What are the negative effects from taking Meto before SN?

[Endisclose]

Just to clarify on my earlier post (post #28) on meto and domperidone, what sets domperidone apart from the rest of the group is that it is less "invasive" and does not cross the blood brain barrier compared to meto and the other antipsychotics. Because it doesn't "intrude" that much into the brain, there is less drowsiness and a lower risk of EPS.

It is nevertheless a "neuroleptic" and acts on the brain by blocking dopamine receptors.

From what I've read, domperidone is said to a weaker antiemetic than meto.

https://www.sciencedirect.com/topics/medicine-and-dentistry/domperidone

Meto is advised as the first choice both in the pph and the book from the wozz foundation. Although domperidone has a lower risk of EPS, it prolongs the QT interval and there is a danger of sudden cardiac arrest from higher doses (above 30 mg per day) and those above 60. For this reason a stat dose of domperidone would be more risky as it would need a higher dosage since it is weaker than meto.

For people choosing domperidone, the 36 hour or 48 hour regimen would be more suitable (10 mg taken every 6 to 8 hours). Half life of domperidone (12-16 hours) is said to be higher than that of meto (5-6 hours), hence more of it will stay in the system over time and the risk can be spread over 48 hours compared to taking a single high stat dose.

https://www.sciencedirect.com/topics/neuroscience/domperidone

With meto, as it crosses the blood brain barrier, there is a risk of not only EPS but also depression. "Testing meto" seems to entail a risk that may well be avoided and I think it is better to take meto as a stat dose directly just before ctb.

Domperidone compared to Reglan . Induced Lactation . Canadian Breastfeeding Foundation . Fondation canadienne de l’allaitement

Domperidone was initially prescribed for people with upper gastrointestinal problems. It was discovered to have a side effect that results in prolactin levels that could in turn cause lactation. A similar drug called Reglan is used in the U.S. to induce lactation, however, it is not recommended...

www.canadianbreastfeedingfoundation.org

Certain medications can be taken to counter the negative effects of meto.

"Antihistamine, benzodiazepines, beta-adrenergic antagonists (propranolol), beta-adrenergic agonists (clonidine), or dopamine agonists (amantadine) may also be used."

Extrapyramidal side effects after metoclopramide administration in a post-anesthesia care unit -A case report-

Although the incidence of extrapyramidal reactions associated with metoclopramide has been reported to be approximately 0.2%, such reactions are rare in the anesthetic field. Several anesthetic adjuvants, including ondansetron and pregabalin, have also ...

www.ncbi.nlm.nih.gov

In the list above benadryl is an antihistamine that's recommended as an antidote to EPS symptoms at 25-50 mg. If benzos are taken with SN, they can be a good counter to any possible EPS symptoms from a Stat dose of meto. So one will not have to be apprehensive of issues due to the meto in case of a failed ctb attempt. In case benzos are not taken, then propranolol can be taken as a counter measure against any possible adverse effects of meto.

As far as I've read, the risk of potentially permanent side effects of meto comes mainly from long term use. Symptoms like tardive dyskinesia and parkinsonism are associated more with the long term.

Reglan: Package Insert / Prescribing Information - Drugs.com

Reglan package insert / prescribing information for healthcare professionals. Includes: indications, dosage, adverse reactions and pharmacology.

www.drugs.com

Whereas symptoms like dystonia, akathesia may possibly appear within a 24 to 72 hour period and should be reversible with a single dose of 25-50 mg diphenhydramine (benadryl). Meto is advised not to be taken longer than 5 days and domperidone more than 7 days.

"Because of the risk of neurological adverse effects, metoclopramide should not be taken for more than 5 days."

"Domperidone can cause serious ventricular arrhythmias due to QT prolongation on the electrocardiogram (ECG). Its use should be limited to no more than 7 days."

https://www.sciencedirect.com/topics/medicine-and-dentistry/domperidone#:~:text=Because%20of%20the%20risk%20of,for%20more%20than%205%20days.&text=Galactorrhoea%2C%20gynaecomastia%20and%20amenorrhoea%20caused,from%20pituitary%20dopamine%20receptor%20blockade.&text=Dry%20mouth%20(with%20domperidone)%2C%20diarrhoea.

From my reading, reversible EPS symptoms occurred mostly in cases where administration was through IV and IM route.

I came across two youtube comments which said they had symptoms after 2 doses (time unknown) and 3 doses (about 18 hours after first dose) of taking 10 mg Reglan per dose.

The cases of akathesia I encountered after a single dose of reglan were all administered through IV and IM route. One such is mentioned earlier in this thread, which occurred in a child. People in the extreme age spectrum - children and the elderly - are at a higher risk for incidence of adverse effects from meto - about 6 times more than adults.

In my research, I haven't come across any case of EPS symptoms after a single dose of meto or a stat dose of meto taken orally in tablet form in a healthy adult so far. I shall update my findings here if I do come across any such case.

