6MP and PSC/AIH

[Guest guest]

Is there anyone out there that has had these as a side effects and their doctors

believe it is related to 6MP? What did your physician recommend? Muscle

wasting and neuropathy in hands and feet & legs. Can anyone provide me with a

link to research information on this? Most of the information on 6MP on the PSC

website is geared towards IBS treatment.

[Guest guest]

Hi ;

As far as I know, there is very little research on 6-mercaptopurine causing

muscle wasting and neuropathy in humans. I've seen research showing that

6-mercaptopurine can cause muscle wasting in rats, but havn't come across

anything like this in human subjects.

On the other hand, there is a fair amount of research showing that muscle

wasting and neuropathy can be associated with inflammatory bowel disease and/or

PSC.

In other words, I wonder whether the muscle wasting and neuropathy that you

report might be due to underlying IBD/PSC rather than the medication(s) used to

treat it?

Yes, most of the information on 6-MP on the PSC Literature site is geared to IBD

because that's what 6-MP is mostly used to treat.

Best regards,

Dave

(father of (23); PSC 07/03; UC 08/03)

>

> Is there anyone out there that has had these as a side effects and their

doctors believe it is related to 6MP? What did your physician recommend?

Muscle wasting and neuropathy in hands and feet & legs. Can anyone provide me

with a link to research information on this? Most of the information on 6MP on

the PSC website is geared towards IBS treatment.

>

[Guest guest]

Hi ;

As far as I know, there is very little research on 6-mercaptopurine causing

muscle wasting and neuropathy in humans. I've seen research showing that

6-mercaptopurine can cause muscle wasting in rats, but havn't come across

anything like this in human subjects.

On the other hand, there is a fair amount of research showing that muscle

wasting and neuropathy can be associated with inflammatory bowel disease and/or

PSC.

In other words, I wonder whether the muscle wasting and neuropathy that you

report might be due to underlying IBD/PSC rather than the medication(s) used to

treat it?

Yes, most of the information on 6-MP on the PSC Literature site is geared to IBD

because that's what 6-MP is mostly used to treat.

Best regards,

Dave

(father of (23); PSC 07/03; UC 08/03)

>

> Is there anyone out there that has had these as a side effects and their

doctors believe it is related to 6MP? What did your physician recommend?

Muscle wasting and neuropathy in hands and feet & legs. Can anyone provide me

with a link to research information on this? Most of the information on 6MP on

the PSC website is geared towards IBS treatment.

>

[Guest guest]

Hi ;

As far as I know, there is very little research on 6-mercaptopurine causing

muscle wasting and neuropathy in humans. I've seen research showing that

6-mercaptopurine can cause muscle wasting in rats, but havn't come across

anything like this in human subjects.

On the other hand, there is a fair amount of research showing that muscle

wasting and neuropathy can be associated with inflammatory bowel disease and/or

PSC.

In other words, I wonder whether the muscle wasting and neuropathy that you

report might be due to underlying IBD/PSC rather than the medication(s) used to

treat it?

Yes, most of the information on 6-MP on the PSC Literature site is geared to IBD

because that's what 6-MP is mostly used to treat.

Best regards,

Dave

(father of (23); PSC 07/03; UC 08/03)

>

> Is there anyone out there that has had these as a side effects and their

doctors believe it is related to 6MP? What did your physician recommend?

Muscle wasting and neuropathy in hands and feet & legs. Can anyone provide me

with a link to research information on this? Most of the information on 6MP on

the PSC website is geared towards IBS treatment.

>

[Guest guest]

Hi ;

A paper on thiopurines (including 6-mercaptopurine and azathioprine (Imuran))

and their toxicity profiles came out today:

__________________________

Actis GC, Pellicano R, Rizzetto M, Ayoubi M, Leone N, Tappero G, Pazienza P,

Rosina F

Individually administered or co-prescribed thiopurines and mesalamines for

inflammatory bowel disease.

World J Gastroenterol 2009 March;15(12):1420-1426

Individually administered or co-prescribed thiopurines and mesalamines for

inflammatory bowel disease

Actis GC, Pellicano R, Rizzetto M, Ayoubi M, Leone N, Tappero G, Pazienza P,

Rosina F.

Division of Gastro-Hepatology, Ospedale Gradenigo, Corso Regina 10, Torino

10153, Italy. actis_g@...

Data from both basic research and clinical experience continue to suggest that

mesalamines and thiopurines are effective and efficient for the maintenance of

remission of inflammatory bowel diseases. Several decades following the

formalization of their indications, attention on these two drugs has been

fostered by recent achievements. Demonstration of the ability of mesalamine to

activate a colonocyte differentiation factor has shed light on its

chemopreventive effects on colorectal cancer; in addition to their

anti-proliferative efficacy, thiopurines have been shown to be specific

regulators of apoptosis. The two drugs are often co-administered in clinical

practice. Recent advancements have shown that mesalamines exert a positive

synergism in this context, insofar as they can inhibit side-methylation of

thiopurines and hasten the function of the main immunosuppressive pathways.

