For more information, visit PharmAcademy at: sites.google.com/exeter.ac.uk/pharmacademy/home
Nitrates work by being converted into nitric oxide and nitric oxide is a systemic vasodilator and so when patients experience angina which is ischemic chest pain they’re having vasospasm in their coronary arteries which is reducing blood flow to the heart tissue they take their gtn and that restores blood flow by vasodilation the coronary arteries now as well as
Coronary arteries nitrates can have spacers elating effects on the systemic arteries and veins which works essentially to reduce the workload on the heart and that’ll be covered in slightly more detail towards the end of the video now let’s have a quick look at how the effects that nitrates have on vascular smooth muscle cells and how that leads to vasodilation
So nitrates are first converted into nitric oxide and then they act on an enzyme in vascular smooth muscle cells called quinella cyclase and that produces a molecule called cyclic gmp and cyclic gmp acts on calcium channels to reduce calcium coming into the cell and calcium is important because it binds to calmodulin which is involved in muscle contraction so it
Essentially causes smooth muscle cell relaxation and as you can see if you get relaxation of the smooth muscle cell that causes vasodilation and so that’s how nitrates cause vasodilation so let’s look at how nitrates work on specific blood vessels so we’ve got coronary arteries here and we’ve got our thrombus in our coronary artery and we’ve got coronary vasospasm
Around that thrombus which is reducing blood flow through the coronary artery and reduced blood flow leads to ischemia because the heart tissue isn’t being refused it’s not receiving enough oxygen and that causes our ischemic chest pain so if a patient comes and takes nitrates gtn spray that causes vasodilation of the coronary arteries and you can see if you basically
Dilates that coronary artery around that thrombus the blood flow is going to be restored and you get a resolution of ischemic chest pain in terms of systemic effects of nitrates if we have faceit sanitation occurring in the veins we get blood pooling in the veins and that has an effect on the heart by reducing the filling pressure in the right ventricle and that’s
Also known as preload so if we reduce the preload i in turn reduces the wall tension within the myocardial of the ventricles and that reduces myocardial oxygen demand and the reason that reducing the oxygen demand of the heart tissue is a good thing is because if you remember the schema is where the heart tissue isn’t receiving enough oxygen if you reduced the
Amount of oxygen the heart actually needs in the first place and it’s less likely to ever become ischemic and it’s for this reason that as well as the resolution of ischemic chest pain in the acute setting nitrates can also be used to prevent chest pain occurring in the first place on the arterial side if we get vasodilation of the arteries we get reduced blood
Pressure and so we get reduced afterload so we get reduced resistance to when the left ventricles trying to eject blood and that reduces the work of the left ventricle and so we get reduced oxygen demand in that way so that was just a very quick summary of how nitrates actually work and the minute they’re looking like a really good medication for the management
And prophylaxis of ischemic chest pain however like all medications there are some side effects to nitrates we don’t just get phased annotation in the vessels that we want you also get faced with annotation in the cerebral vessels and that can cause slightly raised intracranial pressures as the vessels expanded so patients can present with headache another side
Effect of course is the fact that these medications lower your blood pressure and if someone’s already got low blood pressure then they can lower it a bit too much and so they can present with postural hypotension or in severe cases they can actually present as false
Transcribed from video
Nitrates – Mechanism of Action By Matthew Wigley