Moreover presuming half life of meto as 6 hours, as per my estimation roughly 13.8875 mg to 18.125 mg of meto would be left in the system with the 48 hour regime compared to nearly 30 mg with the stat dose. Given the symptoms from meto in most cases were a reaction in time, the stat dose would be a less riskier and more effective option compared to the 48 hour regime.

Thus from my research, my personal choice would be a stat dose of meto taken directly before ctb without any prior testing with the use of propranolol and/or benzos to counter possible negative effects of meto to avoid complications from it in case of failed ctb.

The apprehension from negative effects of meto and other antiemetics is a major issue for a lot of people with the SN method. I hope the information presented above would address those to a large degree and help them make an informed choice in their quest to make their final journey as peaceful as possible.

 

[h.s.p.]

You clearly put much effort into researching and writing. I'm not the most knowledgeable member here but here's my opinion:

what sets domperidone apart from the rest of the group is that it is less "invasive" and does not cross the blood brain barrier compared to meto

Yes, I read that too. Some sources claim it does not, others claim it does very poorly. Anyway, general consensus is there's much less risk of EPS

From what I've read, domperidone is said to a weaker antiemetic than meto.

https://www.sciencedirect.com/topics/medicine-and-dentistry/domperidone

Here's what your sources say about that:

domperidone is a weaker antiemetic than metoclopramide

The prokinetic activity of domperidone is considered to be relatively weak compared with that of metoclopramide.

The first quote doesn't say why D is weaker than M. It may be because of its reduced prokinetic activity or not, I don't know. I'm not knowledgeable enough to give a worthy opinion, but I'm not quite convinced that D is weaker than M

Although domperidone has a lower risk of EPS, it prolongs the QT interval and there is a danger of sudden cardiac arrest from higher doses (above 30 mg per day) and those above 60.

Yes, it may prolong the QT interval. From your sources:

Domperidone use has been associated with an increased risk of sudden cardiac death most likely through its prolonging effect of the cardiac QT interval and ventricular arrhythmias. The cause is thought to be blockade of hERG voltage-gated potassium channels. The risks are dose-dependent, and appear to be greatest with high/very high doses via intravenous administration.

Domperidone at the conventionally used doses to treat gastroparesis (30–80 mg/d) was associated with QTc prolongation in only 6% of patients with no QT interval reaching the point considered to be clinically significant

The leaflet I'm attaching says:

Domperidone is contraindicated in the following situations:

- patients who have known existing prolongation of cardiac conduction intervals, particularly QTc
- patients with significant electrolyte disturbances (hypokalaemia, hyperkalaemia, hypomagnesaemia)
- patients with bradycardia or underlying cardiac diseases such as congestive heart failure
- co-administration with QT-prolonging medicinal products, with the exception of apomorphine
- co-administration with potent CYP3A4 inhibitors (regardless of their QT prolonging effects)

During post-marketing surveillance, there have been very rare cases of QT prolongation and torsades de pointes in patients taking domperidone. These reports included patients with confounding risk factors, electrolyte abnormalities and concomitant treatment which may have been contributing factors.

For this reason a stat dose of domperidone would be more risky as it would need a higher dosage since it is weaker than meto.

For people choosing domperidone, the 36 hour or 48 hour regimen would be more suitable (10 mg taken every 6 to 8 hours). Half life of domperidone (12-16 hours) is said to be higher than that of meto (5-6 hours), hence more of it will stay in the system over time and the risk can be spread over 48 hours compared to taking a single high stat dose.

This is an interesting option. The leaflet recommends "One 10 mg tablet up to three times per day with a maximum dose of 30 mg per day."
So what would a stat dose of domp. be?

"Testing meto" seems to entail a risk that may well be avoided and I think it is better to take meto as a stat dose directly just before ctb.

Very much disagree. I would absolutely test it beforehand. If you're determined to take your own life the last thing you want is a botched attempt with unpredictable consequences. The chances of experimenting EPS from a few meto doses may be low, but not impossible. Check this out: https://sanctioned-suicide.net/threads/meto-fucked-me-up.18696/
I would do exactly what I wrote in my post: check interactions with meds I'm currently taking, read carefully the meto leaflet and then try a normal dosage to see what happens.

As far as I've read, the risk of potentially permanent side effects of meto comes mainly from long term use. Symptoms like tardive dyskinesia and parkinsonism are associated more with the long term.

Agree.

I appreciate your effort since you provided the community with A LOT of information. Just wanted to add that sometimes you may find discordant information when researching medical subjects. A study/research may show that something is true, then another study/research may show the opposite, and this can lead to confusion, and the more you research, the more confusing it gets. Sometimes there's no definitive answer.

