Anesthetic solubility - I don't get it

[CBG23]

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I am reviewing the inhaled anesthetics and am confused about the blood: gas coefficient and solubility of a gas in the blood.


Basically the following is confusing me:

"The less soluble an anesthetic agent is in blood (low blood gas partition coefficient, or ratio of the anesthetic concentration in the blood to the alveolar gas at equilibrium), the more rapid are both the induction of and the emergence from inhalational anesthesia with that agent."

Why wouldn't it be better for a drug to be more soluble in the blood? If a drug is more soluble in the blood, it should be easier to fill the blood with the anesthetic, providing more for the CNS --> more drug in the CNS should lead to faster induction.

On the other hand, if a drug is poorly soluble in the blood, then I wouldn't expect much of the drug to enter the blood from the lungs. As a result, less of the drug is available in the blood perfusing the the CNS --> less delivery of drug to the CNS --> slower rate of induction. In the most extreme case, if the drug is completely insoluble in the blood, it should never be able to reach the CNS.

But this is wrong according to my notes and text and I don't quite get why...🙁

 

[theseeker4]

I am reviewing the inhaled anesthetics and am confused about the blood: gas coefficient and solubility of a gas in the blood.


Basically the following is confusing me:

"The less soluble an anesthetic agent is in blood (low blood gas partition coefficient, or ratio of the anesthetic concentration in the blood to the alveolar gas at equilibrium), the more rapid are both the induction of and the emergence from inhalational anesthesia with that agent."

Why wouldn't it be better for a drug to be more soluble in the blood? If a drug is more soluble in the blood, it should be easier to fill the blood with the anesthetic, providing more for the CNS --> more drug in the CNS should lead to faster induction.

On the other hand, if a drug is poorly soluble in the blood, then I wouldn't expect much of the drug to enter the blood from the lungs. As a result, less of the drug is available in the blood perfusing the the CNS --> less delivery of drug to the CNS --> slower rate of induction. In the most extreme case, if the drug is completely insoluble in the blood, it should never be able to reach the CNS.

But this is wrong according to my notes and text and I don't quite get why...🙁

Just a guess, but is it due to the relative ease with which a less water-soluble drug can pass the blood/brain barrier, and therefore have quicker effect and quicker recovery from the drug? More drug in the blood doesn't necessarily mean more drug in the CNS if it greatly prefers the water of the blood to the lipids of the BBB.

 

[IlDestriero]

Think about it like this. In order for the brain to get the anesthetic, it has to be absorbed in the blood and then delivered to the tissues and then diffused into the tissues. It's not brain specific. Before it can be diffused into the tissues it has to "fill up" first, the blood is a reservoir absorbing and holding onto the anesthetic. A low solubility is like a small hot tub of water vs a large pool. The large pool absorbs much more anesthetic and takes much longer to fill up than the small tub before enough can diffuse into the brain and induce anesthesia . It also works in reverse when it's time to wake the patient. Low blood solubility yields a faster wake up.

 

[DoctwoB]

I am reviewing the inhaled anesthetics and am confused about the blood: gas coefficient and solubility of a gas in the blood.


Basically the following is confusing me:

"The less soluble an anesthetic agent is in blood (low blood gas partition coefficient, or ratio of the anesthetic concentration in the blood to the alveolar gas at equilibrium), the more rapid are both the induction of and the emergence from inhalational anesthesia with that agent."

Why wouldn't it be better for a drug to be more soluble in the blood? If a drug is more soluble in the blood, it should be easier to fill the blood with the anesthetic, providing more for the CNS --> more drug in the CNS should lead to faster induction.

On the other hand, if a drug is poorly soluble in the blood, then I wouldn't expect much of the drug to enter the blood from the lungs. As a result, less of the drug is available in the blood perfusing the the CNS --> less delivery of drug to the CNS --> slower rate of induction. In the most extreme case, if the drug is completely insoluble in the blood, it should never be able to reach the CNS.

But this is wrong according to my notes and text and I don't quite get why...🙁

The anesthetic effect ONLY depends on partial pressure of the gas, not the concentration.

Thus higher solubility means that when you give gas, more of it is dissolving (higher concentration), and less of it remains as a gas (partial pressure is lower).

Then remember that rate of induction and recovery is based on how rapidly you can equilibrate the partial pressures (NOT the concentrations) of gas between the alveoli and bloodstream. A high solubility means that more of the gas that diffuses into the blood dissolves, and less remains as gas, which means that much more gas has to diffuse to achieve equilibration of partial pressures, which takes a longer time.

 

[OPPforlife]

The anesthetic effect ONLY depends on partial pressure of the gas, not the concentration.

Thus higher solubility means that when you give gas, more of it is dissolving (higher concentration), and less of it remains as a gas (partial pressure is lower).

Then remember that rate of induction and recovery is based on how rapidly you can equilibrate the partial pressures (NOT the concentrations) of gas between the alveoli and bloodstream. A high solubility means that more of the gas that diffuses into the blood dissolves, and less remains as gas, which means that much more gas has to diffuse to achieve equilibration of partial pressures, which takes a longer time.

This essentially...Also if it helps you understand/come to terms with this phenomenon, inhalational anesthetics are NOTHING like any other drug known to man. In fact I don't even think their anesthetic effect can even be explained by simple receptor/ligand type of biochem/cell bio.

 

[Aeterni]

The drug can exist in two phases - the drug as a gas moving around in the blood, and as an aqueous solution of the drug in the blood. It seems like the only phase of the drug which is active is the drug as a gas (perhaps due to crossing the BBB, or maybe interacting in whatever way it does, I'm not sure).

So for a less soluble drug, the blood reaches its capacity of the drug as an aqueous solution more quickly; the blood saturates and the partial pressure of gas-phase drug in the blood equilbriates with the partial pressure of gas-phase drug in the alveoli.

The same thing happens at the brain - a higher concentration of gas-phase drug moving in the blood pushes themdrug to whatever site it acts at in the brain more quickly.

 

[Dral]

I'm so glad I'm not doing anesthesiology. I mean, uh, what those guys above me said...yeah. 😳