Psycho-Babble Medication Thread 101843

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FACHAD: 2 questions 4 U (1/2 lives revisited!)

Posted by Janelle on April 4, 2002, at 23:50:20

Hi there!

1) I'm afraid because I typed it all in caps and there is another thread right below it all in caps that my other question regarding half-lives might get missed, so could you please go back up to the HALF-LIFE thread I started and answer the question that begins with "RELATIONSHIP BETWEEN" ... you could answer it up there, that would be great, thanks!

2) Please humor me and bear with me a bit more here cuz I'm still not getting the whole story with this half-life stuff (no pun intended!) ...

Okay, taking your example of a drug concentration of 100mg/l with a 2 hour half-life, the drug would be reduced as follows(?):

1PM 100 mg/l
3PM 50 mg/l
5PM 25 mg/l
7PM 12.5 mg/l
9PM 6.25 mg/l
11PM 3.125 mg/l
1 AM 1.56 mg/l (I suppose at this point the drug could be considered out of the body)

Adding this up, I'm getting 6 half-lives, but you said that after FIVE half-lives, a drug is considered gone??

ALSO, what confuses me even more is what if the concentration was doubled, and it was 200 mg/l of the drug with a 2 hour half life -- wouldn't it take MORE half-lives to get rid of the higher concentration of the drug?

I would think that the higher the concentration of a drug, the more half-lives it would take to eliminate it???????

So, I don't understand how no matter what the concentration of a drug, it is always 5 half lives to eliminate it from the body??????? How can this be? HELP!!!!!!!!

Thanks!

 

Relationship btw 1/2 life and onset of action?

Posted by Janelle on April 5, 2002, at 2:04:32

I'm sorry to post this again, but I'm afraid it will get *lost* above because I mistakenly typed it in all caps and then a post appeared just below it in caps, making the two posts hard to distinguish.

Here's my question:

Is there a relationship between how long it takes a drug to start working (e.g. 2 hours after being taken) and that drug's half life?

Meaning do drugs that take less time to start working also have shorter half-lives? Conversely, do drugs that take longer to start working also have longer half lives?

thanks!

 

SUNNELLY: could you answer this one also please?! (nm)

Posted by Janelle on April 5, 2002, at 2:05:50

In reply to FACHAD: 2 questions 4 U (1/2 lives revisited!), posted by Janelle on April 4, 2002, at 23:50:20

 

Re: Relationship btw 1/2 life and onset of action?

Posted by Elizabeth on April 5, 2002, at 8:42:37

In reply to Relationship btw 1/2 life and onset of action?, posted by Janelle on April 5, 2002, at 2:04:32

AFAIk, you can't predict the time to onset of a drug's action based on its elimination half-life. The time it takes for a drug to start working has to do with things like how fast it's absorbed and taken up into the CNS, not with the rate of elimination.

HTH

-elizabeth

 

elimination half-life stuff

Posted by Elizabeth on April 5, 2002, at 8:52:24

In reply to Re: FACHAD:Thanks, great stuff, one teeny question: » Janelle, posted by fachad on April 4, 2002, at 22:04:53

> I think after 5 half lives have elapsed without any more doses the drug is considered effectively gone.

After 5 half-lives, there's 2^-5 = 1/32 = about 3% of the original amount left. My understanding is that after 7 half-lives the drug is considered to be effectively "gone" (at that point, less than 1% remains).

Of course, this depends on the amount taken in the first place. The elimination half-life also can differ depending on whether you've been taking the drug regularly, or just a single dose.

-elizabeth

 

How Many Half-Lives Until it's Gone? » Janelle

Posted by fachad on April 5, 2002, at 11:51:28

In reply to FACHAD: 2 questions 4 U (1/2 lives revisited!), posted by Janelle on April 4, 2002, at 23:50:20

I think your question turns on exactly what you mean by the word "gone".

5 half-lives was what one pdoc told me was “gone enough” to be considered adequate for wash out to start another drug.

