ketap

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1. hello, i am now reading a master piece from Stoelting's "pharmacology and physiology in anesthetic practice" and i found that he mentioned some new term : the elimination half time and elimination half life...though the book mentioned their each own definition, and i have read it again and again, but i still can't see the difference between both of them..can someone please help describe it to me more clearly?

2. oh ya, i want to ask another thing, how can the (next) larger dose of ephedrine can help reduce the tachyphylaxis? it said that the depleted neurotransmitter is the cause..but i can't see how it correlate with the (must) higher next dose to prevent the tachypylaxis?

please help..thx u very much...:)
 

pgg

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1. hello, i am now reading a master piece from Stoelting's "pharmacology and physiology in anesthetic practice" and i found that he mentioned some new term : the elimination half time and elimination half life...though the book mentioned their each own definition, and i have read it again and again, but i still can't see the difference between both of them..can someone please help describe it to me more clearly?
Half time = half life

Both terms refer to how much time will pass until 1/2 of the substance has been cleared from the site of action (by metabolism, excretion, or redistribution). "Elimination" usually implies that the drug is gone (metabolized or excreted, never to return) but there's some ambiguity to the term.


What's more relevant to anesthesia is context-sensitive half-time, which is generally unrelated to elimination half-times and increases as the duration of an infusion increases. Ie, a 50 mcg dose of fentanyl will last a lot longer if the patient has been receiving an infusion for a while.

The reason for this is that the effect of a drug is a consequence of its concentration at its site of action (some receptor), which is closely correlated to the value we can measure, plasma concentration. Drugs "wear off" because they are metabolized, excreted, or redistributed to tissues where they are not active. It's the redistribution and sequestration of a drug, with eventual re-entry into circulation, that complicates the duration of an observed effect.

The classic example for this is comparing narcotic infusions:



The differences are mainly explained by differing volumes of distribution.

Fentanyl is very fat soluble, and initial doses "wear off" relatively quickly partly because the drug redistributes to adipose. If an infusion is ongoing, it doesn't take long before peripheral compartments have a large store of fentanyl, which rapidly replenishes any drug that is metabolized from the plasma. Consequently, fentanyl's curve gets very steep, very quickly, and later doses last much longer than the initial doses.

Remi is flat because its efficient metabolism by nonspecific plasma esterases renders its half-time more or less constant regardless of dosing or infusion length (at least, for clinically relevant numbers).

This graph isn't totally accurate; Sufentanil doesn't really flatten out like that after just a few hours. It continues to increase, but nowhere near as steeply as fentanyl. Its volume of distribution is gigantic so even after a long infusion is stopped, redistribution still accounts for part of the decrease in plasma concentration.

2. oh ya, i want to ask another thing, how can the (next) larger dose of ephedrine can help reduce the tachyphylaxis? it said that the depleted neurotransmitter is the cause..but i can't see how it correlate with the (must) higher next dose to prevent the tachypylaxis?
"Depleted" doesn't mean "totally 100% gone" ... tachyphylaxis refers to a reduced effect from a subsequent dose of a medication, not no effect. To an extent larger doses can be given to achieve the same effect as earlier doses. The utility of endlessly increasing subsequent doses has a couple of limitations though -
1) eventually there's just no more effect to be had regardless of dose
2) toxicity / side effects (nitroprusside, for example)
 

Planktonmd

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The more you read these text books the more you realize how much BS and controversy they contain.
You will eventually realize that people who pretend to be gurus in this specialty are unfortunately full of themselves.
If you want to get real knowledge you sadly need to read non anesthesiology literature.
 

pgg

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The more you read these text books the more you realize how much BS and controversy they contain.
This thread isn't about cricoid pressure or NPO guidelines; it's about physics and chemistry and pharmacology. If anything I've written above is inaccurate, please correct me. If any of it is BS or controversial, please respond specifically.

He's asking questions that are board testable. WTF do want us to do, tell him to fergettaboutit and play another round of Sudoku?

You will eventually realize that people who pretend to be gurus in this specialty are unfortunately full of themselves.
Care to elaborate?

If you want to get real knowledge you sadly need to read non anesthesiology literature.
Such as? You're telling us that Miller, Barash, Stoelting, the journals Anesthesiology and A&A, etc, aren't sources of "real" knowledge?
 

Planktonmd

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Pgg
My statement was not intended to criticize you or the things you are memorizing to pass your boards.
I am simply pointing out that these books unfortunately have many controversies and weaknesses.
Miller, Barash and the rest of the gang are books that unfortunately contain many issues and sometimes contradictions within the same book.
The vague distinction of Elimination half life versus half time is an example of this BS.
These books are collections of trivia that frequently leave you with unanswered questions.
The more you read these books the more you will understand what I mean.
I don't expect you to fully understand now but in a few years you might.
 

IN2B8R

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Half time = half life

Both terms refer to how much time will pass until 1/2 of the substance has been cleared from the site of action (by metabolism, excretion, or redistribution). "Elimination" usually implies that the drug is gone (metabolized or excreted, never to return) but there's some ambiguity to the term.


