ACS and AMI - Therapy (Clinical Pharmacology) Flashcards
What comprises acute coronary syndromes?
•Increase myocardial oxygen supply
–through coronary vasodilation.
•Decrease myocardial oxygen demand
–Decrease in heart rate,
–Decrease blood pressure,
–Decrease preload or myocardial contractility
Common pathogenesis of ACS?
•Common pathogenesis
–atherosclerotic plaque rupture or erosion
–superimposed platelet aggregation and thrombosis
– Vasospasm, and vasoconstriction
–subtotal or transient total occlusion of vessel
What is the goal of pharmacotherapy?
•Increase myocardial oxygen supply
–through coronary vasodilation.
•Decrease myocardial oxygen demand
–Decrease in heart rate,
–Decrease blood pressure,
–Decrease preload or myocardial contractility
What is the likelihood of coronary thrombus occlusion of the infarct artery in STEMI?
Highe likelihood, •Angiographic evidence of coronary thrombus formation is seen in more than 90% of patients with STEMI
Where does the thrombus which occludes a coronary artery in STEMI lie?
Overlies an atheromatous plaque
When is thrombolysis indicated?
If no PCI within 2 hours
How is thrombolysis by serine proteases achieved?
Work by converting plasminogen to the fibrinolytic agent plasmin.
Plasmin lyses clot by breaking down the fibrinogen and fibrin contained in a clot
What are the two categories of fibrinolytics?
Fibrin-specific agents
Non–fibrin-specific agents
Give examples of fibrin specific agents
- alteplase,
- reteplase,
- tenecteplase
All catalyse conversion of plasminogen to plasmin in the absence of fibrin.
(assuming these agents are therefore inhibited by fibrin)
Give examples of non fibrin specific agents
streptokinase,
which catalyses systemic fibrinolysis
What are the contraindications for thrombolysis?
- Prior intracranial hemorrhage (ICH)
- Known structural cerebral vascular lesion
- Known malignant intracranial neoplasm
- Ischaemic stroke within 3 months
- Suspected aortic dissection
- Active bleeding or bleeding diathesis (excluding menses)
- Significant closed-head trauma or facial trauma within 3 months
What are the benefits of thrombolysis?
- 23% reduction in mortality
- 39% when used with aspirin
What is the acute coronary syndrome medical treatment protocol if there is no evidence of STEMI?
- Aspirin
- Tigagrelor/Clopidogrel (ADP receptor blockers)
- Fondaparinux/LMW heparin
- Intravenous nitrate
- Analgesia
- Beta Blockers
Other Medicines:
- prasugrel
- GIIbIIIa receptor blockers
- Statins
What is the effect of an ADP receptor blocker?
Stops binding of ADP to ADP receptors (P2Y12) Therefore no activation of platelets.
(In normal circumstances an activated platelet produces, thromboxane A2, ADP, Fibrinogen and VWF. Thromboxane activates GP2b/3a receptors which now bind to fibrinogen and cause platelet aggregation - platelet plug and clot)
What is management to reduce risk from NSTEMI?
- PCI or CABG
- Aspirin
- Clopidogrel, prasugrel, ticagrelor, ticlopidine or cilostazol
- Heparin (LMWH)
- Fondaparinux
- GIIb/IIIa receptor blockers
- Statins
- B blockers
Platelet aggregation is important in the pathogenesis of what diseases?
•angina, unstable angina and acute MI
What is the effect of aspirin on thromboxane A2 production?
•Aspirin is a potent inhibitor of platelet thromboxane A2 production
What is the effect of thromboxane?
Stimulates platelet aggregation and vasoconstriction
What is the effect of daily use of aspirin on acute MI?
–reduce mortality by 23%
–in combination with thrombolysis reduce mortality by 42% and reinfarction by 52%
What is the effect of daily use of aspirin on unstable angina?
–reduce MI and death by 50%
What is the effect of daily use of aspirin on secondary prevention?
Reduces reinfarction by 32% and combined vascular events by 25%
Is there a significant difference in the effectiveness of higher dose aspirin versus lower dose aspirin?
No - therefore always a good idea to use low dose aspirin
How does clopidogrel work?
- Clopidogrel is a prodrug
- Inhibits ADP receptor activated platelet aggregation.
- Specifically and irreversibly inhibits the P2Y12 ADP receptor which is important in aggregation of platelets and cross-linking by fibrin
What is the effect of ADP on platelet gpIIb/IIIa receptors?
Changes platelet gpIIb/IIIa receptors to induce binding to fibrinogen
