Talk:Muscle relaxant

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 Muscle relaxant was a good article nominee, but did not meet the good article criteria at the time. There are suggestions below for improving the article. Once these are addressed, the article can be renominated. Editors may also seek a reassessment of the decision if they believe there was a mistake.

Reviewed version: October 13, 2007
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This article was previously a Pharmacology Collaboration of the Month.

.:Wow... what a glaring error. A muslce relaxant affects the gamma fibers on the alpha motor neuron which it turn decreases the tone of the muscle (the last theory that I recall since it still is likely unkown how it works). What is described in this section are Paralytic agents! As in prevent muscles from contracting completely:.

Example of relaxant: flexeril, robaxin Exapmle of paralytic: succinylcholine, rocuronium, pancuronium, vecuronium, etc..

Contents

[edit] Too many errors on this page

hmmm, gues I am too new to request a move, but the topic is completely wrong. Its mixing paralytics and relaxants... two completely different drugs. No wonder why I hate it when I hear patients state that they "read it on the internet."

Given that you clearly know more, could you fix the errors? And why would a move be beneficial here? JFW | T@lk 20:24, 15 January 2006 (UTC)

Okay... moved the paralytics over to paralytic agents. Maybe I'll write aobut the muscle relaxants in the future... its an interesting topicER MD 12:05, 16 January 2006 (UTC)ER_MD

  • Don't bother it's a sockpuppet pretending to be a doctor, oh well, at least it's more origional than the liberatarian lawyer sockpuppet fad that was really big over the summer--205.188.116.202 01:14, 19 February 2006 (UTC)

[edit] Paralytics are not muscle relaxants

While trying to get this page into some sort of clinically relevant form, and had my edits reverted because I removed paralytics from the discussion of muscle relaxants. As I said on Dr Cash's talk page "...Neuromuscular blockers are not muscle relaxants in any reasonable, clinical definition. Indeed, Rang Dale and Ritter specifically state that they should not be considered muscle relaxants because they have no clinical use. Furthermore according to the most recent Cochrane Review, there has never been a clinical trial investigating the use of paralytics in spacticity (apart from local injections of botox)."

As there are already two statements asserting this position, it seems that this consensus agrees, however does anyone think paralytics diserve to be discussed under muscle relaxants? (Apart from in the sense that "Paralytics are not muscle relaxants because they can not be used to clinically treat spasticity). Bilz0r 22:18, 19 September 2007 (UTC)

[edit] Muscle Relaxants are not used in IBS

The "muscle relaxants" that are used in Irritable Bowel are smooth muscle relaxants, i.e. anti muscarinics like cimetropium. If they are considered muscle relaxants then so do all antihypertensives etc... Conclusion: Someoneone got confused, they are not muscle relaxants. Bilz0r 22:22, 19 September 2007 (UTC)

[edit] Lead

Hmm.

A muscle relaxant is a drug which affects skeletal muscle function...

I agree we should focus on skeletal muscle relaxants—but what about antispasmodics acting on smooth muscle? Should they even be covered here?

Muscle relaxants fall into two major therapeutic groups...

May we qualify Muscle relaxants fall into two major therapeutic groups with markedly different clinical applications or uses? I'm altogether not a fan of grouping neuromuscular blockers with antispasmodic/antispasticity agents, but what can we do :) Fvasconcellos (t·c) 22:23, 19 September 2007 (UTC)

Neuromuscular blockers deserve their own article. Phase I and Phase II (non-depolarizing, depolarizing black) is a hard enough concept to explain to students, let alone mixing it up with how GABAmimetics acts. Treatments of IBS and other smooth muscle treatments should likewise get there own article. Bilz0r 22:28, 19 September 2007 (UTC)
I agree, but not making the distinction is pretty pervasive, e.g. ATC groups neuromuscular blockers under "muscle relaxants". The term "muscle relaxant" is after all broad and poorly defined. I hope we can do a good job of explaining it :P Fvasconcellos (t·c) 22:35, 19 September 2007 (UTC)

I oppose separating the two topics. The overall topic of muscle relaxants would be incomplete without mention both classifications of drugs, even though they have drastically different mechanisms of action. I have two textbook sources that DO NOT separate them:

  • Basic & Clinical Pharmacology by Betram G. Katzung (7th Edition, 1998) ISBN 083505651.
  • Goodman & Gilman's The Pharmacological Basis of Therapeutics (9th Edition, 1996); Eds. Joel G. Hardman & Lee E. Limbird. ISBN 0070262667.