What's more relevant to anesthesia is context-sensitive half-time, which is generally unrelated to elimination half-times and increases as the duration of an infusion increases. Ie, a 50 mcg dose of fentanyl will last a lot longer if the patient has been receiving an infusion for a while.

The reason for this is that the effect of a drug is a consequence of its concentration at its site of action (some receptor), which is closely correlated to the value we can measure, plasma concentration. Drugs "wear off" because they are metabolized, excreted, or redistributed to tissues where they are not active. It's the redistribution and sequestration of a drug, with eventual re-entry into circulation, that complicates the duration of an observed effect.

The classic example for this is comparing narcotic infusions:



The differences are mainly explained by differing volumes of distribution.

Fentanyl is very fat soluble, and initial doses "wear off" relatively quickly partly because the drug redistributes to adipose. If an infusion is ongoing, it doesn't take long before peripheral compartments have a large store of fentanyl, which rapidly replenishes any drug that is metabolized from the plasma. Consequently, fentanyl's curve gets very steep, very quickly, and later doses last much longer than the initial doses.

Remi is flat because its efficient metabolism by nonspecific plasma esterases renders its half-time more or less constant regardless of dosing or infusion length (at least, for clinically relevant numbers).

This graph isn't totally accurate; Sufentanil doesn't really flatten out like that after just a few hours. It continues to increase, but nowhere near as steeply as fentanyl. Its volume of distribution is gigantic so even after a long infusion is stopped, redistribution still accounts for part of the decrease in plasma concentration.



"Depleted" doesn't mean "totally 100% gone" ... tachyphylaxis refers to a reduced effect from a subsequent dose of a medication, not no effect. To an extent larger doses can be given to achieve the same effect as earlier doses. The utility of endlessly increasing subsequent doses has a couple of limitations though -
1) eventually there's just no more effect to be had regardless of dose
2) toxicity / side effects (nitroprusside, for example)


:thumbup: Nice post. Plank's statements regarding the texts are indeed factual, but thank goodness we're not psychiatry, where we go from DSM-4 to DSM-5, 6, 7, 8, 9.... Our texts are the best out there and I commend the efforts of your reply.
 

ketap

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hi,PGG: thx u for the nice response...so, the half time is half life then, ..thx u for clearing this things up...it confusing me all the time..thx for a very brief and easy to understand explanation on context sensitive half time..i get it well enough...thx u :)

but i'm still confuse about the ephedrine..i still don't get it..i still confuse about the interactions (pharmacology) of the larger dose and the depleted neurotransmitter so it can solve the tachyphylaxis?
thx u so much :)
 

Jeff05

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hi,PGG: thx u for the nice response...so, the half time is half life then, ..thx u for clearing this things up...it confusing me all the time..thx for a very brief and easy to understand explanation on context sensitive half time..i get it well enough...thx u :)

but i'm still confuse about the ephedrine..i still don't get it..i still confuse about the interactions (pharmacology) of the larger dose and the depleted neurotransmitter so it can solve the tachyphylaxis?
thx u so much :)
what?
ephedrine works primarily be releasing endogenous catecholamines and therefore has diminished effect with repeat dosing secondary to catecholamine depletion (that's the reason for the tachyp).
 

sevoflurane

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Different people are built differently. Pharmacokinetics and pharmacodyamics are different from person to person based on an individuals genetic and physical properties. 85% of Japanese people do have atypical hepatic alcohol dehydrogenase, therefore will not metabolize acetylaldehyde and will ultimately experience flushing. This is genetic variance and is partly responsible for differences in drug effect from person A to person B.

As a consultant anesthesiologist you should know the mechanisms and theory of terms such as context-sensitive half-life. It is not a perfect science as Plank has mentioned, but it does give you depth in your practice. Having some idea of the context-sensitive half-life of the drugs you use in your practice is good knowledge to have, especially after prolonged infusions:

Let's say you are doing a big fusion case in a patient that has known MH:

You look at the surgical field and estimate that your wake up time is in 1.5 hours and you have been going at it for 8 hours. When do you turn off your drips since you don't have the luxury of inhaled agents (let's say your patient has PONV and you don't wanna use N20)? 90% of your decision in based on your experience with the patient during the case. But, I would also argue that knowing the context-sensitive half-life of precedex vs. fentanyl vs. remifentanyl vs. propofol vs. ketamine is useful information that would will aid you in obtaining the perfect anesthetic.

It is critical thinking that often distinguishes MD from nurse. If you do not care about physiology behind what you do you have become an automaton and have narrowed the gap between you and your non-MD colleagues. Nice post PGG.

My 2 cents.
 
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Excellent post Sevo :thumbup:
Gonna hijack this thread and ask you 'bout something else Plank: I'm assuming that you are practicing down in FL.... I'm considering practicing down there in the future (may mean soon or years from now..) and wanted to know several basic things: malpractice paid annualy (avg amount) and what sort of practice tends to predominate down there (hands on vs. supervision)? Feel free to comment on all the +'s and -'s. PM me if you feel more comfortable....thanks.
 

