Pharmacology for Anaesthesia and Intensive Care

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23 Drugs affecting coagulation

Anti-platelet drugs

Cyclo-oxygenase I inhibition

Aspirin

Uses

Aspirin reduces the risk of unstable angina progressing to acute myocardial infarction

(MI) and reduces the mortality following acute MI. The risk of stroke is also reduced

for patients with transient ischaemic attacks.

Mechanism of action

Aspirin acts by irreversible inhibition of cyclo-oxygenase (by acetylation) within the

platelet resulting in reduced production of TXA 2. This may be achieved with only

75 mg daily. Its effects and kinetics are discussed in Chapter9.

Platelet phosphodiesterase inhibition

Dipyridamole

Uses

Dipyridamole has been used with limited success in conjunction with warfarin to

prevent thrombus formation on prosthetic valves. There is some evidence that when

combined with aspirin, dipyridamol may further reduce the risk of stroke, compared

to aspirin alone.

Mechanism of action

Dipyridamole inhibits platelet adhesion to damaged vessel walls (by inhibiting

adenosine uptake), potentiates the affects of prostacyclin and at high doses inhibits

platelet phosphodiesterase activity resulting in increased cAMP levels and lower

intraplatelet calcium levels. Compared to aspirin it inhibits platelet adhesion to ves-

sel walls more than platelet aggregation.

Itis a potent coronary artery vasodilator and may be used in conjunction with

thallium–201 during myocardial imaging.

Inhibition of ADP binding

Ticlodipine and clopidogrel

Like ticlopidine, clopidogrel is a thienopyridine derivative. Neutropenia may be

seen with toclopidine (2.4%) and clopidogrel (0.02%). Thrombocytopenia may also

accompany their use.