Last thing, the first source you posted claims that Anti-emetic doses of antipsychotic drugs are generally less than one third of those used to treat psychoses.
I didn't know that, maybe somebody will find it to be worth researching

 

[Endisclose]

Thanks again for your response. I feel it is always better to have the information we post reviewed by another member to make it more robust and to eliminate any factual errors, check for soundness or see if there are any other issues the Op might be blindsided by.. So thanks a lot for taking the time out and helping in that effort.

This is an interesting option. The leaflet recommends "One 10 mg tablet up to three times per day with a maximum dose of 30 mg per day."
So what would a stat dose of domp. be?

The book "Guide to a humane self-chosen death" by wozz foundation says

"Second choice is:
– domperidon: available from pharmacies in tablet form without a
prescription.
Dose prior to self-chosen death: over a period of 36 hours, every 6 to 8
hours take one tablet of 10 mg or a suppository (on prescription) of 60 mg."



Is "suppository" here the same as "stat dose". It would make sense as domperidone is weaker than meto and might need a really high dose when taken in stat mode in comparison to meto. Given the recommended max dose per day of 30 mg, I felt this would be an unnecessary risk given the possibility of Domperidone causing cardiac related issues at higher doses. Perhaps the 36 to 48 hour regime would make more sense if one is choosing Domperidone.

I came across an article that says that there is a risk of depression with meto. It is not clear whether this can occur after a single oral dose or stat dose.
"Depression warning: This drug may cause depression. This effect can happen even if you don't have a history of depression. Your symptoms may be mild to severe, and may include thoughts of suicide. Call your doctor right away if you have signs of depression."

Metoclopramide | Side Effects, Dosage, Uses, and More

Metoclopramide oral tablet is used to relieve heartburn caused by gastroesophageal reflux disease (GERD). It’s also used to treat symptoms of diabetic gastroparesis. This medication is available as a generic drug and as the brand-name drugs Reglan and Metozolv ODT. Learn about side effects...

www.healthline.com

It's just that with the way meto works by crossing the blood brain barrier, it makes sense to avoid risks as much as possible. I feel one has to distinguish between an unnecessary risk (testing it before hand) and a calculated risk (taking the Stat dose directly) in this context.

Most of the reports I've seen where meto is taken orally in tablet form in which EPS is said to have occurred, have reported experiencing them either after the second dose or the third dose. Even the user in the link that you had shared mentions that he noticed EPS a few hours after ingesting the meto. To me the symptoms from meto seem to be a reaction in time - akathesia and dystonia in the short term (possibly a few hours to over few days) and tardive dyskinesia (possibly over 12 weeks or 6 months)

Meto fucked me up.

Ok, so last month I decided it was finally time to take my meto/Ondansetron 48 hour regime. I decided on this one from wiki books: Wiki author best option Take 15 mg Metoclopramide every 8 hours, i.e. 3 times per day, starting 48 hours in advance. Take the last dose Metoclopramide 45-60 min...

sanctioned-suicide.net

I have not seen any case where symptoms have occurred within an hour of ingestion. The only case I saw was from someone who was grossly underweight about 48 kilos I think. Perhaps for such cases the Stat dose of meto should be restricted to 2 tablets of 10 mg as suggested by the regime according to the book from the wozz foundation mentioned above against that recommended by the pph which suggests taking 3 pills of 10mg each.

I have a few questions based on the information presented regarding the meto..

1) Given all of the above and the potential risks of EPS unfolding over time, and the relatively low risk in experiencing EPS within a short interval of 45 to 60 mins, do you think there is any advantage to be gained by any prior testing of the meto as compared to taking the Stat dose directly?

A user on this forum who posted his goodbye thread recently mentions taking the Stat dose of meto and hasn't reported any EPS symptoms for a period of just over an hour after taking the meto and before drinking the SN. I know first-hand that he did not do any prior testing of the meto and took the Stat dose directly before ctb.

I'm doing it. Tonight is SN night.

Goodnight, I wish you peace

sanctioned-suicide.net

2) Do you think taking propranolol as part of the final regime could help mitigate lingering apprehensions/risks (however slight they may be) of meto causing issues before taking the SN?

3) Do you think taking benzos as part of the final regime could cancel out any EPS causing effects of the meto, so that one may not have any apprehensions of it causing any issues in case there is a failed ctb.. One might have to take the benzos slightly before the SN if using this as a risk mitigation strategy but I don't really see the need for this measure.

 

[h.s.p.]

The book "Guide to a humane self-chosen death" by wozz foundation says

"Second choice is: Domperidon: available from pharmacies in tablet form without a prescription.
Dose prior to self-chosen death: over a period of 36 hours, every 6 to 8 hours take one tablet of 10 mg or a suppository (on prescription) of 60 mg."

View attachment 135033

Is "suppository" here the same as "stat dose". It would make sense as domperidone is weaker than meto and might need a really high dose when taken in stat mode in comparison to meto.