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Florida is nice and once you get used to the warm weather it is very difficult to leave.
Boating and fishing are also very attractive to many people.
The weather I think makes people more cheerful and makes life in general more casual which describes the Florida life style (cheerful and casual).
Unfortunately, you have to pay a premium for these pleasant things, so you make a little bit less money.
And since Florida is a retirement state your payer mix is mainly medicare which forced most private groups to become dependent on hospital subsidy to be able to function and keep their MD's and CRNA's.
South Florida is probably one of the worst places in the U.S. when it comes to malpractice litigation and the number of lawyers ( Nevada and Pennsylvania are strong competitors here I think).
There was a time when you could not find malpractice insurance at all because most of the companies simply stopped operating in Florida.
Things have improved a little and we also benefited from the excellent national record of low litigation risk that Anesthesiologists have achieved over the past few years.
So you can get liability insurance although many people are now going with lower limits like 250,000 / 750,000 compared to 1,000,000/3,000,000 that used to be the average in the past.
You will pay an average of 30,000 - 40,000 a year for that insurance but that varies greatly depending on you level of experience, size of your group, and if you do pain or not.
The state of Florida does not mandate having malpractice insurance to practice medicine and you actually could go "bare" which many surgeons and other specialists elected to do.
All you need to do is inform your patients that you have no insurance.
Unfortunately anesthesiologists are frequently forced by the hospital contract to maintain malpractice insurance which makes you the deepest pocket if you are working with a surgeon who has no insurance, in other words you become the guy in OR with the big bulls eye on your back.
As for which practice model predominates, I would say that the majority of places have ACT model with variable percentage of doing your own cases.
MD only practices do exist but they are rare.
If I was starting my career right now I would probably not go to Florida.





Gonna hijack this thread and ask you 'bout something else Plank: I'm assuming that you are practicing down in FL.... I'm considering practicing down there in the future (may mean soon or years from now..) and wanted to know several basic things: malpractice paid annualy (avg amount) and what sort of practice tends to predominate down there (hands on vs. supervision)? Feel free to comment on all the +'s and -'s. PM me if you feel more comfortable....thanks.
 

IN2B8R

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Florida is nice and once you get used to the warm weather it is very difficult to leave.
Boating and fishing are also very attractive to many people.
The weather I think makes people more cheerful and makes life in general more casual which describes the Florida life style (cheerful and casual).
Unfortunately, you have to pay a premium for these pleasant things, so you make a little bit less money.
And since Florida is a retirement state your payer mix is mainly medicare which forced most private groups to become dependent on hospital subsidy to be able to function and keep their MD's and CRNA's.
South Florida is probably one of the worst places in the U.S. when it comes to malpractice litigation and the number of lawyers ( Nevada and Pennsylvania are strong competitors here I think).
There was a time when you could not find malpractice insurance at all because most of the companies simply stopped operating in Florida.
Things have improved a little and we also benefited from the excellent national record of low litigation risk that Anesthesiologists have achieved over the past few years.
So you can get liability insurance although many people are now going with lower limits like 250,000 / 750,000 compared to 1,000,000/3,000,000 that used to be the average in the past.
You will pay an average of 30,000 - 40,000 a year for that insurance but that varies greatly depending on you level of experience, size of your group, and if you do pain or not.
The state of Florida does not mandate having malpractice insurance to practice medicine and you actually could go "bare" which many surgeons and other specialists elected to do.
All you need to do is inform your patients that you have no insurance.
Unfortunately anesthesiologists are frequently forced by the hospital contract to maintain malpractice insurance which makes you the deepest pocket if you are working with a surgeon who has no insurance, in other words you become the guy in OR with the big bulls eye on your back.
As for which practice model predominates, I would say that the majority of places have ACT model with variable percentage of doing your own cases.
MD only practices do exist but they are rare.
If I was starting my career right now I would probably not go to Florida.

LOL, Thanks for the reply, bro'. I think that I will steer as clear as I can. I thought of the laid back lifestyle and how nice it would be for the entire family, but I ain't about to fork 30-40K/yr and watch a CRNA f*ck up a patient, especially if I'm the guy with the "bulls eye" on his back. In my current practice, I do it all, from cardiac to chronic pain. Our payor mix is about 30% medicare and my malpractice is about 12k/yr (advantage of being in a very large MD group). Ain't about to surrender all of that **** and a very nice salary to just have the joys of year round good weather. Midatlantic ain't that bad after all.... Wife gonna have to suck it up :laugh::laugh:
 

Arch Guillotti

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You will pay an average of 30,000 - 40,000 a year for that insurance but that varies greatly depending on you level of experience, size of your group, and if you do pain or not.
This is astronomical.

I have seen a couple of quotes before and they are WAAY lower than this, but it obviously was not in Florida.