Sodium Nitrite/HNO2

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DocJD

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I am inquiring about the process of conversion of sodium nitrite into HNO2 in the human body (lung). Specifically, how to develop an inhalation solution of sodium nitrite at 15 mM nitrite (NO2) at a pH of 6.5. Any information or helpful reference material would be appreciated as I am writing a paper. Thank you!
 
Thank you for your response npage148. Recent research has suggested that sodium nitrite has the ability to kill mucoid pseudomonas aeruginosa. A lung bacteria that is resistant to conventional anti-biotics.
 
There's a pretty wide variety of buffering solutions available for compounding ophthalmic preparations. Find one that's chemically compatible and physiologically appropriate to put in the lung and you have your answer.
 
Thank you for your response npage148. Recent research has suggested that sodium nitrite has the ability to kill mucoid pseudomonas aeruginosa. A lung bacteria that is resistant to conventional anti-biotics.

Is it due to nitric oxide formation (NO)? then you might be better off administering straight NO or some NO donor instead of acidified nitrite.

I imagine though that the treatment may not be safe. Aside form pulmonary vasodilation, you are going to be introducing huge oxidative stress to the local tissue.
 
[solution of sodium nitrite at 15 mM nitrite (NO2) at a pH of 6.5.]


sodium nitrite has a molecular weight of 68.99 g/mol ([FONT=Arial, Helv, Sans-Serif][SIZE=-1]22.989+[/SIZE].[FONT=Arial, Helv, Sans-Serif][SIZE=-1]14.006+2*[/SIZE].[FONT=Arial, Helv, Sans-Serif][SIZE=-1]15.999[/SIZE].)


so

If you want to make a one liter solution of 15 mM,
you will need 1 liter of ddH2O + 15 *10^-3 mols of NaNO2

15 mM = 15 * 10^-3 mols / L

15 * 10^-3 mol (68.99 g / mol) = 1.035 g

Dissolve 1.035 g crystalline NaNO2 into 1 liter of ddH2O and you will have one liter of 15 mM NaNO2 solution.

Now you must pH the solution, stick in a sterile pH meter and see what pH its at. Make sure there is a magnetic stirbar to mix the solution.

If its higher than 6.5, add HCl very slowly (drop by drop or less) use conc HCl if pH does not change.
If the starting pH is lower than 6.5, add NaOH again drop by drop. This is called adjusting pH, and you must do this very very slowly and carefully or you will overshoot.
 
Excellent information from all who have posted so far. Thank you!
 
Yes npage it has to do with NO and HNO2 conversion in the lung. The bacteria does not have the enzymes to disponse of the nitrite and nitric oxide so it then dies. And yes toxicity and tissue damage are real concerns. Thank you for your responses.
 
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not to be rude but what does a psychologist want to know this info? We cannot give medical advice on this board. Certainly administering a fluid into the lung is not safe.

why cant antibiotics work again?
 
Hi quicksilver, certainly not requesting medical advice as the post suggests jst inquiring info as most everyone else is on here. Also, the method of administration would not be liquid directly into the lungs rather would be nebulized in aerosol form. This is actually being done, however, wanted to know more about the chemistry behind the specifics. Thank you for your input and inquiry.
 
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I GOT IT!. you need to make an NO donor that exploits an uptake transporter that is only expressed in bacteria. you could also go one step further and make the bioactivation mediated by a bacterial enzyme. Then you'd have very little host toxicity.
 
I have seen some research that has used the NONOate donors for vasodialation in hypertension, however, for this use the PH would be a concern since in some of those studies the PH was at around 7.5. When lowering the PH the NONOate became unviable. Also, the half-life of the donor would be of concern as in biological use it would need to last more than several minutes (a sustained release). Excellent ideas npage! Some good food for thought...I will continue researching these ideas.
 
Deta NONOate has a t1/2 of about 20 hours at pgy PH, while Dea NONOate has about a 16 min half life. Both release faster are lower pH's. But if you are giving it as a nebulized tx, you could treat for like an hour a day 4 times a day or something. Sure that sucks but PA in a CF patient is a big problem and this may be acceptable. Maybe time it with the percussion tx.

http://www.caymanchem.com/app/template/Product.vm/catalog/82120/a/z
http://www.caymanchem.com/app/template/Product.vm/catalog/82100/a/z
 
Half life is adequate, however, ph at 7.4 too high. Would have to be in range of 6.5 to be effective in killing the PA. Good website link to find others possibilities! Thanks!
 
Half life is adequate, however, ph at 7.4 too high. Would have to be in range of 6.5 to be effective in killing the PA. Good website link to find others possibilities! Thanks!

I'm not sure if you would need the acidic pH for NONOates. You need a low pH with nitrite ions because the reaction of nitrite to reactive nitrogen species takes place only at an acidic pH. Since you are using an agent which spontaneously releases NO at a neutral pH may work. I'd guess you'd have to try it
 
Sound theory...i'm wondering if the amount of NO released would be in sufficient amounts. I believe from my reading that the more acidic the ph the more NO released. However, this is when using sodium nitrite and not the donor.
 
sodium nitrite release at a 1 to 1 rate while NoNoates are at 2 NO to 1 mol of donor. The rate of release could be controlled by pH, but also the buffering capacity of the lungs would probably neutralize the solution pretty efficiently
 
Thank you for your input npage!!
 
Hi doc JD did you ever get to try the sodium nitrite > My son has Cf and we are currently trying sodium nitrite
 
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