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nitroglycerine isosorbide dinitrate

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Now what about nitroglycerin and isoscorbite nitrate we discussed nitroprusside two slides ago that’s done now let’s talk about two more drugs that belong to the nitro vasodilator group which are nitroglycerin and isosorbide dinitrate or nitrate so if we just kind of look at the structures of the two molecules you can already see that there’s a bunch of enzymes in

Both of these molecules so there’s your nitroglycerin as you can see they have very similar structures there’s some enzymes here some enzymes here enzymes here and well that’s not really that important the important part is you know these have nitrosyl groups within them you know this but let’s go through this again we eventually liberate nitric oxide by both of

These molecules being incorporated into someone’s bloodstream the eventual increase in nitric oxide induces the soluble version of guanolo cyclase to produce more cyclic gmp the eventual increase in cyclo-gmp activates protein kinase g protein kinase g phosphorylates a bunch of proteins particularly the ip3 or inositol triphosphate receptor slapping a phosphate

Under that means that you inhibit its ability to signal to the sarco-endoplasmic reticulum to release calcium what’s important to know about nitroglycerin and isoscerbide dinitrate or nitrate is that they mostly affect veno dilation so as opposed to the other ones hydralazine was purely precalculated arterioles the nitropuraside and phenoldepam caused a pretty wide

Systemic arteriolar and veno dilation the nitroglycerin and isoscorbite dinitrate or nitrate purely veno dilation compared to the other ones there is a little bit of arterial or vasodilation particularly in the distribution of the facial and meningeal arterioles and that is directly responsible for some of the side effects here which is the flushing the headaches

And the dizziness so you get the flushing because you take the vessel diameter and increase it the vessel gets closer to the skin surface and now you have a more prominent vessel lumen closer to the skin surface and that creates a redness as the flushing that you see dilation of meningoarterials can cause irritation of the meninges and it causes a headache and

The dizziness can be related to the dilation of cerebrovasculature causing hypoperfusion of some elements of the brain which causes dizziness now in the treatment of angina acute coronary syndrome and pulmonary edema why would it be important to decrease the preload by giving someone nitroglycerin or isostora by nitrate and causing veno dilation so the veno

Dilation is essentially just a drop in the preload so why is that important for someone with these components of increased myocardial oxygen demand and increased translation of fluid into the pulmonary structures so in the treatment of angina acute coronary syndrome and pulmonary edema why is it important to decrease the preload by causing veno dilation remember

Veno dilation is basically causing a decrease in preload what happens is that the veno dilation causes an increased compliance to the venous vasculature so if you take a vessel from this diameter to this diameter it isn’t too able to accommodate a much larger volume per unit of pressure to take a lot more blood to increase the pressure of this vein compared to

Filling this vein with the same amount of blood and the pressure you would create by doing that so essentially we’ll have more blood just pulling these veins by decreasing the volume of blood returning to the heart because there’s more blood in the veins we decrease the volume of blood in the ventricles and that decreases the wall tension and thus it decreases

The amount of atp required to pump blood out and this helps relieve the ischemic leg pain because we decrease the work and the oxygen demand that the heart will require and pulmonary edema is a rather simple concept you guys already understand but for completeness let’s quickly discuss and integrate something that we reviewed that is particularly high yield for

Your step one exam so think back to the equation that we wrote when we were talking about the capillary microcirculation where jv equals a filtration constant or hydrostatic capillary pressure minus our hydrostatic interstitial pressure minus oncotic pressure of the capillary minus the interstitial oncotic pressure so if someone has pulmonary edema due to

Increased hydrostatic pressure in the pulmonary microvasculature there will be an increase in this value pc because that’s the capillary pressure there will be increased driving force fluid across the capillary wall into the interstitial space and in the pulmonary micro vasculature these vessels are directly associated with the alveolar air spaces and that can

Cause fluid to be in the air spaces and that’s really bad so how can we relieve some of this hydrostatic pressure well how about relieving some of the pressure by decreasing the volume remember compliance is how much these vessels can accommodate changes in volume per units of pressure if you decrease the volume being delivered aka decreased the preload and

You decrease the volume within these vessels and then therefore you decrease the pressure which means that you have a less of a driving force or pc because there’s less pressure within the capillary and less fluid will be pushed across into the alveolar air spaces in interstitium of the lung parenchyma this is super high yield because it makes you understand the

Physiology behind pulmonary edema and the physiology behind augmenting these capillary starling forces using this equation to save your patient from feeling like they’re suffocating so let’s go ahead and talk about the toxicities that are particularly high yield for step one so believe it or not people actually work in industrial settings in which they produce

These drugs and there could be an exposure to inhalation or absorption via the nasal mucosa of these nitro vasodilating agents so during the work week monday through friday which we all love these workers are exposed to these drugs and they develop a tolerance so that every day when they’re exposed they don’t vasodilate as prominently as you would expect and

Remember they are particularly veno dilating instead of vaso referring to the arteries but when they go home for the weekend so friday night through sunday night this tolerance kind of starts to fade so just think about it as if they’re constantly being exposed every time they go to work they always have the nitric oxide circulating around the system the nitric

Oxide is quickly degraded so if you do not have continued exposure friday night through sunday night you quickly lose the nitric oxide circulating around your blood that you had excess levels of because you were at the workplace so it’s not really per se tolerance but it’s a great way to think about it so when they come back to work on the next monday they’re

Re-exposed to those agents and they have a vasodilatory response and then they get the side effects so again we vasodilate drop our blood pressure and this can lead to a reflex tachycardia this can lead to hypoperfusion of important structures such as the brain this can lead to dilated meningeal arteries which irritates the meninges and gives you a headache

Because there’s nerve terminals in those meninges it can give facial artery branch flushing because you increase the diameter of the vessel and making it closer to the superficial skin surface you get nice and cherry red looks another important situation and probably the most high yield because your patients actually come into the clinic and ask about it so

Have you seen those viagra or cialis commercials they usually end with a couple just hugging it out and the announcer saying in the closing segments do not take if you are currently taking nitrates for chest pain now why would that be a bad idea to take a viagra or cialis which are phosphodiesterase inhibitors so you want an erection but you’re also nitrates

For chest pain why is that a bad idea well the nitro vasodilators cause an increase in cyclic gmp so these guys cause increase in cyclic gmp which affects mainly the veins in the situation of nitroglycerin and isoscele by nitrate but also a slight arteriolar component we’re accumulating cycle gmp because we want that erection and we’re also curating cycle gmp

In the situation of nitroglycerin but the two different ways nitroglycerin and isosceles by nitrate cause induction of phonocyclase to get more cyclic gmp and viagra works by inhibiting the breakdown of cycad gmp which is done by the phosphodiesterase enzyme so now we have increased our cyclic gmp by two different mechanisms and this is incredibly dangerous

Because we’ll get excessive dilation of veins and some arterioles which can cause an unsafe drop in blood pressure which means that if you cause a sufficient enough decrease in blood pressure you actually hypoperfuse important structures such as the brain and the heart particularly the coronary arteries so that is why you must listen to that guy at the end of

The viagra commercials who sounds like no one that talks in real life

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nitroglycerine isosorbide dinitrate By medical leactures