin thrombi, so they also convertcirculating plasminogen to plasmin and increasethe risk of bleeding.

Pro-urokinase and altiplase are fibrin-selective

i.e. they bind strongly to fibrin thrombi, so theiraction is more localized on the plasminogen ofthe thrombi and less likely to produce bleeding.


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Uses:

Thrombolytic agents are used by i.v

infusion in cases ofacute MI, pulmonary

embolism and deep venous thrombosis.

There is also several trials to be used in

ischemic stroke (CVA), but with little

benefit.


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A/E:Bleeding . arrhythmias, hypotension& streptokinase may loses its effect or

causes allergy if antibodies was formed

against it.

antiplatelet drugs (2)

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