Renal failure and pseudocholinesterase

[Amik25]

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Can someone please explain to me why patients with renal failure have decreased levels of psuedocholinesterase? I have tried to look this up in Baby Miller, Morgan & Mikhail, Big Miller, and Stoelting's Pharmacology but to no avail. They all just basically state that levels are decreased and I would really like to understand why.

Thanks,
Ami

 

[Cap'nOblivious]

I believe there have been a few studies on prolonged effects of mivacurium in patients with renal and/or hepatic failure....You should look into these and come back and share.

Can someone please explain to me why patients with renal failure have decreased levels of psuedocholinesterase? I have tried to look this up in Baby Miller, Morgan & Mikhail, Big Miller, and Stoelting's Pharmacology but to no avail. They all just basically state that levels are decreased and I would really like to understand why.

Thanks,
Ami

 

[Amik25]

I actually found several of those studies yesterday but could not get to the full text on Med-line so I couldn't read them, only the abstracts.

 

[proman]

I would ask my local medical/hospital library to get copies of the three articles cited by Miller (88,89,90) in the chapter.

 

[SleepIsGood]

post the names of the articles with the author and title. I'll try to look it up for you on PubMed (I have access to some of the 'entire text') stuff. I can then try to post it on here/PM it to ya 👍

 

[sdn1977]

If I remember correctly, this is due the the decreased affinity of the esteratic binding site on the enzyme due to the pH change. Altho ester hydrolysis is affected by pH, those pH effects don't occur within the physiologic range. But...it can affect the affinity of the binding site.

I'd have to go way, way back to my pharmaceutical chemistry stuff to get a reference for you, but I'll try when I get time.....

 

[sdn1977]

I found a very old article...but it may be a start for you:

pH-Dependence of Enzymatic Ester Hydrolysis - Biochem.J. 1956 (63)684-690. You may be able to find more recent literature, but it will be in clinical chemistry or biochemistry literature.

As I said....really, really, old. But..I'm not sure how much work is actually being done on the "whys" & "what's" of why pseudocholinesterase activity is diminished in renal failure. I think because its of not importance until you present something which needs to be hydrolyzed. So...most of the recent articles are on actual drug metabolism by pseudocholinesterase in different clinical conditions & that info is found within specific drug studies & pharmaceutical chemistry literature.

But...I think with a bit of searching, the binding sites on the enzyme are influenced by pH & temperature changes.....

 

[md2k]

I found a very old article...but it may be a start for you:

pH-Dependence of Enzymatic Ester Hydrolysis - Biochem.J. 1956 (63)684-690. You may be able to find more recent literature, but it will be in clinical chemistry or biochemistry literature.

As I said....really, really, old. But..I'm not sure how much work is actually being done on the "whys" & "what's" of why pseudocholinesterase activity is diminished in renal failure. I think because its of not importance until you present something which needs to be hydrolyzed. So...most of the recent articles are on actual drug metabolism by pseudocholinesterase in different clinical conditions & that info is found within specific drug studies & pharmaceutical chemistry literature.

But...I think with a bit of searching, the binding sites on the enzyme are influenced by pH & temperature changes.....

I think you may be on the right track. Im not sure, but with renal failure you have a decrease excretion of H+ ions leading to decrease in pH. I think that the pH changes may affect the enzymatic abililty of the plasmachollinestrase or it may affect the substrates ability to form the pseudocholinestrase in the liver. Is a quantitative effect or does is affect the quality of the enzyme itself? I think possibly both. Also with renal faiulre you may develop uremia which is known to decrease pseudocholinesterase. Is this the cause? The buildup of Nitrogenous end products??? Let me know if you find the answer. 😀