UW Question: 659

[MedicineMike]

---

Members don't see this ad.

I have read this twice answer explanation twice and it still doesn't make sense. I understand if an inhaled anesthetic is less soluble in the blood it has a quicker onset, but that graph does not make sense to me! Can someone explain?

Thx

 

[suji0]

the graph shows "drug A" as having a lower partial pressure in blood compared to NO at all levels

this is because drug A is more soluble, and therefore it gets solubilized and distributed to tissues, and less of it "builds up" and is able to travel to the brain as quickly (because it gets trapped in so many other tissues first)

at least that is how i explained it to myself...again i could be completely wrong or just confusing you more haha.

but simply:

increased solubility -> lower partial pressure because more taken up into other tissues -> less gets to brain as quickly

not soluble -> doesn't build up in other tissues -> high pressure because its not going anywhere else -> gets to brain fast and works fast

 

[MedicineMike]

So Drug A has a high blood/gas partition, which translates to a high blood solubility, but the graph seems to show me the exact opposite. I'm so confused

 

[lira126]

If a drug has a high blood/gas partition coefficient, then it takes a longer time for that drug to saturate the blood and reach its maximum concentration in blood. The slower a given a drug saturates the blood, the longer it will take for a drug to have its therapeutic effect in the CNS.

If I remember this question correctly, Drug A had a relatively low slope on the concentration in blood vs. time plot. This makes sense because it takes a longer time for this drug to reach its maximum concentration in the blood. Because Drug A is highly soluble in blood, it can achieve higher maximum concentrations in blood than less soluble drugs but it may take longer to do so.

 

[suji0]

So Drug A has a high blood/gas partition, which translates to a high blood solubility, but the graph seems to show me the exact opposite. I'm so confused

because the graph is showing partial pressure, not concentration. just think of it as it being more soluble and spreading out everywhere so its partial pressure doesn't rise as much

 

[MedicineMike]

UW says drugs with poor solubility in blood have low blood gas partition.
-based off this would it be safe to say that a low blood gas partition = faster onset?
-if so, how the heck is the answer that drug A has a high blood gas partition? Wouldn't that mean that it is slow onset? When it clearly is faster than the NO?

Thx btw!

 

[sharklasers]

UW says drugs with poor solubility in blood have low blood gas partition.
-based off this would it be safe to say that a low blood gas partition = faster onset?
-if so, how the heck is the answer that drug A has a high blood gas partition? Wouldn't that mean that it is slow onset? When it clearly is faster than the NO?

Thx btw!

1) Yes, that is safe general rule.
2) Blood gas partition represents the amount of anesthetic in the blood compared to the alveoli at equilibrium. If the blood gas partition = 2, that means at equilibrium, there will be 2 times as much anesthetic in the blood as there is in the alveoli. The more anesthetic is needed for the alveoli and blood to be in equilibrium with each other. A high number means that it will take LONGER for the anesthetic to reach equilibrium concentrations in the brain because a greater amount needs to be present in the blood.

The way I think about this is that for an anesthetic to have its effects, it needs to reach equilibrium concentrations in the brain. That is the goal. Before it can do this, it needs to be in equilibrium with the blood. The greater the blood gas partition, the greater amount of anesthetic is needed to reach equilibrium concentrations in the blood, and so it will take longer for the anesthetic to get around to leaving the blood and going into the brain.

 

[withrye]

Before an inhaled anesthetic can have an effect, it has to fully dissolve into the blood.*

That's pretty much all you need to know to figure out the rest of the blood/gas coefficient and onset of action stuff. Working from that first sentence, a high B/G means we need a lot to get fully into blood, which takes a while, which means slower onset. A low B/G means we fully dissolve quickly, so we start working more quickly.

The graph for NO clearly shows that the blood gets saturated (the graph plateaus), which means the NO has already started working in the brain. The graph for Drug A hasn't plateaued. This can be taken to mean it hasn't started working yet, because it hasn't saturated the blood yet. It needs more time to saturate the blood, more time to get to work (slower onset).

Drug A has a higher B/G (more drug will be dissolved in the blood by the time the graph plateaus), higher solubility, slower onset.

*Not super technically true, but we assume it for these types of problems.

n.b. As a caveat, this has nothing to do with potency. Onset of action just means how quickly it gets into brain tissue. Potency is all about how much you need to pump through the tube to get an eventual effect (minimal alveolar concentration), irrespective of how long the effect takes to happen.