anesthetic potency and lipid solubility

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johndoe3344

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What's the relationship between anesthetic potency and lipid solubility? DIT (maybe FA too? I'm not sure... I annotated everything together) said that the more lipid soluble an anesthetic is, the more potent it is. This is supported by: http://en.wikipedia.org/wiki/Theori...rrelation_.28the_Meyer-Overton_correlation.29

However, UW seems quite happy making questions (QID 660, 851) that emphasize the fact that only MAC can determine potency, while everything else (including lipid solubility) will only determine on/off time.

Thoughts?

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What's the relationship between anesthetic potency and lipid solubility? DIT (maybe FA too? I'm not sure... I annotated everything together) said that the more lipid soluble an anesthetic is, the more potent it is. This is supported by: http://en.wikipedia.org/wiki/Theori...rrelation_.28the_Meyer-Overton_correlation.29

However, UW seems quite happy making questions (QID 660, 851) that emphasize the fact that only MAC can determine potency, while everything else (including lipid solubility) will only determine on/off time.

Thoughts?

i'll try and explain it. not sure if this is totally accurate, but it works in getting questions right.

the higher the lipid soubility, the higher the potency (thus the lower the MAC). This makes sense since gasses that are more soluble in lipid will go into the brain.

however, the higher the lipid solubility, the higher the Blood/Gas ratio. This is becuase the amount of anesthetic in the blood is determined by the amount bound to protein (albumin). high protein binding = high lipid solubility. Most of the oxygen in your blood is bound to protein isn't it?

the free gas is what is active. bound gas is useless. Thus drugs like halothane, which are very lipid soluble, have a HIGH blood/gas ratio. they are therefore SLOW acting becuase there is less free gas.

nitric oxide has a low blood to gas ratio. it is less protein bound and thus can fly into the brain, work fast, and fly out.

I find it useful to remember the principle that HIGH b/g ratio means more protein bound, and more protein bound means slower onset of action. its also useful to remember that halothane has the higher b/g ratio


hope that helps. i used those principles and havent had problems answering questions
 
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Well, MAC is a direct measure of potency, so that'd be the right answer in that context.

In general, anesthetics with higher lipid solubility will be more potent. But regardless of the lipid solubility, MAC is the most important thing.

Kind of like malignancy... high-grade tumors are generally worse, but a high-grade tumor that's confined to one tissue layer will still have less malignant potential than a low-grade tumor that's already metastasized.

Or like speed/horsepower. A car with higher horsepower (i.e. lipid solubility) will generally accelerate faster, but the only real way to compare accelerations would be to measure it directly. A school bus has lots of horsepower/lipid solubility, but it's not anywhere near as fast as my motorcycle, which has very little horsepower but still has a much faster 0-60 time (i.e. MAC) for other reasons.
 
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In general, there are two properties of general inhalation anesthetics that we should be familiar with. These are 1) the blood/gas partition coefficient and 2) the lipid/gas partition coefficient.

Blood/gas partition coefficient:
The blood/gas partition coefficient is a measure of the solubility of a gas in the blood and is what determines the SPEED OF ONSET of an inhalation anesthetic. If a gas is MORE soluble in the blood, the blood/gas partition coefficient will be higher. If a gas is LESS soluble in the blood, the blood/gas partition coefficient will be lower. In order for a gas to reach the brain, it must be inhaled. Once in the alveoli, the gas must equilibrate with the blood in the capillaries. The speed at which this occurs is determined by how soluble a gas is in the blood. If a gas is MORE soluble in the blood, more gas particles will exist in the blood and thus the blood/gas coefficient will be higher (ex. 200 particles in the blood and 1 particle in the gas suggests slower equilibration, so the coefficient is 200/1, or 200). In effect, it takes more gas particles dissolving in the blood to have the pressures equilibrate. Conversely, if a gas is LESS soluble in the blood, less gas particles will exist in the blood and the gas will have a lower blood/gas coefficient (ex. 1 particle in the blood and 200 particles in the gas suggests very rapid equilibration, or 1/200, or 0.005). In effect, less gas particles need to dissolve for the partial pressures to equilibrate. So, in summary, the speed at which a gas in the alveoli equilibrates with the blood in the capillaries is determined by its solubility in blood, and this then determines the speed of onset of an inhalation anesthetic.

Lipid/gas partition coefficient:
The lipid/gas partition coefficient is a measure of the lipid solubility of an inhalation anesthetic. The higher the lipid/gas coefficient, the more lipid soluble the gas and thus the easier the drug can cross the blood brain barrier. The lipid/gas coefficient is what determines the MAC. The Minimum Alveolar Concentration is defined as the amount of gas necessary to remove reaction to a noxious stimulus (i.e. surgical incision) in 50% of the population, and is actually a percentage of alveolar gas. For example, a gas with an MAC of 2, or 2%, means that its concentration in the alveoli must only be 2% of the total gas within the alveoli at that time in order to remove reaction to noxious stimulus in 50% of people. MAC also determines potency, and potency is expressed as the inverse of MAC, such that potency=1/MAC. So, a gas (Gas A) with a MAC of 2% will have a high potency, since potency=1/2, or 0.5. Gas B, which has a MAC of 75%, will have a low potency, since potency=1/75, or 0.013. So, in summary, the potency of a gas is determined by its MAC, and is expressed as 1/MAC.

