Antiemetic question?

Discussion in 'Pharmacy' started by NurseDude1966, Feb 10, 2019.

  1. NurseDude1966

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    I am a nursing student and out of curiosity from treating patients during clinicals, I had a question about anti-emetics but was unable to find my specific question anywhere. As someone who really enjoys pharm I just wanted to know more

    So I know that Promethazine which is often used for severe nausea/ vomiting is a Phenothiazine anti-emetic that is structurally related to other Phenothiazine antipsychotics that also have anti-emetic effects such as Thorazine. The primary mechanism of action that accounts for Promethazine's anti-emetic effects is antihistamine, with some anticholinergic and mild antidopamine properties.

    I also, know that all Phenothiazines (again, such as Thorazine, Compazine, etc) regardless of if they are classified as an antihistamine or anti-psychotic have some level of antihistamine and anticholinergic effects.

    With that said, I know Promethazine is the one with the strongest antihistamine/ anticholinergic effect which is why it is so useful for allergies and vomiting due vertigo/vestibular disorders, but do any of these other Phenothiazines have antihistamine/ anticholinergic effects that are comparable to Promethazine and therefore could be used for the same purpose (vertigo, allergies etc.)?
     
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  2. lord999

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    They all have intrinsic properties but the downsides are why they aren't used for those issues. Why would a patient be forced to accept an MAOI lifestyle just for short term vertigo? Some of the agents work better than others. It'd be like granting cocaine intranasal for stuffy nose, it'd work fantastically, but considering the myriad of less burdensome options , the DEA or ENT are going to have a major problem with using it for such a trivial purpose.

    Also, promethazine started its life not as an antiemetic but as an antipsychotic. It's not great for it, but the side effect is what eventually became its major labelled indication.

    Unless, you're rich, of course. Methamphetamine, cocaine, barbiturates (not even benzos) and other meds are a usual profile in certain quarters in DC and everyone turns a blind eye, because they're not going to be a problem. DC needs its high functioning addicts (and blackmail material).
     
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  3. OP
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    NurseDude1966

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    That didn't answer my question in the slighest lol. You gave roundabout examples of every other class of meds other than the ones I was asking abou. Lol

    With that said, I know Promethazine is the one with the strongest antihistamine/ anticholinergic effect which is why it is so useful for allergies and vomiting due vertigo/vestibular disorders, but do any of these other Phenothiazines have antihistamine/ anticholinergic effects that are comparable to Promethazine and therefore could be used for the same purpose (vertigo, allergies etc.)? I want to know this.
     
  4. zelman

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    My psychiatric pharmacy professor described the mechanism of action of most of the older neuroleptics as “garbage pharmacology”. They hit damn near every receptor. We need to just select the agent that hits the receptor we want more than the others. So, yes. You will get antiemetic effects from just about every 20th century antipsychotic. But in a treatment naive patient, most options will result in sleeping or being in a barely-awake drooling stupor for 1-3 days. So, we use the anti-emetic options based on their ability to retain function, rather than their ability to stop nausea.
     
  5. lord999

    Pharmacist Faculty Moderator Emeritus Verified Expert 10+ Year Member

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    (Sigh, I actually did, but let me try again as I forget you don't have the med chem background). Yes, they all do, in fact, every single agent that has the idea of a phenothiazine class though is a later differentiation, they all derivatives of the same parent. We don't even refer to them as "phenothiazines" as much as they are antipsychotics. All of the "typical" ones, including chlorpromazine and phenothiazine (which were designed as an antipsychotic first in a quest for a nonvolatile anesthetic and barbiturate alternative) have this effect. Even ones that are more specialist for centrally acting like haloperidol have the same effect.

    Yep, it's pretty tragic how little we know how they work even now, we still have to stumble into new antipsychotics even now. Also, I'm pretty sure we shared the same lineage of pharmacologists (Temple or Rutgers) as that used to be a heterodox position in psychiatric pharmacology until the last decade.
     
