Long half-life, short half-life, metabolites, washout - what does it all mean?

[InNeedOfHope]

ADMIN NOTE See:  Steady State Diagram Diagram has been copied from this site.

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I am new to this site, but am desperate. I have a question. I only know about SRNI's and think that they are especially evil due to the additional neurotransmitter targeted. Can some people be so sensitive to the short half life that they cannot withdraw? That they are continually in servere withdrawal as the carry on taking it because their body cries out for more within the course of each day. Does the stress of this type of severe withdrawal prevent the brain from healing, as it is in shock every day? So a vicious circle exists?

 

I know that everyones symptoms are different as is the severity. I suppose I am looking for an answer from someone like me who has it had it very severe physically, someone who was on a medicine with a short half life, who had symptoms if they were even a tiny bit late taking it. What did you do? Am I wrong in my thinking. Do I just need time? Can this be done?

 

Edited January 1, 2022 by Altostrata
added link

[Barbarannamated]

I am new to this site, but am desperate. I have a question. I only know about SRNI's and think that they are especially evil due to the additional neurotransmitter targeted. Can some people be so sensitive to the short half life that they cannot withdraw? That they are continually in servere withdrawal as the carry on taking it because their body cries out for more within the course of each day. Does the stress of this type of severe withdrawal prevent the brain from healing, as it is in shock every day? So a vicious circle exists?

I know that everyones symptoms are different as is the severity. I suppose I am looking for an answer from someone like me who has it had it very severe physically, someone who was on a medicine with a short half life, who had symptoms if they were even a tiny bit late taking it. What did you do? Am I wrong in my thinking. Do I just need time? Can this be done?

 

InNeed,

I'm sorry that you are suffering so horribly. You are right in that each of us is different. We are different even from ourselves at various times. I was on Effexor XR for several years after being on short acting Effexor. If I missed one dose, I would feel it that day w/dizziness, brain zaps, etc. I can't imagine how terrible it must be to have the excruciating whole body pain and the additional anxiety of having to keep such a tight schedule of taking your meds. Some people are "fast metabolzers"--their enzymes process meds more quickly. Cymbalta also has a very tricky metabolism that I won't pretend to understand.

 

I switched from Effexor XR to Pristiq a few years ago. The drugs are very similar, from what I understand. However, I did not get the immediate WD effects w/Pristiq that I got with Effexor and I have no idea why. I'm not suggesting

that another drug should be tried, but want you to know that it IS possible for it to get easier.

 

Try to separate out what is effecting you right this moment (pain) from the fear of what might happen in the future (the 'what-ifs?'). I know how very difficult this is to do!

 

I will check back in a little later.

 

Barb

[InNeedOfHope]

Thank you for your reply. I have become phobic about all medicines, supplements and even foods. In some ways I have learnt to cope with certain aspects. Yesterday and the day before my bladder was in excruiciating pain and I need the toilet every fifteen minutes. I did a dip stick test and the result was a trace hardly there.So I kept calm thinking it may pass and be withdrawal. This was the night after changing my usual pattern of taking the pill after food, I took it on an empty stomach (had no choice that day) but will avoid that at all costs in the future. Today the pain is there in a minimal way in the bladder and kidney, but I am burning like I am on fire and every nerve ending is raw, with severe head pain, chest pain and difficulty breathing. Took my tablet a little late last night.

 

I fear I have gone too fast in the earlier stages and now can't seem to correct, today I don't think I have felt as bad physically in all my life, I am clinging on by reading everything I can on this site. I am trying hard to stay in the day, as I know this has helped me in the past, but it is difficult when I feel the pain getting worse day by day. I know I need to stay calm, but even normal things like the kids arguing is ramping up my pain and anxiety. I am praying that if I hold at this dose even for a while it will change, but feel in a kind of spiral. Thinking of getting a scale to weigh medicine.

 

I don't know what I would do without the support of the charity who help me or websites to read like this one. I have heard of Pristiq but don't know what it is.

 

Some of the best things I have been told by doctors and pharmacists are:

 

"It gets easier the lower you go as at a lower dose it is not doing anything"

 

"It is really just like a bad headache"

 

"Foods do NOT cause pain it is in your head"

 

"If you don't eat properly (bearing in mind I am shovelling food in every hour and a half) you have weeks to live"

 

"I take people on and off these drugs in a couple of weeks, you are just anxious and need more"

 

I think of doctors in this way now : A couple of centuries ago people used to let doctors drill holes in their heads for headaches or blood let or have other drastic procedures. We think how could they have done that? Were they stupid? That misguided. I think this is how psychiatric medicine will be viewed in the future, when really mental illnesses in my mind are a result of nutritional imbalances and a environmental toxins and a lack of humanity in society. Sorry to go on, I guess I am trying to distract from my pain.