G&G's also specifically refers to neuromuscular blockers as muscle relaxants.

If separate articles eventually break the two classes into separately, but linked 'see also' type of articles, then that's fine. But a discussion of muscle relaxants as a class is not complete without mentioning both. Dr. Cash 23:07, 19 September 2007 (UTC)

Hmm. As an additional interesting note, I've found articles for both Neuromuscular-blocking drugs and Antispasmodic. The article for Spasmolytic redirects to Antispasmodic, although I don't think that's exactly accurate,... Also, one of the categories for Neuromuscular-blocking drugs is [[Category:Muscle relaxants]]. Dr. Cash 23:22, 19 September 2007 (UTC)
G&G sure does say "Muscle relaxants: See neuromuscular blockers" and I agree, there is -some- use of the term to mean both spasmolytic and neuromuscular blockers. But even G&G have the two sections discussed in vastly different sections (Spasmolytics is in Chapter 22, treatment of CNS degenerative disorders, with Neuromuscular blockers in chapter 9, Agents acting at the neuromuscular junction). I just can't see any reason to join these two sections together apart from a few peoples sloppy use of terminology. they're not chemically similar, they don't act the same way, and they don't treat the same diseases. And it seems that these article is essentially going to have a little section which repeats what is in Neuromuscular-blocking drugs, and a section that repeats spasmolytics, and doesn't add much to either. If you really think that referring to paralytics in this article, maybe this article should just say "Muscle relaxants is a term used to mean either: Neuromuscular blocking drugs, or spasmolytics". Bilz0r 01:57, 20 September 2007 (UTC)
You are correct that G&G discusses these two types in separate sections; sorry for the confusion. However, Katzung does not - both neuromuscular blockers & spasmolytics are covered in the chapter discussing muscle relaxants. To me, it appears that the issue here is that, in common language, most people seem to refer to spasmolytics as muscle relaxants, and don't worry about neuromuscular blockers, since they are not prescribed very often (although I do believe that some of them still have use, although not as frequently, in surgery and anesthesia).
If I look up "muscle relaxant" in a medical dictionary, I get the following definitions: medilexicon and medicinenet. Both definitions refer to both neuromuscular blockers as well as spasmolytic (centrally-acting) muscle relaxants. So I would say that leaving out one group is leaving an incomplete article.
To me, it appears that the general term "muscle relaxant" is a pretty wide-ranging term, encompassing more than one distinct class of drugs with separate mechanisms of action. That's fine. I would think to compare it to a term like "CNS depressant", as there are quite a few different classes of CNS depressants (or stimulants, for that matter), acting by different mechanisms.
So, for this article, I think both classes need to be covered for it to be considered "complete". I don't think we need huge amounts of details on both classes in this article specifically, as it would be much more efficient and effective to provide some good, general info about each class, with separately linked articles (both already have two separate articles, though I'm not sure if the spasmolytic one is the correct one?). Dr. Cash 04:00, 20 September 2007 (UTC)
Okay yeah, those definitions include both, and so does cancerweb. So it seems like I was wrong (though I don't like it!). Bilz0r 04:10, 20 September 2007 (UTC)
Even weirder, mayo clinic and WebMD don't cover neuromuscular blockers at all, and only refer to the spasmolytic definition. I am beginning to think that the term is just part of a very broad classification, and both are technically correct, although perhaps in modern, everyday language, the spasmolytic group is gaining dominance in the group, probably because these are the drugs that are more commonly prescribed and have more of a therapeutic use (neuromuscular blockers don't have much therapeutic use, at least outside of the OR, so when people think "muscle relaxant", they're thinking something like valium). I've added a sentence to the lead to help clarify this, though I hope it doesn't get too close to original research,... Dr. Cash 04:27, 20 September 2007 (UTC)
Well, IMHO there's little reason for them to cover neuromuscular blockers; they have pretty much no clinical use except in anesthesia. For the lay reader, I guess there isn't much interest. Fvasconcellos (t·c) 12:59, 20 September 2007 (UTC)

