antiplatelet drugs (vk)
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LIFEBLOODTHE
ThrombosisCHARITY
Antiplatelet and thrombolytic drugs
These slides were kindly provided by AstraZeneca
Antithrombotic drugsAntithrombotic drugs
Fibrinolytics
Antithrombotic drugsAntithrombotic drugs
Fibrinolytics
Antithrombotic drugsAntithrombotic drugs
Fibrinolytics
Antithrombotic drugsAntithrombotic drugs
Fibrinolytics
The role of plateletsThe role of platelets
The role of plateletsThe role of platelets
The role of plateletsThe role of platelets
The role of plateletsThe role of platelets
Antiplatelet drugsAntiplatelet drugs
Antiplatelet drugs
Acetylsalicylicacid (aspirin)
P2Y12 antagonists
Dipyridamole GPIIb/IIIaantagonists
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)
Acetylsalicylic acid – mechanism of actionAcetylsalicylic acid – mechanism of action
Acetylsalicylic acid – mechanism of actionAcetylsalicylic acid – mechanism of action
Acetylsalicylic acid – mechanism of actionAcetylsalicylic acid – mechanism of action
Acetylsalicylic acid – mechanism of actionAcetylsalicylic acid – mechanism of action
Acetylsalicylic acid – mechanism of actionAcetylsalicylic acid – mechanism of action
Acetylsalicylic acid – pharmacokinetics 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)
Acetylsalicylic acid – major useAcetylsalicylic 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
Acetylsalicylic acid – major drawbacksAcetylsalicylic 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
ADP-receptor antagonists – mechanism of action
ADP-receptor antagonists – mechanism of action
ADP-receptor antagonists – mechanism of action
ADP-receptor antagonists – mechanism of action
ADP-receptor antagonists – mechanism of action
ADP-receptor antagonists – mechanism of action
ADP-receptor antagonists – mechanism of action
ADP-receptor antagonists – mechanism of action
ADP-receptor antagonists – pharmacokinetics
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
ADP-receptor antagonists – major useADP-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
ADP-receptor antagonists – major drawbacks
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
Dipyridamole – mechanism of action
Dipyridamole – mechanism of action
Dipyridamole – mechanism of action
Dipyridamole – mechanism of action
Dipyridamole – mechanism of action
Dipyridamole – mechanism of action
Dipyridamole – pharmacokinetics 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
Dipyridamole – major useDipyridamole – major use
Secondary prevention of ischaemic complications after transient ischaemic attack (TIA) or ischaemic stroke (in combination with aspirin)
Dipyridamole – major drawbacksDipyridamole – 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
GPIIb/IIIa-receptor antagonists – mechanism of action
GPIIb/IIIa-receptor antagonists – mechanism of action
GPIIb/IIIa-receptor antagonists – mechanism of action
GPIIb/IIIa-receptor antagonists – mechanism of action
GPIIb/IIIa-receptor antagonists – mechanism of action
GPIIb/IIIa-receptor antagonists – mechanism of action
GPIIb/IIIa-receptor antagonists – mechanism of action
GPIIb/IIIa-receptor antagonists – mechanism of action
GPIIb/IIIa-receptor antagonists – mechanism of action
GPIIb/IIIa-receptor antagonists – mechanism of action
GPIIb/IIIa-receptor antagonists – pharmacokinetics
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
GPIIb/IIIa-receptor antagonists – major use
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
GPIIb/IIIa-receptor antagonists – major drawbacks
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
Thrombolytic drugs – mechanism of actionThrombolytic drugs – mechanism of action
Thrombolytic drugs – mechanism of actionThrombolytic drugs – mechanism of action
Thrombolytic drugs – mechanism of actionThrombolytic drugs – mechanism of action
Thrombolytic drugs – mechanism of actionThrombolytic drugs – mechanism of action
Thrombolytic drugs – pharmacokinetics 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
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 useThrombolytic drugs – major use
Thrombolytic drugs – major drawbacksThrombolytic 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