It is absolutely possible to have a drug with high blood solubility and low lipid solubility, such that time of onset is slow and potency is low. The opposite (fast onset and high potency) is also true, and, as pointed out, is what makes for a favorable inhalation anesthetics. Hope this helps.
 
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In general, there are two properties of general inhalation anesthetics that we should be familiar with. These are 1) the blood/gas partition coefficient and 2) the lipid/gas partition coefficient.

Blood/gas partition coefficient:
The blood/gas partition coefficient is a measure of the solubility of a gas in the blood and is what determines the SPEED OF ONSET of an inhalation anesthetic. If a gas is MORE soluble in the blood, the blood/gas partition coefficient will be higher. If a gas is LESS soluble in the blood, the blood/gas partition coefficient will be lower. In order for a gas to reach the brain, it must be inhaled. Once in the alveoli, the gas must equilibrate with the blood in the capillaries. The speed at which this occurs is determined by how soluble a gas is in the blood. If a gas is MORE soluble in the blood, more gas particles will exist in the blood and thus the blood/gas coefficient will be higher (ex. 200 particles in the blood and 1 particle in the gas suggests rapid equilibration, so the coefficient is 200/1, or 200). Conversely, if a gas is LESS soluble in the blood, less gas particles will exist in the blood and the gas will have a lower blood/gas coefficient (ex. 1 particle in the blood and 200 particles in the gas suggests very slow equilibration, or 1/200, or 0.005). So, in summary, the speed at which a gas in the alveoli equilibrates with the blood in the capillaries is determined by its solubility in blood, and this then determines the speed of onset of an inhalation anesthetic.

Lipid/gas partition coefficient:
The lipid/gas partition coefficient is a measure of the lipid solubility of an inhalation anesthetic. The higher the lipid/gas coefficient, the more lipid soluble the gas and thus the easier the drug can cross the blood brain barrier. The lipid/gas coefficient is what determines the MAC. The Minimum Alveolar Concentration is defined as the amount of gas necessary to remove reaction to a noxious stimulus (i.e. surgical incision) in 50% of the population, and is actually a percentage of alveolar gas. For example, a gas with an MAC of 2, or 2%, means that its concentration in the alveoli must only be 2% of the total gas within the alveoli at that time in order to remove reaction to noxious stimulus in 50% of people. MAC also determines potency, and potency is expressed as the inverse of MAC, such that potency=1/MAC. So, a gas (Gas A) with a MAC of 2% will have a high potency, since potency=1/2, or 0.5. Gas B, which has a MAC of 75%, will have a low potency, since potency=1/75, or 0.013. So, in summary, the potency of a gas is determined by its MAC, and is expressed as 1/MAC.

It is absolutely possible to have a drug with high blood solubility and low lipid solubility, such that time of onset is quick but potency is low. The opposite (slow onset and high potency) is also true. Hope this helps.

Can I nominate you as the official question answerer? That was very clear and helpful.
 
It is absolutely possible to have a drug with high blood solubility and low lipid solubility, such that time of onset is quick but potency is low. The opposite (slow onset and high potency) is also true. Hope this helps.

correct me if I'm off BUT seems like the last statement you made, beau, is a bit twisted ya? low blood to gas means quicker gas --> blood equilibration and hence induction. I'll agree that brain:gas ie lipid:gas reflects MAC - but as far as b:g goes, "time of onset" if reflected by equilibration with the blood. It's quicker with agents that have LOW b:g (im not an anesthesiologist but is this why N2O is sometimes used for induction of anesthesia while a higher b:g agents like halothane maintain anesthesia??)

in brief: ANESTHETICS like DESFLURANE, N2O, SEVOFLURANE (b:g @ .45, .46, .65 respectively) will equilibrate with blood much quicker, and it will be easier for the pts to blow the halogenated compound off after surgery. Their blood doesn't have to make as many passes through the lungs for this to happen vs a pt on halothane with b:g ratio of around 2.6.

IDEAL anesthetic has LOW MAC and a LOW b/g!!! So the poison does not stay in pt long after surg ///can induct and recover quicker AND so doc can use less (MAC).
 
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correct me if I'm off BUT seems like the last statement you made, beau, is a bit twisted ya? low blood to gas means quicker gas --> blood equilibration and hence induction. I'll agree that brain:gas ie lipid:gas reflects MAC - but as far as b:g goes, "time of onset" if reflected by equilibration with the blood. It's quicker with agents that have LOW b:g (im not an anesthesiologist but is this why N2O is sometimes used for induction of anesthesia while a higher b:g agents like halothane maintain anesthesia??)

in brief: ANESTHETICS like DESFLURANE, N2O, SEVOFLURANE (b:g @ .45, .46, .65 respectively) will equilibrate with blood much quicker, and it will be easier for the pts to blow the halogenated compound off after surgery. Their blood doesn't have to make as many passes through the lungs for this to happen vs a pt on halothane with b:g ratio of around 2.6.

