Flashcards in Acute Coronary Syndrome and Acute Myocardial Infarction Therapy Deck (40)
What is the basic spectrum of acute coronary syndromes?
Non-ST elevation MI
ST elevation MI
Sudden cardiac death
What is the goal of pharmacotherapy in acute coronary syndrome?
Increase myocardial oxygen supply through coronary vasodilation
Decrease myocardial oxygen demand through decreasing HR, BP and preload/contractility
What is there a risk of in patients with STEMI?
High likelihood fo coronary thrombus occluding the infarcted artery
Angiographic evidence of a coronary thrombus formation is seen in what percentage of patients with STEMI?
More than 90%
What is a STEMI usually the result of?
Coronary artery occlusion due to the formation of thrombus overlying an atheromatous plaque
When is thrombolysis indicated?
If there can be no access to the cath lab within 2 ours
What are the thrombolytic agents available today? How do they work?
Serine proteases that work by converting plasminogen to plasmin
Plasmin lyses the clot by breaking down the fibrin and fibrinogen contained within it
Fibrinolytics are divided into two categories, what are these? Give an example of each
Fibrin specific agents e.g. alteplase, reteplase, tenecteplase
Produce limited plasminogen conversion in the absence of fibrin
Non-fibrin specific agents e.g. streptokinase
Catalyse systemic fibrinolysis
Why can antibody-generating agents not be used more than once?
They will cause an anaphylactic response on subsequent exposure
What are the contraindications to thrombolysis?
Previous intracranial haemorrhage
Known structural cerebral vascular lesion
Known malignant intracranial neoplasm
Ischaemic stroke within 3 months
Suspected aortic dissection
Active bleeding or bleeding diathesis (excluding menstruation)
Significant closed-head trauma or facial trauma within 3 months
What are the benefits of thrombolysis?
Timely thrombolysis associated with 23% reduction in mortality, or 39% reduction when used with aspirin
Immediate reduction in death rate shown to continue throughout life, morbidity and mortality are significantly reduced over time
What is the dose of aspirin used in treatment of MI?
300mg loading dose then 75-150mg daily
How can aspirin be used to treat MI?
Formation of platelet aggregates is important in the pathogenesis of MI
Thromboxane stimulates platelet aggregation and vasoconstriction
Aspirin is a potent inhibitor of platelet thromboxane production
What effect can the regular daily use of aspirin have on mortality in acute MI?
Can reduce mortality by 23%
In combination with thrombolysis it can reduce mortality by 42% and reinfarction by 52%
What effect can the regular daily use of aspirin have in unstable angina?
Reduce MI and death by 50%
What effect can the regular daily use of aspirin have in secondary prevention?
Reduce re-infarction by 32% and combined vascular events by 25%
What is the standard dose of clopidogrel used in treatment of MI?
300mg loading dose then 75mg once daily
How does clopidogrel work?
Inhibits ADP receptor-activated platelet aggregation
Specifically and irreversibly inhibits the P2Y12 ADP receptor which inhibits platelet aggregation by blocking activation of the GP IIb/IIIa pathway
What is the IIb/IIIa complex a receptor for?
Fibrinogen, fibronectin and vWF
What is the activation of IIb/IIIa complex the final common pathway for?
Platelet aggregation and the cross-linking of platelets by fibrin
What drug is clopidogrel used in combination with?
What is the relative risk reduction when clopidogrel is used in combination with aspirin?
What percentage of the population will demonstrate resistance to clopidogrel?
14% due to low CYP 2C19 levels
What class of drug is prasugrel?
Member of the thienopyridine class of ADP receptor inhibitors
What is the difference between prasugrel and clopidogrel?
Prasugrel inhibits ADP-induced platelet aggregation more rapidly and more consistently, and doesn't rely on metabolism in the liver
What are the products of low molecular weight heparin?
Why is fondaparinux recommended?
Single chemical entity
Highly selective for its target
Once daily administration
No need for platelet monitoring
What is glycoprotein IIb/IIIa?
Integrin complex found on platelets
Receptor for fibrinogen aids in platelet activation
What does platelet aggregation by ADP lead to in platelet glycoprotein IIb/IIIa receptors?
Conformational change that induces binding to fibrinogen