Antiplatelet drugs (VK)

1. LIFEBLOOD
THE
Thrombosis
CHARITY
Antiplatelet and thrombolytic drugs
These slides were kindly provided by AstraZeneca

2. Antithrombotic drugs
Fibrinolytics

3. Antithrombotic drugs
Fibrinolytics

4. Antithrombotic drugs
Fibrinolytics

5. Antithrombotic drugs
Fibrinolytics

6. The role of platelets

7. The role of platelets

8. The role of platelets

9. The role of platelets

10. Antiplatelet drugs
Antiplatelet drugs
Acetylsalicylic
acid (aspirin)
P2Y12
antagonists
Dipyridamole
GPIIb/IIIa
antagonists
Used widely
in patients
at risk of
thromboembolic
disease
Beneficial in the
treatment and
prevention of ACS
and the prevention
of thromboembolic
events
Secondary
prevention in
patients following
stroke, often in
combination with
aspirin
Administered
intravenously, are
effective during
percutaneous
coronary
intervention (PCI)

11. Acetylsalicylic acid –
mechanism of action

12. Acetylsalicylic acid –
mechanism of action

13. Acetylsalicylic acid –
mechanism of action

14. Acetylsalicylic acid –
mechanism of action

15. Acetylsalicylic acid –
mechanism of action

16. Acetylsalicylic acid – pharmacokinetics
·Rapid absorption of aspirin occurs in the
stomach and upper intestine, with the peak
plasma concentration being achieved 15-20
minutes after administration
·The peak inhibitory effect on platelet
aggregation is apparent approximately one
hour post-administration
·Aspirin produces the irreversible inhibition of
the enzyme cyclo-oxygenase and therefore
causes irreversible inhibition of platelets for the
rest of their lifespan (7 days)

17. Acetylsalicylic acid – major use
·Secondary prevention of transient ischaemic
attack (TIA), ischaemic stroke and myocardial
infarction
·Prevention of ischaemic events in patients with
angina pectoris
·Prevention of coronary artery bypass graft
(CABG) occlusion

18. Acetylsalicylic acid – major drawbacks
·Risk of gastrointestinal adverse events
(ulceration and bleeding)
·Allergic reactions
·Is not a very effective antithrombotic drug but is
widely used because of its ease of use
·Lack of response in some patients (aspirin
resistance)
·The irreversible platelet inhibition

19. ADP-receptor antagonists – mechanism
of action

20. ADP-receptor antagonists – mechanism
of action

21. ADP-receptor antagonists – mechanism
of action

22. ADP-receptor antagonists – mechanism
of action

23. ADP-receptor antagonists –
pharmacokinetics
·Both currently available ADP-receptor
antagonists are thienopyridines that can be
administered orally, and absorption is
approximately 80-90%
·Thienopyridines are prodrugs that must be
activated in the liver

24. ADP-receptor antagonists – major use
·Secondary prevention of ischaemic
complications after myocardial infarction,
ischaemic stroke and established peripheral
arterial disease
·Secondary prevention of ischaemic
complications in patients with acute coronary
syndrome (ACS) without ST-segment elevation

25. ADP-receptor antagonists – major
drawbacks
·Clopidogrel is only slightly more effective than
aspirin
·As with aspirin, clopidogrel binds irreversibly to
platelets
·In some patients there is resistance to
clopidogrel treatment

26. Dipyridamole –
mechanism of action

27. Dipyridamole –
mechanism of action

28. Dipyridamole –
mechanism of action

29. Dipyridamole – pharmacokinetics
·Incompletely absorbed from the gastrointestinal
tract with peak plasma concentration occuring
about 75 minutes after oral administration
·More than 90% bound to plasma proteins
·A terminal half-life of 10 to 12 hours
·Metabolised in the liver
·Mainly excreted as glucuronides in the bile;
a small amount is excreted in the urine

30. Dipyridamole – major use
·Secondary prevention of ischaemic
complications after transient ischaemic attack
(TIA) or ischaemic stroke (in combination with
aspirin)

31. Dipyridamole – major drawbacks
·Is not a very effective antithrombotic drug
·Dipyridamole also has a vasodilatory effect and
should be used with caution in patients with
severe coronary artery disease; chest pain may
be aggravated in patients with underlying
coronary artery disease who are receiving
dipyridamole

32. GPIIb/IIIa-receptor antagonists –
mechanism of action

33. GPIIb/IIIa-receptor antagonists –
mechanism of action

34. GPIIb/IIIa-receptor antagonists –
mechanism of action

35. GPIIb/IIIa-receptor antagonists –
mechanism of action

36. GPIIb/IIIa-receptor antagonists –
mechanism of action

37. GPIIb/IIIa-receptor antagonists –
pharmacokinetics
·Available only for intravenous administration
·Intravenous administration of a bolus dose
followed by continuous infusion produces constant
free plasma concentration throughout the infusion.
At the temination of the infusion period, free
plasma concentrations fall rapidly for
approximately six hours then decline at a slower
rate. Platelet function generally recovers over the
course of 48 hours, although the GP IIb/IIIa
antagonist remains in the circulation for 15 days or
more in a platelet-bound state

38. GPIIb/IIIa-receptor antagonists –
major use
·Prevention of ischaemic cardiac complications
in patients with acute coronary syndrome
(ACS) without ST-elevation and during
percutaneous coronary interventions (PCI), in
combination with aspirin and heparin

39. GPIIb/IIIa-receptor antagonists –
major drawbacks
·Can only be administered by intravenous
injection or infusion and are complicated to
manufacture
·Oral drugs have been investigated but were not
effective and have therefore not reached the
market

40. Thrombolytic drugs –
mechanism of action

41. Thrombolytic drugs –
mechanism of action

42. Thrombolytic drugs –
mechanism of action

43. Thrombolytic drugs –
mechanism of action

44. Thrombolytic drugs – pharmacokinetics
·The plasma half-life of the third generation drugs is
14-45 minutes, allowing administration as a single
or double intravenous bolus. This is in contrast to
second generation t-PA, which with a half-life of 3-
4 minutes, must be administered an initial bolus
followed by infusion

45. ·Thrombolysis in patients with acute myocardial
infarction (MI)
·Thrombolysis in patients with ischaemic stroke
·Thrombolysis of (sub)acute peripheral arterial
thrombosis
·Thrombolysis in patients with acute massive
pulmonary embolism
·Thrombolysis of occluded haemodialysis shunts
Thrombolytic drugs – major use

46. Thrombolytic drugs – major drawbacks
·Treatment is limited to acute in-hospital
treatment. There is a high risk of bleeding
inherent in this treatment
·Patients using anticoagulants are
contraindicated for treatment with thrombolytics