Pharmacology for Anaesthesia and Intensive Care

P1: PSB Printer: Yet To Come
9780521704632c23 CUFX213A/Peck 9780521618168 December 29, 2007 14:58

Section IVOther important drugs

Uses


Clopidogrel – When used for patients with peripheral vascular disease it reduces

the risk of ischaemic stroke and myocardial infarction when compared to aspirin.

Itis also used following coronary artery stenting in combination with aspirin to

prevent stent thrombosis. It is associated with less gastrointestinal bleeding than

aspirin but severe rash is more common.


Ticlodipine – Because of its side effects ticlodipine should only be used when

aspirin has failed. It may be used to prevent stroke and during coronary stenting.

Mechanism of action

Clopidogrel and ticlodipine irreversibly prevent ADP from binding to its receptor

on the platelet surface, thereby preventing the glycoprotein IIb/IIIa-receptor trans-

forming into its active form.

Kinetics

Clopidogrel’s effects are apparent 2 hours after an oral dose but its full effects are

seen only after 3 to 7 days of treatment. Therapy should be stopped for a minimum

of 7 days preoperatively to prevent excessive bleeding.

Glycoprotein IIb/IIIa-receptor anatagonists

Abciximabis a monoclonal antibody with a high affinity for the platelet glycoprotein

IIb/IIIa receptor. It has a plasma half-life of 20 minuts but remains bound in the

circulation for up to 15 days with some residual activity.

Eptifibatideis a cyclic heptapeptide with a lower receptor affinity and a plasma

half-life of 200 minutes. Fifty percent undergoes renal clearance.

Tirofibanhas intermediate receptor affinity and undergoes renal (65%) and faecal

(25%) clearance.

Uses

They are used around the time of acute coronary events. They are used intravenously

for a short duration during concurrent unfractionated heparin therapy with close

control of APTT and or ACT. They carry the rare but serious complication of throm-

bocytopenia.

Mechanism of action

They act by inhibiting the platelet glycoprotein IIb/IIIa-receptor and as such block

the final common pathway of platelet aggregation. However, they do not block

platelet adhesion, secretion of platelet products, inflammatory effects or thrombin

activation.