Hydroxyzine and domperidone for 2 days, then stat dose of meto?

[Mbound]

Does anyone have further info about hydroxyzine? I have meto and am in the process of ordering domperidone. I have heard domperidone might not be as effective as meto though, and I've taken drugs like hydroxyzine before without bad effects, so I thought maybe combining them would work even better. I can't vomit at the last minute. Fuck. What do you guys think?

 

[Soul]

I was prescribed hydroxyzine to sleep better - does it also work as an antiemetic?

I think I'm likely to get EPS from meto, and personally would trust the domperidone to do the job, without that stat dose of meto. But that's only because I'm a trusting soul and not because I'm convinced it's medically sound.

I hope you get the input you need, and that you make the best possible choices for yourself.

 

[KnightOfEnceladus]

Hydroxyzine is a first-generation antihistamine, if we're being pharmacological. It's used for sedation and anxiolysis because, like all first-gen H1 antagonists, it knocks you dafuq out, as the kiddies say. OD on hydroxyzine would be as unpleasant as OD on diphenhydramine (Benadryl) and for the same reasons. You could take one or two to aid in calming down but it shouldn't be a part of the actually lethal cocktail of whatever you intend to use.

Also, hydroxyzine is one of many, many, many drugs that have anticholinergic effects, so long-term use leads to dementia...

 

[Aliaiactaest]

How do you know so much about hydroxyzine and long term use? I have used hydroxyzine for many years and only thought of it as an antihistamine. Where do you read about dementia?

 

[Bentham]

Acute dystonic reactions induced by high-dose MCP are a significant problem, particularly in younger patients. It was soon verified that the addition of diphenhydramine or lorazepam resulted in a significant reduced incidence of extrapyramidal adverse effects.
MCP=metoclopramide
see P.3 Metoclopramide: An Antiemetic in Chemotherapy Induced Nausea and Vomiting

Hydroxyzine has some affinity with D2 receptors and thus may increase the probability of EPS when using with metoclopramide or other BBB penetrable D2 blockers such as antipsychotics.
If I want to take H1 antagonists as a supportive antiemetic and EPS blocker, my choice is diphenhydramine.

Hydroxyzine, unlike diphenhydramine, has a lower affinity with muscarinic acetylcholine receptors, which results in low anticholinergic effects.

 

[Ἡγησίας]

I'm very interested about this... Would it be possible to use hidroxyzine or diphenhydramine as antiemetic? Or is it a must to take meto/domperidone for assuring not throwing up with N?

 

[KnightOfEnceladus]

@Bentham: it's true hydroxyzine has lower antimuscarinic activity than other H1 antagonists, and thank you for mentioning its dopamine antagonism as I truly did not know it had any affinity for the D2 receptors! I'd also read somewhere it can prolong the QT interval, which again is something a truly disturbing number of drugs do...

Meclizine would be better as an antiemetic if one is going the OTC route, no? I've heard it can be purchased OTC in some places as essentially a stronger version of Dramamine, and exerts its action mainly by central ACh antagonism.

Still, I don't trust OTC antiemetics for this. They're for motion sickness and vertigo, not the kind of chemical signalling that the body would produce with an OD on prescription drugs. Metoclopramide and/or ondansetron sound like the way to go.

 

[Mbound]

Hydroxyzine is a first-generation antihistamine, if we're being pharmacological. It's used for sedation and anxiolysis because, like all first-gen H1 antagonists, it knocks you dafuq out, as the kiddies say. OD on hydroxyzine would be as unpleasant as OD on diphenhydramine (Benadryl) and for the same reasons. You could take one or two to aid in calming down but it shouldn't be a part of the actually lethal cocktail of whatever you intend to use.

Also, hydroxyzine is one of many, many, many drugs that have anticholinergic effects, so long-term use leads to dementia...

Someone, in another thread about N, suggested taking a high dose of hydroxyzine as an antiemetic. Like instead of meto. They then said meto was more powerful, but god I know myself and I just know I'll get some really unpleasant side effects from meto. So I was thinking if maybe I combined it with the domperidone it would work about as well as meto.

Not super worried about my long term health at this point lmao, but I have seen that research and can see how it's true as I have noticed memory issues just taking Benadryl for like a few weeks every night.