Considering that up to 40% of patients cannot tolerate thiopurines, such

renovated targets have stimulated efforts to improve compliance by research on

the toxicity mechanisms. The definition of genetic polymorphisms in the enzymes

of thiopurine metabolism, and the uncovering of synergistic drug interactions,

such as that with allopurinol, are just two of the results of such efforts.

Interaction between basic research and clinical practice has continued to inform

indications and refine the prescriptions of mesalamines and thiopurines; these

have not been restrained (they have been implemented in some cases) by the

advent of the novel biological molecules with anti-cytokine activity.

full text available at:

http://www.wjgnet.com/1007-9327/15/1420.pdf

__________________________

However, there doesn't seem to be any mention of neuropathy or muscle wasting

with 6-MP or azathioprine.

I'm so sorry to hear that your loved-one is suffering from neuropathy and

becoming so frail. I hope that his doctor's can figure this out soon.

Best regards,

Dave

(father of (23); PSC 07/03; UC 08/03)

>

> Thanks for the information it helps and I am going to read the research.

He is on 6MP & Pred for the AIH. Urso for PSC. He was off the Pred for 2 1/2

yrs but had a flare last April. He had intense joint pain from Imuran. Their

goal is to find out what is causing the neuropathy and stop it or slow it's

progress. He's becoming very frail very quickly and we need to figure out why.

[Guest guest]

Hi ;

A paper on thiopurines (including 6-mercaptopurine and azathioprine (Imuran))

and their toxicity profiles came out today:

__________________________

Actis GC, Pellicano R, Rizzetto M, Ayoubi M, Leone N, Tappero G, Pazienza P,

Rosina F

Individually administered or co-prescribed thiopurines and mesalamines for

inflammatory bowel disease.

World J Gastroenterol 2009 March;15(12):1420-1426

Individually administered or co-prescribed thiopurines and mesalamines for

inflammatory bowel disease

Actis GC, Pellicano R, Rizzetto M, Ayoubi M, Leone N, Tappero G, Pazienza P,

Rosina F.

Division of Gastro-Hepatology, Ospedale Gradenigo, Corso Regina 10, Torino

10153, Italy. actis_g@...

Data from both basic research and clinical experience continue to suggest that

mesalamines and thiopurines are effective and efficient for the maintenance of

remission of inflammatory bowel diseases. Several decades following the

formalization of their indications, attention on these two drugs has been

fostered by recent achievements. Demonstration of the ability of mesalamine to

activate a colonocyte differentiation factor has shed light on its

chemopreventive effects on colorectal cancer; in addition to their

anti-proliferative efficacy, thiopurines have been shown to be specific

regulators of apoptosis. The two drugs are often co-administered in clinical

practice. Recent advancements have shown that mesalamines exert a positive

synergism in this context, insofar as they can inhibit side-methylation of

thiopurines and hasten the function of the main immunosuppressive pathways.

Considering that up to 40% of patients cannot tolerate thiopurines, such

renovated targets have stimulated efforts to improve compliance by research on

the toxicity mechanisms. The definition of genetic polymorphisms in the enzymes

of thiopurine metabolism, and the uncovering of synergistic drug interactions,

such as that with allopurinol, are just two of the results of such efforts.

Interaction between basic research and clinical practice has continued to inform

indications and refine the prescriptions of mesalamines and thiopurines; these

have not been restrained (they have been implemented in some cases) by the

advent of the novel biological molecules with anti-cytokine activity.

full text available at:

http://www.wjgnet.com/1007-9327/15/1420.pdf

__________________________

However, there doesn't seem to be any mention of neuropathy or muscle wasting

with 6-MP or azathioprine.

I'm so sorry to hear that your loved-one is suffering from neuropathy and

becoming so frail. I hope that his doctor's can figure this out soon.

Best regards,

Dave

(father of (23); PSC 07/03; UC 08/03)

>

> Thanks for the information it helps and I am going to read the research.

He is on 6MP & Pred for the AIH. Urso for PSC. He was off the Pred for 2 1/2

yrs but had a flare last April. He had intense joint pain from Imuran. Their

goal is to find out what is causing the neuropathy and stop it or slow it's

progress. He's becoming very frail very quickly and we need to figure out why.

[Guest guest]

Hi ;

A paper on thiopurines (including 6-mercaptopurine and azathioprine (Imuran))

and their toxicity profiles came out today:

__________________________

Actis GC, Pellicano R, Rizzetto M, Ayoubi M, Leone N, Tappero G, Pazienza P,

Rosina F

Individually administered or co-prescribed thiopurines and mesalamines for

inflammatory bowel disease.