Thank you for sharing this document. My opinion on the stat dose is slightly different from yours. The book only mentions a 36-hour regimen and the oral dosage is the same both for Meto and for Domp: "every 6 to 8 hours take one tablet of 10 mg"
Considering this, if the oral dosage is the same for both meds, I'd assume both have the same strength - not sure about the dosage difference for the suppositories but I believe nobody here's going to take an AE rectally.
So, the way I see it, if a stat dose of Meto is 30mg then a stat dose of Domp should be 30mg as well.

Given the recommended max dose per day of 30 mg, I felt this would be an unnecessary risk given the possibility of Domperidone causing cardiac related issues at higher doses. Perhaps the 36 to 48 hour regime would make more sense if one is choosing Domperidone.

I think I understand what your idea is, but I don't fully agree. Let's compare the 48 hour Regimen and the Stat dose in Stan's guide: both regimens involve a last dose of 3 x 10mg of AE 45 minutes before drinking SN. So, you're supposed to down that much AE anyway. Unless you want to follow another protocol, I see no benefit in doing a 36 to 48 hour Domp. regimen. But I give you the credit for having researched more than me so I may be wrong

I came across an article that says that there is a risk of depression with meto. It is not clear whether this can occur after a single oral dose or stat dose.

"Depression warning: This drug may cause depression. This effect can happen even if you don't have a history of depression. Your symptoms may be mild to severe, and may include thoughts of suicide. Call your doctor right away if you have signs of depression."

Metoclopramide | Side Effects, Dosage, Uses, and More

Metoclopramide oral tablet is used to relieve heartburn caused by gastroesophageal reflux disease (GERD). It’s also used to treat symptoms of diabetic gastroparesis. This medication is available as a generic drug and as the brand-name drugs Reglan and Metozolv ODT. Learn about side effects...

www.healthline.com

Interesting, but I never investigated the topic so I can't give any opinion

Most of the reports I've seen where meto is taken orally in tablet form in which EPS is said to have occurred, have reported experiencing them either after the second dose or the third dose. Even the user in the link that you had shared mentions that he noticed EPS a few hours after ingesting the meto. To me the symptoms from meto seem to be a reaction in time - akathesia and dystonia in the short term (possibly a few hours to over few days) and tardive dyskinesia (possibly over 12 weeks or 6 months)

Meto fucked me up.

Ok, so last month I decided it was finally time to take my meto/Ondansetron 48 hour regime. I decided on this one from wiki books: Wiki author best option Take 15 mg Metoclopramide every 8 hours, i.e. 3 times per day, starting 48 hours in advance. Take the last dose Metoclopramide 45-60 min...

sanctioned-suicide.net

I have not seen any case where symptoms have occurred within an hour of ingestion. The only case I saw was from someone who was grossly underweight about 48 kilos I think. Perhaps for such cases the Stat dose of meto should be restricted to 2 tablets of 10 mg as suggested by the regime according to the book from the wozz foundation mentioned above against that recommended by the pph which suggests taking 3 pills of 10mg each.

You're right, our fellow member Mofreeko apparently went for a 48 hour regime. Anyway, you have researched Meto more than me so you're more trustworthy

I have a few questions based on the information presented regarding the meto..

1) Given all of the above and the potential risks of EPS unfolding over time, and the relatively low risk in experiencing EPS within a short interval of 45 to 60 mins, do you think there is any advantage to be gained by any prior testing of the meto as compared to taking the Stat dose directly?

The only advantage to be gained by any prior testing of the meto is your safety. I already stated that I would definitely test it beforehand - just once, a small dose of 10 to 20 mg.
Case 1: you have side effects (quite unlikely, as you remarked) => you know what to expect when you CTB and can decide whether switching to a different AE or sticking with Meto
Case 2: you have NO side effects => you'll be more confident in your plan, and hopefully calmer

2) Do you think taking propranolol as part of the final regime could help mitigate lingering apprehensions/risks (however slight they may be) of meto causing issues before taking the SN?

Propanolol is a beta-blocker used for heart conditions, I don't see how it may help with issues caused di Meto. As far as I know, it can be used to lower the increased heart rate caused by Methemoglobinemia. By doing so, unconsciousness should be quicker. @Goku Black is very knowledgeable about this

3) Do you think taking benzos as part of the final regime could cancel out any EPS causing effects of the meto, so that one may not have any apprehensions of it causing any issues in case there is a failed ctb.. One might have to take the benzos slightly before the SN if using this as a risk mitigation strategy but I don't really see the need for this measure.

I'm definitely not knowledgeable enough. Here's what I gathered with a quick Google search for "benzodiazepines eps":

[...] In cases of tardive dystonia, additional therapeutic strategies include administration of benzodiazepine [...] Additional therapeutic strategies more specific to akathisia include administration of a beta-blocker (most commonly propranolol), amantadine, clonidine, benzodiazepines, mirtazapine, mianserin (tetracyclic antidepressant), cyproheptadine, and propoxyphene [...] Tardive dyskinesia is treated by [...] benzodiazepines

Source here

A wide range of strategies have been used to help manage TD, and for those who are unable to have their antipsychotic medication stopped or substantially changed, the benzodiazepine group of drugs have been suggested as a useful adjunctive treatment.

