see also:

• anticoagulants
• antithrombotic Rx for prevention of stroke
• Mx of possible acute coronary syndrome without ST elevation (NSTEACS)
• acute myocardial infarction (AMI/STEMI/NSTEMI)

• see aspirin (acetylsalicylic acid) (acetylsalicylic acid)
• It inhibits platelets by irreversibly covalently acetylating the active site of cyclooxygenase which is the enzyme that produces the cyclic endoperoxide precursor of thromboxane A2.
• Since platelets do not synthesise new proteins, this action is permanent, lasting the life of the platelet (7-10days).
• Repeated doses produce a cumulative effect on platelet function.
• Complete inactivation is achieved when 160mg is taken daily.
• 300mg is given to be chewed in a single dose as early as possible in pts with AMI.
• Higher doses do not improve efficacy but increase bleeding & produce aspirin's other actions.

• see clopidogrel
• a thienopyridine derivative structurally related to ticlodipine
• prevents ADP-mediated activation of GP IIb/IIIa complex and thus prevents platelet aggregation.
• mainly used in acute coronary syndromes

• Combined thromboxane A2 synthase inhibitor & endoperoxide blocker;

• same class as clopidogrel, introduced in Australia in 2009 as Effient
• fewer non-fatal MI's but more serious bleeds than clopidogrel
• give with aspirin (acetylsalicylic acid)
• adult dose:
  • usual dose: 60 mg loading dose, then 10 mg once daily maintenance.
  • weight < 60 kg: 60 mg loading dose, then 5 mg once daily maintenance.
  • elderly >= 75 yrs: 60 mg loading dose, then consider 5 mg once daily maintenance.
  • endstage renal disease, Asian patients, galactose intolerance: monitor closely

• see ticagrelor (Brilinta)
• marketed in Australia in 2011 as Brilinta 90mg tablets
• give with aspirin 75-150 mg/day.
• adult dose:
  • 180 mg loading dose, then 90 mg twice daily;
  • switching from clopidogrel: give 90 mg 24 hrs after last clopidogrel dose

• GP IIb/IIIa blockers refer to drugs that block the integrin receptor alphaIIIbbeta3 which normally binds to glycoprotein GP IIb/IIIa, thereby inhibiting platelet aggregation without compromising platelet adhesion to the subendothelial matrix, thereby reducing risk of bleeding whilst still providing anti-platelet activity.

• see ticlodipine
• A thienopyridine that inhibits platelet function by inducing a thrombasthenia-like state.
• It interacts with platelet glycoprotein IIb/IIIa in an unknown way to inhibit the binding of fibrinogen to activated platelets. It thus inhibits platelet aggregation & clot retraction & prolongs bleeding time.

• 1st agent used in humans acting specifically on the platelet GP IIb/IIIa receptor
• monoclonal Fab fragments (IV use only)
• EPIC trial: compared with placebo, 41% reduction in composite endpoint of AMI, death, urgent revascularisation at 30 days in high risk pts undergoing PTCA
  • ⇒ approved by FDA for Rx of pts undergoing high-risk PTCA
• subsequent trials: EPILOG, CAPTURE

• research drugs only but all have shown a class effect in reducing mortality in PTCA & acute coronary syndromes, with a 0.1-0.5% risk of developing severe thrombocytopenia < 20,000/uL.
• integrilin (a peptide)
• tirofiban
• lamifiban

• sibrafiban

• 1st used in IHD as known to have a potent coronary vasodilator effect without increasing oxygen consumption. It was later shown to also exert a direct effect on cell metabolism as it protects sarcomeres from hypoxic damage & has a beneficial effect on ATP synthesis, & delays the deamination of adenosine.
• It interferes with platelets by increasing cellular c-AMP via inhibition of cyclic nucleotide phosphodiesterase &/or by blockade of uptake of adenosine, which acts at A2 receptors & stimulates adenylyl cyclase.
• But its prime action that seems to be beneficial in IHD is its reduction in platelet aggregation & hence antithrombotic activity.
• By itself, it has little anti-thrombotic activity but when used with:
  • warfarin it inhibits emboli from prosthetic heart valves this remains its only current recommended use.
  • aspirin (acetylsalicylic acid) it reduces thrombosis in pts with thrombotic diseases BUT the Antiplatelet Trialists Collaboration in 1988 showed that it was not of any additional benefit cf aspirin alone.