[Shanti]

I am new to this site, but am desperate. I have a question. I only know about SRNI's and think that they are especially evil due to the additional neurotransmitter targeted. Can some people be so sensitive to the short half life that they cannot withdraw? That they are continually in servere withdrawal as the carry on taking it because their body cries out for more within the course of each day. Does the stress of this type of severe withdrawal prevent the brain from healing, as it is in shock every day? So a vicious circle exists?

 

I know that everyones symptoms are different as is the severity. I suppose I am looking for an answer from someone like me who has it had it very severe physically, someone who was on a medicine with a short half life, who had symptoms if they were even a tiny bit late taking it. What did you do? Am I wrong in my thinking. Do I just need time? Can this be done?

 

Hi InNeed,

 

I started having the physical symptoms of withdrawals while at my full dose of Paxil. Paxil has a very short half life. This is what made me decide to go off it. It was so severe with the brain zaps, twitches and jerks that I had an EEG. While on the EEG, I did have zaps and jerks and they didn't show up on the EEG. I've been having them for months and it hasn't caused any damage. I've read many success stories from people coming off these meds with severe symtpoms and they are doing fine now. Here's a link to some at my website.

[Altostrata]

InNeed, half-life has something to do with withdrawal but it's not the whole story.

 

Some people are more sensitive than others when they reduce these medications.

 

Medicine is complacent about how easy withdrawal is. Many doctors don't understand that the rate of tapering is individual, and some people have to go very, very slowly.

 

There is a lot of misinformation among doctors and druggists. I am trying to find doctors who grasp the problem of withdrawal. David Healy in Wales is one of them. He had done a lot of courageous publishing and speaking on the issue.

 

Withdrawal can be done, but we have seen Paxil, Effexor, and now Cymbalta can be extremely difficult to taper off of.

 

It's very important to stay calm and don't panic. When you stir yourself up to a peak of worrying, you make your symptoms worse. We suggest practicing breathing meditation to calm the nervous system.

 

You will need to stay calm so you can take care of yourself and heal. I've suggested you contact Dr. Healy and see if he can help you or refer you to a doctor nearer you.

[Altostrata]

Switching to Prozac is indeed a method to taper off a short half-life antidepressant.

 

I moved the Prozac switch discussion here -- to its own topic. Thanks for adding this information, Strawberry.

[Rhiannon]

Ciprofloxacin interacts with GABA receptors (blocks them) and causes nasty symptoms in people struggling with benzo withdrawal. I wouldn't be surprised if GABA receptors are part of the picture with Cymbalta, given how drastic its effects are and how hard it is to get off of. Plus, as you know, all neurotransmitter systems are connected and affect each other. Could be part of the story.

 

Given your history you might see if your doc will help you avoid the fluoroquinolone family of antibiotics.

[Barbarannamated]

Is that secondary to myelin sheath

[areyouthere]

What are and how do "metabolites" of drugs have anything to do with withdrawal? Thanks. RU

[Skyler]

What are and how do "metabolites" of drugs have anything to do with withdrawal? Thanks. RU

RU, are you asking this because you heard them referred to when describing benzos? How about posting this thread in the benzo section, or maybe one of the admins can move it there....

[areyouthere]

Not sure where I read it on the forum.... but yah... move it if need be.

[Skyler]

Seems like it's time for you to start reading up diazepam. Not sure where I read it on the forum.... but yah... move it if need be.

You saw it mentioned in conjunction with diazepam. I'm a tad confused as to the reason you asked about metabolites when you did not know what drug category (benzos) you were referencing?

 

I'm not the one who can move this thread, but one of the staff can do so.

[Skyler]

Ohhh, I think this may be the post you are referencing (mia culpa). This is kind of a big question. Still, take a stab at it by reading up on diazepam?

 

As everyone knows here, I am not a doctor.

 

flower, I believe I told you several times if taking Celexa makes you feel worse, DO NOT INCREASE IT.

 

I also mentioned Celexa may be conflicting with trazodone's nasty metabolite mCPP (not gabapentin). I believe it was RebelMaven who had this problem.

 

Increasing Celexa will increase the problem with mCPP, which can cause many uncomfortable symptoms emerging when you take Celexa in the morning.

 

If I were you, I might REDUCE THE TRAZODONE slightly and see if the symptoms get better. If you're taking Vistaril to get some sleep, the trazodone isn't helping there anyway.

