Angina and MI Flashcards
What is angina?
Clinical syndrome of chest pain caused by an imbalance of myocardial blood flow supply and demand
What is variant angina?
Associated with eating, may present with SOB and is often due to coronary spasm
What is myocardial infarction?
Myocyte death caused by prolonged ischaemia
What is ischaemia caused by?
Oxygen supply/demand imbalance
Describe what happens in the majority of myocyte metabolism
Oxidative phosphorylation:
Uses fatty acids from breaking down triglycerides
Smaller amount of breakdown of glucose and lactate to pyruvate
Fatty acids and pyruvate oxidised to acetyl CoA, which is further oxidised in Krebs cycle leading to electrons which can be used to make ATP
What inhibits the breakdown of glucose and lactate to pyruvate?
Fatty acid oxidation
What happens to myocyte metabolism in the ischaemic myocardium?
There is a reduction in ATP formation by oxidative phosphorylation therefore a switch to glucose metabolism using glycolysis, leading to a build-up of lactate due to inability to oxidise pyruvate
What happens as a consequence of the ischaemic myocardium not being able to oxidise pyruvate?
There is a build-up of lactate leading to increase in H+ and lactate, and a decrease in pH leading to altered cell homeostasis
The amount of ATP produced by the Ca2+ pump is greater/less when pH is decreased
Greater
What is coronary autoregulation?
How the coronary arteries adjust to maintain a constant blood flow regardless of perfusion pressure
What mediates coronary autoregulation?
Myocyte
Vascular endothelial cell
Vascular smooth muscle cell
Describe the endothelial injury theory
Healthy endothelium is anti-inflammatory
Injury causes inflammatory response
Cytokines attract monocytes which cause increased endothelial permeability
Monocytes differentiate into macrophages which take take up oxidised LDL to become foam cells
How do T cells effect the injured endothelium
They secrete cytokines that induce smooth muscle cells to migrate from media to intima, and continue to proliferate to cause obstruction
Treatments for symptom relief that help the supply
Short acting nitrates
DHP calcium channel blockers
Long acting nitrates
Nicorandil
Treatments for symptom relief that help the demand
Beta blockers
Non-DHP calcium channel blockers
Ivabradine
Ranolazine
Examples of nitrates used for angina
Isosorbide mononitrate (or dinitrate), GTN
How do nitrates work in angina?
Decrease preload and afterload
They act as NO donor to muscle converting GTP to cyclic GMP causing vasodilation
Examples of beta blockers
Bisoprolol
Metoprolol
Carvedilol
Atenolol
How do beta blockers work?
Reduce HR and contractility reducing demand
Block beta-adrenoreceptors in mycoytes and nodal tissues
Prevent adrenaline/noradrenaline binding, reducing calcium entry and myocyte contraction and activity
Reducing isotropy and chronotropy
Examples of DHP CCBs
Amlodipine
Nifedipine
How to CCBs work?
Cause smooth muscle relaxation and therefore vasodilation
Which channels do CCBs work on?
LTCC
Examples of non-DHP CCBs
Verapamil
Diltiazem
Modes of action of nicorandil
Potassium channel activator, allowing potassium ions to exit the cell
Nitric oxide donor effect
How does nicorandil shorten the action potential?
Reducing calcium entry into smooth muscle
Mode of action of ivabradine
Funny current inhibitor (funny current only in the sinus node), reducing depolarisation, reducing HR without reducing inotropy or BP
How does aspirin work?
Inhibits platelet activation and aggregation by inhibiting COX1, reducing thromboxane A2
Also increase prostaglandin I2