World J Gastroenterol 2009 March;15(12):1420-1426

Individually administered or co-prescribed thiopurines and mesalamines for

inflammatory bowel disease

Actis GC, Pellicano R, Rizzetto M, Ayoubi M, Leone N, Tappero G, Pazienza P,

Rosina F.

Division of Gastro-Hepatology, Ospedale Gradenigo, Corso Regina 10, Torino

10153, Italy. actis_g@...

Data from both basic research and clinical experience continue to suggest that

mesalamines and thiopurines are effective and efficient for the maintenance of

remission of inflammatory bowel diseases. Several decades following the

formalization of their indications, attention on these two drugs has been

fostered by recent achievements. Demonstration of the ability of mesalamine to

activate a colonocyte differentiation factor has shed light on its

chemopreventive effects on colorectal cancer; in addition to their

anti-proliferative efficacy, thiopurines have been shown to be specific

regulators of apoptosis. The two drugs are often co-administered in clinical

practice. Recent advancements have shown that mesalamines exert a positive

synergism in this context, insofar as they can inhibit side-methylation of

thiopurines and hasten the function of the main immunosuppressive pathways.

Considering that up to 40% of patients cannot tolerate thiopurines, such

renovated targets have stimulated efforts to improve compliance by research on

the toxicity mechanisms. The definition of genetic polymorphisms in the enzymes

of thiopurine metabolism, and the uncovering of synergistic drug interactions,

such as that with allopurinol, are just two of the results of such efforts.

Interaction between basic research and clinical practice has continued to inform

indications and refine the prescriptions of mesalamines and thiopurines; these

have not been restrained (they have been implemented in some cases) by the

advent of the novel biological molecules with anti-cytokine activity.

full text available at:

http://www.wjgnet.com/1007-9327/15/1420.pdf

__________________________

However, there doesn't seem to be any mention of neuropathy or muscle wasting

with 6-MP or azathioprine.

I'm so sorry to hear that your loved-one is suffering from neuropathy and

becoming so frail. I hope that his doctor's can figure this out soon.

Best regards,

Dave

(father of (23); PSC 07/03; UC 08/03)

>

> Thanks for the information it helps and I am going to read the research.

He is on 6MP & Pred for the AIH. Urso for PSC. He was off the Pred for 2 1/2

yrs but had a flare last April. He had intense joint pain from Imuran. Their

goal is to find out what is causing the neuropathy and stop it or slow it's

progress. He's becoming very frail very quickly and we need to figure out why.

[Guest guest]

Re: 6MP and PSC/AIH

Posted by: " " rhodesdavid1@... rhodesdavidwl

Fri Mar 27, 2009 7:57 am (PDT)

Hi ;A paper on thiopurines (including 6-mercaptopurine and azathioprine (Imuran)) and their toxicity profiles came out today:

Hi there,

I've just been alerted to this discussion by Penny W.

As the "old timers" here will know I've had UC for 52 years (I'm 59). I've undergone every treatment available over the years, including a colostomy and eventually developed a toxic megacolon resulting in ileostomy in 1986. I later underwent an ileorectal anastomosis. Despite all clues my hepatologist(s) refuse to diagnose PSC..... probably I have small duct type. This is the VERY short version.....LOL

I have responded badly to all UC meds (and URSO) and have never been in clinical remission for the UC UNTIL I was given 6-MP 2+ years ago. For that reason alone I am prepared to put up with "my" side effect of unpleasant headaches permanently. I have had one immunosuppression crisis on the 6-MP when my leucocytes and Hb dropped precipitously and was forced to stop the 6-MP. I was then put on Imuran and had to give that up within 12 days. I had been given the 6-MP in preference to Imuran in the first place because it is a metabolite of Imuran and the argument was that a shorter chemical chain might give me less chance of severe side effects. Certainly seems to have been the case.

I do now have a "punishment" for this remission in that the anastomosis has now healed and become scar tissue and has narrowed down to 4mm... with resulting severe obstructive symptoms. I am to return next week to my "alma mater" hospital in the UK, St. Mark's Hospital (a hospital dealing ONLY with colorectal diseases http://www.stmarkshospital.org.uk/) for an attempt at balloon dilatation of the stricture. Hopefully the Paneth cell metaplastic tumour they found in my rectum in October will not have "morphed" into something else!!

I think the only advice I can give is that if you are given the advice/suggestion to try 6-MP don't reject it out of hand. I have been really glad of 2 years remission in all those 57 years and the regular blood tests for the leucocytes etc are no issue at all.

I was also told it would take 3 months to show any effect but I had a dramatic reduction in my UC symptoms within a couple of weeks and endsocopic signs of remission withinn 8 weeks. We're all different.

Hope that helps.

DutchPat

PS. I'm now on a waiting list for mesenchymal stem cell therapy as soon as it is approved for trial in UC... it's already being trialled for Crohn's I've been told. That might be my best hope of all.