[edit] "Centrally acting"

I reverted the "centrally acting muscle relaxants" subsection header, for two reasons. One, per wikipedia manual of style, the article title itself should not be contained within section headers (specifically, see WP:MSH). Second, "centrally acting", while being the 'traditional' name, is actually not entirely accurate, as not all of these agents have CNS activity (specifically, dantrolene, has no central effects), yet is considered to fall under the 'spasmolytic' category. Dr. Cash 07:18, 20 September 2007 (UTC)

I have to say I'm personally not familiar with the use of "spasmolytic" to refer to skeletal muscle relaxants, only to traditional antispasmodics (i.e. acting on smooth muscle). Interestingly, these authors make the distinction between "antispasmodics" and "antispasticity" agents. Fvasconcellos (t·c) 13:44, 20 September 2007 (UTC)
Yeah, I totally see your points Dr Cash, and Fvasconcellos. It was because of Fvasconcellos point that I went with Centrally acting muscle relaxants. Couldn't it be split up, So Centrally acting muscle relaxants, and then misc ones, like dantrolene. Also, doesn't the Manual of style say the article title should be be contained within section headers? Isn't it more saying, in an article about muscle relaxants, you should have a section title "Mechanism of action", not "Mechanism of action of muscle relaxants". I.e. "avoid redundancies", not "don't use the same words". Bilz0r 22:53, 20 September 2007 (UTC)
The term "spasmolytic", I am seeing in Katzung's Basic & Clinical Pharmacology (7th edition). Furthermore, the wikipedia article Antispasmodic specifically refers to smooth muscle relaxants, which we've agreed act by a totally different mechanism than skeletal muscle relaxants, and should not be part of this particular article. There is clearly some confusion here, because Spasmolytic goes to a disambiguation page which links to the Antispasmodic article, as well as an album by the band Skinny Puppy.
Katzung's Pharmacology text also places Dantrolene in the 'Spasmolytic' category with the other 'centrally-acting' muscle relaxants as well. Dr. Cash 21:28, 23 September 2007 (UTC)
OK then. I don't have access to Katzung right now (I usually favor G&G, but I don't have access to any scholarly sources at the moment). Perhaps we could add a note at the top of Antispasmodic, e.g., For spasmolytics acting on skeletal muscle, see muscle relaxant. Fvasconcellos (t·c) 21:31, 23 September 2007 (UTC)
Good idea. Done. I've also rephrased the text on the Spasmolytic disambiguation page, pointing here instead. Dr. Cash 21:44, 23 September 2007 (UTC)

[edit] Again, muscle relaxants are not used in IBS.

"gastrointestinal overactivity, such as in irritable bowel syndrome". While these drugs relax smooth muscle, they are antimuscarinics. Only the sloppiest users of the language would accept this(and yes I have seen in it peer-reviewed journals, but I don't think that is an excuse). If these drugs are considered muscle relaxants, then so do alpha-blockers, and any number of drugs. Even the article on Dicyclomine doesn't call it a muscle relaxantBilz0r 23:00, 20 September 2007 (UTC)

I've been bold and removed it altogether. Fvasconcellos (t·c) 23:03, 20 September 2007 (UTC)

[edit] New Image

I made an image of the spinal cord showing the action of the muscle relaxants. Do you guys think adding another section to that image showing the neuromuscular junction would be called for, i.e. to replace the first image? Bilz0r 06:59, 23 September 2007 (UTC)

Why not make this diagram the lead image? The article doesn't have one yet. Fvasconcellos (t·c) 16:00, 23 September 2007 (UTC)
The image is excellent! Nice work! But I think the current placement of both images within their respective sections is adequate - moving either one to the top could be misleading. Not sure what to put as a lead image, though. Dr. Cash 21:46, 23 September 2007 (UTC)
That's a tough one. I personally think Bilz0r's diagram in the lead would strengthen the article's focus on spasmolytics rather than neuromuscular blockers. Perhaps no lead image at all? I normally use structures of a representative compound (e.g. the structure of propranolol in beta blocker, and ondansetron in 5-HT3 antagonist), but the muscle relaxants are such a heterogeneous group. Fvasconcellos (t·c) 21:50, 23 September 2007 (UTC)
I'm all for keep all the information, I was just wondering if I could essentially make them one image, i.e. show a zoom in on Neuromuscular synapse, as well as the current, zoom in on the spinal synapse. i.e. two birds with one stone. Bilz0r 23:41, 23 September 2007 (UTC)

