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[jean]

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 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 reducing the tachyphylaxis?
thx u very much...

regards ,Jean

[jafo1964]

2. THe answer to your second question first
TACY PHYLAXIS or ACUTE TOLERANCE is when the same dose of drug fails to produce the same effect seen earlier
or
to produce the same earlier effect,  you need to give more drug

So if you want to produce the same response as first,  you have to increase the dose of drug

Lets say you gave a spinal, and BP fell from 120 systolic to 90 and you gave ephedrine 6 mg and the BP went upto 118 mm

But again the bp fell to 90 systolic,  and if you repeat 6 mg and tacypylaxis is on,  the BP will go upto only say 100 mm. If you need to go upto 120 mm probably you will have to give 9-12 mg ephedrine.

Just need to remember that not all patients develop tachyphylaxis with the same severity and speed. So you will find a huge amount of variation in patient response.
IF you have a patient crashing BP after spinal and no good response to ephedrine bolus, you have to quickly think of tahyphylaxis and go with a higher dose, failing which patient may become significantly hypotensive for a long period.
This is more of significance,  if you are worried about maintaining uteroplacental blood flow and also in patients who have autonomic neuropathy in whom fluid preloading and small dose vasopressors may not be enough to compensate the sympathetic block.

1. Half life got very complicated these days.
If I recall right we have 3 kinds of half life
t1/2 alpha - or the distribution half life
t1/2 beta - or the elimination half life
context sensitive half life - time taken to reach t1/2 beta after cessation of a prolonged infusion of a drug.

HALF LIFE is the time taken for the serum concentration of a drug to be reduced by 50% from the intial peak concentration. It does not define the process how this decrease in concentration occurs


You give 2 mg/kg (100 mg) of propofol for induction. It acheives a serum concentration of 2.2 microg/dl at its peak effect.

Half life is when the total body concentration of Propofol gets to 50 % ie 50 mg


t1/2 alpha
You give 2 mg/kg (100 mg) of propofol for induction. It acheives a serum concentration of 2.2 microg/dl at its peak effect. Patient will wake up say if the concentration goes down below 1 microg/dl. Patient usually wakes up in 5 minutes but Propofol is still in the body as kidney has not yet eliminated it. Then the concentration in serum decereased because the propofol was redistributed to other tissues in the body

t1/2 beta
the kidney has eliminated 50% of the propofol dose given so that the body propofol concentration is reduced to 50 mg

context sensitive half life
you give propofol 2mg/kg and follow it with an infusion of 8 mg/kg/hour for 4 hours.
In such a situation the redistribution sites get saturated with propofol.
Now on stopping infusion, the time taken for patient to wake up and the time taken for serum concentration of propofol to be reduced by 50%  takes a much longer time. T

regs

[sandiphari]

Exellent explaination. THANKS.

[yogenbhatt1]

I do not know where and who you might be.
But we, at the site are proud to have an excellent teacher with vibrant knowledge and willingness to share and guide us.
Bravo,
Keep it up. It is all for free for all of us.
Only we have to come out with questions. You always have a scientific reply for it.
Regards

[jean]

jafo1964: thx u so much for the respond and giving great explanations but, i'm very sorry, it didn't really answer my questions..
1. i'm actually having some trouble regarding the pharmacology of the Ephedrine..i read that the cause of the ephedrine tachyphylaxis is the depleted neurotransmitter, but i am having hard time to understand how giving the next higher dose will help resolve the tachyphylaxis because of that depleted neurotransmitter?
2. regarding those 3 half life u mentioned...so, which one is the elimination half time?
please help me...thx u

and warm regards too ,

[jafo1964]

Let me see how we can make you understand this concept better
If you have read neuromuscular transmission , you would have come across 2 theories
The older- QUANTAL THEORY
The newer – SNARE CONCEPT

The QUANTAL CONCEPT will help understand the tachyphylaxis best

At the alpha and beta receptors let us assume there are 100 molecules of neurotransmitter, of this
50 mols are available for immediate release – lets call them “A”
30 mols, although not immediately available can be mobilized with a little bit of difficulty, using more stimulus – lets call them “B”
20 mols usually cannot be mobilized or may require super supramaximal stimulus to make a few of them available – lets call them “C”. These C mols are immature or are not completely functional as say A or B

Now after SAB, hypotension (<90mm) occurs
You give 6 mg ephedrine
It mobilizes 30 mols of “A” and produces the desired effect (> 100 mm.)
BP again drops (<90 mm)
You give 6  mg ephedrine
It can now only mobilize 20 mols of “A”
Hence you have a decreased effect (92 mm) for the same drug dose
“B” molecules are difficult to mobilize
But we can mobilize them with larger dose of ephedrine say 12 mg
It now mobilizes 20 mols of “A” + 10 mols of “B”
So the desired effect (> 100 mm)

It kind of works like this
Not the exact numbers though

After about 60 mg of ephedrine
“A” are depleted
“B” are depleted
“C” 5 – 10 mols left

Now ephedrine stops working
You can no longer use an indirect acting vasopressor because all the neurotransmitters are depleted.
We should now switch to a direct acting vasopressor to get the desired effect like phenylephrine or adrenaline or noradrenaline



Elimination of a drug involves conversion of the lipid soluble ionic form to a water soluble ionic form in the liver and elimination by the kidney.

Elimination half life is after an initial bolus ( eg 100 mg)
Drug gets eliminated by  the kidney at a particular rate controlled by certain factors
When 50% of the drug has been eliminated by the kidney
Only 50% of the original bolus (50 mg) is present in the body

This is the ELIMINATION HALF LIFE for that drug


regs

[jean]

thx u, Jafo1964: i understand it quiet well now..sorry for have bothered u so much ..thx u a lot

regards,Jean