Antiplatelet and fibrinolytic drugs Flashcards
What are antiplatelet drugs primarily used for
Arterial thrombosis
- Acute myocardial infarction
- In patients with risk of myocardial infarction
- Following coronary bypass
- Unstable coronary syndromes
- Following coronary artery angioplasty
- Transient cerebral ischaemic attack or thrombotic stroke
Give an example of an COX inhibitor that is an antiplatelet
Asprin
what is the mechanism of action of asprin
- It irreversibly inactivates COX 1/ 2 (cyclooxygenase) resulting in decreased levels of TXA2 and consequentially inhibition of vasoconstriction and platelet aggregation
- Platelets then take 7-10 days to replace COX but endothelial cells can replace it immediately
Describe the different dosages of asprin and what they are used for
- Low dose (180mg/day) → effective in preventing a mini storke
- 335mg/day → reduce risk of heart attack
- > 1000mg/day → no effect die to great inhibiton of endothelial COX
What is the clinical use of asprin
•In acute myocardial infarction in combination with fibrinolytic drugs
Give examples of antiplatelet drugs that are ADP receptor antagonists
Ticlopidine
Clopidogrel
Prasugrel
Ticagrelor
What is the mechanism of action of Ticlopidine,
Clopidogrel and Prasugrel
- Irreversible antagonist at the ADP receptor thereby reducing the release of ADP
- This prevents the expressing of glycoprotein IIBb/IIIa receptors and consequentially reduces platelet aggregation
what is the mechanism of action of Ticagrelor
- Reversible antagonist at the ADP receptor thereby reducing the release of ADP
- This prevents the expressing of glycoprotein IIBb/IIIa receptors and consequentially reduces platelet aggregation
what is the onset of action of Ticlopidine
•Slow onset of 3-7 days
What is the clinical use of Ticlopidine
•Reducing the risk of stroke
What are the side effects of Ticlopidine (which consequentially limit the use of the drug)
- Rash
- Dirrhoea
- Neutropenia
How is Clopidogrel administrated
• Prodrug, oral administration
What is the clinical use of Clopidogrel
- In combination with asprin
* It reduces the risk of ischaemic stroke, myocardial infarction and vascular death
What are the side effects of Clopidogrel
•Less side effects than Ticlopidine especially neutropenia
What is the onset of Prasugrel
- Faster onset than clopidogrel
* Hours
What are the side effects of Prasugrel
•More efficacious than clopidogrel so greater chance of bleeding
what is the efficacy of Ticagrelor
•Similar efficacy to prasugrel and clopidogrel
what is the clinical use of Ticagrelor
•Its reversibility is an asset in certain clinical scenarios
give examples of antiplatelet drugs that are IIb/IIIa receptor antagonists
Abciximab/ Tirfiban
Tirofiban/ Eptifibatide
what is the mechanism of action of Abciximab and Tirfiban
•It is an antibody fragment directed at inhibiting the GP IIb/IIIa receptor and consequentially inhibiting platelet aggregation
What is the clinical use of Abciximab and Tirfiban
•Used by IV infusion in high risk coronary angioplasty patients with heparin and asparin
Why can Abciximab and Tirfiban only be administered once
•Its immunogenicity limits the use to a single administration
What is the platelet recovery time following Abciximab or Tirfiban use
•Platelet function is recovered in days
What is the mechanism of action of Tirofiban and Eptifibatide
•Cyclic peptides which lesemble IIb/IIIa ligands
How ar Tirofiban and Eptifibatide administrated
•IV
What is the platelet recovery time following Tirofiban or Eptifibatide use
•hours
give an example of an antiplatelet drug that is a Prostaglandin agonist
Epoprostenol
How is Epoprostenol given
IV
When is Epoprostenol given (clinical use)
Administered in patients undergoing haemodialysis where heparin contraindicated
Give an example of an antiplatelet drug that is a Phosphodiesterase inhibitor
Dipyridamole
what is the mechanism of action of Dipyridamole
•Inhibits phosphodiesterase and increase platelet camp levels
When is Dipyridamole used?
•In conjunction with asparin
Give examples of fibrinolytic agents
streptokinase Recombinant tPA (tissue plasminogen activator)
What is the mechanism of action of streptokinase
•It binds and activates plasminogen so that the clot is then broken down
What is the pharmacokinetics of streptokinase and how often can it be given
- Action is blocked by antistreptococcal antibodies after 4 days
- Therefore you must wait one year before it can be administrated again
Give examples of Recombinant tPA (tissue plasminogen activator) and the administrtation/half life
Alteplase → Short half life so IV infusion
Duteplase→Short half life so IV infusion
Reteplase→ longer half-life so can give as IV bolus
what is the mechanism of action of Recombinant tPA (tissue plasminogen activator)
Converts plasminogen to plasmin which breaks down the clots
It is more acitive at fibrin bound plasminogen so it is ‘clot’ specific
what are the Absolute containidictions of fibrinolytic agents
Active or recent internal bleeding
•Recent cerebrovascular accident
•Invasive procedures where haemostasis is important
what are the Relative containidictions of fibrinolytic agents
- Pregnancy
- Cardiopulmonary resuscitation
- Trauma
- Bacterial endocarditis
what are the Unwanted effects of fibrinolytic agents
- GI haemorrhage / stroke (treat with tranexamic acid)
- Low grade allergic reactions / fever
- Burst of plasmin generated by steptokinase can generate kinins thereby causing hypotension
what are the Clinical uses of fibrinolytic agents
- In acute myocardial infarction (within 12 hrs of onset, sooner the better)
- Acute thrombotic stroke
- Clearing thrombosed shunts / cannulae
- Acute arterial thromboembolism
