# Acetylcholine Agonist?



## slacker (Mar 23, 2002)

Is there such a thing, Rx or not? That is, besides nicotine. Cigarettes (yeah, I know) help me a lot, 1-2 a day. I don't want to inhale burning plant material, either. But I can't afford the gum. Damn. Slacker


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## flux (Dec 13, 1998)

There are two types of cholinergic receptors: muscarine and nicotinic. The nicotinic receptors are called by this because of the fact they are stimulated by nicotine. Anyway, the effect of nicotine on the gut is complicated by the fact it is present on both excitatory and inhibitory portions of the autonomic nervous system, so the effects it will have hard to predict. In general, I think it is better for someone with a functional gut problem to avoid nicotine (and for obvious other reasons).The receptors that are important are the muscarinic ones because their effects are clear cut. Antagonists such as hyoscyamine (Levsin and friends) block it and reduce gut motility and agonists such as *bethanechol*. It is also possible to have a drug that keeps acetylcholine around longer producing an agonist effect. The primary drug that does this is *neostigmine*.


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## slacker (Mar 23, 2002)

Flux, Thanks for the info. Is there any reason why these agents aren't used very often for IBS-C and other conditions? Do you think it would be useful for some people? And by not used very often, I mean I've not seen such a thing mentioned a single time on this board, which I have read for almost a year. I have searched on the web about such a thing before and found only limited info on the bethanecol, and the only indications mentioned are bladder problems. Never heard of Neostigmine. Would a doctor just think I'm an idiot if I mentioned such a thing?







Slacker


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## flux (Dec 13, 1998)

> quote:aren't used very often for IBS-C and other conditions? Do you think it would be useful for some people?


Not all C is the result of dysmotiliy. You should be tested first.In the case of positive test, it might, in fact, be helpful. But it is more of last-resort option over things (such as Miralax) and most constipation probably doesnï¿½t warrant it.


> quote:Would a doctor just think I'm an idiot if I mentioned such a thing?


It always makes sense to ask for tests (transit time and manometry) to learn more about the problem, but because these are specialized tests, it is unlikely the doctor will be able to do them.


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## trbell (Nov 1, 2000)

one of the complications is that many (like me) have smoked for years and come to rely on this for getting things going.tom


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## slacker (Mar 23, 2002)

trbell, Thats part of the reason I thought of acetylcholine agonists. I used to smoke 2 packs per week (stupid). Do you smoke at all now? Helpful? So maybe I "messed something up." Go ahead and lay into me on the technical aspect of that, flux =). Flux, I don't have IBS, I don't have D, and I don't have C (amazingly). My problems are up higher. Dysphagia, Reflux (acid and bile), regurgitation. Severe nausea, no appetite. Have lost 20 pounds, and still losing, BMI is currently 19.5, The pain is tolerable. I have been tested, I had the gastric empty test (radioactive breakfast) and the god-awful gastro-duodenal motility test at Mayo, in Rochester. Got the reports right here..1 hour, 14% had left the stomach (normal 11-39%)2 hours 30% (normal 40-76%)4 hours 90% (normal 84-98%)6 hours 0% had left the Small Bowel (normal 46-98%)So the stomach is a little slow but catches up later, and the Small Bowel, well, it sucks.Gastro-duodenal motility (to check for myopathy or neuropathy, he said)No evidence of either one, although the doctor did say it doesn't test the whole small bowel, just the beginning part. "Normal gastroduodenal motility."Can you translate this? "predominantly phase II type activity during the fasting period.""no phase III migrating motor complexes were observed during this time, but this is within the normal range" Hes callin it "small-bowel dysmotilty."Told me to go on a liquid diet (Instant Breakfast) and soft foods as tolerated, no fat, no fiber. Try Zelnorm when approved. No other advice or help, says it "may" improve "in time," no follow up because there's nothing he can do. This helped the pain some but not the nausea, which is the debilitating part. I gag down on average about 1500 calories per day, 1000 from instant breakfast. Also have edema in hands and lower legs, Raynaud's in hands and feet, cold extremeties, Atrial Fib, tachycardia (80-120 at rest), my normal temp is about 97.0 F. Also, numbness, tingling, burning type pain in my abdomen, back, sides, perineum, whole lower body below waist, this is on and off but frequent. Doctor doesn't know why, about this. So what's your opinion on all this? (I realize you're not a doctor, not trying to use you as one, just curious for educated viewpoints.)19 yrs old (yeah thats right) and going on 85.Slacker


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## flux (Dec 13, 1998)

> quote:6 hours 0% had left the Small Bowel


Are they still feeding people in the middle of this test? If so, it's makes it harder to judge because that is a very complicating variable.I assume 6 hours is the total figure. We should try to take into the account the stomach being slow in the beginning, but this does sound long.


> quoteredominantly phase II type activity during the fasting period.""no phase III migrating motor complexes were observed during this time, but this is within the normal range"


How long was the test for? You should see a cycle every 90 minutes (phase I to phase II to phase III), but all that was seen was just phase II. It could be you don't have phase III and that would explain why food had not left the intestine. Phase III is the most important one. Did they give you *erythromycin*? Have you ever taken it and did they suggest it?


> quote:This helped the pain some but not the nausea,


Have you tried granisetron or ondanestron? It would curious to know your fasting serum serotonin levels.


> quote:Also have edema in hands and lower legs, Raynaud's in hands and feet, cold extremeties, Atrial Fib, tachycardia (80-120 at rest), my normal temp is about 97.0 F.


You might want an evaluation by a rheumatologist.