Elizabeth's 7 half lives uses a definition of "gone" as less than 1% of the original concentration remaining.

So it depends on what you mean by gone. If you mean totally absent from the body, even that is going to depend on how sensitive the equipment is that is used to analyze your blood.

If you had an analytical GC/MS set up that could detect concentrations down to ppt (parts per trillion) you might find a molecule or two of the drug floating around years after you stopped taking the drug.

But in science and medicine words like "gone" have *practical*, not *absolute* definitions. So if there is so little of the drug that it does not exert any clinical effects, or so little that it does not react with another drug, it is said to be gone, even if there's some really there.

 

Re: Relationship btw 1/2 life and onset of action? » Janelle

Posted by IsoM on April 5, 2002, at 12:15:56

In reply to Relationship btw 1/2 life and onset of action?, posted by Janelle on April 5, 2002, at 2:04:32

Janelle, there's no relationship between the two & much depends on what drugs are being taken (& I don't just mean psych meds only). Some drugs just take a while before they exert their effect on the body as expected even when they reach their desired blood concentration. Other meds need to reach a steady-state plasma level before they work - it gets far more complicated - suffice to say half-life has no bearing on it.

 

ELIZabeth: what does ^- mean? (nm) » Elizabeth

Posted by Janelle on April 5, 2002, at 14:41:23

In reply to elimination half-life stuff, posted by Elizabeth on April 5, 2002, at 8:52:24

 

How can 1/2 life be SAME for DIFF concentrations?

Posted by Janelle on April 5, 2002, at 14:45:06

How can the number of half lives required to eliminate a drug (5-7 half lives and it's gone from body) be the SAME for DIFFERENT concentrations of the drug?

Meaning, wouldn't a drug with a 100 mg/l concentration have fewer half-lives than one with say 350 mg/l concentration?

I don't get this! Please help! Thanks!

 

FACHAD: what does GC/MS stand for? (nm) » fachad

Posted by Janelle on April 5, 2002, at 14:46:52

In reply to How Many Half-Lives Until it's Gone? » Janelle, posted by fachad on April 5, 2002, at 11:51:28

 

ELIZABETH: what do AFAIk and HTH stand for?! (nm) » Elizabeth

Posted by Janelle on April 5, 2002, at 14:49:07

In reply to Re: Relationship btw 1/2 life and onset of action?, posted by Elizabeth on April 5, 2002, at 8:42:37

 

FACHAD: you forgot my second question, here it is: » fachad

Posted by Janelle on April 5, 2002, at 14:56:44

In reply to How Many Half-Lives Until it's Gone? » Janelle, posted by fachad on April 5, 2002, at 11:51:28

Fachad - I had asked two questions about half-lives and elimination of meds, but you seem to have missed the second one so I've copy/pasted it here for you to please answer! Thanks:
------------------------------
2) Please humor me and bear with me a bit more here cuz I'm still not getting the whole story with this half-life stuff (no pun intended!) ...

Okay, taking your example of a drug concentration of 100mg/l with a 2 hour half-life, the drug would be reduced as follows(?):

1PM 100 mg/l
3PM 50 mg/l
5PM 25 mg/l
7PM 12.5 mg/l
9PM 6.25 mg/l
11PM 3.125 mg/l
1 AM 1.56 mg/l (I suppose at this point the drug could be considered out of the body)

Adding this up, I'm getting 6 half-lives, but you said that after FIVE half-lives, a drug is considered gone??

ALSO, what confuses me even more is what if the concentration was doubled, and it was 200 mg/l of the drug with a 2 hour half life -- wouldn't it take MORE half-lives to get rid of the higher concentration of the drug?

I would think that the higher the concentration of a drug, the more half-lives it would take to eliminate it???????

So, I don't understand how no matter what the concentration of a drug, it is always 5 half lives to eliminate it from the body??????? How can this be? HELP!!!!!!!!

Thanks!

 

What does ^- mean in a computation?

Posted by Janelle on April 5, 2002, at 15:05:40

Example 2^-5 = 1/32

What function(s) are being done with the ^- part? Thanks.