Source here

Benzodiazepine drugs are sometimes prescribed to help counteract extrapyramidal side effects.

Source here

But guess what? This article claims that "Serious side effects of lorazepam include extrapyramidal symptoms (muscle spasms, restlessness, slow movement, tremors, and jerky movements)" - This article is far from being a verified source and may be totally unreliable, but I report it because, if memory serves me right, you posted a YT video on the same subject in this thread not long ago.

We should ask a pharmacist or a doctor. I may be able to gather some info, but first let's discuss it privately please

 

[Endisclose]

The book only mentions a 36-hour regimen and the oral dosage is the same both for Meto and for Domp: "every 6 to 8 hours take one tablet of 10 mg"
Considering this, if the oral dosage is the same for both meds, I'd assume both have the same strength - not sure about the dosage difference for the suppositories but I believe nobody here's going to take an AE rectally.
So, the way I see it, if a stat dose of Meto is 30mg then a stat dose of Domp should be 30mg as well.

As per Wikipedia, the elimination half life of metoclopramide is 5-6 hours while that of domperidone is listed as 7-9 hours. This particular website states that half life of domperidone as 12-16 hours.

https://www.sciencedirect.com/topics/neuroscience/domperidone

I am not sure if this is right though. There is agreement between Wikipedia and the leaflet you had shared on your post earlier about domperidone. At any rate, the half life of domperidone seems to be higher than that of metoclopramide, hence a greater amount of domperidone will stay in the system over a period of time (either 36 or 48 hours) compared to the same strength of meto.

Assuming half life of meto as 6 hours and that of domperidone as 9 hours, if equal amounts of domperidone and Meto are ingested, amount of domperidone that will remain in system will be at least 1.5 times more than that of meto. The amount of domperidone prescribed for the 36 hour regimen in the book from wozz foundation has been suggested keeping its elimination half life in mind in comparison to metoclopramide. Consequently, one may deduce that a stat dose of domperidone should be at least 1.5 times more than that of meto to have the same efficacy. So if the stat dose of meto was 30 mg, it should be at least 45 mg for domperidone.

If the half life value was more and perhaps keeping in mind the weaker efficacy of domperidone, the strength of its Stat dose could go upto even 60 mg which is the recommendation in the wozz foundation book. I wonder if "suppository" has a different meaning like it may also mean a bunch of pills together.

The article below states for domperidone, "Equal oral and rectal doses gave a similar bioavailability."

On the pharmacokinetics of domperidone in animals and man. IV. The pharmacokinetics of intravenous domperidone and its bioavailability in man following intramuscular, oral and rectal administration - PubMed

The pharmacokinetics and bioavailability of domperidone, a novel gastrokinetic, were studied in healthy male subjects by comparing plasma concentrations and urinary excretion following intravenous, intramuscular, oral and rectal administration. Two oral dosage forms were studied: 10-mg tablets...

pubmed.ncbi.nlm.nih.gov

Given my earlier arguments based on half life and relative efficacy of both antiemetics, the 60 mg figure appears closer to what might reasonably be a stat dose for domperidone that would be on par with that of meto.

I think I understand what your idea is, but I don't fully agree. Let's compare the 48 hour Regimen and the Stat dose in Stan's guide: both regimens involve a last dose of 3 x 10mg of AE 45 minutes before drinking SN. So, you're supposed to down that much AE anyway. Unless you want to follow another protocol, I see no benefit in doing a 36 to 48 hour Domp. regimen. But I give you the credit for having researched more than me so I may be wrong

The 48 hour regimen should actually be just one tablet of 10 mg taken every 6 to 8 hours with only one tablet at the end of that period as stated by the wozz foundation book. The stat dose is 3 pills of 10 mg taken together 45 mins before the SN. What's listed in Stan's guide under the 48 hour regimen is actually the combined stat dose, where both 48 hour and stat doses are combined together. Perhaps @Goku Black can confirm this. Imo, this is highly risky as it would entail not only the reactions from meto in time, but also possibly exceeding a certain threshold value that may prompt EPS symptoms.

The symptoms from meto being a reaction in time seem to be validated by this document below (page 4 sub heading 5.2) I have attached the relevant pdf file in this post.

"Extrapyramidal symptoms, manifested primarily as acute dystonic reactions, occur in approximately 1 in 500 patients treated with the usual
adult dosages of 30 to 40 mg/day of metoclopramide. These usually are seen during the first 24 to 48 hours of treatment with metoclopramide,
occur more frequently in pediatric patients and adult patients less than 30 years of age and are even more frequent at higher doses."

