Lecture 23: Acute chest pain Flashcards
What are the symptoms of acute chest pain?
Chest pain +/- Shortness of Breath
What are some of the chest pain differentials?
Cardiac
- MI, Myocarditis, Pericarditis, HF
Vascular
- Aortic stenosis
Respiratory
- PE, Infection; Pneumonia, Bronchitis, COPD, Asthma, Pneumothorax
Vascular
- Aortic dissection
What are the investigations to make for diagnosis of acute chest pain?
- History and examination
- Blood tests; Full blood count, blood gases, troponin, D dimer
- ECG
- Radiology (CXR, CTPA)
- Coronary angiogram
What are the two types of acute MI?
ST elevation MI (STEMI)
Non-ST elevation MI (Non-stemi)
What triggers a STEMI?
Full occlusion of CA
What triggers a non-stemi?
Very dynamic situation, can open, vasospasm, closed, clot
What is the pathophysiology of vascular occlusion?
- Plaque fissure
- Platelet adhesion
- Platelet activation
- Platelet aggregation
(Anti-platelet medications)
- Thrombotic occlusion (LMWH + Thrombolytics)
What does non-STEMI lead to on ECG?
ST depression
What is non-STEMI initial management?
- Pain relief (morphine, anti-emetic)
- Nitrate (Coronary vasodilator)
- Aspirin (+/- other platelets)
- Beta-blockers
- Low Molecular Weight Herapin (LMWH)
- Stent
What is the initial treatment of STEMI MI?
- Pain relief (morphine, anti-emetic)
- Nitrate (Coronary vasodilator)
- Aspirin (+/- other platelets)
- Beta-blockers
- Thrombolytic + LMWH
- NB Stent (Urgent) (Current standard)
What was found when streptokinase and aspirin were given together?
Synergistic effect
i.e thrombolysis and aspirin
What are some thrombolytics?
- Streptokinase
- Alteplase (human t-PA)
- Tenecteplase (t-PA variant) (More specific human types)
Describe the action of thrombolytics;
Plasminogen in blood (endogenous thrombolytic)
(Streptokinase activates)
Plasminogen binds to fibrin
(alteplase, reteplase - activates plasminogen on fibrin)
Plasmin produced on fibrin. Fibrin broken down.
Fibrin degredation products
When are thrombolytics given? and how are they given
Within 12 hrs of chest pain
Describe streptokinase;
Streptokinase
- Streptococci-synthesised protein
- Streptokinase-plasminogen complex
- Renal excretion
Describe tenecteplase:
Tenecteplase
- Bolus
- Liver metabolised
What are the thromoblysis risks?
All:
- Bleeding
+ Local (To lure site)
+ Intracerebral
Streptokinase
- Allergy / anaphylaxis
- Hypotension
What are contraindications for thrombolysis?
Surgery
Bleeding
and many more
What are the anti-platelet agents?
Aspirin
Clopidogrel
Ticagrelor
What is the action of aspirin?
- Inhibits platelet aggregation
- Anti-inflammatory
- Analgesic
- Anti-pyretic
What is the mechanism of action for aspirin?
Inhibits platelet COX 1 (Irreversible)
- Acetylates serine residue at active site
- Arachidonic acid unable to access active site
- Prostaglandin / thromboxane production inhibited (decreased bioavailability)
Aspirin metabolised to salicylic acid
What is the secondary prevention of aspirin?
Secondary prevention
- Vascular events
- Mortality
What vascular events does aspirin prevent?
CAD
- MI
- Chronic Angina
Stroke
Peripheral vascular disease
What are aspirin side effects?
Upper GI effects
- Reduced production of protective prostaglandin E2 (bicarb and mucous)
- Dyspepsia, upper GI ulcers
Asthma (sensitive people)
What is the action of clopidogrel?
- Antithrombotic / antiplatelet drug (irreversible)
- Absorbed -> CYP P450 metabolism -> active metabolite.
- > Inhibits P2Y platelet receptor
What are the limits of clopidogrel?
Ceiling effect (50-60% platelet aggregation inhibition)
Time and dose dependant
What are the side effects of clopidogrel?
- GI bleeding
- Upper GI symptoms
- Rash
- Beware if concurrently on warfarin
When should you use clopidogrel?
- Acute coronary syndromes
- Aspirin allergy
- Vascular stening (b.c foreign material)
Write some notes on ticagrelor?
Efficacy > Clopidogrel
- Reversible antagonist
Whats the risk of ticagrelor?
Dyspnoea
Bleeding
What are LMWH?
Take naturally occuring herapins which have varying KDA, and take the specific subset with LMW
How do LMWH do?
Inhibit factor Xa
When do you use LMWH?
Indications:
- Non-STEMI
- STEMI
What are the adverse effects of LMWH?
Bruising/bleeding sites
- Intra-cranial
- Injection sites
- Gastro-intestinal loss
- Epistasis
Thrombocytopenia (Next year, autoimmune phenomenon)
What really increases the risk of bleeding?
Post MI - Fibrinolysis \+ - LMWH \+ - Antiplatelet agent
When do you use nitrates?
- Acute coronary disease
- Chronic angina
What are the potential mechanisms of nitrate administration?
Rapidly absorbed;
- Oral
- Intravenous
- Sublingual
- Transdermal
What are the pharmacodynamics of nitrates?
- Uncertain mechanism
+ Biotransformation
+ Denitration
+ Increased bioavailability/activity Nitric Oxide
What do nitrates do?
Vascular smooth muscle relaxation
- Arterial Dilation (Coronary and Peripheral)
- Veno dilation (decreased cardiac work)
What is nitrate tolerance?
Loss of haemodynamic and anti-anginal efficacy during sustained therapy
How can nitrate tolerance be prevented?
- Nitrate dosing
- Nitrate-free period
What are the mechanisms of action for beta blockers?
- Antagonise b adrenoreceptors
- Reduced cardiac work
- Negatively inotropic (acutely)
- Negatively chronotropic
Whats the relative selectivity of metoprolol / atenolol?
B1»_space;» B2
Whats the differences of the various Beta blockers?
- Selectivity (B1 or B2)
- Elimination (Renal vs Liver)
- Half life
- Solubility (water vs fat)
- Additional properties / mechanisms
What beta blockers are used in an acute MI?
Metoprolol
Carvedilol
What are the potential adverse effects of beta blockers?
Resp.
- Asthma exacerbation
CVS
- Hypotension
- Bradycardia
- CCF exacerbation
- Vasospasm