  6. CetiAlphaFive

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    The real answer is that the person who asked you that question was posturing, and trying to flex on a student by pulling a question out of their butts.
    In other words, they didn't know enough to know that they're asking an unanswerable question.

    Lord999 answered your question the only way it can be answered.
     
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  7. RxVampire

    RxVampire PharmDruggist
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    Promethazine has very weak dopamine antagonism/antipsychotic effect (not used for) only about ~10% of the other phenothiazines from the literature sources I've read regarding promethazine. Other phenothiazines are used for psych disorders as well as N/V (would be "dirtier options"...ex) chlorpromazine); not sure why you are looking for a phenothiazine in particular or maybe you are also overlooking some basic OTCs (meclizine).
     
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  8. OP
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    NurseDude1966

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    Uhh yeah, not exactly. I love how some of you people on here love to start trouble. We are all supposed to be professionals here no? But instead we have some people on their high horse and thinking their superiority is being challenged when in fact that is not the case.

    Oh and by thw way... The question was answered so jokes on you! Get your all mighty jollies out yet?
     
    #8 NurseDude1966, Feb 10, 2019
    Last edited: Feb 11, 2019
  9. OP
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    NurseDude1966

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    Well part of what I am trying to understand is what makes promethazine such a much stronger antiemetic compared to other antihistamines?

    We often see Promethazine used for a wide variety of situations that cause nausea and vomiting (post surgical, chemotherapy, vertigo, gastroenteritis, etc) and it is very effective. Except for vertigo and maybe motion sickness, we don't see other antihistamines such as diphenhydramine or hydroxyzine being used for antiemetic effects like that. Why is this and what accounts for this difference?
     
  10. lord999

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    Sigh, promethazine is actually not all that effective compared with other members in that group, that's the point. Haloperidol turns out to work MUCH better as an antiemetic. There are actually more effective antiemetics (H1 antagonists) but all of them have real serious other effects (clinical in most cases, toxic in others) that we don't use because it's far overkill. Anything in that particular group is "clean" enough that it'd work. Cyproheptadine has almost exactly the same effect pharmacologically, but it's not used because it has this annoying anesthetic effect that most ambulatory cases don't care for. Promethazine has the balance of not being too dirty, pharmaceutically able to formulate in injectable and suppository forms stably, is fairly easy to manufacturer, and if the patient is irresponsibly stupid with promethazine, they probably won't die from it unlike many of other choices and you can charcoal them out of an OD. It's for all those reasons, but "most effective" is not one of them. Effective enough given the other advantages/disadvantages is what you're looking for, a balance. For pure effectiveness, the most effective antiemetic in that class happens to be mepyramine, which is so @#*$ing unsafe systemically that current usage confines itself to topical stuff for bug bites (it's on the order of 100,000X more potent than diphenhydramine which made OD's really common back in the day; diphenhydramine was made to find an effective but less potent form of mepyramine). This is a lesson I pound in my own students that the most effective agent for any receptor is almost always a fatal poison that has no safe pharmacologic potential. You want something that works just enough, but not too little or too much.

    Then again, you can abuse the pharmacology in ways. In the present day, this practice is highly frowned upon, but nurses used to use haloperidol as a "cure all" insomnia, antiemetic, and patient agitation drug injected indiscriminately before shift transition to the night. The depot form of haloperidol (deconoate) was used before ondansetron for cancer chemotherapy as it's a give once every three months, but no one does that nowadays (I hope). Pharmacologic practices change and evolve due to what we know now about the bigger picture, and a pure focus on effectiveness is not looking at it, that's toxicology.
     
    #10 lord999, Feb 10, 2019
    Last edited: Feb 10, 2019
  11. spacecowgirl

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    No.

    [​IMG]


    Now, yes.
     