Furthermore with meto, with just the way it works, the depression risk seems to be a bigger danger especially for people like me. I suffer from bipolar disorder, borderline, ptsd, Ocd and some other issues. For people who are neurodiverse, I feel this is a "known unknown" that might pose a bigger risk. The problem is if this does indeed happen, one may have to contend with it till the length of time it stays before ctb which won't make it easier for those already facing difficulties arranging things for their final departure. This could be a big call for them.

The only advantage to be gained by any prior testing of the meto is your safety. I already stated that I would definitely test it beforehand - just once, a small dose of 10 to 20 mg.
Case 1: you have side effects (quite unlikely, as you remarked) => you know what to expect when you CTB and can decide whether switching to a different AE or sticking with Meto
Case 2: you have NO side effects => you'll be more confident in your plan, and hopefully calmer

Question is which is safer? Testing the meto would entail the possibility of reactions in time typically 24 to 48 hours as stated in the document attached. Apparently, this is rare and occurs in about 1 in 500 cases.

If most of the symptoms from meto ingestion appear from few hours after the first dose to a window of 24 to 48 hours, don't you think one may avoid them by taking the meto directly? If one follows the protocol, one shouldn't be around when they could possibly occur.

Also under case 1 - depends on what side effects. Symptoms like akathesia and dystonia seem like they can be treated with benadryl while depression is a much bigger risk. I am particularly worried this might be triggered by the Stat dose of 30 mg. And if the testing involves an amount under that figure, why bother testing?

The only thing that would prompt me to test would be to see if there is an immediate reaction to meto as a substance itself. There could technically be an allergic reaction to the meto although this is said to be rare. Perhaps a single dose of 10 mg might suffice for this purpose, not more than that.

There is a case of a lady having transient dyspnea after the first dose of 10 mg in solution adminstered orally. She went into respiratory failure due to anaphylaxis after the second. I wonder if the 10mg in solution makes a difference compared to it being a tablet?

Respiratory failure following oral administration of metoclopramide - PubMed

The use of metoclopramide in patients with pulmonary dysfunction may warrant caution.

pubmed.ncbi.nlm.nih.gov

I am wondering about case 2. Let's say there were no reactions after taking the Stat dose, can one reliably conclude that no reactions would occur if meto is taken at a later time. I read somewhere that taking it once, only makes one prone to getting EPS when taking a second time. I don't know if second time here was within the time meto was still in the system or if it was outside it. Not sure if meto breaching the blood brain barrier once could leave one more vulnerable in some way..

There is some evidence that propranolol is used on the treatment of EPS. I'll definitely keep it in the mix at least 120 mg. Recommended amount in pph is 400 mg.

Propranolol in the treatment of neuroleptic-induced akathisia - PubMed

Fourteen patients with neuroleptic-induced akathisia were treated with propranolol in an open trial. All patients demonstrated substantial improvement of their akathisia; nine of the 14 obtained complete remission. Response was quite rapid, occurring within 24 hours in most cases. Doses required...

pubmed.ncbi.nlm.nih.gov

The EPS from lorazepam regarding the lady in the video I had shared earlier in this thread was from benzo withdrawal. She had physical complications within 2 months of use. Another doc stopped it abruptly and she had these symptoms. Unfortunately she had to ctb because she couldn't find a way out. Link to the file is provided in the video..

Christine’s Story: Ativan, Withdrawal, Akathisia and Suicide - Benzodiazepine Information Coalition

Christine Anne Narloch passed away on June 16, 2017 at the age of 48 after a long struggle with benzodiazepine withdrawal syndrome that ended in suicide. Her husband, Mike, describes her as “an intelligent woman...

www.benzoinfo.com

I am sorry, I don't know of any doctor or pharmacist to whom I can ask these questions.. I agree we can discuss new info privately, but I thought it better to cross vett information already put out so as to address any inaccuracies lest someone reading this thread should be mislead in any manner.

 

[h.s.p.]

As per Wikipedia, the elimination half life of metoclopramide is 5-6 hours while that of domperidone is listed as 7-9 hours. This particular website states that half life of domperidone as 12-16 hours.

https://www.sciencedirect.com/topics/neuroscience/domperidone

I am not sure if this is right though. There is agreement between Wikipedia and the leaflet you had shared on your post earlier about domperidone. At any rate, the half life of domperidone seems to be higher than that of metoclopramide, hence a greater amount of domperidone will stay in the system over a period of time (either 36 or 48 hours) compared to the same strength of meto.

Assuming half life of meto as 6 hours and that of domperidone as 9 hours, if equal amounts of domperidone and Meto are ingested, amount of domperidone that will remain in system will be at least 1.5 times more than that of meto. The amount of domperidone prescribed for the 36 hour regimen in the book from wozz foundation has been suggested keeping its elimination half life in mind in comparison to metoclopramide. Consequently, one may deduce that a stat dose of domperidone should be at least 1.5 times more than that of meto to have the same efficacy. So if the stat dose of meto was 30 mg, it should be at least 45 mg for domperidone.

