Isosorbide Mononitrate Mechanism precautions let us discuss one of the drug isosorbide mononitrate. What is this drug isosorbide mononitrate? Within the name, we can observe the suffix nitrate. So this drug is one of the organic nitrate. Nitrate groups can be attached to organic compound which produce organic nitrates.
And here this isosorbide mononitrate is having a single nitro group attached by an ester link case. We have so many types of organic nitrates. For instance, one of the well known drug is the Glyceryl Trinitrate, which is commonly known as GTN.
This drug is also called as nitroglycerin, which is one of the drug of choice in the acute treatment of Angina. And this drug is simply a glycerin chain attached with three nitro groups by esterling case. Similarly, we have other organic nitrates such as isosorbide dinitrate, erythritol tetra nitrate, and penta erythritol tetra nitrate.
All these drugs are the organic nitrates with different number of nitro groups attached to organic chain. And here isosorbide mononitrate is one of the well known drug for the chronic treatment of Angina. And this drug is commonly known as ISMN. This isosorbide mononitrate is the active metabolite of isosorbide dinitri.
And this is the active metabolite which is useful in the treatment of Angina. Now, ISMN acts as vasodilator. So this drug produces a vasodilatation which affects the function of heart. I sosorbide mononitrate can act on the veins as well as it can also act on the arteries. So it can produce the venular vasodilatation, resulting in the decreased filling pressure so that the preload is going to be reduced.
Similarly, this drug can produce rtol or vasodilatation, which results in the decreased pumping pressure, thereby afterload is going to be reduced. So ISMN can reduce both preload as well as afterload. And this drug can also increase the coronary vasodilatation, thereby oxygen supply to the cardiac muscle is going to be increased. Along with increase the cardiac oxygen supply, this drug can also reduce the cardiac oxygen consumption by reducing the cardiac work.
That’s why this drug can be used in the treatment of Angina, where it can reduce both preload as well as afterload, thereby reduce the cardiac work. And this drug is having few of the advantages. Ismn is having no first pass metabolism. Nitrochlorine is having the high first pass metabolism. On the other hand, isosorbid mononitrate is having no significant first pass metabolism.
So this drug can be given as a tablet, and this truck shows 100 % bioavailability, and even the peak plasma concentration can be achieved within 30 to 60 minutes. Even this is not sufficient for acute treatment of Angina. But in the chronic management of Angina, mononitrate can be given where it can work within 30 to 60 minutes to produce vasodilatation and to relieve the symptoms of Angina.
we are going to see how this drug acts, what is its chemical nature, what are the important precautions, side effects, doses, all these things we will discuss in this . First of all, it is the chemical nature of this drug.
So this is a simple structure of isosorbate mononitrate. Here we can observe nitro group is attached by an esterling case. But another group is the free hydroxyl group. That’s why this drug is a mononitrate instead of dinitrate. And here the ring system is formed by fusion of two furan rings. So this is one of the furan ring and this is the ender furan ring. So this ring system can be written as furo furan. But where is the point of fusion?
In order to show the location of fusion, we can give the numbering to one of the ring. So let us give the numbering to this ring. This is one, two, three. And now let us label the sides of the end of the ring. So this is A side, this is the B side.
Now, if we carefully observe, the third and second side of the one of the furon ring is fused with the B side of the end of the furan ring. So we can write this as 3,2B. So the ring system in the isosorbide mononitrate is F uro 3,2B furon. Then let us give the numbering to the main ring system. So this is 1, 2, 3, 4, 5, and 6. So a nitro group is attached by sixth position as a nitrate.
So we can write this as 6L nitrate. And hydroxyl group is present at the third position. So three hydroxyl and all the elements are saturated. So hexahydro, and it is saturated second, third, fourth and fifth position along with bridge heads. So we can write this as 2L 2A 566A. So that is the complete name of isosorbide mononitrate. Now, let us the precautions of this drug.
One of the important precaution of isosorbide mononitrate is that this drug acts as a vasodilator. So this drug may produce some significant hypotension in the patients which is more observed in the volume depleted patients.
That means the patients who are suffering with severe diarrhea are those patients who are using high ceiling diuretics. In such patients, the hypertension is more pronounced with the use of isosorbide mononitrate. And this hypertension is more pronounced when the patient is changing from sitting position to the applied position. In such conditions, care should be taken to avoid any accidental fall and injuries.
And because of this significant hypertension, this truck can also produce some dizziness, fainting, and even it can increase the hot rate by reflex action. So reflex tachycardia can be produced by isosarbit mononitrate. But sometimes you can also observe bradycardia, which is a paradoxical effect. That means the quite opposite effect that can be observed with isosarbit mononitrate.
It can also reduce the cardiac rate and even it can increase the angina. So care should be taken when this isothermic mononitrate is prescribed for long term as it can produce some significant hypotension. Similarly, this drug can produce some severe hadak, which is commonly observed with many of the organic nitrates.
But this hadak simply indicates that organic nitrates are acting like vasodilators and they can relieve the symptoms of angina. Due to the development of Hedak, the patient should not stop the use of isosorbid mononitrate because hadak is a phan classical effect produced by this drug. And this hadak is because of cranial vasodilatation produced by isosorbid mononitrate since this drug acts as vasodilator.
And the effect is observed on the heart. So ISMN can produce some ventricular hypertrophy. So the patients with already any cardiac myopathy along with hypertrophy, in such patient, this drug may further increase the hypertrophy prolpherase of cardiac muscle, which may result in the decreased cardiac output because of increased obstruction in the flow.
So this may develop the symptoms of angina and even it can increase the myocardial infarction. So in those patients with any risk of hypertrophy, this isosorbid mononitrate should be carefully used. Now, that is the contraindications of this drug.
Since isosorbent mononitrate acts as a vasodilator, this drug should not be combined with fast food estates type 5 inhibitors. The drugs like tadalafil, sildenafil, vatdenafil, evanafil, all these drugs are used to treat pulmonary hypertension as well as erectile dysfunction.
And these drugs should not be combined with isosorbid mononitrate in order to avoid severe hypotension. Now, let us the side effects of this drug. As we have discussed earlier, this drug may produce a headache as important side effect, which is commonly observed in many of the patients. And it can also produce hypotension and dizziness.
It may also produce some dysmia difficulty in breathing. At high dose, it can induce the nausea in the patients. As a paradoxical effect, ISMN can produce bradycardia. Even it can increase the chest pain and symptoms of angina. So in such conditions, this drug should be carefully used. Now, let us see how it works. Within this vascular smooth muscle, MLCK plays an important role.
This MLCK is going to be converted into MLCK activated form, which is then going to act on the MLC myosine light chains such that it can produce a fast fallation of this chain, resulting in the production of MLC phosphate.
Now, this MLC phosphate can combine with the actin such that it can produce actomyosin complex. This produce a contraction of the vascular smooth muscle. Now, ISMN acts as a vasodilator. It can release the nitric oxide such that this nitric oxide can stimulate the gone L cyclate system.
