 Hello everyone, welcome back to another session in dentistry and more. In pharmacology today we have nitrates. Nitrates are nothing but pro-drex that are sources of nitric oxide. So what are the pro-drex? Why it is known as pro-drex? Okay, it is because it is a medication or a compound upon administration it is metabolized into a pharmacologically active trick. So it is converted within the body and it becomes a pharmacologically active trick. So usually we just take a drug directly but this is pro-drex which becomes pharmacologically active only after the metabolization. Okay, so pro-drex can be used instead of a direct trick to improve the absorption, distribution or such things. Okay, so nitrates are pro-drex. So usually the drug includes our glyceryl trinitrate which is also known as nitroglycerine and we have isosorbide mononitrate and isosorbide dinitrate. So these are the tricks. Now let's learn the mechanism of action. So what happens when we take these tricks? So these organic nitrates leads to the formation of the reactive gaseous free radical nitrous oxide. So there will be formation of free radical nitric oxide. So free radicals will be formed free radicals nitric oxide and related nitric oxide containing compounds. So this is the basic mechanism of action. Okay, so mechanism of action. So this nitric oxide can activate the glenylyl cyclase. It can activate the glenylyl cyclase and it can increase the cellular level of cyclic GMP and it can activate the PKG and it can modulate the activities of cyclic nucleotide phosphor diastries. So in smooth muscles what happens is there will be reduced phosphorylation of myosin light chain. Okay, in smooth muscles what happens? Smooth muscle there will be reduced phosphorylation of myosin light chain and there will be reduced calcium concentration in cytosol. So there will be relaxation. Okay, so this will ultimately leads to relaxation of smooth muscle. So that is the mechanism of action of nitric oxide. So it promotes relaxation of smooth muscles. So in low concentration, in low concentration what happens with nitroglycerine? It prevents preferentially dilate the veins. Okay, more than the arterioles. So veins is dilated more rather than the arterioles. So the dilation is more with the veins. So it decreases the venous return. It leads to fall in left and right ventricular chamber size and end diastolic pressure. So diastolic pressure will be reduced and there will be systemic arterial pressure falling. Systemic arterial pressure also will be falling. Okay, this happens in low concentration. Okay, so it directly affects on the veins rather than arterioles. Whereas with respect to high concentration what happens is so further venous pooling and may decrease the arterial resistance as well thereby decreasing the blood pressure and cardiac output. So it can cause pallor weakness, dizziness and activation of compensatory sympathetic reflexes. So it reduces myocardial oxygen demand. It decreases both preload and afterload. Hope you all know all these terminologies. So it reduces preload and afterload. It reduces the oxygen demand and it dilates the coronary arteries and by increasing the coronary blood flow. Okay, so it increases the coronary blood flow. That is the most striking coronary blood flow, most striking feature of this natural glycerine. So that was the effect of low concentration and high concentration. High concentration it also has effect on arterioles. Ultimately it reduces the blood pressure and cardiac output. So it's common uses or the very basic use is on angina pectoris, congestive cardiac failure or myocardial infarction can also be used in cases of portal hypertension. So it's action of dilation of the arteries or veins and relaxation of the smooth muscles helps to recover from these conditions that is angina pectoris, congestive cardiac failure or myocardial infarction all related to the cardiac system where the occlusion or the proper blood flow is not happening. Definitely this nitrate can be a life saving trick because of its wonderful property. That is the venous and arterial dilation. So it's dosage in sublingual tablets. It can be 0.3 to 0.6 milligram that is sublingually 0.6 mg can be given spray it can be given 0.4 milligram can also be given as ointment, transterminal or IV. So this isosorbide dinitrate can be again given sublingually or least pre-ituable tablets all those things. So this table gives you an idea about the dosage and its duration of effect. So the most preferred one is sublingual tablet in case of this angina pectoris or MI. So it brings out action within 10 minutes. So what are the adverse effects of this nitrates? The most common adverse effect is a headache okay adverse effect. It is most common one is headache. Then there will be transient episodes of dizziness, weakness, dizziness, weakness and other manifestation associated with postural hypertension. High doses of organic nitrates causes postural hypertension. That is related to high concentration, postural hypotension. Prolonged therapy causes endothelial dysfunction. Endothelial dysfunction with respect to prolonged usage. So its tolerance level is important. So tolerance to the actions of nitrates develops rapidly and blood vessels become desensitized to vasodilation. So reduce capacity of the vascular smooth muscle to convert nitroglycerin to nitric oxide. That is the true tolerance it is known as. That is the vascular smooth muscle is not able to convert this nitroglycerin to nitric oxide. That is the true tolerance. So we are talking about the tolerance okay true tolerance whereas the pseudo tolerance is an activation of mechanisms extraneous to the vessel wall. So that was true and pseudo tolerance. So that was all about nitrates. It is a very small topic usually comes as a short note. So you can write about the prodrick and various types, its dosages, its mechanism of action and its uses and little bit about the adverse effect and regarding tolerance okay. So whenever you write the pharmacology you need to follow that peculiar pattern mechanism of action, adverse effects, interactions, tolerance, uses and first part that is the introduction how the trick activates amachokinetics all those things. So more suppettings or more content you get more marks. So I will come up with a new topic in pharmacology. Thank you.