If the half life value was more and perhaps keeping in mind the weaker efficacy of domperidone, the strength of its Stat dose could go upto even 60 mg which is the recommendation in the wozz foundation book.

Didn't consider the half-life. Very interesting, thank you. You really got knee-deep into it

I wonder if "suppository" has a different meaning like it may also mean a bunch of pills together.

The article below states for domperidone, "Equal oral and rectal doses gave a similar bioavailability."

On the pharmacokinetics of domperidone in animals and man. IV. The pharmacokinetics of intravenous domperidone and its bioavailability in man following intramuscular, oral and rectal administration - PubMed

The pharmacokinetics and bioavailability of domperidone, a novel gastrokinetic, were studied in healthy male subjects by comparing plasma concentrations and urinary excretion following intravenous, intramuscular, oral and rectal administration. Two oral dosage forms were studied: 10-mg tablets...

pubmed.ncbi.nlm.nih.gov

Given my earlier arguments based on half life and relative efficacy of both antiemetics, the 60 mg figure appears closer to what might reasonably be a stat dose for domperidone that would be on par with that of meto.

As far as I know, suppository = rectal administration, I don't think there's another meaning to it - medically speaking, at least.
Your argument makes sense, I can't argue since you've researched so much more than me

The 48 hour regimen should actually be just one tablet of 10 mg taken every 6 to 8 hours with only one tablet at the end of that period as stated by the wozz foundation book. The stat dose is 3 pills of 10 mg taken together 45 mins before the SN. What's listed in Stan's guide under the 48 hour regimen is actually the combined stat dose, where both 48 hour and stat doses are combined together. Imo, this is highly risky as it would entail not only the reactions from meto in time, but also possibly exceeding a certain threshold value that may prompt EPS symptoms.

I wasn't aware that Stan's 48-hour regimen differed from wozz's. I never read the wozz foundation manual in its entirety, only the PPH. Since opinions may vary, I guess there's not one single source of truth - both manuals are trustworthy, but procedures may be slightly different. I would never do a multiple days regimen because I see no benefit in doing so and tend to agree with your argument: "exceeding a certain threshold value that may prompt EPS symptoms."

The symptoms from meto being a reaction in time seem to be validated by this document below (page 4 sub heading 5.2) I have attached the relevant pdf file in this post.

"Extrapyramidal symptoms, manifested primarily as acute dystonic reactions, occur in approximately 1 in 500 patients treated with the usual
adult dosages of 30 to 40 mg/day of metoclopramide. These usually are seen during the first 24 to 48 hours of treatment with metoclopramide,
occur more frequently in pediatric patients and adult patients less than 30 years of age and are even more frequent at higher doses."

Furthermore with meto, with just the way it works, the depression risk seems to be a bigger danger especially for people like me. I suffer from bipolar disorder, borderline, ptsd, Ocd and some other issues. For people who are neurodiverse, I feel this is a "known unknown" that might pose a bigger risk. The problem is if this does indeed happen, one may have to contend with it till the length of time it stays before ctb which won't make it easier for those already facing difficulties arranging things for their final departure. This could be a big call for them.

Agree with all you said.

About the "Case 1 and Case 2"-thing, sorry but I honestly find it hard to keep up with all your doubts and questions.
You did A LOT of research, far more than I did, and asked me many times why testing Meto would be advised. I already said what I would do and you don't seem to agree.
I have no more arguments and nothing constructive to add to the topic, I'm sorry. But I believed you answered your own question: you don't feel like testing Meto would be a good idea for you. I think you should do what you feel it's best for you. I don't mean to be rude and I hope you don't get this wrong.

For me it's pretty simple: I'm on Quetiapine and won't be taking Meto because of some major interactions (EPS), and probably won't be taking Domp either for the same reason (higher risk of prolonged QT interval, arrhythmias, sudden cardiac death - even if the latter wouldn't be so bad). In case I survive, I'd rather not have everlasting physical damage.
I'm researching another dopamine-blocking AE instead, and if you're interested we can discuss it.
I may be able to get additional info from members who apparently have expertise in medicine or pharmacology. My PMs stay open of course

 

[Itty bitty]

I have more fear about the side effects from meto than drinking SN and vomiting

 

[h.s.p.]

I have more fear about the side effects from meto than drinking SN and vomiting

Meto is not the only option. Domperidone and a few others may be used too

 

[Endisclose]

About the "Case 1 and Case 2"-thing, sorry but I honestly find it hard to keep up with all your doubts and questions.
You did A LOT of research, far more than I did, and asked me many times why testing Meto would be advised. I already said what I would do and you don't seem to agree.
I have no more arguments and nothing constructive to add to the topic, I'm sorry. But I believed you answered your own question: you don't feel like testing Meto would be a good idea for you. I think you should do what you feel it's best for you. I don't mean to be rude and I hope you don't get this wrong.