 

Re: What does ^- mean in a computation? » Janelle

Posted by JohnX2 on April 5, 2002, at 15:16:18

In reply to What does ^- mean in a computation?, posted by Janelle on April 5, 2002, at 15:05:40

> Example 2^-5 = 1/32
>
> What function(s) are being done with the ^- part? Thanks.

This is exponentiation.

2^2 = 4
2^3 = 8
2^-5 = 1/(2^5) = 1/32

redirect in the works...?

John

 

What ^(-5) means » Janelle

Posted by IsoM on April 5, 2002, at 15:19:30

In reply to ELIZabeth: what does ^- mean? (nm) » Elizabeth, posted by Janelle on April 5, 2002, at 14:41:23

The layout of the page Dr. Bob uses doesn't allow subscripts of superscripts to be used. So if someone wanted to write four squared equals sixteen, it would look like 4^2 = 16.

So 2^-5 = 1/32 means 2 raised to negative 5 equals 1/32. Might be a little clearer as 2^(-5). It's a simple math formula to figure out what's left after so many half-lives - in this case 5 half-lives (that's why a negative number is used).

 

AFAIk/as far as I'm concerned HTH/hope that helps (nm) » Janelle

Posted by IsoM on April 5, 2002, at 15:22:47

In reply to ELIZABETH: what do AFAIk and HTH stand for?! (nm) » Elizabeth, posted by Janelle on April 5, 2002, at 14:49:07

 

GC/MS = Gas Chromatography / Mass Spectrometry » Janelle

Posted by fachad on April 5, 2002, at 15:23:54

In reply to FACHAD: what does GC/MS stand for? (nm) » fachad, posted by Janelle on April 5, 2002, at 14:46:52

GC/MS = Gas Chromatography / Mass Spectrometry

It's a very sensitive analytical technique that chemists use to determine what chemicals are present in a sample, and at what concentrations they are present.

Here's a few links if you want to see more, but its heavy chemistry type stuff, so be forewarned:

http://www.shsu.edu/~chemistry/primers/gcms.html

http://ull.chemistry.uakron.edu/gcms/

http://www.home-healthtesting.com/gcmstests.htm


 

Re: How can 1/2 life be SAME for DIFF concentrations? » Janelle

Posted by IsoM on April 5, 2002, at 15:33:38

In reply to How can 1/2 life be SAME for DIFF concentrations?, posted by Janelle on April 5, 2002, at 14:45:06

It's not simply the measurement of a drug but but how much is needed to work. If 500 mg of drug X has the proper effect then at 5-7 half-lives, what's left of it would have little effect on the body & not even be noticed.

On the other hand, if only 5 mg of drug Y is needed for effectiveness, then with just one half-life, concentration would be at 2.5 mg - much less than 15.625 mg of drug X (now at 5 half-lives) still it's not the amount left but how much is needed to cause an effect.

Think of the difference in how much salt as compared to sugar is needed in a cake to be good tasting as a comparison.

 

Re: How can 1/2 life be SAME for DIFF concentrations? » Janelle

Posted by JohnX2 on April 5, 2002, at 15:51:32

In reply to How can 1/2 life be SAME for DIFF concentrations?, posted by Janelle on April 5, 2002, at 14:45:06

> How can the number of half lives required to eliminate a drug (5-7 half lives and it's gone from body) be the SAME for DIFFERENT concentrations of the drug?
>
> Meaning, wouldn't a drug with a 100 mg/l concentration have fewer half-lives than one with say 350 mg/l concentration?
>
> I don't get this! Please help! Thanks!

Its not *exactly* the same, but its *really miniscule* after many half lifes relative to the base dose, if you use a really simplistic model of exponential 1/2 life decay.

