Pepto bismol ?

[CAH]

Since Pepto Bismol prevents vomiting directly, would that work for SN?

 

[mimo5555]

It will work as an antacid. It won't work to prevent vomiting, it only helps in some cases of food poisoning or eating too much. You need something that inhibit the vomiting response directly like a 5-HT3 antagonist or a dopamine antagonist.

 

[autumnal]

It will work as an antacid. It won't work to prevent vomiting, it only helps in some cases of food poisoning or eating too much. You need something that inhibit the vomiting response directly like a 5-HT3 antagonist or a dopamine antagonist. [my emphasis]

Yep largely this. However more accurately, you need something which is primarily a dopamine (D2) antagonist. Any 5-HT3 effects it may have are purely secondary.

Standalone 5-HT3 antagonists cover a different mechanism of nausea from that relevant to SN.

 

[mimo5555]

Standalone 5-HT3 antagonists cover a different mechanism of nausea from that relevant to SN.

I have seen this information before but I haven't seen a reliable source. Ondansetron (Zofran) is exclusively a 5-HT3 antagonist without dopamine effects and it is recommended by the PPH and other sources as a valid antiemetic. It is also often prescribed by doctors for all types of nausea. In fact ondansetron is more effective than metoclopramide for preventing vomiting in case of acetaminophen overdose:

Use of ondansetron and other antiemetics in the management of toxic acetaminophen ingestions - PubMed

Ondansetron should be utilized as a second-line agent in the management of acetaminophen toxic patients with vomiting. Because of its lower failure rate, ondansetron should be administered as a first-line agent in patients with a delay in N-acetylcysteine administration approaching 8 or more hours.

pubmed.ncbi.nlm.nih.gov

 

[autumnal]

I have seen this information before but I haven't seen a reliable source. Ondansetron (Zofran) is exclusively a 5-HT3 antagonist without dopamine effects and it is recommended by the PPH and other sources as a valid antiemetic. It is also often prescribed by doctors for all types of nausea. In fact ondansetron is more effective than metoclopramide for preventing vomiting in case of acetaminophen overdose:

Use of ondansetron and other antiemetics in the management of toxic acetaminophen ingestions - PubMed

Ondansetron should be utilized as a second-line agent in the management of acetaminophen toxic patients with vomiting. Because of its lower failure rate, ondansetron should be administered as a first-line agent in patients with a delay in N-acetylcysteine administration approaching 8 or more hours.

pubmed.ncbi.nlm.nih.gov

I don't know a great deal more than the information I have provided.

However @Quarky00 is experienced (he wrote a number of the SN FAQs) and he says a similar thing.

Also, I have would strongly recommend you...

​

...have a read of my existing response regarding ondanestron here. Note that following it is some technical debate on the issue between two users with a lot more medical knowledge than myself. From their discussion, it seems there are competing views on whether or not ondansetron would work as an antiemetic with SN, and it is not inconceivable that this argument could also extend to mirtazapine.​

 

[Quarky00]

I have seen this information before but I haven't seen a reliable source. Ondansetron (Zofran) is exclusively a 5-HT3 antagonist without dopamine effects and it is recommended by the PPH and other sources as a valid antiemetic. It is also often prescribed by doctors for all types of nausea. In fact ondansetron is more effective than metoclopramide for preventing vomiting in case of acetaminophen overdose:

Use of ondansetron and other antiemetics in the management of toxic acetaminophen ingestions - PubMed

Ondansetron should be utilized as a second-line agent in the management of acetaminophen toxic patients with vomiting. Because of its lower failure rate, ondansetron should be administered as a first-line agent in patients with a delay in N-acetylcysteine administration approaching 8 or more hours.

pubmed.ncbi.nlm.nih.gov

PPH recommendation is recent and flimsy (will explain) . As mentioned it is of limited effects . Ondansteron targets vagus nerve in the stomach , thus 'communicating' to vomiting zone in the brain that "there isn't really something toxic" . In contrast the 6 recommended AEs target the brain in the part the facilitate the actual decision and action of vomiting , and they're also pro-kinetic and help stomach emptying . Ondansteron is also a selective 5HT3 antagonist (it doesn't affect all receptors) . See explanation bellow .


