antiplatelet drugs (vk)

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