antiplatelet drugs

Question 0

aspirin/acetylsalicyclic acid

- nature 
MOA
consequence 
uses
pharmacokinetics 
S/Es

Answer 0

nature - COX1 inhibitor!
low dose aspirin 75mg profoundly inhibits platelet TXA2 synthesis.
COX1 helps w synthesis of TXAw which helps w the inside-out signalling for integrin2b3a protein/platelet agonist –> positive feedback for platelet activation.

consequences:
platelets cannot replace cox1 hence txa2 synthesis does not recover for the lifespan of the platelet - 7 to 10 days

uses:
- low dose 75mg - for antiplatelet effect
- high dose - analgesic/anti-inflammatory effect
- patients at high risk of arterial thrombosis, stable and unstable angina,
MI history, stroke, transient ischaemic attack

pharmacokinetics:

• peak plasma 30-40 minutes
• inhibit platelet in PRESYSTEMIC circualation
• adverse effect when inhibits COX2

SEs

• inhibit gastric PGE2 - GI upset and bleeding
• risk is dose dependent

Question 1

name the 5 drug categories for antiplatelet drugs

Answer 1

aspirin - cox1 inhibitor
clopidogrel - ADP receptor antagonist
abciximab - glycoprotein 2b3a receptor antagonist
epitibatide (integrelin) - small molecular 2b3a antagonist
tirofiban (aggrastat) - 2b3a inhibitor

Question 2

clopidogrel 
nature
MOA
consequence
uses
pharmacokinetics                          
S/Es

Answer 2

nature – ADP receptor antagonist – a prodrug

• inhibit ADP-produced platelet aggregation by IRREVERSIBLY binding to ADP P2Y12 receptor to which they link via disulfide bond
• prodrug - hence activated by hepatic metabolism via cytochrome p450 (susceptible to drug interactions)

consequence: inhibit ADP induced aggregation of platelets

uses:
- slightly more effective than aspirin in MI or ischaemic stroke
- those intolerant to aspirin
can administer w aspirin – more effective tgt!

pharmacokinetics:
-large dose 40mg
effective in 2hours last 2 days
requires loading dose + maintenance dose

SEs
- GI bleeding (less than aspirin), more rash due to metabolism in r=liver, diarrhea, thrombotic thrombocytopenic purpura ( low platelet count hence PURPLE!)

Question 3

abciximab 
nature
moa
consequence
uses
pharmacokinetics 
SEs

Answer 3

2b3a integrin receptor antagonist
moa: 2b3a is the final common pathway for platelet activation and hence antagonist of this receptor will inhibit platelet activation

consequence: inhibit fibrinogen from binding to 2b3a integrin which allows for platelet aggregation.
uses: percutaneous coronary intervention (angioplasty/stent) used as adjunct to aspirin and heparin (anticoagulant) =, but no effect on thrombolysis

pharmacokinetics:
- inhibit aggregation at >50% occupancy
- bleeding time prolonged at >90% occupancy

SEs

• bleeding
• thrombocytopenia - low platelet count, immune mediated platelet destruction <- might require platelet transfusion

Question 4

epitibatide and tirofiban

Answer 4

epitibatide / integrelin - small molecule 2b3a antagonist/cyclic peptide
tirofiban/aggrastat - 2b3a inhibitor; synthetic non-peptide