Acute coronary syndromes pharmacology Flashcards
(36 cards)
Ischaemia is caused when there is an imbalance between supply and demand of oxygenated blood
How is this corrected by drugs?
Increase supply through vasodilation
Decrease demand by decreasing heart rate, decreasing blood pressure and decreasing preload or myocardial contractility
What is typically the state of the coronary arteries of someone with a STEMI
High likelihood (>90%) of a coronary thrombus occluding the infarct artery. This is usually overlying an atheromatous plaque.
To correct the supply/demand imbalance that causes ischaemia and infarction, the thrombus must be removed
What are the ways that thrombi in coronary arteries are removed?
Primary PCI
Thrombolysis
What are the indications for primary PCI?
First line for removal of a thrombus provided it can be done quickly (door - balloon in less than 90 mins)
Also better if:
- High bleeding risk
- Heart failure / cardiogenic shock
- Diagnosis is uncertain
What are the indications for thrombolysis?
Alternative to primary PCI angioplasty if time before surgery is too long (door - balloon > 90 mins)
How do thrombolytic agents work?
Serine proteases that work by converting plasminogen to the natural fibrinolytic agent plasmin
Plasmin breaks down the fibrin and fibrinogen that is in clots
What are the types of thrombolytic (fibrinolytic) agents?
Fibrin specific agents
Non fibrin specific agents
Give some examples of fibrin specific agents and explain how they work
Alteplase
Reteplase
Tenecteplase
These catalyse conversion to plasminogen to plasmin, only in places where there is fibrin
So basically, plasmin is only produced at the site of the clot
Give an example of a non-fibrin specific agent and explain how it works
Streptokinase
These convert plasminogen to plasmin all over the body, so there is a systemic catalysis of fibronolysis
What are the contraindications to 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 other agent is typically given with thrombolytics?
Aspirin
What is the benefit of thrombolysis
23% reduction in mortality
39% reduction in mortality when given with aspirin
(However, Primary PCI is better than thrombolysis so is first line)
What is the ACS treatment protocol?
If no evidence of STEMI:
Aspirin Tigagrelor / Clopidogrel Fondaparinux / LMW heparin IV nitrate Analgesia Beta Blockers
Summarise the agents used to reduce the risk from NSTEMI
PCI or CABG Aspirin Clopidogrel, prasugrel or ticagrelor Heparin (LMWH) Fondaparinux GIIb/IIIa receptor blockers Statins B blockers
Describe the mechanism of Aspirin and why it is used for management of ACS
Aspirin is a potent inhibitor of platelet thromboxane A2 production
Platelet thromboxane A2 stimulates platelet aggregation and vasoconstriction
Low dose Aspirin (75-150mg)
What are the benefits of regular daily use of Aspirin if someone has an acute MI?
reduce mortality by 23%
in combination with thrombolysis: reduce mortality by 42% and reinfarction by 52%
Why is regular Aspirin good for someone who has an episode of unstable angina?
reduce likelihood of MI and death by 50%
Why should Aspirin be given to a patient, post acute coronary event?
reduce reinfarction by 32% and combined vascular events by 25%
How long post ACS event should Aspirin be prescribed?
Up to 2 years
Reduce risk of reinfarction, combined vascular events
Describe the mechanism of Clopidogrel and why it is used for treatment of ACS
Clopidogrel is a prodrug that specifically and irreversibly inhibits the P2Y12 ADP receptor
Stops ADP receptor activated platelet aggregation and cross-linking by fibrin
What important clotting enzyme pathway thing does clopidogrel block?
Blocks activation of the GP IIb/IIIa pathway
The GP IIb/IIIa receptor is found on platelets and binds to fibrinogen once the platelet is activated by ADP
What system in the body can be damaged by clopidogrel?
Clopidogrel can cause GI bleeding
Although it has a claimed lower risk than previously used agents
A small proportion of the population are resistant to Clopidogrel
Why?
Clopidogrel activated by Cyp 2C19
14% of population have low CYP2C19 levels
What is an alternative to Clopidogrel if it doesnt work?
Prasugrel