I stand by my comment despite PPH and members pushing alternatives . PPH is not always reliable especially when it comes to side notes , alternatives , or new suggestions . I find some of that reasonable and natural (underlined) but some like Dramamine flimsy -- it doesn't even work on the same "circuits" ..

others AEs may help nausea but are not systematic , while this doesn't negate usage of alternatives it suggests those should be used as last resort .

------------------------------------------------------------------------------------------------------------------

TLDR: For vomiting , there is the stomach and the brain , and 5HT3 receptors as well as Dopamine receptors . The stomach signals the brain which then mediate the reaction . It is either vomiting (5HT3) or allowing substance to enter stomach (Dopamine) .

• Ondansteron is a 5HT3 selective at stomach thus may reduce vomiting .
• Metoclopramide is non-selective 5HT3 antagonist at stomach so it has more effects , plus it is a Dopamine antagonist -- in the brain vomiting center (it crosses blood-brain barrier) .
• Domperidone also acts in the stomach only and does not cross the blood-brain barrier , but it affects Dopamine receptors in the stomach directly to the brain vomiting center .
• The combination of 5HT3 and Dopamine neurons is the strongest .

------------------------------------------------------------------------------------------------------------------

Introduction to AEs and Alternatives

Why Meto preferred?	Only antiemetic that: Targets both dopamine and 5HT3, and Crosses into the brain This means: Strong stomach emptying effect Strong anti-vomiting effect
Strong effects without Meto?	Ondansetron and Domperidone target peripheral receptors, not the brain (less side effects): Domperidone (Dopamine, less EPS) + Ondansetron (5HT3, less EPS) = Metoclopramide (Dopamine+5HT3 , Brain/EPS)

The reason alternatives are less effective (I wouldn't say "DO NOT USE"..):

Other AEs?	DO NOT use – Ondansetron/Zofran Diphenhydramine/Benadryl Dimenhydrinate/Dramamine Serotonin or Histamine only are not as effective. No promotion of gastric emptying Less effective on brain vomiting mechanism for severe poisoning (wide & systematic). D2 receptors go through brainstem and stomach, Histamine do not (History of Drug Discovery for Treatment of Nausea and Vomiting – Figure 5) Effective AE targets both neural & muscular receptors. Read guide ; List of AE by type – dopamine antagonists (Wikipedia)
Why not Dramamine?	Histmine is responsible for body movements (Vestibular nucleus) , treats motion sickness Little to do with poisons, stomach, or CTZ . Lack prokinetic activity See here Dramamine is not a good solution , though won't harm (unkown why PPH push these)
Why not Ondansetron?	spanishguy22 said: "Metoclopramide is used by Dignitas and i think it's the recommened antiemetic in OD, the second one being domperidone, both dopamine antagonists. Ondansetron (Zofran) is a serotonin receptor antagonist and it's used for cancer patients undergoing chemotherapy because the irritation of the GI mucosa by the medication used in chemotherapy (which is cytotoxic and increase the levels of serotonin in the blood) are transmitted through the vagal nerve to the chemoreceptor trigger zone via activating serotonin receptors (5-HT3). It has no effect on dopamine receptors. "
In simple words?	Need broad systematic AE targeting both CTZ (brain) and stomach plus prokinetic.

------------------------------------------------------------------------------------------------------------------

Ondansteron in Medical Procedures

There is a reason Ondansteron is less potent overall despite it having more affinity than meto and used as first line treatment for CINV ( @Aap -- did you mention it?) . It is meant for symptomatic relief of nausea and vomiting cause by chemotherapy , or poisons after charcoal and stomach pump , or after an operation . In all of these situations the body experiences much less toxins and strong response than SN intake while the patient is being medically treated . It is not like SN intake .