I'll take your example into account:

time ----dose---------
t1 350.0 100.0
t2 175.0 50.0
t3 87.5 25.0
t4 43.7 12.5
t5 21.8 6.2
t6 10.9 3.1
t7 5.4 1.5
t8 2.7 0.8

John

 

2nd Question- It's All Relative » Janelle

Posted by fachad on April 5, 2002, at 15:51:45

In reply to FACHAD: you forgot my second question, here it is: » fachad, posted by Janelle on April 5, 2002, at 14:56:44

Janelle,

Your second question turns on your definition of "gone".

Take another look at my earlier post

http://www.dr-bob.org/babble/20020402/msgs/101982.html

In your question, you are assuming that less than 1 mg/l is "gone".

But remember that gone is a *relative* term, meaning that there is no longer a significant amount in the system, not an *absolute* term, meaning that there is absolutely none of it present at all.

For example, 1mg/l, what you were assuming meant "gone" could also be written as 1,000 mcg/l (micrograms per liter). You could watch it go from 1000 mcg/l to 500 mcg/l, and then from 250 mcg/l to 125 etc. At 1 mcg/l you are now at 1000 ng/l (nanograms per liter) and so on forever. If you have sensitive enough equipment, you could continue to measure decreasing concentrations long beyond when the drug was exerting any effects or causing any problems.

So, no matter what your starting concentration is, after 5 half-lives you are at 1/32 of where you started, which is *effectively* gone, no matter what the actual number is.

Hope this doesn’t' confuse you more.

 

See Above Post » Janelle

Posted by fachad on April 5, 2002, at 16:12:06

In reply to How can 1/2 life be SAME for DIFF concentrations?, posted by Janelle on April 5, 2002, at 14:45:06

See my post above for my version of the answer:

http://www.dr-bob.org/babble/20020402/msgs/102016.html

 

Re: FACHAD: 2 questions 4 U (1/2 lives revisited!) » Janelle

Posted by Sunnely on April 5, 2002, at 17:09:09

In reply to FACHAD: 2 questions 4 U (1/2 lives revisited!), posted by Janelle on April 4, 2002, at 23:50:20

I'll do my best.

First, as a general rule, it takes 4-5 half-lives to eliminate greater than 90% of the amount of drug given. The drug is not completely "gone" from the body but at this point, no longer considered clinically significant.

If a drug's half-life is determined to be 2 hours, it doesn't matter whether the drug is given single doses of 100 mg or 200 mg, it will take approximately 4-5 half-lives to eliminate greater than 90% of the drug. (Provided there are no other interfering factors.)

For example, a drug with 2 hour half-life, given a single oral dose of 100 mg:

100 mg given at the onset

amount drops to estimated 50 mg after 2 hours (1 half-life)

amount drops to estimated 25 mg after 4 hours (2 half-lives)

amount drops to estimated 12.5 mg after 6 hours (3 half-lives)

amount drops to estimated 6.25 mg after 8 hours (4 half-lives)

amount drops to estimated 3.125 mg after 10 hours (5 half-lives)

So, based on this, for a drug with a half-life of 2 hours, given as a single oral dose of 100 mg, it will take about 8-10 hours to eliminate >90% (greater than 90%) of the drug given.

A drug with half-life of 2 hours given at a single oral dose of 200 mg:

200 mg at the onset

amount drops to estimated 100 mg after 2 hours (1 half-life)

amount drops to estimated 50 mg after 2 hours (2 half-lives)

amount drops to estimated 25 mg after 2 hours (3 half-lives)

amount drops to estimated 12.5 mg after 2 hours (4 half-lives)

amount drops to estimated 6.25 mg after 2 hours (5 half-lives)

Based on this, it will take about 8-10 hours to eliminate >90% of the drug with a half-life of 2 hours, given 200 mg single oral dose.

So, both drugs whether given at 100 mg and 200 mg single oral dose, with similar half-lives of 2 hours, will take 8-10 hours to be eliminated from body, >90% of the amount given.

In conclusion, as a general rule, no matter what the concentration of a drug is, it will take between 4-5 half-lives to eliminate >90% of the drug from the body, provided there are no other interfering factors.