[edit] Spasmolytics

Dr. Cash has nicely expanded the Spasmolytics section. May I suggest we make it into indented list format? It would look something like this:

  • Baclofen is considered to be at least as effective...
  • Clonidine and other imidazoline compounds...
  • The hydantoin derivative dantrolene is a spasmolytic agent with a unique mechanism of action...

Thoughts? Fvasconcellos (t·c) 21:27, 23 September 2007 (UTC)

Not real crazy about moving those items to a bulleted list. I generally favor using bulleted lists in very limited cases, and in this case, I think simple prose is adequate to get the point across. I also don't think that the bold text is necessary, either, and may go against the manual of style's excessive bold guidelines. Dr. Cash 21:36, 23 September 2007 (UTC)
Well, it might indeed look too...busy. I'm guessing the text will expand further, so there would really be no point then. Fvasconcellos (t·c) 21:39, 23 September 2007 (UTC)

[edit] Cellular Mechanism of Alpha2 Agonists.

Nice fleshing out of the spasmolytic section, I'm unsure of one bit thought. Quoting "Neurophysiologic studies also indicate that it reinforces both presynaptic and postsynaptic inhibition in the spinal cord, as well as inhibiting nociceptive transmission in the spinal dorsal horn". I can't comment on pain the the dorsal horn; and maybe I'm taking the rest of it too litterally (i.e. there is a difference between enhancing inhibition on a system level, and enhancing an inhibitory synapse), but it makes me a little uneasy. To quote from a 2003 Journal of Neuroscience paper (PMID: 12514232):

The investigated neurons included neurons of origin of the VSCTs [ventral spinocerebellar tract] (Jankowska et al., 1998; Hammar et al., 2002) and the two populations of inhibitory interneurons (Jankowska et al., 2000) further investigated in the present study, interneurons mediating reciprocal inhibition of motoneurons from group Ia afferents, and interneurons mediating nonreciprocal inhibition from group Ia and Ib afferents. The results reported in this study show that the previously described facilitatory actions of NA on these neurons are reproduced by ionophoretic application of the alpha 1-receptor agonist phenylephrine and, although to a lesser degree, by the beta -receptor agonist isoproterenol, but not by the alpha 2-receptor agonists clonidine and tizanidine. Clonidine, instead, has been found to depress activation of these interneurons (i.e., to have an effect opposite of that of NA), and tizanidine has been found to lack any effect. These drugs also would weaken rather than enhance the inhibition of motoneurons by group I afferents (present study) and would not have any effect on the presynaptic inhibition of group I afferents (Anden et al., 1966). alpha 2-Receptor agonists, therefore, could not be expected to counteract spasticity by acting directly on motoneurons or by modulating input from group I afferents to these neurons.

That is to say alpha2 agonists either depress or have no effect on inhibitory interneurons of the spine.

Thankfully we find a paper My Jankowaska from 1990, in EJN (PMID: 12106064), showing the likely action.

Tizanidine depressed responses induced by stimulation of group II afferents in [excitatory] intermediate zone interneurons. [Conversley] injuries to the descending monoaminergic pathways might thus contribute to the development of exaggerated stretch reflexes, and spasticity, in at least two ways. One of these was discussed previously − by weakening tonic inhibition by NA, releasing neurons of transmission from group II afferents to intermediate zone interneurons which excite alpha- and gamma-motoneurons ( Eriksson et al. 1996; Jankowska et al. 1998).

That is to say alpha2 receptors depress the synapse between group II afferents (secondary spindle endings), and excitatory interneurons which then excite primary motor neurons.

