Pharmacokinetics of inhaled anesthetics

[LuckiestOne]

There's a US WORLD q that asks about inhaled anesthetic and the pharmacokinetics and I am having trouble understanding the explanation that they provide.

I understand that blood:gas partition coefficient is inversely proportional to the speed of onset/offset.

1. US World explanation says that blood:lipid partition coefficient is a measure of the solubitliy of anesthetic in tissue, and it is directly proportional to the arteriovenous concentration gradient. Highly lipid-soluble anesthetics have high blood:lipid partition coefficient, high arteriovenous concentratino gradient, and slow onset of action.

I am confused by this statement because high blood:lipid partition coefficient means that there's more drug solubilized in the blood that lipid, right? So just like having high blood:gas coefficient, I see that it may cause slow onset of action.

But how does that relate to arteriovenous concentration gradient? If the blood:lipid coefficient is higher then less of the drug is absorbed through the tissue as it circulates from arteries to veins and shouldn't it have LESS arteriovenous concentration gradient?

2. Another explanation of an answer choice says steepness of arterial tension curve depends on solubility of anesthetic in the blood. In less soluble gases, the partial pressure in the blood rises rapidly, and the curve is steep.

I am not sure what arterial tension curve has to do with partial pressure of the anesthetic. if anyone can provide some clarification it would be great! Thanks.

The question ID is 8831491 if anyone wants to take a look at it.

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[Dallas]

For question 1, I think you have it backwards on blood:lipid coefficient. Lippincott says that a low soluble gas like nitrous oxide has a low MAC and a highly lipid soluble anaesthetic has a high MAC (makes sense, high lipid solubility more drug needed to sedate 50% of people). Thus the potency is inversely proportional to MAC and is defined as 1/MAC.

This gives low lipid soluble anaesthetics a high potency and a high 1/MAC. I think you are confusing 1/MAC for blood:lipid coefficient without taking into consideration that it is inversely proportional.

For question 2, the arterial tension curve is the driving force behind the delivery of the anaesthetic. In low blood soluble anaesthetics the coefficient is small, and thus very little gas is required to reach full saturation in blood. Thus the curve is going to be steep upwards in saturating the blood with the gas because the partial pressure in alveoli will quickly match (and thus fully saturate) the partial pressure of anaesthetic saturated in blood.

 

[LuckiestOne]

For question 1, I think you have it backwards on blood:lipid coefficient. Lippincott says that a low soluble gas like nitrous oxide has a low MAC and a highly lipid soluble anaesthetic has a high MAC (makes sense, high lipid solubility more drug needed to sedate 50% of people). Thus the potency is inversely proportional to MAC and is defined as 1/MAC.

This gives low lipid soluble anaesthetics a high potency and a high 1/MAC. I think you are confusing 1/MAC for blood:lipid coefficient without taking into consideration that it is inversely proportional.

For question 2, the arterial tension curve is the driving force behind the delivery of the anaesthetic. In low blood soluble anaesthetics the coefficient is small, and thus very little gas is required to reach full saturation in blood. Thus the curve is going to be steep upwards in saturating the blood with the gas because the partial pressure in alveoli will quickly match (and thus fully saturate) the partial pressure of anaesthetic saturated in blood.

Thanks, Dallas. I understand the relationship between the MAC and potency, I guess I am confused to why they did not write it as lipid:blood coefficient rather than blood:lipid coefficient. High blood:lipid coefficient makes it seem like there's more drug solubilized in the blood and thus the drug is less lipophillic. Should I just regard as high blood:lipid coefficient = high lipophillicity?