I would also view that from medical perspective . Ondansteron is first in protocol while Metoclopramide is third and last . That has a reason . In a medical setting we look at the average and seek relief for most people , while causing little harm as possible -- if that doesn't work we move to the next medication in the protocol . In that sense Metoclopramide has more side effects but it is the "ultimate" antiemetic . Ondansteron simply works well with more people , while providing a more moderate relief overall -- it's better to give 60% relief with no harm than to give 90% relief while patients suffer serious side effects . That's why Ondansteron is such a 'gold standard' as first treatment . SN intake is not a medical procedure but severe fatal quick poisoning . So it's not prefferable to use such medical metrics .

A comparison , although problematic , can be made with psychiatry: SSRI for a depressive person first (statistically less side effects) , but TCAs (harsher more side effects) if it is severe or complex . You may not like that statement -- 'of course SSRI have side effects!' I hear you say . But modern medicine is about statistics and averages , tailoring medication to situation and patient with careful attention is less practiced (perhaps with private healthcare). But this stupid comparison can give some insight as to why and when doctors sometimes use a medication that is "more systematic". The last medications in a protocol (like Metoclopramide) are usually strong with more side effects (hence less preffered by doctors).

------------------------------------------------------------------------------------------------------------------

Efficacy & Affinity

Meto=Ond+Dom. Wanted to mention that in so many threads, but thought it would confuse, or regarded as minutia. There's more to it than receptor affinity or selectivity. In addition to what you wrote:

• In that context (receptors), 5HT3 antagonists [Ondansteron] are more potent than Meto. But their sites of action are different – Ond in stomach, Meto all over.
  • As a note, being a selective antagonist (local or specific) could be a pro or a con. Hence systematic broad AE, targeting both CTZ (brain) and stomach, plus prokinetic. "One pill to rule them all".
• Meto not that weak: Ondestron 5HT3A potency ~ 8.0 , Metoclopramide ~ 6.0 . See here.
  • I know it's significant but is it crucial? I don't know.
• They could actually complement, as you and k75 suggested. May enhance AE effects, could change common practice (more feedback required).
• Overall Meto vs 5HT3 antagonists is not such a big medical question, depends on patient, conditions, practice, etc. CINV, poison, pre-op etc. Affinity is indicative, but in terms of efficacy all three considered similarly effective.

Another interesting point: "non-selective 5HT3 receptor antagonist at high dosage". Regimen exceeds max daily dosage – actually doubling it to 60mg daily. Overall Regimen accumulates to rather high peak – up to 45mg. Is that enough? Does it work? I don't know.

Meto discussions go neither here nor there in terms of bottom line. Though theoretically interesting and enlightening :)
Well said -- no 'one size fits all'..

I'm writing so much in the hope this will bring an end to claims about Ondansteron , which may be suggested , but please remember the caveats . Do not suggest it to members off the cuffs .

------------------------------------------------------------------------------------------------------------------

Dramamine

I'm also adding the Dramamine note , to make this post encompassing and complementing the FAQ :
Daramaine affects motion not stomach chemoreceptor input . It affects sensory information from the ear (sensing motion/balance):

The drug depresses labyrinth excitability and vestibular stimulation

So it really treats a totally different input than toxins . It may reduce sensory input from the ear regarding balance and motion , but that won't stand against the strong signaling from vagus nerve chemoreceptors regarding severe toxin in stomach ..

 

[mimo5555]

PPH recommendation is recent and flimsy (will explain) . As mentioned it is of limited effects . Ondansteron targets vagus nerve in the stomach , thus 'communicating' to vomiting zone in the brain that "there isn't really something toxic" . In contrast the 6 recommended AEs target the brain in the part the facilitate the actual decision and action of vomiting , and they're also pro-kinetic and help stomach emptying . Ondansteron is also a selective 5HT3 antagonist (it doesn't affect all receptors) .

There is a reason Ondansteron is less potent overall despite it having more affinity than meto and used as first line treatment for CINV ( @Aap -- did you mention it?) . It is meant for symptomatic relief of nausea and vomiting cause by chemotherapy , or poisons after charcoal and stomach pump , or after an operation . In all of these situations the body experiences much less toxins and strong response than SN intake while the patient is being medically treated . It is not like SN intake .

