Fa/Fi ratio question

[RT2MD]

We are in our pharm block now, and I am studying for our final. I noticed on a graph about the Fa/Fi of various inhaled agents, nitrous oxide reaches a higher ratio (faster) than desflurane. I'm a little confused as to why this is, since Des has a lower blood:gas partition coefficient. Shouldn't that mean that Des would reach a higher ratio faster? I have a couple of ideas to explain what happens, but don't know what the right answer is... I would be very interested in any explanations:

1) Does the size of the molecule cause a difference in diffusion, resulting in the lower ratio?

2) Could the fat:blood partition coefficient play any part in this? I know the coefficient is ~10 x more for desflurane. Can the difference be explained by the fact that there is so much more des being taken up into adipose? Wouldn't you eventually exhaust that adipose 'sink' and see the ratio approach 1?

Thanks in advance for any help!

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[vector2]

We are in our pharm block now, and I am studying for our final. I noticed on a graph about the Fa/Fi of various inhaled agents, nitrous oxide reaches a higher ratio (faster) than desflurane. I'm a little confused as to why this is, since Des has a lower blood:gas partition coefficient. Shouldn't that mean that Des would reach a higher ratio faster? I have a couple of ideas to explain what happens, but don't know what the right answer is... I would be very interested in any explanations:

1) Does the size of the molecule cause a difference in diffusion, resulting in the lower ratio?

2) Could the fat:blood partition coefficient play any part in this? I know the coefficient is ~10 x more for desflurane. Can the difference be explained by the fact that there is so much more des being taken up into adipose? Wouldn't you eventually exhaust that adipose 'sink' and see the ratio approach 1?

Thanks in advance for any help!

Nitrous having a higher ratio is due to the higher tissue:blood solubility of the other volatile anesthetics according to baby miller (predominantly fat as you pointed out). As for exhausting the adipose reservoir, someone with greater expertise in the specific kinetics will have to address that one....here are the relevant baby miller graphs:

 

[RT2MD]

Thank you for the reply. 👍

 

[lord_jeebus]

I think that the tissue:blood solubility is not a significant factor compared to the "concentration effect," especially early on that curve. I don't have the strength to explain the concentration effect this morning, but I found a paper and a few links:

http://www.pharmacology2000.com/physics/Chemistry_Physics/physics10.htm
http://web.squ.edu.om/med-Lib/MED_CD/E_CDs/anesthesia/site/content/v02/020065r00.htm

It's definitely not diffusion limitation, the uptake of both N2O and Desflurane is perfusion-limited at pretty much any physiologic level of cardiac output.

 

[RT2MD]

Thanks for the links to that paper/sites. I checked them out, this is what I am taking away from this discussion:

It seems that the difference between the curves can be explained by the concentration effect, which is based on the fact that the inhaled concentrations of nitrous oxide are so much higher than desflurane (or any others, for that matter). The tissue:blood solubility might play some role in this process, but not nearly as significant as the concentration effect, and my idea about diffusion differences is pretty much wrong. 😎

I hope I'm getting that right. I guess it's back to studying things that are less interesting, but more relevant for my tests next week.