No, I think you have a very valid point. I had overlooked the possibility of an allergic reaction leading to anaphylaxis which although very rare is a risk nevertheless. One may be allergic to anything - even food items such as nuts can be dangerous and even fatal. There is a risk of anaphylaxis with domperidone as well (1 in 10000 cases).

I think you are right. This is probably why hospitals administer test doses of certain medications to check for allergic reactions. I think there is greater value in doing some preliminary testing to eliminate the risk of anaphylaxis in particular, more than the the one from EPS. Anaphylaxis is dangerous and can prove fatal if not treated in time. Treatment is with epinephrine administered in a hospital or with an epipen at home.

I don't know how to judge this as the worst case here is not an unfavourable outcome in a ctb scenario, but there are cases of people being paralysed permanently after going into anaphylactic shock. I guess when it comes to wanting to reach a destination, there is a sense of safety in following the beaten path.

In the case of the lady who had the anaphylatic reaction the first dose of 10 mg caused transient dyspnea and the second dose sent her into respiratory failure due to anaphylaxis.

I think it's a good idea to take a single dose of 10 mg and check for reactions. If this causes any kind of symptoms within a 24 to 72 hour period, I think its better to avoid meto altogether. The sooner the symptoms occur, the greater the sensitivity of the body and the greater would be the risk of a severe reaction with a higher dose. Anaphylaxis can occur anywhere between a 20 min and 2 hour period. This falls in the 45-60 min waiting period after taking meto and before taking the SN. I think one may do well to eliminate this risk and avoid any nasty surprises.

If the 10 mg dose doesn't cause any symptoms, I think it's better to wait for 25-30 hours (time taken by meto to be flushed out of the system completely), maybe even 3-4 days to be completely safe. Then take 20 mg, wait for a further period to flush meto out again.. Then take 30 mg and look for reactions.

Alternatively if one doesn't feel any negative reactions from the first 10 mg dose, if one feels comfortable, one may straightaway take the 30 mg stat dose as risk from anaphylaxis can probably be ruled out although risk from EPS remains.

In my research, although these doses fall within the therapeutic range, the risk from EPS although rare (about 1 in 500 cases) is present nevertheless and may occur usually from a few hours to within a 24 to 48 hour period.

If EPS does occur 25-50 mg benadryl should do the job of controlling it. Although, from what I've read, it must be pointed out that diphenhydramine (benadryl) here only controls the symptoms and does not address the underlying cause. The primary treatment for this is the stoppage of metoclopramide. Symptoms are said to go away with time in say one or two days but it's better to take benadryl in case they do occur.

However, there is a caveat to this testing. This is the response from an AI chat bot I had asked a question about meto.. What if I took 30 mg of meto, had no EPS, and took 30 mg again after a month (paraphrased)

"However, the fact that you did not experience EPS after a single 30 mg dose of metoclopramide does not necessarily mean you won't experience them if you take another 30 mg dose later on. Each individuals response to medications can vary, and factors such as genetics, sensitivity to medications, and other underlying health conditions can influence the likelihood of developing EPS."

I definitely see value in testing at least a 10 mg dose and watching reactions from it. Above that, I think I feel each person will have to decide for themselves if they see any value in testing with higher amounts..

I did some further research as regards the depression risk and found that it is mostly associated with chronic use.

"Otherwise, depression associated with metoclopramide has been repeatedly reported, however, mostly with chronic treatment."

https://onlinelibrary.wiley.com/doi/full/10.1111/j.1440-1819.2007.01637.x#:~:text=Otherwise%2C%20depression%20associated%20with%20metoclopramide,however%2C%20mostly%20with%20chronic%20treatment.&text=functional%20imaging%20studies%20showed%20a,phobia%20compared%20to%20healthy%20controls.

I am sorry if I have been too persistent in my questioning about the meto. This has been a bugbear for me for quite a while and I think I may have tested your patience with it. I agree there is no more value to be gained by discussing this subject further.

I am still very much in the testing phase as far as antiemetics are concerned and I'd be interested in finding out more about any other alternatives. We can take this up privately as you say. Thanks once again for your time and valuable contributions which I am sure will be very useful in helping people make an informed choice regarding the use of these medications.

 

[h.s.p.]

I am sorry if I have been too persistent in my questioning about the meto. This has been a bugbear for me for quite a while and I think I may have tested your patience with it. I agree there is no more value to be gained by discussing this subject further.

I am still very much in the testing phase as far as antiemetics are concerned and I'd be interested in finding out more about any other alternatives. We can take this up privately as you say. Thanks once again for your time and valuable contributions which I am sure will be very useful in helping people make an informed choice regarding the use of these medications.

No need to be sorry, everything's ok. I understand the subject is of great concern for you because it is for me as well, let alone the toll that planning an attempt takes on your mental energies. As for the other dopamine-blocking AE I've been researching, I'll be sharing it with you if you're interested. Just need a little time to finish my research. I'll be in touch via PM