Acute Coronary Syndromes Flashcards
Some causes of chest pain (10)
Broken rib
Collapsed lung
Nerve infection (shingles)
“Pulled” muscle
Infection
Heart burn (hernia)
Pericarditis
Blood clot in the lungs (PE)
Angina
Myocardial infarction
Why is it important to define the type of IHD? (4)
need to know if Stable Angina vs Acute Myocardial Infarction
for:
Treatment
Prognosis
Management
Assessment of IHD (6)
- Medical history
- Risk factors
- Presenting signs and symptoms
- ECG
- Biomarkers
- Imaging/scans
Chronic and acute coronary heart disease branching graph (6)
image
chronic HD vs acute CS
c:
- stable angina
-variant angina
-silent myocardial ischaemia
a:
- unstable angina
-non ST-segment elevation MI
- ST-segment elevation MI
Characterisation of acute coronary syndromes
flowchart for diagnosis
Acute coronary syndromes (3)
thinking about vessel occlusion
unstable: more flow + potential thrombus
Non-stemi: sig reduced lumen + sig platelet + thrombus activation (areas of necrosis)
stemi: full occlusion - severe disease
Treatment aims (4)
*Relieve symptoms
* Improve survival
* Minimise cardiac risk
Major aim of treatment should be to facilitate a
return to normal activities
2 options for ST segment(2)
Surgical/Intervention: PCI
Balloon angioplasty
Stent
Coronary bypass
or
Pharmacological treatment - thrombolytic therapy (if no access to primary angioplasty)
image
imaging -Cardiac CT angiography benefits (4)
vital for patient management
location of occlusion
location of stent
follow up
images
ST-segment elevation myocardial infarction - initial (5)
oxygen (shortness of breath)
anti-emetic (IV morphine)
aspirin + clopidogrel
betablocker
GTN (reduce work of heart)
Thrombolytics/Fibrinolytics (3)
- Streptokinase
- Urokinase
- Tissue plasminogen activators
Tissue plasminogen activator-mediated
thrombolysis (5)
image
t-PA + urokinase- A: both convert plasminogen > plasmin
plasmin = potent proteolytic enzyme - degrades fibrin net (fibrin degradation products)
- tPA is a plasminogen
activator - Catalyst
- Fibrin selectivity
fibrin binding sites on t-PA + plasminogen: fibrinolysis specific to this
t-pa kept in inactive conformation (t-PAi complex) = prevents activating circulating plasminogen
because t-PA has high affinity for fibrin so can dissociate and bind to it = degradation
Tissue plasminogen activator versus
streptokinase (4)
SK is bacterial (beta-haemolytic streptococci)
possible immune recognition (allergic)
- SK will bind circulating plasminogen not associated with fibrin – generalised plasmin generation (bleeding)
- SK is less fibrin specific, more systemic plasminogen activation and bleeding
- Antibodies generated that thwart subsequent doses and possible allergic reaction
MoA Streptokinase (2)
- SK binds with free circulating
plasminogen/plasmin - Forms an active complex that can convert additional
plasminogen to plasmin
Structural differences b/w Alteplase and newer
formulations of tPA (Reteplase and Tenecteplase):
how structural differences affect mode of action (3)
Alteplase (Actilyse/Activase) - full length t-PA
- Reteplase - t-PA deriv (fragment)
- Tenecteplase - modifed t-PA
t-PA structure (3)
- finger domain (N term):
GF/ GF-like domain = High affinity for fibrin, Low affinity receptor binding/clearance
-kringles: 2x
1 = Liver clearance, Glycosylation
2=Interaction with PAI-1, Fibrin binding
-protease: Proteolytic activity, Interaction with PAI-1
Kringle domains (4)
Kringles are triple-looped, disulphide cross- linked domains found in a varying number of copies, in some serine proteases and
plasma proteins
- evolutionary conserved
- in GF’s
- in coag factors
- etc
Apolipoprotein A= 38 copies
Blood coagulation factor XII= 1 copy
Hepatocyte growth factor (HGF) (4 copies)
Hepatocyte growth factor like protein (4
copies)
Plasminogen (5 copies)
Thrombin (2 copies)
Tissue plasminogen activator (tPA) (2
copies)
Urokinase-type plasminogen activator (1
copy)
derivatives of t-PA (4)
Alteplase=tPA
Reteplase =r-PA or K2P
Lanoteplase =nPA (not as useful)
Tenecteplase =TNK-PA
Reteplase =r-PA or K2P (4)
- Deletion of finger region, EGF-like domain and kringle 1, & carbohydrate side chains
- Hepatic elimination of the
molecule is reduced - Plasma half life is increased to 14–18 minutes (versus 3–4 minutes with alteplase)
- Diminished fibrin binding
Tenecteplase modifications (2)
has: EGF-like domain, 2 kringles + protease domain (full length)
Modified glycosylation
residues/sites (in K1 Asn-103 for Thr Gln-117 for Asn) =prolonged half-life (necessary in liver clearance)
4 alanine substitutions at
296-299 in Protease = enhanced fibrin specificity and resistance to PAI-1 inhibition, reduced systemic
plasmin activation
Treatment of
ACS summary (6)
Time from onset and severity of symptoms is critical
medical:
* General myocardial
oxygenation
* Antiplatelet/Antithrombotic
* Analgesia
* Myocardial energy
consumption
* Coronary vasodilatation
* Anticoagulation
* Thrombolysis
* Plaque stabilization
surgical:
* Reperfusion
* Re-vascularisation
- Arrival to ECG: within10 min
- Door-to-needle for thrombolysis: within 20 min
- Door-to-balloon time for PCI: within 60 min
Thrombolysis versus Angioplasty: Pros and Cons (12)
Thrombolysis:
* 55-60% recanalisation within 90 mins
* 5-15% risk of reocclusion
* Worsening ventricular
function
* 1-2% risk of intracranial
haemorrhage with 40%
mortality
* 15-20% of patients have a
contraindication to
thrombolysis
Angioplasty:
* 95% recanalisation within 60 mins
* No systemic fibrinolysis
* Reduced rates of death,
cerebrovascular events and
re-infarction
* Costly
* Specialist facilities and staff
Long term management after a myocardial infarction (8)
- Smoking cessation
- Physical activity
- Diabetes management
- Diet and weight reduction
- Blood pressure control
- Lipid management
- Management of heart failure or LV dysfunction
- Prevention of sudden death
