AMI- Therapy Flashcards
What is included in the spectrum of ACS?
- Unstable angina
- NSTEMI
- STEMI
- Sudden cardiac death
What is the common pathogenesis of ACS?
- 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
- Decrease myocardial oxygen demand
How is myocardial oxygen supply increased through pharmacotherapy?
Coronary vasodilation
How is myocardial oxygen demand decreased through pharmacotherapy?
- Decrease in heart rate
- Decrease in blood pressure
- Decrease preload or myocardial contractility
Patients with a STEMI have a high likelihood of what?
A coronary thrombus occluding the infarct artery
What do STEMIs usually occur as result of/
Coronary artery occlusion due to the formation of thrombus overlying an athermatous plaque
When is thrombolysis indicated?
If PCI is not available within 2 hours
What are the thrombolytic agents available today?
Serine proteases
How do the serine proteases work?
- Convert plasminogen to the natural fibrinolytic agent plasmin
- Plasmin lyses clot by breaking down the fibrinogen and fibrin contained in a clot
What are the 2 categories of fibrinolytics?
- Fibrin specific agents
- Non-fibrin specific agents
What do all fibrin specific agents do?
Catalyse conversion of plasminogen to plasmin in the absence of fibrin
Give 3 examples of fibrin specific agents.
- Alteplase
- Reteplase
- Tenecteplase
What are the contraindications for thrombolysis?
- Prior intracranial bleeding
- 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 timely thrombolysis?
- 23% reduction in mortality
- 39% when used with aspirin
If there is no evidence of a STEMI, what protocol should be followed?
ACS medical treatment protocol
What is the ACS medical treatment protocol?
- Aspirin
- Tigagrelor/clopidogrel
- Fondaparinux/ LMW heparin
- IV nitrate
- Analgesia
- B-blockers
Other than ACS medical treatment protocol, what other medications should patients be put on?
- Prasugrel
- Statins
- Glycoprotein IIb IIIa receptor blockers
What is the management to reduce risk from NSTEMI?
- PCI or CABG
- Aspirin
- Clopidogrel, prasugrel, ticagrelor, ticlopidine or cilostazol
- LMW heparin
- Fondaparinux
- GIIb/IIIa receptor blockers
- Statins
- B blockers
What is aspirin?
Antiplatelet agent
What type of aspirin is used in ACS?
Low dose aspirin 75-150mg
Why is aspirin used in ACS?
- The formation of platelet aggregates are important in the pathogenesis of angina, unstable angina and acute MI
- Aspirin is a potent inhibitor of platelet thromboxane A2 production
- Thromboxane stimulates platelet aggregation and vasoconstriction
What is the benefit of regular daily us of aspirin in acute MI?
- Reduce mortality by 23%
- In combination with thrombolysis, reduce mortality by 42% and reinfarction by 52%
What is the benefit of regular daily use of aspirin in unstable angina?
Reduce MI and death by 50%
What is the benefit of regular daily use of aspirin as secondary prevention?
Reduce reinfarction by 32% and combined vascular events by 25%
What is clopidogrel?
Pro drug
What does clopidogrel do?
- 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 does blockade of the P2Y12 ADP receptor result in?
-Inhibtion of platelet aggregation by blocking activation of the GP IIb/IIIa pathway.
What is the IIb/IIIa complex?
- A receptor for fibrinogen, fibronectin and von WF
- Activation of this receptor is the ‘final common pathway’ for platelet aggregation and cross-linking of platelets by fibrin
What are clopidogrel/ticagrelor always used in combination with?
Aspirin
What is the relative reduction when clopidogrel/ticagrelor are used in combination with aspirin?
21%
What is important to not with the combination use of aspirin and clopidogrel/ticagrelor?
- Lower incidence rate of GI bleeding however GI bleeding remain very common
- Possible interaction with PPI with a reduction in effect
Why do some people have resistance to clopidogrel?
- Clopidogrel is active by Cyp2C19
- 14% of the population have low Cyp2C19 levels and demonstrate resistance to clopidogrel
What is prasugrel?
Member of the thienopyridine class of ADP receptor inhibitors, like clopidogrel
How does prasugrel compare to clopidogrel?
Prasugrel inihibits ADP-induced platelet aggregation more rapidly and more consistently
Give examples of 4 different LMWH products.
- Enoxapirin
- Dalteparin
- Tinzparin
- Fondaparinux
What is fondaparinux?
A selective inhibitor of factor Xa
What are the properties of fondaparinux?
- Single chemical entity
- Synthetic pentasaccaride
- Highly selective for antithrombin
- Once-daily administration
- No need for platelet monitoring
What is GPIIb/IIIa?
- An integrin complex found on platelets
- Receptor for fibrinogen aids in platelet activation
What does platelet activation by ADP lead to?
A conformational change in platelet GPIIb/IIa receptor that induced binding to fibrinogen
Give 2 examples of drugs that target the GPIIb/IIIa receptor.
- Tirofban
- Abciximab
How do IV GPIIb/IIIa inhibitors block platelet aggregation?
Inihibit fibrinogen binding to a conformationally activated form of the GPIIb/IIIa receptor on 2 adjacent platelets
What is the major adverse effect of anti-thrombotic drugs?
Bleeding
Why are B-blockers used post MI?
- In the treatment of acute MI
- For secondary prevention in the survivors of an acute MI
Give 2 examples of B-blockers used post MI.
- Atenolol
- Metoprolol
How do B-blockers work/
-Competitively inhibit the myocardial effects or circulating catecholamines and reduce myocardial oxygen consumption by lowering hear rate, blood pressure and myocardial contractility
Who is at risk of cardiogenic shock?
- Age>70
- Heart rate>110bpm
- Systolic BP<120mmHg
Who should B-blockers not be given to?
- Patients at risk of cardiogenic shock
- Patients with symptoms possibly related to coronary vasospasm or cocaine use
