ACE inhibitors

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thecalccobra

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How do ACE inhibitors cause dry cough? I know they increase Bradykinin levels and that Bradykinin is a vasodilator but how would that have anything to do with cough? Is it because Bradykinin also has a Histamine-like action and stimulates allergic reactions?

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How do ACE inhibitors cause dry cough? I know they increase Bradykinin levels and that Bradykinin is a vasodilator but how would that have anything to do with cough? Is it because Bradykinin also has a Histamine-like action and stimulates allergic reactions?

While this is a good question and I applaud your interest in it the most important thing you need to get out of it is the cough can lead to discontinuation of use.

The irony of it all is ARB's still cause dry cough its just less common (Google search one study says equal to placebo, but <<< ace inhibitor).

Good luck.
 
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Increased vasodilation means edema is more likely. More fluid in bronchi ---> cough
 
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While this is a good question and I applaud your interest in it the most important thing you need to get out of it is the cough can lead to discontinuation of use.

The irony of it all is ARB's still cause dry cough its just less common (Google search one study says equal to placebo, but <<< ace inhibitor).

Good luck.
How is that irony?
 
How is that irony?

Because the whole point of ARBs is you bypass bradykinin production to prevent cough. And yes the bradykinin is what causes the cough, according to the cardio i shadowed in school

(MS1 u mirin?)
 
If you REALLY want the answer, its a little long winded.

Let's back it up a little.

There are a couple of forces at work when it comes to fluid out of a capillary.

First You have the Hydrostatic Capillary Pressure pushing fluid out into the interstitium and the Hydrostatic Interstitial Pressure pushing fluid back into the capillary. The capillary hydrostatic pressure is usually stronger, this pushes fluid out.

Next you have the oncotic capillary pressure pulling fluid into the capillary from the intersititum. These are osmoles like protein and red blood cells. The interstitium SHOULDNT have a whole lot of protein, so the oncotic interstitial pressure pulling fluid out is negligible. The capillary hydrostatic pressure is usually stronger, pulling fluid in.

Overall, the hydrostatic capillary pressure pushing fluid out is stronger in the arterial side of the capillaries (pushing fluid out) and weaker on the venous side (which is why most fluid comes back into the venous system instead of causing edema). Your questions focuses on the arterial side.

Finally, there is the permeability coefficient, K. The tigheter the endothelial cells are linked together, the less diffusion there can be. The wall is tighter. The looser they are connected the more fluid can move. "K is a Konstant" mathematically, but it can be changed, influenced by hormones and cytokines.

Maybe you remember this from physio?

Diffusion = K [(Pcap-Pinter) - (pcap - pinter)]
K goes up = more fluid shift (think the liver)
K goes down = less fluid shift (think the blood brain barrier)​

In the case of ACE-inhibitors, excess bradykinin production in the lungs results in "vasodilation." But what it ACTUALLY MEANS is that the walls of the endothelium get looser. K goes up. K goes towards 1. That means ALOT of fluid can now move. With hydrostatic capillary pressure winning the day, fluid leaks out into the interstitium, which both interferes with gas exchange and acts an irritant.

You cough.

Theoretically, switching from an ACE-inhibitor (works "in the lungs" where "Ang I is converted to Ang II") to an ARB (works "at the kidneys" where "Ang II activates the receptors") should eliminate the excess bradykinin, and with it, vasodilation, permeability, and fluid shifts into the interstitium

The summary "bradykinin's histamine-like activity" sums it up, but without understanding the fundamentals, other's reading this might miss what that means.
 
Because the whole point of ARBs is you bypass bradykinin production to prevent cough. And yes the bradykinin is what causes the cough, according to the cardio i shadowed in school

(MS1 u mirin?)
I'm not sure what the parenthetical aside means, but if arbs cause less cough than standard ace inhibitors, where is the irony?
 
If you REALLY want the answer, its a little long winded.

Let's back it up a little.

There are a couple of forces at work when it comes to fluid out of a capillary.

