Acute coronary syndromes - therapy Flashcards
Name examples of acute coroary syndromes
- sudden cardiac death
- STEMI
- Non- STEMI
- unstable angina
Causes of ACS
- atherslerotic rupture > platelet aggregation ? thrombus > vasospasm and vasoconstriction > transient total occlusion of vessel
Goal of pharmacoptherapy of ACS
- increase myocardial O2 supply through coronary dilation
- decrease myocardial oxygen demand ( decrease in HR, BP, preload/myocardial contractility)
What condition predisposes a patient to coronary thrombus?
Patients with STEMI have a liklihood of a coronary thrombus occluding the infarct artery
ACS with STEMI treatment + explain how they work
ACS with STEMI ; thrombolysis
- serine proteases that work by converting plasminogen into plasmin.
- This breaks down the fibrinogen and fibrin contained in the clot
Fibrolytic categories
- Fibrin specific agents
- Non fibrin specific agents
Name fibrin-specific agents + their function
- altepase
- reteplase
- tenecteplase
All catalyses conversion of plasminogen > plasmin in abscence of fibrin
Name non-fibrin specific agents
-streptokinase
Catalyses systemic fibrinolysis
Contraindictions to fibrinolysis
- prior intracranial hemorrhage
- known structural cerebral vascular lesion
- known malignant intracranial neoplasm
- ischaemic stroke within 3 months
- suspected aortic dissection
- active bleeding/bleeding diathesis (excluding menses)
- signifficant closed head trauma/facial trauma within 3 months
Thrombolysis + aspirin
geater reduction in mortality/increased survival rate
Treatment for no evidence of a STEMI
- aspirin
- tigagrelor/clopidogrel
- fondaparinux/LMW heparin
- IV nitrate
- analgesia
- beta blockers
Others
- prasugrel
- Bllibllla receptor blockers
- statins
Treatment 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
Name Antiplatelet agents
-low dose aspirin ( 75-150mg)
How does aspirin work in preventing platelet aggregation
- asprin inhibits platelet aggregation by inhibiting thromboxane A2 production
- thromboxane stimulates platelet aggregation + vasoconstriction.
- formation of PA leads to angina, unstable angina + acute MI
The effect of using aspirin in the treatment of acute MI, unstable+ secondary prevetation
Unstable angina
-reduces MI and death by 50%
Acute MI
-in combination with thrombolysis reduces mortality by 42% and reinfarction by 52%
Doses of aspirin and its effect
- no difference between higher and lower dose
What is clopidogrel? What does it do
- a prodrug that inhibits P2Y12 ADP receptor which is involved in PA and crosslinking by fibrin
- always used in combination with aspirin ( risk reduction)
Effect of blocking ADP receptor
-blocking of receptor inhibits platelet aggregation by blocking activation of GP IIa/IIa pathway
What is llb/llla complex?
- a receptor for fibrinogen, fibronectin and von WF
- Activation of this receptor complex is the ‘ final pathway ‘ for platelet aggregation and crosslinking of platelets by fibrin
Side effects of clopidogrel
GI bleeding
-prevented when using PPI
Explain why clopidogrel resistance occurs
-activated by CYP2C19 and 14% of the population have low levels and demonstrates resistance to clopidogrel
Name ADP receptor inhibitors
-clopidogrel, prasugrel
members of thienopyridine class
What is the difference between prasugrel and clopidogrel?
- prasugerel inhibits ADP-induced aggregation more rapidly
What is low molecular weight heparin?
-also a component of ACS protocol
Name the Low molecular weight heparin products
-Enoxaparin
-Dalteparin
-Tinzeparin
-Fondaparinux
DEFT
What is fondaparinux ?
- a selective inhibitor of factor Xa
- highly selective for antithrombin
- once daily administation, no need to monitor platelet
- less risk of GI bleeding compared to enoxaparin
What is Glycoprotein llb/llla
- integrin complex found on platelets
- receptor for fibrinogen aids in platelet activation
- platelet activation by ADP ( blocked by clopidogrel) > confomrational change in platelet GPllb/llla receptor that induces binding to fibrinogen
- receptor is a target for several drugs including abcixmab, tirofiban
GPllb/llla inhibitors mechanism
IV GPllb/llla inhibitors block platelet aggregation by inhibiting fibrinogen binding to a conformationall activated form of thw GPllb/llla receptor on 2 adjacent platelets
Side effects of GPllb/llla inhibitors
- major/minor bleeding
- in event of bleeding, blood tranfusion required to improve bleeeding related anaemia in 4% of all patients
- thrombocytopenia more often with tirofiban + heparin than with heparin only
Beta blockers in post MI
- used in treatment of acute MI + secondary preventation
- IV atenolol/metoprolol reduces mortalitly following acute MI by 10-15%
- oral beta blockade started weeks/months after ,O reduce cardiac death by 22% and second MI by 26%
Function of beta blockers
-inhibits myoacrdial effects of circulating catecholamines + reduces myocardial O2 consumption by reducing HR, BP and MC
Beware
In patients at risk of developing cardiogenic shock (i.e. age >70 years, heart rate >110 beats/min, systolic blood pressure < 120 mmHg) the observed shock or death rate was significantly increased in patients receiving beta-blockers within 24 h of hospital admission.
Avoid in these and patients with symptoms possibly related to coronary vasospasm or cocaine use.