 

[Jemima]

Definition of metabolite:

 

metabolite /me·tab·o·lite/ (-līt) any substance produced by metabolism or by a metabolic process.

 

Dorland's Medical Dictionary for Health Consumers. © 2007 by Saunders, an imprint of Elsevier, Inc. All rights reserved.

 

 

me·tab·o·lite (m-tb-lt)

n.

1. A substance produced by metabolism.

2. A substance necessary for or taking part in a particular metabolic process.

 

The American Heritage® Medical Dictionary Copyright © 2007, 2004 by Houghton Mifflin Company. Published by Houghton Mifflin Company. All rights reserved.

 

 

As for the question about what metabolites have to do with drug withdrawal, I haven't got a clue.

[Altostrata]

As drugs get metabolized, natural processes break them down. The results are metabolites -- chemical relatives of the original drug. Eventually, they are excreted.

 

The understanding of the metabolic stages of a drug is called pharmacokinetics.

 

Many metabolites are inactive, having no effect on any body processes. Others are active. Active metabolites may cause odd reactions, adverse effects, or have similar effects to the original drug.

 

Active metabolites may conflict with other drugs and their metabolites.

 

In psychiatric drugs, active metabolites may extend the half-life of the drug, as it can take additional metabolism to break them down further. Metabolites can have metabolites of their own, some of them being active, too.

 

Estimating half-life with active metabolites creating other active metabolites can be very confusing. Often, the half-life of drugs with active metabolites, is expressed as a wide range.

 

For example:

• Amitriptyline The overlapping metabolism of amitriptyline and its 2 active metabolites nortriptyline and 10-hydroxynortriptyline is probably why it's so difficult to estimate the half-life of this medication:

   

  amitriptyline (10-26 hrs) ---> nortriptyline (18-44 hrs) ---> 10-hydroxynortriptyline (8-10 hrs) ---> other metabolites

   

  (See http://survivingantidepressants.org/index.php?/topic/1099-tips-for-tapering-off-amitriptyline/ )

• Trazodone Trazodone itself takes 3-6 hours to break down into its metabolites. One active metabolite is mCPP, with a half-life of 2-6 hours. While trazodone may make you sleepy, mCPP has the opposite effect, sometimes very unpleasantly.

   

  trazodone (3-6 hrs) ---> mCPP (2-6 hrs) ---> other metabolites

   

  (See http://survivingantidepressants.org/index.php?/topic/2883-tips-for-tapering-off-trazodone-desyrel/ )

• Effexor (venlafaxine) Regular-release Effexor has a half-life of about 4 hours; its active metabolite, O-desmethylvenlafaxine or desvenlafaxine, has a half-life of 10 hours. Pristiq is made from desvenlafaxine.

   

  venlafaxine (4 hrs) ---> desvenlafaxine (10 hrs) ---> other metabolites

   

  (See http://survivingantidepressants.org/index.php?/topic/272-tips-for-tapering-off-effexor-and-effexor-xr-venlafaxine/ )

• Prozac (fluoxetine) Prozac has an active metabolite, norfluoxetine; fluoxetine and norfluoxetine inhibit each other's metabolism extending the half-life of the drug. Because the half-lives are so long, the full effect of Prozac on the brain may not be felt for several weeks.

   

  fluoxetine (1-6 days) ---> norfluoxetine (up to 16 days) ---> other metabolites

   

  (See http://survivingantidepressants.org/index.php?/topic/759-tips-for-tapering-off-prozac-fluoxetine )

[areyouthere]

As drugs get metabolized, natural processes break them down. The results are metabolites -- chemical relatives of the original drug. Eventually, they are excreted.

 

The understanding of the metabolic stages of a drug is called pharmacokinetics.

 

Many metabolites are inactive, having no effect on any body processes. Others are active. Active metabolites may cause odd reactions, adverse effects, or have similar effects to the original drug.

 

Active metabolites may conflict with other drugs and their metabolites.

 

In psychiatric drugs, active metabolites may extend the half-life of the drug, as it can take additional metabolism to break them down further. Metabolites can have metabolites of their own, some of them being active, too.

 

Estimating half-life with active metabolites creating other active metabolites can be very confusing. Often, the half-life of drugs with active metabolites, is expressed as a wide range.