First You have the Hydrostatic Capillary Pressure pushing fluid out into the interstitium and the Hydrostatic Interstitial Pressure pushing fluid back into the capillary. The capillary hydrostatic pressure is usually stronger, this pushes fluid out.

Next you have the oncotic capillary pressure pulling fluid into the capillary from the intersititum. These are osmoles like protein and red blood cells. The interstitium SHOULDNT have a whole lot of protein, so the oncotic interstitial pressure pulling fluid out is negligible. The capillary hydrostatic pressure is usually stronger, pulling fluid in.

Overall, the hydrostatic capillary pressure pushing fluid out is stronger in the arterial side of the capillaries (pushing fluid out) and weaker on the venous side (which is why most fluid comes back into the venous system instead of causing edema). Your questions focuses on the arterial side.

Finally, there is the permeability coefficient, K. The tigheter the endothelial cells are linked together, the less diffusion there can be. The wall is tighter. The looser they are connected the more fluid can move. "K is a Konstant" mathematically, but it can be changed, influenced by hormones and cytokines.

Maybe you remember this from physio?

Diffusion = K [(Pcap-Pinter) - (pcap - pinter)]
K goes up = more fluid shift (think the liver)
K goes down = less fluid shift (think the blood brain barrier)​

In the case of ACE-inhibitors, excess bradykinin production in the lungs results in "vasodilation." But what it ACTUALLY MEANS is that the walls of the endothelium get looser. K goes up. K goes towards 1. That means ALOT of fluid can now move. With hydrostatic capillary pressure winning the day, fluid leaks out into the interstitium, which both interferes with gas exchange and acts an irritant.

You cough.

Theoretically, switching from an ACE-inhibitor (works "in the lungs" where "Ang I is converted to Ang II") to an ARB (works "at the kidneys" where "Ang II activates the receptors") should eliminate the excess bradykinin, and with it, vasodilation, permeability, and fluid shifts into the interstitium

The summary "bradykinin's histamine-like activity" sums it up, but without understanding the fundamentals, other's reading this might miss what that means.
You excel at emphasis.
 
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I'm not sure what the parenthetical aside means, but if arbs cause less cough than standard ace inhibitors, where is the irony?

They still cause cough...are you that thick? He was infinitely curious about the cough which has been determined to be bradykinin related, hence a ARB not leading to a rise in bradykinin still causing cough being an irony of the significance of that cough. Irony being in the people who still have a cough while taking an ARB my literal friend.

Keep the nose out of the dictionary, it makes life more interesting.
 
The dangers of misinformation over the internet. First there is no known mechanism that is 100 percent. Many speculated pathways, however none of the leading candiates involve what was said above.

The ACE inhibitor cough is thought to be linked to the suppression of ACE, which is proposed to result in an accumulation of substances normally metabolized by ACE: bradykinin or tachykinins (with the consequent stimulation of vagal afferent nerve fibers) and substance P.

Stopping here is one major theory-which is bradykinin (while yes being a dilator) is a major inflammatory initiator which promotes inflammation in the bronchial tissues. Substance P and the like is a direct irritant and direct vagal nerve irritation also incudes cough (just like hiccups from irritated nerves). This is why the characteristic "dry" cough is correct. If the mechanism above were anything to do with it, the cough would not be dry but rather secretions from the excess fluid.

More on bradykinin-it produces arachidonic acid metabolites and nitric oxide, and there is some evidence that these products, which are subject to regulation by other pathways, may promote cough through proinflammatory mechanisms.

As far as ARB's, the likely mechanism involved increased action at angiotensin 2-type 2 receptors which are left unopposed from angiotensin 2 type 1 receptors which mediate the cardiac effects of angiotensin (such as activating aldosterone, pressor effects on vessels, kidney modulation etc.) The angiotensin 2 now is more plentiful to bind to receptor type 2 which among things like helping with apoptosis and contractions of the uterus, increased nitric oxide substantially. This again goes back to induction of inflammatory mechanisms and chemotaxins that are now able to seep into locations previously constricted and act as irritants.

This is the broad conceptual way to think of it as we are just not there yet with complete molecular understanding. But this is the most accurate explanation we have as of now.
 
