First Aid Multiple Sclerosis Treatment Question

[DroptheBop]

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On p 465 of FA 2012 they mention that muscarinic agonists are used to treat neurogenic bladder. I'm confused as to why you would use an agonist if they are having urinary incontinence issues. Would that not exacerbate the problem? I would assume that anti-cholinergics would make more sense, based on MOA. Any explanations for this?


http://www.msif.org/en/about_ms/ms_by_topic/continence/articles/bladder_manageme.html

 

[AndyRSC]

Cholinergic agonists (and alpha blockers) are used because the bladder loses its tone in the face of denervation. It becomes overdistended with a huge residual amount, and small amounts are continuously lost because it's stretched to its limits, leading to the incontinence.

 

[DroptheBop]

Makes sense. Thanks! Very helpful.

 

[Phloston]

Just thought I'd throw in that aside from interferon-beta, which FA mentions, natalizumab is a monoclonal antibody against alpha-4 integrin, which is also used in MS. I'm fairly sure I had encountered that in Rx.

 

[loveoforganic]

And to complete the last snippet, since it got added on, the a-4 integrin binding inhibits lymphocyte VCAM-1 / MAdCAM-1 interaction to prevent lymphocyte extravasation from the CV system

 

[DroptheBop]

Just thought I'd throw in that aside from interferon-beta, which FA mentions, natalizumab is a monoclonal antibody against alpha-4 integrin, which is also used in MS. I'm fairly sure I had encountered that in Rx.

Yeah they just sort of throw natalizumab into the FA entry without any context or telling you it's an antibody against alpha-4 integrin. Had to look that up.

 

[Valadi]

And to complete the last snippet, since it got added on, the a-4 integrin binding inhibits lymphocyte VCAM-1 / MAdCAM-1 interaction to prevent lymphocyte extravasation from the CV system

An apparently causes progressive multifocal leukoencephalopathy.

Also, love your quoting Man's Search

 

[loveoforganic]

Thanks, one of my favorite reads 🙂

 

[ipizzy]

On p 465 of FA 2012 they mention that muscarinic agonists are used to treat neurogenic bladder. I'm confused as to why you would use an agonist if they are having urinary incontinence issues. Would that not exacerbate the problem? I would assume that anti-cholinergics would make more sense, based on MOA. Any explanations for this?


http://www.msif.org/en/about_ms/ms_by_topic/continence/articles/bladder_manageme.html

It looks like FA has an error. I think it should read muscarinic antagonists. The website you quoted, Goljan RR Path, as well as my annotations into FA from UWorld about neurogenic bladder all say muscarinic antagonists, not agonists. Here's what I have annotated about neurogenic bladder from UWorld:

After spinal cord injury (such as demyelination in MS), the parasympathetic voiding reflex becomes hypersensitive --> detrusor hyperreflexia (similar to how UMN lesions cause hyperreflexia). Treatment = block muscarinic receptors in detrusor with tolterodine. Alpha blockers (sphincter control) and beta blockers (detrusor relaxation) are not helpful since parasympathetic overactivity is what leads to detrusor contraction/incontinence.

From RR Path: urge incontinence is caused by OVERACTIVITY of detrusor resulting in production of low urine volumes. Treat with anticholinergics to inhibit parasympathetic mediated detrusor contraction.

RR Path also talks about the other types of incontinence, such as obstruction incontinence (caused by outflow obstruction from BPH or detrusor UNDERactivity, as in autonomic neuropathy in diabetes); stress incontinence (caused by weakness of pelvic floor muscles); functional incontinence (inability to reach toilet in time, as in diuretics or coffee consumption).

I don't quite understand the explanation offered by AndyRSC so I'd appreciate it if anyone could help me see what he's trying to say. To me it sounds like he's talking about obstruction incontinence, whereas multiple sclerosis involves *urge* incontinence.

 

[Phloston]

Cholinergic agonists (and alpha blockers) are used because the bladder loses its tone in the face of denervation. It becomes overdistended with a huge residual amount, and small amounts are continuously lost because it's stretched to its limits, leading to the incontinence.

I don't quite understand the explanation offered by AndyRSC so I'd appreciate it if anyone could help me see what he's trying to say. To me it sounds like he's talking about obstruction incontinence, whereas multiple sclerosis involves *urge* incontinence.