I would also view that from medical perspective . Ondansteron is first in protocol while Metoclopramide is third and last . That has a reason . In a medical setting we look at the average and seek relief for most people , while causing little harm as possible -- if that doesn't work we move to the next medication in the protocol . In that sense Metoclopramide has more side effects but it is the "ultimate" antiemetic . Ondansteron simply works well with more people , while providing a more moderate relief overall -- it's better to give 60% relief with no harm than to give 90% relief while patients suffer serious side effects . That's why Ondansteron is such a 'gold standard' as first treatment . SN intake is not a medical procedure but severe fatal quick poisoning . So it's not prefferable to use such medical metrics .

I understand ondansetron works mainly though peripheral action but I haven't seen any source claiming this peripheral action will make it less effective. In fact it seems it is more effective than metoclopramide for most uses like vomiting induced by opioids:

Ondansetron: a selective 5-HT(3) receptor antagonist and its applications in CNS-related disorders - PubMed

Ondansetron is a selective 5-hydroxytryptamine(3) (5-HT(3)) receptor antagonist that has been introduced to clinical practice as an antiemetic for cancer treatment-induced and anesthesia-related nausea and vomiting. Its use under these circumstances is both prophylactic and therapeutic. It has a...

pubmed.ncbi.nlm.nih.gov

It is also more effective than metoclopramide for avoiding vomiting in acetaminophen overdoses:

Use of ondansetron and other antiemetics in the management of toxic acetaminophen ingestions - PubMed

Ondansetron should be utilized as a second-line agent in the management of acetaminophen toxic patients with vomiting. Because of its lower failure rate, ondansetron should be administered as a first-line agent in patients with a delay in N-acetylcysteine administration approaching 8 or more hours.

pubmed.ncbi.nlm.nih.gov

Given this I think ondansetron will have similar effectiveness to metoclopramide (minus the prokinetic effects) in preventing vomiting in a drug overdose.

 

[Quarky00]

I understand ondansetron works mainly though peripheral action but I haven't seen any source claiming this peripheral action will make it less effective. In fact it seems it is more effective than metoclopramide for most uses like vomiting induced by opioids:

Ondansetron: a selective 5-HT(3) receptor antagonist and its applications in CNS-related disorders - PubMed

Ondansetron is a selective 5-hydroxytryptamine(3) (5-HT(3)) receptor antagonist that has been introduced to clinical practice as an antiemetic for cancer treatment-induced and anesthesia-related nausea and vomiting. Its use under these circumstances is both prophylactic and therapeutic. It has a...

pubmed.ncbi.nlm.nih.gov

It is also more effective than metoclopramide for avoiding vomiting in acetaminophen overdoses:

Use of ondansetron and other antiemetics in the management of toxic acetaminophen ingestions - PubMed

Ondansetron should be utilized as a second-line agent in the management of acetaminophen toxic patients with vomiting. Because of its lower failure rate, ondansetron should be administered as a first-line agent in patients with a delay in N-acetylcysteine administration approaching 8 or more hours.

pubmed.ncbi.nlm.nih.gov

Given this I think ondansetron will have similar effectiveness to metoclopramide (minus the prokinetic effects) in preventing vomiting in a drug overdose.

What do you want? You simply repeated yourself .

"I haven't seen any source" -- given in previous comment -- did you read ?

"it is more effective than metoclopramide" -- where did you see that ?




The research you linked said nothing about it being more effective than metoclopramide , and it is for different type of poisoning (as I explained) . I suggest you read resources and write replies in a more careful thoughtful manner .

 

[Aap]

I don't necessarily agree that zofran's primary actions are peripheral, and certainly the manufacturer states the mechanism is both peripheral and central in the CTZ as well as other central locations. As far as efficacy of reglan vs zofran for SN induced NV, I'd simply state that I don't know, and no one on this board does either. There will not be a double blind test comparing the two for SN.

The studies you posted are consistent with the reason zofran replaced reglan by a large margin in the US. Reglan does have the important prokinetic effect of removing SN from the stomach, reducing the time in the reactive acidic environment and reducing fraction in stomach.

