Symptoms of angina…
Pain in the chest - goes down arm/neck/jaw
Often occurs during exertion
What is angina ?
Strangling of the chest
What is the cause of angina ?
Insufficient coronary blood flow so insufficient oxygen supply
- needed to produce ATP
Important as entire ATP content is turned over every 45 seconds
Describe the coronary circulation ?
Come out at the level of the aorta
Tree like structure to ensure the whole heart is well perfused
Pressure in aorta drives its blood flow
Contains collaterals to help if there are any blockages
What causes the development of more collaterals in the coronary circulation?
Develop more as you get older
Doing more exercise increases the number
When is coronary blood flow highest ?
During diastole when aortic pressure is greater than ventricular pressure because during ventricular systole the ventricles compress the coronary vessels so little flow can occur
Which surface of the heart is more vulnerable to cell death and why ?
Sub endocardium surface because it is at the end of coronary flow
What are the types of angina?
Stable angina
Unstable angina
Prinzmetal angina (variant)
Explain stable angina ?
Partial blockage of coronary arteries
Pain when oxygen demand is increased
It’s intermittent
It’s stable because the pain is the same each time
Explain unstable angina?
Plaques rupture and produce blood clots that occlude the arteries
Level of severity increases with level of activity
Unstable as the pain can vary at the same level of exertion
Explain variant angina…
Spasm of the coronary artery which occurs at rest
May be caused by increased extracellular potassium and calcium because is can cause membrane depolarisation
What is syndrome X ?
Angina which occurs in post menopausal women however their coronary arteries are fine
How do the drugs to treat angina work ?
Readdress oxygen balance
Decrease cardiac oxygen demand to decrease cardiac work
Increase oxygen supply by vasodilation of systemic and coronary circulation
What are the effects of angina drugs on vasculature ?
Dilation of coronary vessels increases perfusion and therefore oxygen supply
Dilation of venous vessels reduces venous return which reduces EDV which reduces stress of ventricular wall which reduces work of the heart so reduces oxygen demand - also increases sub endocardium perfusion
Dilation of arterial blood vessels reduces TPR which reduces after load and therefore the work of the heart
What are the effects of angina drugs on the heart ?
Reduce heart rate and force of contraction
- reduces work of the heart so reduces oxygen demand
- increases duration of diastole so it increases the perfusion time.
What are the drugs used in the treatment of angina ?
Nitrates
Calcium channel blockers
Beta blockers - can’t be used in variant angina
Potassium channel openers
Examples of nitrates…
Glyceryl trinitrate
- used for < 2 attacks per week
- sublingual or aerosol admin
- taken before activity prior to onset of an attack
- aerosol is used when your having an attack
Isosorbide mononitrate
- for > 2 attacks per week
-taken orally for the prevention of attacks
What are the haemodynamic effects of nitrates ?
Dilation of venous vessels to reduce venous return
Dilation of arterial vessels to reduce TPR
Dilation of coronary vessels to increase perfusion
What is the mechanism of action of nitrates ?
Produce nitric oxide which activate guanyl Cyclase
This increases cGMP
cGMP activates protein kinase g
pKG cause potassium to leave cells causing hyperpolarisation and so calcium channels won’t open and let calcium in which would cause more calcium release which produces calcium calmodulin complex to phosphorylates myosin light chain kinase which causes contraction
- pKG also activates myosin light chain phosphate see which phosphorylates myosin so it stops contraction
What are the adverse effects of nitrates ?
Headache Flushing Postural hypotension - theses are caused by vasodilation Tolerance
Examples of cardiac selective calcium channel blockers and there effects…
Verapamil and dilitazem
Block L type channels to reduce calcium current
Decreases heart rate and force of contraction
Therefore decreasing work to reduce oxygen demand
Also increases perfusion during diastole
Examples of vascular selective calcium channel blockers and their effects…
Nifedipine and nicardipine
Vasodilation of venous vessels to reduce venous return and therefore reduce work of heart
Vasodilation of coronary vessels to increase perfusion
Vasodilation of arterial vessels to reduce TPR to rescue work of heart
What is the mechanism of action of calcium channel blockers ?
Stop entry of calcium which prevents phosphorylation of myosin to prevent contraction
What are the adverse effects of calcium channels blockers ?
Headache Flushing Ankle swelling Heart block - blocking of calcium channels in the heart can limit conduction Can worsen heart failure
Example of beta blockers and their effects…
Atenolol and bisoprolol
Reduce sympathetic activity on the heart which reduces work of the heart
Can’t be used in variant angina because they can block beta-2 adrenoreceptors in the blood vessels causing vasoconstriction
What are the adverse effects of beta blockers ?
Fatigue
Headache
Sleep disturbances
Examples of potassium channel activators and their effects…
Nicorandil
Cause vasodilation by activating potassium channels and through nitric oxide
Vasodilation of venous vessels to decrease venous return
Vasodilation of arterial vessels to decrease TPR
Vasodilation of coronary arteries to increase perfusion
What is the mechanism of action of potassium channel activators ?
Increase nitric oxide production which activates guanyl Cyclase and increases cGMP which increases pKG which activates potassium channels
What are the adverse effects of potassium channels activators ?
Headache
Flushing
Dizziness
What are additional angina treatments in unstable angina ?
Anti platelet - aspirin to reduce clots
Anticoagulant - heparin-
Revascularisation to improve blood supply by removing occlusions
What are the treatments for coronary artery disease ?
Statins - reduce serum cholesterol to reduce plaques
ACE inhibitors- for vasodilation, antithrombic and antiproliferative
- antiproliferative is important because it limits proliferation of vascular smooth muscle which is an important part of forming plaques
What does ivabradine do ?
It slows heart rate by inhibiting the sinus node funny current