Tamsulosin, at least in men, is an A,D-selective alpha-1-blocker that can be used if overflow incontinence occurs secondary to BPH, where the detrusor muscle contracts less efficaciously (following initial hypertrophy) secondary to chronic urinary outflow obstruction.

As far as I'm aware, bladder-neck dyssynergia can occur in both men and women, so even tamsulosin could be used in women if this were the aetiology of the flaccid detrusor.

If the detrusor denervates, secondary to vascular disease / diabetes, etc., the outcome would also be flaccidity, so it's possible that bethanechol could be possible treatment.

 

[ipizzy]

Tamsulosin, at least in men, is an A,D-selective alpha-1-blocker that can be used if overflow incontinence occurs secondary to BPH, where the detrusor muscle contracts less efficaciously (following initial hypertrophy) secondary to chronic urinary outflow obstruction.

As far as I'm aware, bladder-neck dyssynergia can occur in both men and women, so even tamsulosin could be used in women if this were the aetiology of the flaccid detrusor.

If the detrusor denervates, secondary to vascular disease / diabetes, etc., the outcome would also be flaccidity, so it's possible that bethanechol could be possible treatment.

Yes, but OP's question is very clearly about multiple sclerosis, which involves spasticity and urge incontinence due to *CNS* demyelination. Alpha blockers are not used for urge incontinence as far as I'm aware.

 

[AndyRSC]

Actually, the OP's question is very clearly about neurogenic bladder.

Both presentations can occur depending on where the damage is. For hypertonic bladders, anticholinergics and perhaps tricyclics are used. For hypotonic bladders, it'll be cholinergics and perhaps alpha blockers or intermittent catheterization. Your response on the exam will be guided by the presentation and symptomatology, not the underlying disease.

 

[ipizzy]

Actually, the OP's question is very clearly about neurogenic bladder.

Both presentations can occur depending on where the damage is. For hypertonic bladders, anticholinergics and perhaps tricyclics are used. For hypotonic bladders, it'll be cholinergics and perhaps alpha blockers or intermittent catheterization. Your response on the exam will be guided by the presentation and symptomatology, not the underlying disease.

Check the title - OP's question refers to a specific reference in First Aid under multiple sclerosis.

 

[AndyRSC]

Check the post.

On p 465 of FA 2012 they mention that muscarinic agonists are used to treat neurogenic bladder.

And my explanation was why they are used.

 

[ipizzy]

Check the post.



And my explanation was why they are used.

Chill out man, I actually went to the page OP referenced and the muscarinic agonists bit was under multiple sclerosis, not "neurogenic bladder." I was confused why you seemed to be answering a different question than the one I understood OP to be asking.

EDIT: I was trying to upload a picture of a kitty saying "why can't we be friends" but apparently I am ******ed at the internet

Also 2nd edit: the chill out was in reference to the huge "neurogenic bladder" text that was previously emphasized but is now no longer 😉 Things are getting blown way out of proportion here, I was just curious if I was misunderstanding a concept.

 

[AndyRSC]

The page he referenced also says muscarinic agonists are used for neurogenic bladder. Not sure where the confusion's coming from, but no need to get defensive.

 

[ipizzy]

The page he referenced also says muscarinic agonists are used for neurogenic bladder. Not sure where the confusion's coming from, but no need to get defensive.

Agreed. I understand what you were explaining now - my confusion was coming from thinking you were saying muscarinic agonists should be applied to neurogenic bladder due to MS, which would make things worse. As you pointed out, if the neurogenic bladder is peripheral in origin (i.e. due to detrusor underactivity), muscarinic agonists make sense. 👍

 

[AndyRSC]

my confusion was coming from thinking you were saying muscarinic agonists should be applied to neurogenic bladder due to MS, which would make things worse.

Not necessarily. Hypertonic and atonic bladder are both seen in MS. Again, the presentation of the incontinence will guide treatment, not the fact that they have MS.

 

[ipizzy]

Not necessarily. Hypertonic and atonic bladder are both seen in MS. Again, the presentation of the incontinence will guide treatment, not the fact that they have MS.

Ooo I see. Makes even more sense now. Thank you!