NOTE: For some drugs, their half-lives change (or become more stabilized) after repeated doses.


> Hi there!
>
> 1) I'm afraid because I typed it all in caps and there is another thread right below it all in caps that my other question regarding half-lives might get missed, so could you please go back up to the HALF-LIFE thread I started and answer the question that begins with "RELATIONSHIP BETWEEN" ... you could answer it up there, that would be great, thanks!
>
> 2) Please humor me and bear with me a bit more here cuz I'm still not getting the whole story with this half-life stuff (no pun intended!) ...
>
> Okay, taking your example of a drug concentration of 100mg/l with a 2 hour half-life, the drug would be reduced as follows(?):
>
> 1PM 100 mg/l
> 3PM 50 mg/l
> 5PM 25 mg/l
> 7PM 12.5 mg/l
> 9PM 6.25 mg/l
> 11PM 3.125 mg/l
> 1 AM 1.56 mg/l (I suppose at this point the drug could be considered out of the body)
>
> Adding this up, I'm getting 6 half-lives, but you said that after FIVE half-lives, a drug is considered gone??
>
> ALSO, what confuses me even more is what if the concentration was doubled, and it was 200 mg/l of the drug with a 2 hour half life -- wouldn't it take MORE half-lives to get rid of the higher concentration of the drug?
>
> I would think that the higher the concentration of a drug, the more half-lives it would take to eliminate it???????
>
> So, I don't understand how no matter what the concentration of a drug, it is always 5 half lives to eliminate it from the body??????? How can this be? HELP!!!!!!!!
>
> Thanks!

 

ISO: thx, how do you raise to a negative number:

Posted by Janelle on April 5, 2002, at 17:10:39

In reply to What ^(-5) means » Janelle, posted by IsoM on April 5, 2002, at 15:19:30

How do you raise 2 to the negative 5?

 

ISO: you are GREAT! But shouldn't it be AFAIc for:

Posted by Janelle on April 5, 2002, at 17:12:34

In reply to AFAIk/as far as I'm concerned HTH/hope that helps (nm) » Janelle, posted by IsoM on April 5, 2002, at 15:22:47

As Far As I'm CONCERNED - the word CONCERNED begins with a C, not a K! So why would it be AFAIk, not AFAIc ???? LOL???!!!???

 

Re: Relationship btw 1/2 life and onset of action? » Janelle

Posted by Sunnely on April 5, 2002, at 17:19:32

In reply to Relationship btw 1/2 life and onset of action?, posted by Janelle on April 5, 2002, at 2:04:32

There is no relationship between half-life of a drug and its onset of action.

For drugs given orally, the rate of drug absorption from the gastrointestinal tract, for example, largely determines the speed of onset of action after a single dose. Drugs that are absorbed rapidly produce a faster and more intense onset of clinical effects, whereas the reverse is true for more slowlly absorbed drugs. No surprise that drugs given intravenously has the most rapid onset of action because it goes directly into the circulation.

The termination of a drug's effects after a single oral dose is largely determined by the rate and extent of the drug's distribution. For example, highly lipid-soluble (fat-soluble) drugs tend to be rapidly and extensively distributed throughout the body's tissues, which indicates a relatively brief duration of clinical effects following a single dose. Distribution, rather than elimination half-life of the drug, determines the duration of action after a single dose, but after repeated dosing, the elimination half-life becomes clinically important. For example, diazepam (Valium) has more rapid onset of action than lorazepam despite the former drug's longer half-life. This is due to diazepam's greater lipid solubility and more extensively distributed.

> I'm sorry to post this again, but I'm afraid it will get *lost* above because I mistakenly typed it in all caps and then a post appeared just below it in caps, making the two posts hard to distinguish.
>
> Here's my question:
>
> Is there a relationship between how long it takes a drug to start working (e.g. 2 hours after being taken) and that drug's half life?
>
> Meaning do drugs that take less time to start working also have shorter half-lives? Conversely, do drugs that take longer to start working also have longer half lives?
>
> thanks!


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