Question about MAC and the Meyer Overton Rule

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I think my brain is turning to mush, I have been reviewing my MAC lecture and cannot quite put the concept together. I am sure someone can help

My understanding is that Meyer-Overton Rule says: Anesthetic potency correlates directly with lipid solubility.

MAC measures anesthetic potency. The MAC value is inversely proportional to its potency.

So when we say Methoxyflurane is the most potent inhalational agent we are talking about this in terms of solubility in the blood (blood:gas partition coefficient) and insolubility in lipid?

So if I look at Methoxyflurane and correlate it with the Meyer-overton Rule it is saying that it has low potency because it is not very lipid soluble?

I am confused because I would think that if I go by the Meyer-overtin theory then Methoxyflurane would have low potency and desflurane would have high potency due to its high solubility in lipid.

Where am I getting screwed up here?

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Methoxyflourane is the most potent agent because it's MAC is.......well, I don't know what the heck it is but it's less than halothane (halothane being .8%ish). It is the most potent agent because it takes the least amt of agent to acheive MAC. Des....well, actually nitrous is the least potent because it, takes the most agent to achieve MAC (104%). So.......if it takes 1.2% forane to achieve MAC but 6% Des to achieve the same effect (also MAC) then forane is the more potent of the two. The least potent agents are also the least soluble in Blood. The most potent agents are the most soluble in blood. As far as the Meyer/overton rule.......that's talking about solubility in OIL. Here the most potent agents are also the most soluble in olive oil while the least potent agents are the least soluble in olive oil. Someone correct me if I'm mixed up here.......

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I just had this lecture and my limited understanding is that blood:gas coefficient measures solubility in the blood. The lower the b/g cofficient # the quicker the agent is taken up and eliminated (fastest onset). So des would have the quickest onset and recovery time.

Oil:gas solubility indicates potency. The higher the cofficient # is, the more potent the agent is. So Halothane would be the most potent at 224, and nitrous the least at 1.4

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Mac has nothing to do with blood gas partition. Blood gas coefficient has to do with speed of uptake. Think of it as the volatile doesn't want to stay in the blood. It would rather cross over into tissue, ie brain, or AC membrane. Quick on quick off.

MAC can be represented by percent dialed in or exhaled. (i'm paraphrasing alot here) Think of it as a percent of inspired gas. .75 of halothane is one MAC. 50% of people will not respond to incision with an exhaled concentration of .75 halothane. Halothane is very potent and very slow. Suprane is not very potent(6.6%) and is quick on and off.

I think you are basically confusing potency and speed. Forane is potent, and slow. Halothane is potent and slow. Des is not potent but is fast. Sevo is not potent and fast. Nitrous is very fast and very weak.

Hope this helps

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Thanks for clearing things up...it's easy to get hung up on words and being a kinetic learner I know this gumbo of info will congeal when I can put things into a real context

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The Myertoverton is saying that its not the type of gas molecules that reaches this certain lipid tissue in the brain that causes effect, but it is the number of gas molecules that reach this area. Therefore Methoxy and halothane are highly lipid soluable, so more will reach the brain and it will stay longer. Onset of effects are also slower because it is highly lipophillic taking longer to reach equilibium. A slower FA/FI, tissues keeping taking it up and you can never build that gradient. Elimination also prolonged because more is distributed to fat tissue which then will have slower redistribution back to the central compartment for elimination. N20 is poorly soluable, tissues dont take it up, FA/FI fast, you get the gradient. Equilibrium acheived rapidly. Effects rapid. Elimation rapid b/c little in tissues. Solubility is not effected by other drugs ect but increased fat tissues ect may effect uptake.

Dont think of MAC of having anything to do with potency. Just think of movement here. Mean alveolar conc that 50% of pt's not moving to pain at atmospheric pressue. MAC can be decreased by adjunctive meds or altered by atmopheric pressures ect.

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Specializes in CRNA, ICU,ER,Cathlab, PACU.

Just remember that the brain is not made out of olive oil, and that "Rule" is assuming way too much. I like it when it is termed a "hypothesis" better. See the exceptions in 5th edition Miller pages 58-61.

One of the things that helped me the most to get through those types of lecture notes is that there are alot of exceptions to these "rules". I was just reviewing the LA's and was amused that although pka's closer to physiologic pH should have fast onset, 2Chlorprocaine with a pka of 9 has a faster onset than lidocaine...this is probably due to the concentration usually administered however since it is not very potent (3%).

Our instructors seem to test a lot about these exceptions.

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Dont think of MAC of having anything to do with potency.

Not to confuse things further, but a relationship does exist between MAC and potency, in that the two are inversely related. MAC is how we compare potency amongst the inhalation agents.

Agents in order from least to most potent and respective MAC values:

N2O (104%), Des (6.0%), Sevo (2.0%), Enf (1.6%), Iso (1.2%), and Hal (0.75%)

Notice that the more potent the agent, the lower its MAC value.

Also, there is a rough parallel between oil solubility and potency (and thus MAC) shared between the agents, however Enf is the exception being slightly more lipid soluble than Iso, but a little less potent.

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Not to confuse things further, but a relationship does exist between MAC and potency, in that the two are inversely related. MAC is how we compare potency amongst the inhalation agents.

Agents in order from least to most potent and respective MAC values:

N2O (104%), Des (6.0%), Sevo (2.0%), Enf (1.6%), Iso (1.2%), and Hal (0.75%)

Notice that the more potent the agent, the lower its MAC value.

Also, there is a rough parallel between oil solubility and potency (and thus MAC) shared between the agents, however Enf is the exception being slightly more lipid soluble than Iso, but a little less potent.

Yeah I understand that, you need a greater concentration to get the same result but to think of it purely as an inverse relationship is not a great understanding of both concepts. MAC can be effected by things that at the same time don't effect the potency of the drug.

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High lipid solubiliy = Potent Agent = Lower MAC, which mean less dose or concentation of agent needed for desired effect.

Blood:OIL partition coefficient converse relationship to potentcy

MAC value inverse relationship to potentcy

Meyer-Overton Rule is not exact, becuase halogenation, how flurinated the agents are is also a factor.

Low Blood:Gas = faster rate of rise FA/Fi or faster onset. Not related to potentcy

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