 

For example:

• Amitriptyline The overlapping metabolism of amitriptyline and its 2 active metabolites nortriptyline and 10-hydroxynortriptyline is probably why it's so difficult to estimate the half-life of this medication:

   

  amitriptyline (10-26 hrs) ---> nortriptyline (18-44 hrs) ---> 10-hydroxynortriptyline (8-10 hrs) ---> other metabolites

   

  (See http://survivingantidepressants.org/index.php?/topic/1099-tips-for-tapering-off-amitriptyline/ )

• Trazodone Trazodone itself takes 3-6 hours to break down into its metabolites. One active metabolite is mCPP, with a half-life of 2-6 hours. While trazodone may make you sleepy, mCPP has the opposite effect, sometimes very unpleasantly.

   

  trazodone (3-6 hrs) ---> mCPP (2-6 hrs) ---> other metabolites

   

  (See http://survivingantidepressants.org/index.php?/topic/2883-tips-for-tapering-off-trazodone-desyrel/ )

• Effexor (venlafaxine) Regular-release Effexor has a half-life of about 4 hours; its active metabolite, O-desmethylvenlafaxine or desvenlafaxine, has a half-life of 10 hours. Pristiq is made from desvenlafaxine.

   

  venlafaxine (4 hrs) ---> desvenlafaxine (10 hrs) ---> other metabolites

   

  (See http://survivingantidepressants.org/index.php?/topic/272-tips-for-tapering-off-effexor-and-effexor-xr-venlafaxine/ )

• Prozac (fluoxetine) Prozac has an active metabolite, norfluoxetine; fluoxetine and norfluoxetine inhibit each other's metabolism extending the half-life of the drug. Because the half-lives are so long, the full effect of Prozac on the brain may not be felt for several weeks.

   

  fluoxetine (1-6 days) ---> norfluoxetine (up to 16 days) ---> other metabolites

   

  (See http://survivingantidepressants.org/index.php?/topic/759-tips-for-tapering-off-prozac-fluoxetine )

Thank you.

[Happy2Heal]

can someone tell me what it means when a drug has a half life of say, 32 hrs?

does that mean it's still having an effect on you for at least 32 hrs after taking a dose?

if you take a dose in 24 hrs after the first one, does the effect accumulate, because the part of the first dose is still affecting you?

 

 

Edited July 21, 2017 by Altostrata
merged topics and retitled

[nz11]

Great question H2H

 

The half life is the period of time required for the amount [concentration] of drug in the body to be reduced by one-half.

 

if you take a dose in 24 hrs after the first one, does the effect accumulate, because the part of the first dose is still affecting you?

you're onto it H2H!

 

I just looked up half-life of zyprexa and it says 30 hours. So i guess thats close to 32 so i assume you are referring to zyprexa's half life here.

 

What this means is that if one takes a 2.5 mg tablet then it will take  30 hours (1.5 days) (lets go with 30 hrs it makes things easy(er)...you'll see in a minute),  for the amount of zyprexa in the blood to fall to 1.25mg

 

However thats not what will be in the blood cos in the meantime you just swallowed another one.

 

I'm not an expert in this so dont hold me to anything here but lets have a look at whats going on  based on the defn of half life.

This is also slightly tricky cos we want to find out how much drops out in 24 hrs not 30 hrs so by ratio i would assume its  equivalent to a drop of 1mg after 24 hrs

 

So levels in your blood i assume go like this...

day 1

2.5mg                                         total in blood 2.5mg

 

day 2

2.5( another 2.5 is swallowed),  1.5  (day one's dose has now dropped 1mg to 1.5mg)            total 4.0 mg in blood

 

day 3

2.5,  1.5, 0.5  (day ones dose is now dropped to 0.5)                     total 4.5

day4

2.5, 1.5, 0.5, -    (day ones dose has now gone)                                total 4.5mg

 

day5

2.5, 1.5, 0.5, -                                                                                 total 4.5 mg

 

etc

 

Note how after three days there is now a constant amount of 4.5mg in the blood. A steady state now exists. ie the introduction of the drug keeps pace with its removal.

 

This is why the moderators will tell you it takes about 4 days for the drug to reach a steady state in the blood.

 

I've made one or two wee assumptions here so it could be oversimplified....but i think this is basically it.

 

nz11

 

edit: I just posted and i see that Lex posted in the meantime.

Sorry for the doubleup.

 

Edited March 30, 2022 by ChessieCat
changed member name

[Sertralinsomnia]

I was wondering, i dont know very much about half lifes of meds and steady states, etc. But i am curious on something, lets take zoloft for example, it has a half life of 24 to 26 hours. this would mean that if you take 50 mg today, tomorrow you would still have 25 mg in your blood, but tomorow you would take another 50 mg tablet, if the half life of the first pill is still there, it would mean that on the second day, we would have 75 mg of zoloft in our blood right? And then Since they are separate doses, they half lives would vanish indepedently, if so it would accumulate, i am missing something here, sorry for my curiosity., can someone explain how this reallly works?

