ACE Cough

[tpchristifulli]

What is the mechanism of action behind the dry cough associated with people who begin taking ACE Inhibitors? I know that the angtn1 to angtn2 primarily takes place in the lungs, wonder if this plays into the MOA?

 

[JPINFV]

ACEi increases bradykinin levels, which can lead to bronchoconstriction, and thus coughing.

 

[Ewok Jerky]

The renin-angiotensin-aldosterone system is the main pathway of physiologic control of blood pressure. It can get pretty complicated but a thorough understanding can be very beneficial at all levels of medicine.

When the kidneys sense a low BP a cascade is set in motion, a component of which involves angiotensin 1 being converted to angiotensin 2 by angiotensin-converting-enzyme (ACE). Angiotension 2 continues along the pathway eventually raising blood pressure through vasoconstriction and increasing renal sodium retention. Another function of ACE is to metabolize bradykinin (which as a vasodilator, lowers BP) making it inactive. Bradykinin also acts as a broncho constrictor.

One way to combat HTN is to interrupt the the renin-angiotensin-aldosterone pathway. ACE inhibitors simply block the enzyme from converting A1 to A2, and in the process ACE is also blocked from deactivating bradykinin, leading to a build up of bradykinin and in some people increased bronchoconstriction leading to dry cough.

If ACEi are causing a problem we can also interrupt the pathway somewhere else, with a different class of medications...anyone anyone beuller?

 

[Akulahawk]

The renin-angiotensin-aldosterone system is the main pathway of physiologic control of blood pressure. It can get pretty complicated but a thorough understanding can be very beneficial at all levels of medicine.

When the kidneys sense a low BP a cascade is set in motion, a component of which involves angiotensin 1 being converted to angiotensin 2 by angiotensin-converting-enzyme (ACE). Angiotension 2 continues along the pathway eventually raising blood pressure through vasoconstriction and increasing renal sodium retention. Another function of ACE is to metabolize bradykinin (which as a vasodilator, lowers BP) making it inactive. Bradykinin also acts as a broncho constrictor.

One way to combat HTN is to interrupt the the renin-angiotensin-aldosterone pathway. ACE inhibitors simply block the enzyme from converting A1 to A2, and in the process ACE is also blocked from deactivating bradykinin, leading to a build up of bradykinin and in some people increased bronchoconstriction leading to dry cough.

If ACEi are causing a problem we can also interrupt the pathway somewhere else, with a different class of medications...anyone anyone beuller?

I'll take ARBs for $200...

 

[tpchristifulli]

Beta or calcium channel blockers?

 

[Aprz]

Damn it, Akulahawk! You stole my answer!

 

[Ewok Jerky]

ARBs, AKA angiotensin 2 receptor blockers. The -sartan drugs (losartin, valsartin etc.)

This class works by blocking the pathway further down the cascade. By blocking the angiotensin 2 receptors down in the kidney, ACE is free to deactivate bradykinin, preventing the cough side effect, while still stopping renin-angio-aldo from raising blood pressure.

renin-angio-aldo...there is still another class of medication further down the cascade...although not used for blood pressure control.

 

[Underoath87]

ARBs, AKA angiotensin 2 receptor blockers. The -sartan drugs (losartin, valsartin etc.)

This class works by blocking the pathway further down the cascade. By blocking the angiotensin 2 receptors down in the kidney, ACE is free to deactivate bradykinin, preventing the cough side effect, while still stopping renin-angio-aldo from raising blood pressure.

renin-angio-aldo...there is still another class of medication further down the cascade...although not used for blood pressure control.

That's a pretty open-ended question. Could you narrow it down a bit for us?

 

[Ewok Jerky]

hint 1: renin-angiotensin-ALDOSTERONE

hint 2: Al likes salt.

 

[STXmedic]

That's a pretty open-ended question. Could you narrow it down a bit for us?

I'm assuming he's referring to Aldosterone receptor antagonists, ie Spironolactone.

 

[STXmedic]

hint 1: renin-angiotensin-ALDOSTERONE

hint 2: Al likes salt.

You have impeccable timing... Lol

 

[tpchristifulli]

I had read that the right atrium regulates renin as well

 

[STXmedic]

I had read that the right atrium regulates renin as well

Via ANP, yeah?

 

[Brandon O]

ANP actually does its own thing. (Well, I think it actually does have some effect on renin -- it has a bunch of pathways -- but that's not its main show.)

One of the tricky things about BP regulation is not just how many mechanisms are involved, but how many of them are totally separate and run by different organs... and they don't always agree.

 

[Underoath87]

I'm assuming he's referring to Aldosterone receptor antagonists, ie Spironolactone.

Spironolactone is a diuretic, so it is used to control BP (which Beano stated it isn't used for).

 

[Nova1300]

I don't know if you guys are running across Tekturna, but it's another option for that same pathway.

http://en.m.wikipedia.org/wiki/Aliskiren

 

[samiam]

Just want to point out that these are all "theories" and there have not really been too many resultant studies on this. Its still not officially known what causes it. At one point the brakdykinin theory was the main idea but the recent literature I have been reading thinks there is something more complex going on even though they dont exactly know. Something with NO (Nitric Oxide) and Arachidonic acid causing cascading pro-inflammatory responses.

 

[Handsome Robb]

I'm assuming he's referring to Aldosterone receptor antagonists, ie Spironolactone.

I thought ARBs were "sartans". Isn't Aldactone a diuretic?

EDIT: I'm way slow on that one haha

 

[STXmedic]

I thought ARBs were "sartans". Isn't Aldactone a diuretic?

EDIT: I'm way slow on that one haha

ARB: Angiotensin II Receptor Blocker (-sartans) [emoji6]