Antiplatelet Drugs

Mechanism and Therapeutic effects

Indications

Side effecs and contraindications

Rational: 1)lower patelet fxn (activation and aggregation), 2)Inhibt Thromboxane A2 (TXA2) synth., 3)Prevent release of other platelet products that promote atherogensis.

Aspirin

81-325mmg/day

• For inhibition fo Platelet aggregation

• Cox inhibitor. Inhibition of thromboxane synthesis. There are no thromboxane receptor antagonists

• Note: Endogenous Prostacycline [PGI2] and NO inhibit platelet aggregation by an increase in c[AMP]

• Effect is greatest when chewed followed by dissolved in sol, and finally In tablet form.

• Halfprin marketing strategy for 162mg asprin for MI and stroke. No therapeutic diff. than 81 mg

• Lowered incidence of MI and death by 30-50% in people with unstable angina

• Benefit to MI survivors less clear.

• Increases bleading time nd average of 11 min

• Dose related risk to gastro-intestinal ulceration with long term tx

• Antithrombotic effect persists for 7-10 days after cessation of tx.

• Test platelet fxn using bleeding time. Normal is 5 min

• Also causes a reversible decrease in prostacycline (this does not occur with Ticlid or Plavix)

• Higher doses are several times more gastro toxic but don’t appear to be more efficacious

• Do not take Ibuprofen. It blocks the effects of asprin

Dipyridamole

• Increases c[AMP]

• Usually used in combination with low dose aspirin (aggrenox)

Ticlopodine

Ticlid

• Blocks ADP induced aggregation at low-affinity purinergic receptor (type II)

• Irreversible effect on platelet

• Not a salicylate

• Nearly identical therapeutic effect as ASA

• For pts intolerant to aspirin

• Management of pt at risk of thrombotic stroke

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• Risk of Aggranulocytosis necessitates regular lab tests, and thrombotcic thrombocytopenia purpura 2.4%

Clopidogrel

Plavix

• risk of aggranulocytosis is lower than toclopodine

Tirofiban

Aggrastat

• Non-peptide antagonist of GPIIb/IIIa platelet receptor involved in binding of fibrinogen causing aggregation of platelets

• Reversible platelet aggregation inhibition

• Indicated in unstable angina and acute coronary syndromes

• I.V. only