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Comment by nkrumm | Hacker News Reader

Everyone is welcome to take their own health into their own hands. However, for others looking to this as advice, please be aware that:

1) ACE inhibitors (lisinopril, etc.) are generally though to be enzymatic inhibitors of ACE, not ACE2 [1]. Also, enzymatic inhibition of the enzyme does not mean that it will prevent a virus from using that protein as an entry mechanism.

2) Chloroquine is an old drug with a well known safety profile, but it is certainly not a "safe" drug-- there are many known side effects including life threatening or severely disabling ones. As an MD, I recommend always consulting with your own medical provider(s) before starting any medications.

[1] e.g., https://www.ncbi.nlm.nih.gov/pubmed/15897343

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> ACE inhibitors (lisinopril, etc.) are generally though to be enzymatic inhibitors of ACE, not ACE2

Correct. Ace inhibitors have shown no effect on ACE2.

https://www.nrcresearchpress.com/doi/10.1139/y02-021

Some more recent research seem to at least partially contradict this statement and seem to suggest ACE inhibitors do affect ACE2.

https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1440-1681....

https://www.ncbi.nlm.nih.gov/pubmed/15897343

In addition there is also this specific recent Covid19 paper which does cautiously attract attention on this matter.

https://www.nature.com/articles/s41569-020-0360-5

I had a talk with 2 cardiologists and their response (this is not medical advice, talk to your cardiologist) was that it would be reasonable at least until further research is completed to for instance switch medication from ACE inhibitors to a Calcium Channel Blocker (such as Lercanidipine). At least until the pandemic gets under control and/or vaccine/treatment is available and validated.

There are very few cons to this safety measure if this can prevent complications. But that's my sole opinion and again, not medical advice. This might be worth at least an inquiry to your cardiologist. Especially if you're over 60.

(Sorry for by bad English, not a native speaker)

I thought your English was great. Your post is perfectly readable. :)

I am a native English speaker, and your English was literally flawless.

Your English is fine.

However, your first two papers seem to state ACE inhibitors makes ACE2 worse in terms of COVID-19.

"Losartan increased plasma levels of both Ang II and Ang-(1-7), as well as cardiac ACE2 mRNA and cardiac ACE2 activity"

The last one does nothing except say, "someone should look at it."

upregulation of ACE2 means the mRNA that is responsible for the code to make ACE2 protien is being transcribed.

this does not mean the ACE2 enzyme activity or concentration is increased

So, looking at the NIH conclusion, if I'm on a *saratan and read this:

"Selective blockade of either Ang II synthesis or activity induced increases in cardiac ACE2 gene expression and cardiac ACE2 activity, whereas the combination of losartan and lisinopril was associated with elevated cardiac ACE2 activity"

should I check in with my cardiologist?

first off drugs that influence the components of the RAS are not childs play, so yes consult your doctor[s] rather than experimenting with dosages.

This is only just starting to see clinical trials, meaning the people involved are under direct physician supervision.

regarding ACE2:

this increased production of ACE2 is an indirect effect of ACE2 disruption.

you have to be careful with these sorts of experiments. when you block angiotensin II receptors that means there is a reduction of signal for angiotensin II being present.

This angiotensin that would ordinarily be interacting with the ATreceptors is now available for ACE2 to operate upon.

the summary here is that increased enzymatic product doesnt mean the enzyme has been "turbocharged" . If there is an increased ratio of reactants to products this will cause increased concentration of products in total but does not change the intrinsic rate at which the enzyme actually operates.

This looks like a case of substrate concentration dependent equilibrium driving reaction rate.

Thank you very much for the info and taking a look at it!

basically ACE2 is a regulator that converts between angiotensin II <--> angiotensin 1,7

these have opposite effects , angiotensin II is a vaso-constrictor, thus increases blood pressure.

angoitensin 1,7 is a vaso-dialator, thus decreases blood pressure. so there is an equilibrium state of the two established by ACE2. this is something that ACE inhibitors or ARB blockers dont directly influence.

Your english is fine! Better than mine and I have been a native speaker for 32 years!

Everyone is welcome to take their own health into their own hands.

Since when? Last time I checked my body my choice does not apply to the vast majority of pharmaceuticals unless a third party approves it.

It is illegal to take them? Or are you merely referring to the fact that it's illegal to sell them?

Since that's the only legal way of acquiring them, yes.

Did you check using a for loop or a while loop?

I think it wasn't ACE inhibitors but sartans (telmisartan losartan, etc.) that were being discussed as possible prophylaxes, potentially via inhaler.

Consulting with your medical provider so they can deny life saving drugs to you?

Your GP knows what other drugs you are on (maybe not in your case) and can tell you about counter-indications when combining them. Could easily save your life.

But go ahead, see a witch doctor and a herbalist and take some random medication you read about in the internet.

Hopefully your GP can tell you about counter-indications when combining drugs. There is a lot to stay on top of as so much new research is being done so often. Also, things like pharmacogenetics are often not considered to the extent that they maybe should be. In taking drugs, I'd say do your own research and talk to your GP.

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