  12. OP
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    NurseDude1966

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    This was really insightful and helpful and I appreciate you taking the time to write all of this! So with what you provided above, are you stating that the other medications in the same group as Promethazine such as the Haloperidol or Thorazine can be used, and effective to prevent or treat motion sickness or vertigo just like Promethazine does?

    Also, the Cyproheptadine that you mentioned above, it has the same effect pharmacologically as what? You didn't state what it was similar to?

    And I actually came across Mepyramine while I was searching for some information related to this topic. You stated that it is 100,000 times more potent than Diphenhydramine, but when I came across the information on Mepyramine online, it stated that its anticholinergic properties are negligible compared to Diphenhydramine with an antihistamine to anticholinegic ratio of 130,000 :1 compared to 20:1 for Diphenhydramine. I'm not questioning you, I just got confused. Did I interpret the information wrong?
     
  13. Carboxide

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    Compazine is going to be the closest, I think, but as lord999 said, you would never use one of them for allergies. If you had a patient who came in with nausea and allergic symptoms you would give a second drug for allergies. This would be regardless of severity of symptoms.
     
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  14. lord999

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    You answered your own question in both cases.
     
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  15. OP
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    NurseDude1966

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    How? i was asking a question not answering one lol
     
  16. OP
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    NurseDude1966

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    So even though Compazine is the closest, would the other drugs in that class like Thorazine work as well?

    And would compazine and these other meds technically work for motion sickness or allergies even though most would never prescribe them for that purpose?
     
  17. owlegrad

    owlegrad Uncontrollable Sarcasm Machine
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    Yes.
     
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  18. OP
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    NurseDude1966

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    Yea to which part of which question lol.
     
  19. OP
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    NurseDude1966

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    So Mepyramine has stronger antihistamine but weaker anticholinergic effects that Diphenhydramine? If so, how does it make an all around stronger medication than diphenhydramine if part of its action is weaker?
     
  20. Carboxide

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    Thorazine isn't the same class. Its dopaminergic activity is much, much stronger and it is an AP, not an antiemetic. I would say no, neither Thorazine or Compazine would work for allergies. I'm not sure about vertigo (which can be distinct from motion sickness, btw), but my guess is no because they are not part of any recommended regimens for treating vertigo. I recently looked up treatments for that in the literature, so I'm fairly confident on that. They've been around long enough that we would know.
     
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  21. Carboxide

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    Diphenhydramine is basically, IMO, one of the strongest anticholinergics and antihistamines there is.

    You can't consider drugs as "all around" better or worse than another when considering multiple effects together. They're all distinct. For example, Zyprexa is great for n/v and for AP, but I wouldn't consider it a 'better' drug than clozapine just because clozapine isn't used for n/v. You have to consider each possible usage separately.
     
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  22. OP
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    NurseDude1966

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    Now I'm very confused. When I read, it stated that they are all phenothiazines and it stated that Thorazine is an an antiemetic (in addition to antipsychotic) but then you stated its not. And also above you stated that promethazine is not as effective an antiemetic as other members of that group (antihistamines or antidopaminergic?) But now are stating that you don't think those other members of the group such as compazine or holdol would work for vertigo or motion sickness. I'm just a little confused.

    Also in the first post you stated that mepyramine is wayy stronger than diphenhydramine, but then in this last post you stated that diphenhydramine is the strongest antihistamine and anticholinergic.

    I know these drugs all have different mechanisms of actions and different uses, but I'm wondering about their use specifically for nausea and vomiting... Or to some extent allergies.

    Like how I was asking in my first post why is promethazine so much more effective for nausea /vomiting due to vertigo or motion sickness as opposed to diphenhydramine meclizine which are all antihistamines?

    Or if as like you stated that haldol or compazine is a much stronger/ effective antiemetic than promethazine, then why wouldn't it be effective for vertigo/ motion sickness as well?

    Or if antipsychotic medications such as compazine or haldol are related to promethazine and also have some degree of histaminergic activity in addition to dopamine activity, why couldn't they theoretically treat allergic symptoms like promethazine (even though a physician probably wouldn't write a script due to the side effects).
     
