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Anti-platelet agents
Site of action
Aspirin
Pharmacodynamics
- irreversibly acetylates and inactivates cyclo-oxygenase: enzyme responsible
for conversion of membrane arachidonic acid to prostaglandin endoperoxides and
thromboxane A2
- platelets lack nuclear machinery to replenish enzyme so platelets are affected
for their lifespan
- platelet release inhibited and platelet aggregation impaired
- clinically translates into a prolonged bleeding time and potential for
bleeding during surgical procedures for up to 8 days after last dose of aspirin.
In most bleeding tendency mild and causes no problems during surgical procedures
however in some patients, particularly those with mild associated haemostatic
problems, bleeding can be pronounced and troublesome
Ticlopidine
- Thioenopyridine platelet inhibitor
- Prodrug. Requires activation by cytochrome P450 in
liver
- Irreversibly modifies platelet ADP receptor and thus
blocks pro-aggregatory effects of ADP
Pharmacokinetics
- Administration: PO. Almost completely absorbed
- Platelet inhibition reaches a maximum after 5-8 days
of repeated doses
- 50-60% of oral dose eliminated in urine, remainder
in faeces
Clinical uses
Unclear. Appears to be more effective than aspirin in preventing stroke in
patients who have already had a stroke or a TIA. However aspirin remain
treatment of choice because of ticlopidine’s bone marrow suppressant effects.
Ticlopidine plus aspirin is more effective than aspirin alone or aspirin plus
anticoagulants in preventing thromboembolic complications related to coronary
stenting, but it is not licensed for this use.
Adverse effects
- Neutropaenia in 2.4%, severe in 0.8%
- TTP in 0.02%
- Nausea, diarrhoea.
- Rashes
- Abnormal liver function tests rarely. Cholestatic
jaundice has been reported
- Rashes and diarrhoea are more common than with aspirin but other GI effects,
including peptic ulceration are less common.
Contraindications
- history of leucopaenia, thrombocytopaenia or
agranulocytosis
- blood diseases that prolong bleeding time
- lesions likely to bleed (eg active peptic ulcer,
acute haemorrhagic stroke)
- caution in patients with impaired liver function.
Should be discontinued if hepatitis or jaundice develops. There is little
experience of its use in patients with renal impairment
Clopidogrel
Similar to ticlopidine in that it is also a thioenopyridine platelet
inhibitor and requires activation by cyctochrome P450. Same mode of action
Pharmacokinetics
- Administration: PO. After repeated oral doses >50% is absorbed.
- Inhibition of platelet function reaches a maximum after 3-7 days
- Elimination: 50% of a single oral dose is excreted in the urine and 46% in
faeces
Clinical uses
Unclear. Appears to offer little or no worthwhile advantage over aspirin.
Little data to support its use in combination with aspirin instead of
ticlopidine combined with aspirin.
Adverse effects
- rash (severe rash more common than with aspirin)
- GI haemorrhage (severe haemorrhage less common than
with aspirin)
- diarrhoea, upper GI symptoms, neutropaenia,
intracranial haemorrhage (similar incidence to aspirin)
Contraindications
- Severe liver impairment
- Active bleeding
- Breast feeding women
- In first few days following acute myocardial
infarction
- Manufacturer does not recommend its use in unstable angina, in those
undergoing PTCA or CABG.
- Should be used with caution in patients who may be at risk of increased
bleeding and should be stopped 7 days prior to surgery if anti-platelet effect
is not desired.
- Use with caution in patients with renal or hepatic impairment.
Further reading
Clopidogrel and ticlopidine – improvements on aspirin? Drugs and
Therapeutics Bulletin, 1999, 37:59-61
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