I don't know how much more I can add to the discussion. From my perspective, it's a losing game trying to establish which is more effective for SN, as clinical answer hasn't and won't be had. Zofran is viewed as more effective in the US for drug (by drug I mean an exogenous chemical compound) induced NV (though perhaps a view not shared by the entire world). Reglan and zofran have complementary mechanisms of action.

certainly no antiemetic is required for SN, but it seems clear to me the question being asked should be is there a solid basis for suggesting BOTH should be recommended? For zofran and reglan, the answer is yes (though not so with reglan and say Meclizine). I don't have anything to do with the guide here, but I'd just simply state take both and be done with it whenever possible. The guide already recommends a handful of other compounds such as acid reducers or pain reducers

 

[mimo5555]

What do you want? You simply repeated yourself .

"I haven't seen any source" -- given in previous comment -- did you read ?

"it is more effective than metoclopramide" -- where did you see that ?




The research you linked said nothing about it being more effective than metoclopramide , and it is for different type of poisoning (as I explained) . I suggest you read resources and write replies in a more careful thoughtful manner .

The research I linked is available here:

Sci-Hub | Ondansetron: A Selective 5-HT3 Receptor Antagonist and Its Applications in CNS-Related Disorders. CNS Drug Reviews, 7(2), 199–213 | 10.1111/j.1527-3458.2001.tb00195.x

Sci-Hub | Use of Ondansetron and Other Antiemetics in the Management of Toxic Acetaminophen Ingestions. Journal of Toxicology: Clinical Toxicology, 36(1-2), 19–25 | 10.3109/15563659809162578

I have read the sources in the previous comment but they just explain the different mechanism of action between metoclopramide and ondansetron. I fail to see why the peripheral action of zofran would mean it is less effective. My point is, there is no reason to believe zofran would be less efective than metoclopramide at preventing vomiting.

 

[Quarky00]

I don't necessarily agree that zofran's primary actions are peripheral, and certainly the manufacturer states the mechanism is both peripheral and central in the CTZ as well as other central locations.

Please provice research about Ondansteron 5HT3 affinity after it crosses blood-brain barrier , and compare it to selective vs non selective antagonist efficacy . You state claims -- bring sources .

The fact that you don't agree or manufacturer claims are of little usage to me . I brought a hefty medical book -- history of anti vomiting medication -- so I expect more reliable , through , consensual sources . You are free to express your impressions . I'm into the detailed scientific explanation .

As far as efficacy of reglan vs zofran for SN induced NV, I'd simply state that I don't know, and no one on this board does either. There will not be a double blind test comparing the two for SN.

SN double blind is not in question , and I addressed that , but this is a sound basis for preference of AEs . One can take the best AE at the best regimen and vomit , yet another can take none and not vomit -- that is not the point in question . We can safely assume it is better and this is substantiated and researched . Being prokinetic is significant : expelling poison vs opening sphincters . Saying that without experiment we don't know is irrelevant .


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The research I linked is available here:

Sci-Hub | Ondansetron: A Selective 5-HT3 Receptor Antagonist and Its Applications in CNS-Related Disorders. CNS Drug Reviews, 7(2), 199–213 | 10.1111/j.1527-3458.2001.tb00195.x

Sci-Hub | Use of Ondansetron and Other Antiemetics in the Management of Toxic Acetaminophen Ingestions. Journal of Toxicology: Clinical Toxicology, 36(1-2), 19–25 | 10.3109/15563659809162578

I have read the sources in the previous comment but they just explain the different mechanism of action between metoclopramide and ondansetron. I fail to see why the peripheral action of zofran would mean it is less effective. My point is, there is no reason to believe zofran would be less efective than metoclopramide at preventing vomiting.

Brain facilitates vomiting with Dopamine , yet you fail to see why zofran which is not Dopamine is less effective ? This digressing into the absurd .

https://sanctioned-suicide.net/attachments/vomiting-centres-png.12442/

Zofran is selective 5HT3 local (vagus) firing . It is less effective than 5HT3+Dopamine inside the brain/CTZ . I am losing patience and interest since you haven't made yourself versed yet you reiterate false information .