IDEAL anesthetic has LOW MAC and a LOW b/g!!! So the poison does not stay in pt long after surg ///can induct and recover quicker AND so doc can use less (MAC).

You're absolutely correct. I edited my original post, and thanks for pointing that out.
 
...
nitric oxide has a low blood to gas ratio. it is less protein bound and thus can fly into the brain, work fast, and fly out.
...
This is a very helpful thread. To help anyone else coming across it in a search for information, just one 'typo' needs correction:
nitric oxide should be nitrous oxide.

The agent is correctly identified in following posts, but only by its chemical formula.
 
One of my professors went over this in class last year and I finally understand it.

This question comes from a historical perspective. Originally, scientists believed that anesthetics functioned as a direct result of their lipid solubility interfering with membrane function. They noticed that the potency of early anesthetics directly related to their lipophilicity. Over time a few exceptions were noted and the theory was overturned. Now it is recognized that anesthetics interact with some unknown receptors in the brain. Interaction with receptors is a function of "shape" (among other things) which is not the same as lipid solubility.

So even though there are very few exceptions to the rule that increased potency relates to lipid solubility, this question is testing if you are up to date on the latest theory that inhaled anesthetics interact with receptors of some kind rather than membrane function.
Modern_protein_hypothesis_of_mechanism_of_general_anesthesia.png

^Current theory
The_Meyer-Overton_correlation.png

Rational for original theory.
 
Also, on a graph, potency will move along the x-axis and it's reversible/competitive.

If they ask about efficacy, it will move along the y-axis and is noncompetitive.
 
this is a stupid question, but why is it important that equilibrium has to happen fast for fast induction

and also why does high potency = slow induction? i thought something that crosses the BBB (something w/ high lipid solubility) would result in faster induction
 
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this is a stupid question, but why is it important that equilibrium has to happen fast for fast induction

and also why does high potency = slow induction? i thought something that crosses the BBB (something w/ high lipid solubility) would result in faster induction

the faster the inspired anesthetic equilibrates with the alveoli (FA/FI closest to 1.0 in a short period of time), the faster it will be delivered to your target tissue - the brain. this is also important for the safety of the patient, as recovery will be much faster since the anesthetic spends less time in the blood (bound to proteins in a reservoir-like state) and is essentially in and out of the body (efficient) as opposed to lingering.

a high potency anesthetic like halothane with a low MAC has a slow induction, because it has a higher blood:gas coefficient. halothane is much more soluble in blood than xenon or nitrous oxide and will spend some time in the blood as opposed to being delivered to the brain, hence the reason why it has a slow induction.

before you even think about getting to the blood brain barrier, the anesthetic has to first traverse the blood in the body where lots of plasma proteins reside. an anesthetic that is highly soluble in the blood can potentially get tied up and thus have a slower induction.

just remember that having a faster induction/delivery/alveolar equilibration does NOT make it a more potent anesthetic i.e. inhibiting noxious stimuli in 50% of patients (halothane > laughing gas in terms of inhibiting noxious stimuli)
 
the faster the inspired anesthetic equilibrates with the alveoli (FA/FI closest to 1.0 in a short period of time), the faster it will be delivered to your target tissue - the brain. this is also important for the safety of the patient, as recovery will be much faster since the anesthetic spends less time in the blood (bound to proteins in a reservoir-like state) and is essentially in and out of the body (efficient) as opposed to lingering.

a high potency anesthetic like halothane with a low MAC has a slow induction, because it has a higher blood:gas coefficient. halothane is much more soluble in blood than xenon or nitrous oxide and will spend some time in the blood as opposed to being delivered to the brain, hence the reason why it has a slow induction.

before you even think about getting to the blood brain barrier, the anesthetic has to first traverse the blood in the body where lots of plasma proteins reside. an anesthetic that is highly soluble in the blood can potentially get tied up and thus have a slower induction.

just remember that having a faster induction/delivery/alveolar equilibration does NOT make it a more potent anesthetic i.e. inhibiting noxious stimuli in 50% of patients (halothane > laughing gas in terms of inhibiting noxious stimuli)
what does FA/FI mean though? i've looked it up but am still confused about that equation? maybe b/c i haven't had the respiratory block yet
 
what does FA/FI mean though? i've looked it up but am still confused about that equation? maybe b/c i haven't had the respiratory block yet
FA/FI is the ratio of inspired anesthetic that actually makes it into the alveoli

FA = concentration of anesthetic in the alveoli
FI = concentration of anesthetic inspired

obviously, the closer the FA/FI ratio is to 1.0 the better, as delivery is maximized. Increasing ventilation will help equilibrate an anesthetics alveolar and inspired concentrations
 
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