Drugs ppt - د. منوع

Antithrombotic drugs

Fibrinolytics

Antithrombotic drugs

Fibrinolytics

Antithrombotic drugs

Fibrinolytics

Antithrombotic drugs

Fibrinolytics

The role of platelets

Antiplatelet drugs

Antiplatelet drugs
Acetylsalicylicacid (aspirin)
P2Y12 antagonists/Clopidogrel
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 action

Acetylsalicylic acid – mechanism of action

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 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 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 – 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 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 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 – 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 use Secondary prevention of ischaemic complications after transient ischaemic attack (TIA) or ischaemic stroke (in combination with aspirin)

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

GPIIb/IIIa-receptor antagonists – mechanism of action

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 termination 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 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 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 action

Thrombolytic drugs – mechanism of action

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 use

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