Antiplatelets
our main antiplatelet is aspirin
Drug: oral low dose aspirin
Pharmacology
Pharmacodynamics:
Acetylsalicylate: nonselective COX inhibitor
Mechanism of action: Acetylsalicylate inhibits platelet aggregation and reduced risk of thrombus formation. It achieves this by irreversibly acetylating platelet cox reducing TXA2 production for lifetime of platelet (7-9 days)
How does it not affect endothelial COX-2 which makes PGI2?
A combination of rapid turnover of COX by endothelium (platelets don’t have transcription capability), and the fact the most of the aspirin doesn’t even reach it. As it is orally prescribed it is absorbed into the stomach vasculature and goes to the liver where esterase action deactivates acetylsalicylate through CYP2C9. however in the period before this it will irreversible disable the cox enzymes of passing platelets, which will retain this for the entirety of circulation. This is only the case in low dose aspirin
Most low dose aspirin is metabolised High doses of NSAIDs can lead to thrombosis risk (due to inhibition of cox2 whick makes prostacyclin)
Pharmacokinetics:
Metabolism: esterase action in liver breaks it down to salicylate which is broken down by hepatic/renal CYP2C9 and glucuronidation.
Risks and ADRS:
Due to overcooking:
- Haemorrhage
- Gastric ulceration and blooding
- Reyes syndrome (if used with viral illness) (esp in children)
General NSAID side effects (incl. aspirin)
GI mucosa
Prostaglandin E2 leads to more mucus secretion, more bicarb, and more mucosal blood flow. All of this is decreased with NSAID cox-1 inhibition which results in peptic ulcers and GI bleeding
Kidney
Prostaglandin E2 and prostacyclin lead to afferent arteriolar vasodilation (increasing GFR) leading to increased Na and water excretion. NSAID COX1 and 2 inhibition will lead to, NA and water retention, Hypertension, and Haemodynamic acute kidney injury
Cardiovascular
COX-1 makes thromboxane and COX-2 makes prostacyclin. These have 2 different effects. when vascular effect of NSAIDs or aspirin is greater than platelet effect stroke and MI infarct can result
Interactions:
Other notes
Drug: Clopidogrel
Pharmacology
Pharmacodynamics:
Mechanism of action: This is a noncompetitive ADP receptor blocker. It therefore prevents GPIIb-IIIa receptor reducing platelet activation by preventing fibrinogen receptor from being primed
Pharmacokinetics:
prodrug so metabolised to CYPC19 CYP3A4 CYP2C9 and CYP2B6
Indications:
Used when patient cannot tolerate aspirin
Contraindications:
Risks and ADRS:
Interactions:
This drug is valuable when on its own and combined with aspirin.