Acute Chest Pain - Therapeutics Flashcards
Two common acute coronary syndromes
ST-elevation MI (STEMI)
non ST-elevation MI (non-STEMI)
What do MI’s feel like?
Feels like elephant is sitting on your chest.
Comes on very suddenly.
Sweating, nausea.
Often occurs in patients who smoke, diabetes, high blood cholesterol etc.
STEMIs and non-STEMIs share a common pathological pathway
In coronary artery, if you get a rupture of an atherosclerotic plaque, release of endocardial muck.
Activates platelets and clotting cascade > thrombosis > occlusion of Blood flow.
What do we use to stop the pathological process that leads to MIs?
- Anti-platelets: reduce platelet activation and aggregation
- Low mol weight heparin: anticoagulates
- Thrombolytics: to activate patients own plasmin to breakdown plaques
STEMI explaination and ECG
Shown in the ECG. ST segment is usually around isoelectric (on flat line)
STEMI: gets elevated, ~1cm above isoelectric line. Caused by ruptured atherosclerotic plaque > full occlusion of the coronary artery. Leads to ischaemia.
non-STEMI explanation and ECG
Shown in the ECG. ST segment is usually around isoelectric (on flat line)
non-STEMI: ST segment is actually depressed. Caused by ruptured atherosclerotic plaque > activation of platelets and CC, but then ones own endogenous plasmin partially lysis it ( and around the partial occlusion you get vasospasm).
Much more dynamic then STEMI
“BOTH STEMI and non-STEMI are treated with……. but STEMI is treated also with …. and non-STEMI with …….”
BOTH STEMI and non-STEMI are treated with
- Pain-relief
- Nitrate
- Aspirin (anti-platelet)
- Beta-Blocker
but STEMI is treated also with
-Thrombolytics +LMWH
and NB stents
and non-STEMI with
LMW heparin
Why is the anti-platelet effect of aspirin relatively limited??
As there are many DIFFERENT pathways that platelets can be activated, only inhibits thromboxane
Beta-blockers action??
reduce sympathetic drive. Decrease HR, force of contraction
Why is the NB stent (done once angiogram is done) in a STEMI so urgent?
Because there is a time-constraint in that the myocardial tissue will undergo ischaemia and infarction within 12 hours post onset of chest pain.
NB stent
-1st line therapy, resource heavy, angiogram lab open 24/7, so not always accessible. Thrombolytic may have to be used, 2nd line. Only use one or the other!
There is less of a time pressure in non-STEMI
angiogram done within a day or so. As vessel NOT completely occluded
Why are Streptokinase and aspirin used together??
Individually they BOTH decreased mortality rates, but synergistically an even higher decrease
Thrombolytics, how they work?
2nd line of action if stent doesn’t work
- intravenous
- infusion or bolus
- Bind to ones own plasminogen and catalyse to plasmin
- Plasmin Lyses the thrombus by breaking down the fibrin.
Given within 12 hours of chest pain
Types of thrombolytics
Streptokinase
Human t-PE
Thrombolysis risks
Bleeding
- local
- intracerebral/GI (worry as you can apply pressure to stop!)
Streptokinase
- allergy
- hypotension
Has a # of contraindications: just had surgery or strokes etc, LIMITATIONS
Low Molecular Weight Heparins
- Small chains derived from depolymerisation of unfractionated heparin
- Binds to ones endogenous antithrombin 3, inhibits factor Xa stops thrombotic tendency
Examples of LMWH
Enoxaparin
within 12 hours, used for BOTH non-STEMI and STEMIS,
-subcutaneous injections, for 2-8 days
Adverse effects if LMWH
Can also cause bleeding
- intercranial
- injection sites
- GI loss
Antiplatelet Agents: Aspirin
Acetylation site/group.
- inhibits platelet aggregation
- anti-inflam
- analgesic
- anti-pyretic
Inhibits platelet COX 1 (irreversible)
- acetylates serine residue at active site.
- cant access active site
- prostoglandin/thromboxane production inhibited
Lots of evidence it reduces mortality
Aspirin side effects
Upper GI effects
- Reduced protective PGF2
- Dyspepsia and, upper GI ulcers
Asthma
Clopidogrel
Anti-platelet drug, substitute for aspirin, antithrombotic, irreversible
Inhibits purine platelet receptor.
Pro-drug, needs liver activation, so takes longer.
Effect of Clopidogrel
50-60% effect
New drug that has overtaken clopidogrel
Ticagrelor.
Not a pro-drug, doesn’t need to be activated.
Paired with aspirin.
SOme people get dysponea
Why are there bleeding risks?
Post MI
-fibrinolysis + LMWH + AP
Nitrates
Rapidly absorbed: many ways as it is so lipophilic and easily absorbed.
Hepatic metabolism : oral route > low bioavailability
Prodice NO-like substance > vasorelaxation in arteries and veins (reduce cardiac work)
Nitrates
Decrease BP > giddy
Headaches
How to prevent Nitrate tolerance
Do “nitrate dosing” and have nitrate free periods
Beta-blockers
Antagonise beta-adrenoreceptors in the heart, reduce that tachycardia and force of contraction (necessary in acute MI) > reduce cardiac work
different selectibility, elimination half life and solubility.
Adverse effects of Beta-blockers
Resp : asthma exacerbation
CVS: hypotension, bradycardia, CCF exacerbation, vasospasm
Fatigue, impotence, nightmare
Drug withdrawal
Hypoglycemia
Someone comes in with chest pain, if MI what are you looking for, what do you do?
History of cardiac issues, stroke etc.
Crushing chest, sudden onset.
Pale, sweaty, nausea.
Check Troponin levels in blood (cardiac myocyte necrosis/breakdown)
Do ECG (look for STEMI or non-STEMI)
immediate morphine, maybe O2 if hypoxic. Give aspirin/ LMWH or clopidogrel immediately