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They still cause cough...are you that thick? He was infinitely curious about the cough which has been determined to be bradykinin related, hence a ARB not leading to a rise in bradykinin still causing cough being an irony of the significance of that cough. Irony being in the people who still have a cough while taking an ARB my literal friend.

Keep the nose out of the dictionary, it makes life more interesting.

Ah, the OP's infinite curiosity of cough, and dictionaries. Would you mind explaining again how bradykinin and cough are related?

To clarify:
If ARBs cause brady cough less frequently than ace inhibitors, that they still cause cough does not qualify as irony. It would be ironic if ARBs some how caused an increase in cough relative to the prils.
 
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The dangers of misinformation over the internet. First there is no known mechanism that is 100 percent. Many speculated pathways, however none of the leading candiates involve what was said above.

The ACE inhibitor cough is thought to be linked to the suppression of ACE, which is proposed to result in an accumulation of substances normally metabolized by ACE: bradykinin or tachykinins (with the consequent stimulation of vagal afferent nerve fibers) and substance P.

Stopping here is one major theory-which is bradykinin (while yes being a dilator) is a major inflammatory initiator which promotes inflammation in the bronchial tissues. Substance P and the like is a direct irritant and direct vagal nerve irritation also incudes cough (just like hiccups from irritated nerves). This is why the characteristic "dry" cough is correct. If the mechanism above were anything to do with it, the cough would not be dry but rather secretions from the excess fluid.

More on bradykinin-it produces arachidonic acid metabolites and nitric oxide, and there is some evidence that these products, which are subject to regulation by other pathways, may promote cough through proinflammatory mechanisms.

As far as ARB's, the likely mechanism involved increased action at angiotensin 2-type 2 receptors which are left unopposed from angiotensin 2 type 1 receptors which mediate the cardiac effects of angiotensin (such as activating aldosterone, pressor effects on vessels, kidney modulation etc.) The angiotensin 2 now is more plentiful to bind to receptor type 2 which among things like helping with apoptosis and contractions of the uterus, increased nitric oxide substantially. This again goes back to induction of inflammatory mechanisms and chemotaxins that are now able to seep into locations previously constricted and act as irritants.

This is the broad conceptual way to think of it as we are just not there yet with complete molecular understanding. But this is the most accurate explanation we have as of now.

What I placed in bold is what I learned during 1st year
 
The dangers of misinformation over the internet. First there is no known mechanism that is 100 percent. Many speculated pathways, however none of the leading candiates involve what was said above.

The ACE inhibitor cough is thought to be linked to the suppression of ACE, which is proposed to result in an accumulation of substances normally metabolized by ACE: bradykinin or tachykinins (with the consequent stimulation of vagal afferent nerve fibers) and substance P.

Stopping here is one major theory-which is bradykinin (while yes being a dilator) is a major inflammatory initiator which promotes inflammation in the bronchial tissues. Substance P and the like is a direct irritant and direct vagal nerve irritation also incudes cough (just like hiccups from irritated nerves). This is why the characteristic "dry" cough is correct. If the mechanism above were anything to do with it, the cough would not be dry but rather secretions from the excess fluid.

More on bradykinin-it produces arachidonic acid metabolites and nitric oxide, and there is some evidence that these products, which are subject to regulation by other pathways, may promote cough through proinflammatory mechanisms.

As far as ARB's, the likely mechanism involved increased action at angiotensin 2-type 2 receptors which are left unopposed from angiotensin 2 type 1 receptors which mediate the cardiac effects of angiotensin (such as activating aldosterone, pressor effects on vessels, kidney modulation etc.) The angiotensin 2 now is more plentiful to bind to receptor type 2 which among things like helping with apoptosis and contractions of the uterus, increased nitric oxide substantially. This again goes back to induction of inflammatory mechanisms and chemotaxins that are now able to seep into locations previously constricted and act as irritants.

This is the broad conceptual way to think of it as we are just not there yet with complete molecular understanding. But this is the most accurate explanation we have as of now.

Thanks! I get it now.
 
I was in the same quandary now I got it.
 
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