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On Mon, 08 Jul 96 16:52:15 EDT, you wrote: >John Dunk wrote: > >>>You keep making this claim but have not supplied any proof. >>> >>>So in the case of *dissolved* N2, just how is it that it's >>>distribution and elimination depend on Vd ? >> >>The statement about drug elimination is correct.I'm still not sure if >>it is correct to consider N2 as a drug (waiting for some clarification >>from Pete myself on this) but his premise on volume of distribution is >>a known pharmacological relationship. >> >>Volume of distribution is based on a known quantity of a drug >>divided by the concentration achieved when that drug is dissolved. >>Example: say you had 10 grams of a drug,and a swimming pool of unknown >>volume.you dissolve the drug in the pool & then take a sample and >>assay it for concentration.Let's say it shows a concentration of >>01grams/liter.You can then determine that the volume of the pool is >>1,000 liters by a simple math relationship.In the body,the fluid >>sampled is blood.Now here's where Vd comes into play.Not all of a >>dissolved drug is contained in the bloodstream.Sometimes the drug is >>taken up in the tissues,resulting in a higher than expected Vd.For >>instance,disolve that same 10 grams of a particular drug in the >>body,and you might find a concentration of .001 grams/liter,giving you >>an APPARENT volume of distribution of 10,000 liters.Now we all know >>that the body does not contain 10,000 liters of fluid;what has >>happened is some of the drug has been taken up by the tissues,and does >>not show up as concentration in the bloodstream.In order for this >>concentration to be eliminated,it must first move out of the tissues & >>into the bloodstream. > >You use the total quantity and the volume to derive a concentration. >I assume you agree to that the amount of drug and the volume of >the pool (Vd) is unimportant and that the significant parameter >is the *concentration*. read the post a little closer.In the first place,as I said,I'm still not sure you CAN treat N2 as a drug for the purposes of relating DCS to drug toxicity.I said his statement regarding Vd and k as it relates to DRUG elimination was correct.That's all(or at least that's all I intended).I dont think Vd is necessarily unimportant,however.It's an indication of how much of the substance is taken up by tissues,bound to protein,or otherwise generally unavailable in a free state to the circulatory system. > >If you agree to that the blood is always saturated with N2 you have >your concentration directly. Yes,concentration in the blood,but that is obviously not the only factor here.Otherwise,why do we use so many different tissue compartments in determining decompression?as a fluid the blood probably does equilibrate almost immediately with the ambient pressure,but the other tissues do not.each tissue type effectively has its own k factor.Here's where APPARENT volume comes in. >You state that sometimes N2 is taken up in tissue. >I submit that the *concentration* of N2 in tissue groups >are mathematically related to the concentration of N2 in >the blood. I.e., the Haldanean model has for about 100 years >done directly what Peter wants to do through measurements >of N2 uptake and Vd measurements. no argument here (i think)that the concentration in the tissues bears a mathematical relationship to the PPN2 in the blood .But I understood Pete's post to mean that he wants to expand the model to show the conditions of saturation/elimination profile that result in actual DCS,based on a total quantity of N2 held in the entire body. whether THIS statement is valid,I'm not knowledgeable enough to say.the problem has been that it is very difficult to directly analyze the quantity of a dissolved substance directly in the tissues.That's why Vd and k are used to interpolate the quantity of a substance held in the tissues based on the known amount introduced to the system and how much actually shows up in the circulation. > >>Clearance is defined as the rate the drug is >>eliminated ( in liters/hour) and is equal to Vd times k (k being an >>elimination constant for that particular drug). > >And if the lung's k(N2) is very large, ppN2 in the blood is fixed >to ppN2 ambient. Then use ppN2(tissue) = function of ppN2(blood) >and Vd never has to enter. Sure it does.Apparent Vd is what you use to determine that function. >>There can be many other factors that influence the rate at which a >>drug is absorbed/eliminated in the body,but Vd and k are two of the >>major ones FOR A DRUG. > >But maybe there is a better way to specify elimination of drugs >diven given based on partial pressures as opposed to doses measured >in grams ? unless it's a dissolved gas,it doesnt have a partial pressure.it may have an osmotic pressure,but that's not the same thing. >John >cc015012@br*.br*.ed* John L. Dunk Tallahassee,Fl. screwloose@ne*.co*
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