 

According to what i understand this simple table shows that at the seventh day we would still have 98,8 mg on blood?  The numbers separated from / are the half lives of the pill from the day before.

 

 

DAY        1           2                                         3                                4                                                  5                                                        6                                                      7                              
DOSE    50     25/50 = 75 mg           12.5/25/50 = 87,5 mg    6.25/12.5/25/50 = 93,75 mg   3.2/6.25/12.5/25/50 = 93,95    1.2/3.25/6.25/12.5/25/50 = 98,2 mg   0.6/1.2/3.25/6.25/12.5/25/50 = 98,8 mg

 

 

So this would mean a dose of 50 every day would mean that a steady state is double the dose we take every day? If so that is way to huge. ????

 

 

Since i am only taking 2 mg a day, my steady state is in fact the double of it:

 

DAY           1         2         3            4                          5                                 6                                           7                              
dose           2     1/2   0.5/1/2   0.25/0.5/1/2  0.125/0.25/0.5/1/2    0.06/0.125/0.25/0.5/1/2    0.03/0.06/0.125/0.25/0.5/1/2 = 3.965 mg

[scallywag]

I posted a chart with the half-lives for Cymbalta, the medication I'm taking, in this post in my intro topic.

[scallywag]

The body is continually metabolizing the medication, even after the first half-life has expired. The approved and published daily maximium dose for a medication takes into account the ability of the body to metabolize that medication so that repeated daily doses do not lead to toxicity. This area of knowledge is called "pharmacokinetics."  If other medications are taken during the day, the capacity to metabolize may be affected. This is why we urge people taking more than one drug to obtain and post an interactions report. Drugs-dot-com Drugs Interactions Checker.

 

If you want to delve into these questions further, a web search using keywords "drug name " and "pharmacokinetics "

[arwilliams]

How do injections factor in to half life?  For example is the in dosage as high as a weeks dosage to the brain and get even crazy during an injection(considering lots of injections are for a week)?  Does the injection release the drug slowly with a special chemical maybe?  Just to add there appears to be long lasting and short lasting injections.

 

Also do some basic logic a drug with a 33 hour half life will be 50% or 2.5 mg at a 33 hours.

 

Does that mean I could stagger dosages to get a more consistent dosage across the day but still have the same dosage over several hours?

[Altostrata]

Merged related topics.

 

The liquid in a drug injection is not timed-release. Most injections deliver a very high initial dosage of the drug, the dosage being calibrated to take X days for metabolization.

 

The drug in an injection is not released slowly. Adverse effects are highest at the time of the injection, then supposedly decrease as the drug is metabolized.

 

Most injectable psychiatric drugs, which are  tend to be anti-psychotics with long half-lives and very serious side effects, are timed to for a minimum of 4 weeks. Injectable anti-psychotics are intended for people who cannot be trusted to take their drugs regularly and may be societal problems. The dosing of injectable anti-psychotics is purposely high so as to reliably subdue the patient's behavior.

 

If you get injections of these drugs at shorter intervals than for which they are intended, you will be getting higher, possibly toxic, dosages of these drugs. elevating risk of severe, possibly permanent adverse effects.

 

Think of graphing half-lives of drugs as sloping lines, peaking when the drug is ingested or injected. Overlapping half-lives are additive.

 

Staggering injections of psychiatric drugs at intervals shorter than for which they are designed doesn't make any sense and it is highly unlikely you will find a reputable doctor who will prescribe injections like this.

 

 

[Altostrata]

 

DRUG HALF-LIFE CALCULATOR

 

This is a simple mathematical calculation of the time to washout (0% of the drug left in your bloodstream) based on your drug's half-life.

 

Please note other factors, such as other drugs you're taking or liver condition, will affect the metabolization of a drug, and consider this calculation only an estimate.

 

http://www.drugsdb.com/resources/drug-half-life-calculator/

 

Look up the "Half Life" of your drug at https://www.drugbank.ca/

 

[ChessieCat]

This diagram gives a good visual of what happens as a drug is started and gets to steady state.

 

The highest part of the curve is the maximum peak concentration and the lowest part of the curve is the minimum peak concentration.  Once the drug is at steady state then the max and min are at a higher concentration than during the first four days of starting the drug.

 

 

 

Diagram has been copied from this site.

 

 

Edited December 30, 2021 by ChessieCat
added where diagram from