So I'm changing that section to reflect those facts. (Primary research beats textbook) Bilz0r 23:37, 23 September 2007 (UTC)

[edit] Pancuronium

Would anyone mind if I created another version of Image:Pancuronium.jpg highlighting its similarity with acetylcholine by using color instead of thicker bonds? I find the current diagram a little confusing—it's hard to parse thicker bonds as not indicative of stereochemistry at first glance. Fvasconcellos (t·c) 13:33, 29 September 2007 (UTC)

Here it is. Fvasconcellos (t·c) 14:29, 29 September 2007 (UTC)
I have fixed my image and replaced it already. Dr. Cash 19:42, 29 September 2007 (UTC)
Thanks! Fvasconcellos (t·c) 19:49, 29 September 2007 (UTC)

[edit] Help - Centrally Acting Skeletal Muscle Relaxants

I was shocked to view this page after having it listed in my talk section as a weekly cleanup topic. The most commonly used SMRs such as Cyclobenzaprine, Chlorzoxazone, Carisoprodol, Gabapentin (to a lesser extent), and many more are not mentioned at all for the entirety of this article, with exception to a note at the end for a few. These agents, however, make up the primary foundation of the overwhelming majority of commonly prescribed SMRs currently on the market and used today. I will begin working with this page by expanding the information available regarding the above mentioned agents (and their counterparts), but I have no clue how to go about getting rid of the large amount of garbage on this article that has almost nothing to do with the typical (or even atypical) SMRs. Any suggestions or comments for me? --Wikisystole 22:23, 29 September 2007 (UTC)

If you can expand this article with relevant information, then please do. That's the purpose of a wiki. But I take offense to your comment regarding, "getting rid of the large amount of garbage on this article", as most of the information is well sourced with quite reliable academic publications and textbooks, and the overall quality has increased tremendously from what it used to be. Dr. Cash 07:01, 30 September 2007 (UTC)

[edit] Semi Auto Peer Review

Semi Auto Peer Review has been done of this article Muscle_relaxant. It can be perused at the above link to allow for changes and improvements to help Muscle_relaxant achieve GA status. SriMesh | talk 01:46, 8 October 2007 (UTC)

I personally don't find these automated per reviews helpful in any way. Most times in the past, the automated scripts suggest things to improve the article that just aren't issues, because the scripts lack the "intelligence" of a real human reviewer. It should also be pointed out (a) the review you're referring to is not "semi-automated" - it's "full automated" (you didn't post any of your own comments or assessment there, and just let the script's answers stand on their own), and (b) none of the comments that are suggested on the page relate to the actual Good Article criteria. As an experienced GA reviewer myself, I should also point out that the use of automated reviewing scripts in the GA process is strongly discouraged, and should generally not be done. Dr. Cash 18:56, 8 October 2007 (UTC)

[edit] Failed "good article" nomination

This article failed good article nomination. This is how the article, as of June 13, 2008, compares against the six good article criteria:

1. Well written?: Fair
  1. Lead is confused, uses are not grouped together and the explanation that the term is used for two main groups of drugs appears twice.
  2. "enzymatically destructed by acetylcholinesterase" - this is not a good way of putting this - what about "broken down into choline and acetate by acetylcholinesterase"
2. Factually accurate?: Not wholly
  1. "The combination of two acetylcholine molecules results in the opening of the sodium-potassium channel of the nicotinic receptor" - two molecules of acetylcholine do not combine at receptors, this is a binding reaction, not a chemical reaction.
  2. "All neuromuscular blocking drugs are structurally similar to acetylcholine" - might be true for agonists/antagonists but certainly not for AchE inhibitors.
3. Broad in coverage?: No
  • The major problem. The article covers how these drugs act very thoroughly, however what they are used for is only briefly touched on in the lead. There needs to be an "Applications" section that explains why they are used in surgery and what other major uses the drugs have.
4. Neutral point of view?: Yes
5. Article stability? Yes
6. Images?:
Could use an image of acetycholine next to the picture of pancuronium to allow easy comparison with the highlighted parts of the structure.

When these issues are addressed, the article can be renominated. If you feel that this review is in error, feel free to take it to a Good article reassessment. Thank you for your work so far. Tim Vickers 02:15, 13 October 2007 (UTC)

rewrote some of the content so as to address point 2. in the Good article nomination 140.203.12.243 16:08, 18 October 2007 (UTC) (if you don't like what I done with it your welcome to change it back)