@Bentham: it's true hydroxyzine has lower antimuscarinic activity than other H1 antagonists, and thank you for mentioning its dopamine antagonism as I truly did not know it had any affinity for the D2 receptors! I'd also read somewhere it can prolong the QT interval, which again is something a truly disturbing number of drugs do...

Meclizine would be better as an antiemetic if one is going the OTC route, no? I've heard it can be purchased OTC in some places as essentially a stronger version of Dramamine, and exerts its action mainly by central ACh antagonism.

Still, I don't trust OTC antiemetics for this. They're for motion sickness and vertigo, not the kind of chemical signalling that the body would produce with an OD on prescription drugs. Metoclopramide and/or ondansetron sound like the way to go.

Hydroxyzine isn't OTC, at least not where I live.

 

[Soul]

LoL I'm so confused!

 

[Bentham]

@Mainlænder: Meto is an empirically well confirmed antiemetic for N (pentobarbital sodium). I have not found any document, however, that mentions the mechanism of emesis induced by N and particularly the dopamine release in connection with N. Meto has other receptor affinities: a weak 5-ht3 antagonist and 5-ht4 agonist. So I can not conclude that D2 antagonism is the necessary and sufficient feature that alleviates the emesis.

@KnightOfEnceladus: I have almost no knowledge about which one of the 1st gen. antihistamine drugs is the best or better antiemetic among them. But M3 and M5 antagonists have some role in treatment of motion sickness. So I think 1st gen. H1 blocker with high affinities with those muscarinic subtypes like diphenhydramine would be a better choice for that purpose.
Comparison of the effects of a selective muscarinic receptor antagonist and hyoscine (scopolamine) on motion sickness, skin conductance and heart rate

I come mostly in line with your thought that metoclopramide and/or ondansetron would be the first line choice for OD. I would add NK-1 antagonist like aprepitant on the list and might take the combination of meto 20mg, ondansetron 10mg and aprepitant 125mg if the SN method is the case, and money and availability don't matter.

 

[Mbound]

LoL I'm so confused!

They recommended hydroxyzine because it's easier to get prescribed. I know it's side effect profile is also a lot better, but it's obviously not as strong. I worry about the meto side effects, especially in terms of the two day regiment...so I thought maybe the combination of domperidone and hydroxyzine would be as good as meto. At least for the two day regiment. Idk though, I know nothing about chemistry.

 

[KnightOfEnceladus]

@Bentham: agreed on all accounts, though the antimuscarinic ones seem better for motion sickness than chemical emesis...would rather have them than nothing, but would rather have a good heavy dose of metoclopramide if possible. D2 antagonism is metoclopramide's (and domperidone's) main pharmacodynamic action, but antagonizing the 5-HT3 receptor (which ondansetron does) is as you pointed out part of its profile and also helpful.

Very interesting that it's specifically the M3 and M5 receptors, too. I know much less about the genetics and function of receptors than I do about what turns them on or off; I come at this as a (largely self-taught...) pharmacist-type, rather than a trained biologist. This is fascinating stuff, how biology is basically just applied chemistry...

@Mbound: be very careful with that combination, as both of those drugs are known to prolong the QT interval. I mean, who knows, maybe a fatal episode of VTach or VFib would be a feature rather than a bug for someone suicidal? But it doesn't sound fun.

 

[Mbound]

@Bentham: agreed on all accounts, though the antimuscarinic ones seem better for motion sickness than chemical emesis...would rather have them than nothing, but would rather have a good heavy dose of metoclopramide if possible. D2 antagonism is metoclopramide's (and domperidone's) main pharmacodynamic action, but antagonizing the 5-HT3 receptor (which ondansetron does) is as you pointed out part of its profile and also helpful.

Very interesting that it's specifically the M3 and M5 receptors, too. I know much less about the genetics and function of receptors than I do about what turns them on or off; I come at this as a (largely self-taught...) pharmacist-type, rather than a trained biologist. This is fascinating stuff, how biology is basically just applied chemistry...

@Mbound: be very careful with that combination, as both of those drugs are known to prolong the QT interval. I mean, who knows, maybe a fatal episode of VTach or VFib would be a feature rather than a bug for someone suicidal? But it doesn't sound fun.

I have no idea what those words mean hahaha what is the QT interval and what is Vtach and vfib???

 

[Soul]

Tachycardia and fibrillation?
I know the QT interval is something an EKG shows, but beyond that, I'm googlebound.