You are linking these 2 articles again and again . What's the point ? .... What are you achieving by repeating irrelevant thing ? .... Are you okay (perhaps tired or not focused)? .......

there is no reason to believe zofran would be less efective than metoclopramide at preventing vomiting.

False . There are reasons .

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@mimo5555 , @Aap , I'm not interested nor having a discussion about what folks believe . It is not out of disrespect , I'm simply not interested . Your impressons were made clear , respected , addressed , and dully noted by members , and there's no need to repeat those . I'm not interested . Show me the damn neurons firing or move on .

 

[mimo5555]

Brain facilitates vomiting with Dopamine , yet you fail to see why zofran which is not Dopamine is less effective ? This digressing into the absurd .

https://sanctioned-suicide.net/attachments/vomiting-centres-png.12442/

5-HT3 is also involved in vomiting so I don't think it is absurd to make comparisons between a 5-HT3 antagonist and a dopamine antagonist.

Zofran is selective 5HT3 local (vagus) firing . It is less effective than 5HT3+Dopamine inside the brain/CTZ .

I know that SN is a different poison but we don't have empirical data about antiemetics in SN overdoses. We do have data that shows Zofran has similar or better effectiveness than metoclopramide in multiple applications (source), including opioid induced vomiting (source) and acetaminophen overdose (source). For this reason the belief that zofran would be less effective than metoclopramide for this specific use (SN) seems unfounded.

I am losing patience and interest since you haven't made yourself versed yet you reiterate false information .

You are linking these 2 articles again and again . What's the point ? .... What are you achieving by repeating irrelevant thing ? .... Are you okay (perhaps tired or not focused)? .......

False . There are reasons .

----------------------------------------------------------------------------------------------------------------------------------------------

@mimo5555 , @Aap , I'm not interested nor having a discussion about what folks believe . It is not out of disrespect , I'm simply not interested . Your impressons were made clear , respected , addressed , and dully noted by members , and there's no need to repeat those . I'm not interested . Show me the damn neurons firing or move on .

Sorry @Quarky00 I did not see your edit before posting my last message. I apologize if my discussion seems false or repetitive. I did not intend to disrespect.

 

[Quarky00]

I know that SN is a different poison but we don't have empirical data about antiemetics in SN overdoses. We do have data that shows Zofran has similar or better effectiveness than metoclopramide in multiple applications (source), including opioid induced vomiting (source) and acetaminophen overdose (source). For this reason the belief that zofran would be less effective than metoclopramide for this specific use (SN) seems unfounded.

The source is selective and so is the reading of it . Ondasteron more effective for specific situation , considering safety (not just efficacy) , and with limited research mentioned . There are dozen more papers (search and read) .

5-HT3 is also involved in vomiting so I don't think it is absurd to make comparisons between a 5-HT3 antagonist and a dopamine antagonist.

That sentence doesn't make sense .
Making the comparison is not absurd , I made those myself .. Conclusion that Ondasnteron more effective is .
If 5HT3+D2 is vomiting , then 5HT3 less potent .

I know that SN is a different poison but we don't have empirical data about antiemetics in SN overdoses.

I have addressed that:

We can safely assume it is better and this is substantiated and researched . Being prokinetic is significant : expelling poison vs opening sphincters . Saying that without experiment we don't know is irrelevant .

Sorry @Quarky00 I did not see your edit before posting my last message. I apologize if my discussion seems false or repetitive. I did not intend to disrespect.

Cool . Let's move on . ( I can continue replying , like an android robot ... )

 

[Aap]

Huh? I don't know why you mentioned me in the first place. I don't care in the slightest if the mechanism of zofran is peripheral or central, nor does it make any difference to anyone on this forum. I'm not fully understanding the point you are trying to make, unless it is only D2 antagonists are useful for SN, period. If so, great; you're certainly entitled to your opinion.

If that's not your point, then we agree that An antiemetic isn't required and that both should be used if possible.