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## slacker (Mar 23, 2002)

Ack, my post is confusing. I had the Gastric Empty test one day, and based on the results, they scheduled a gastro-duodenal motility for the next day to hopefully see WHY the small bowel is so slow. Didn't find out. I fasted for both tests, of course. For the Gastric Empty test, I ate the eggs, bread, milk. Then when I was done eating (5 min or so), they took a "picture" with me laying on a table, which took about 5 min each time, at 1 hour, 2 hours, 4 hours, 6 hours. They told me not to eat or drink anything else for the duration of the test. I didn't. Before each picture they asked if I had vomited or had a bowel movement. I didn't. My stomach is barely slow..they know the S.B is the problem.. Although on another test, earlier, (I think barium swallow with small bowel follow through? I drank the stuff, I walked around, they took pictures every 10-20 minutes, I don't remember, for about 40-60 min) I had "moderate gastric retention." Maybe if the S.B. worked the stomach would speed up a bit. (dumb, uneducated guess) Next day, gastro-duodenal motility. They did a quick endoscopy, "normal," then passed a tube into my small bowel (not fun). You have the thing in for about 6 1/2 hours.3 hours empty, you eat a small meal with a 30 minute time limit, then 3 hours fed. They log the whole thing on the computer. You don't eat or drink for the first 3 hours, and have fasted since the night before. "During the three hour fasting observation period, the amplitude of contractions at all levels was normal, excluding a myopathic process." "predominantly phase II type activity during the fasting period." "no phase III migrating motor complexes were observed during this time, but this is within the normal range" Then at 3 hours, They fed me chicken, potatoes, pudding, some water, (500 calories). Then they log the next 3 hours. "well developed fed patterb in the antrum and small intestine" "no manometric features to suggest neropathy, pseudo-obstruction, or mechanical obstruction."What action goes on during each of the phases? What if I don't have much or any phase I? What phase(s) should be seen during a fast? I've taken ondanestron and mirtazapine. Doctor doesn't want me to take ondanestron long term. I don't know why. Take mirtazapine now, its cheaper anyway. 7mg works as good as 60mg, nausea/vomiting wise. Stops vomiting, helps nausea. Not hungry at all, always force feeding. More nausea if I eat too much too fast. Small serving of rice and a banana is about all I can take at once. What about my fasting serum serotonin levels? Think acetylcholine agonist would help? erythromycin: no they didn't, no i haven't. no one has ever mentioned it. What would that do?I'm apprehensive of antibacterials. I was taking minocycline (acne) when this whole thing started. Oh, what are the findings on blood tests, etc, in Rheumatic illnesses? Just glancing over some Scleroderma signs and symptoms, I have +80% of it..Slacker


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## trbell (Nov 1, 2000)

I know it doesn't help at this point but it sounds like you've been going in circles on the meds since this mincyline thing?tom


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## slacker (Mar 23, 2002)

This is long I had no GI troubles at all prior to minocycline. I started having problems after I took it for a bit (few months?). Also had food poisoning bad somewhere in this time, but didn't go to the hospital (Stupid). No improvement with PPI's. I think they made it worse. PPI's concurrently with anti-bacterials sounds like a bad idea to me. No improvement with anti-spasmodics, and they made the reflux worse, as they are known to do. Then, apparently got food poisoning again. REALLY hardcore, the worse of it starts here. Crappy ER in a college town ran a couple basic tests and didn't give me anything. Didn't know what the problem was. GP decides its anxiety, Xanax, worthless. This GP I had is an idiot. He proceded to put me on Asacol (Crohn's, UC drug), without a colonoscopy. It made me hardcore sick, ER style. They are enteric coated so they disolve where you need them to with Crohn's..in me they kinda disolved in my dysfunctional small bowel, which I later find out lets stuff leak into my stomach. Well, I was feeling this all along but no one believed it until the Mayo GI agreed this is happening. Yikes. Then an Endoscopy and Colonoscopy. GERD, "just IBS" and "You look depressed." Put me on more PPI's, Metoclopramide, Zoloft. Worthless. ER again. Finally get admitted to Hospital for a week or so. Enlarged spleen, bilirubin elevated and in the urine, don't remember what else. No psych tests. Im all doped on Demerol and Benzos, I.V. Only remember talking to one guy, a GI. "Do you have HIV?" No. (wtf?)"you know, theres nothing wrong with you" they flip flip around on whether its anxiety, malingering, adjustment disorder, depression, or stress because my parents don't get along. Apparently another guy talked to me and they decided I'm schizophrenic and its all in my head. So I'm on Remeron, Ativan, Vicodin, and Zyprexa, very high doses, and later Seroquel for my alleged schiz. All worthless, psychologically and physically. Pain gets better on its own, Vicodin adds to nausea too much, can't take it. Schiz drugs make me stupid and weak. Psychotherapy, worthless. Esophageal manometry, perfectly normal, no GERD. The GI who did the Endo said I had GERD. Both are from the same practice. Doctors suck. Eventually they realize im not Schiz, no anxiety disorder, and I'm not makin it up. A shrink gets me into Mayo as I have been on high doses of everything and nothing helped. Finally get the Gastric Empty test I need, get DXed, small bowel dysmotility. Do a liquid diet, no fat no fiber, try Zelnorm if it comes out, no follow up, good luck buddy. I'm on Remeron and Adderall now. The pain is either somewhat better or I'm getting used to it, mostly liquid diet prevents some pain. I require Remeron to eat and not vomit, and Adderall helps with nausea, "depression." Start of Major problems, to diagnosis, time elapsed: a solid Year, June '01-July '02. I feel really, really sick. Still. Year has gone by. Zelnorm is basically my last hope. Very difficult to maintain weight, even doing nothing. Do they all really need to ask if I'm depressed now? Doctors suck.Slacker


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