  23. Carboxide

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    Whoa now.

    A). Structure =/ class. These are completely different things.
    B). I never mentioned mepyramine and I never said that or Benadryl are better at treating n/v. They're not.
    C). Because motion sickness isn't just regulated by antihistaminergic pathways, and nausea and vomiting are multifactorial.
    D). Haldol and Compazine aren't more effective antiemetics than Phenergan, and I never said they were. Well, Compazine is proven to be better in migraines, but only in migraines. No idea why. I never even mentioned Haldol, and it's not more effective except in specific situations like cannabinoid hyperemesis or cyclic vomiting. This is because of the specific pathways involved. Nausea and vomiting is a very complex physiological illness and has many pathways that cause it.
    E). Because their degree of antihistaminergic activity is minimal enough that it won't suffice to treat active allergic symptoms.
    F). Thorazine is not used for antiemetic effect. It may help with it, but it's not as good as Haldol or Zyprexa.


    I think we will be able to help you better if you tell us exactly what you're trying to get at. Why is this important? Where did this question come from? It's really out of the blue and no one here has any idea why you're asking about allergic relief from n/v drugs.
     
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  24. Rouelle

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    To clarify, what (if any) are the current active/unanswered questions on this thread?

    Some general thoughts after reading through most of this:

    -Meclizine is very commonly used for nausea (see brand name Less Drowsy Dramamine) and vertigo (very descriptive brand name Antivert), although it seems to be implied in previous posts that first gen antipsychotics are the major players here.

    -Some phenothiazines are common for nausea, but bring baggage with them. Some of the other drugs in class could theoretically have the same effect, but often at the expense of way more baggage.

    -Just because a drug has an effect, that doesn’t mean it will be used for that particular effect. Metformin often causes diarrhea, but it is not routinely used to treat constipation.

    -You can’t just look at it from a histamine point of view. Or dopamine. Or acetylcholine. There’s not one single thing going on here. Consider Emend...it certainly doesn’t even kind of fit into one of those classes.
     
  25. OP
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    NurseDude1966

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    I appologize, I confused you with another poster and thought some of what they wrote was from you.

    And these questions came from learning about these medications in pharm class, using them often in clinical, taking an interest and wanting to know more.

    Part of what I am trying to find out is this: I often see Promethazine being used in a wide variety of situations to treat nausea and vomiting (post surgical, chemotherapy, vertigo, gastroenteritis, etc) and it is very effective. Except for maybe vertigo (or motion sickness in non medical settings) don't see other antihistamines such as diphenhydramine or hydroxyzine for example being used for antiemetic effects like that. Why is this and what accounts for this difference? If they are all potent, 1st generation antihistamines, why cant they all be used as antiemetics? What makes the antiemetic effects of Promethazine so much more potent?

    Like wise (and I ask this because I will be going on a cruise soon so this applies more to me but also helpful for clinical) I have left over Compazine from a surgery that worked well and had minimal side effects so I figured I would bring it on the cruise in case of persistent seasickness, when I looked it up though it said it's not effective for vertigo/motion sickness. But I didn't understand why because if it's structurally related to Promethazine which is used for those purposes and it has histaminergic and anticholinergic in addition to its dopaminergic effects, why couldn't it be used for that as well?
     
    #25 NurseDude1966, Feb 11, 2019
    Last edited: Feb 11, 2019
  26. Carboxide

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    Ahhhh. This is a much easier question to answer.

    Antihistamines don't have much effect on nausea. It IS part of the pathway, but it's minimal. The efficacy of Phenergan is from the dopaminergic effect, which is the primary effect of Phenergan. We classify it as a dopaminergic drug. Benadryl, etc don't have that, so they don't have potent antiemetic effect.
     
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  27. OP
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    NurseDude1966

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    Thank you so much for this response! So then what accounts for the antiemetic effects in vertigo/ motion sickness medications since most of them are antihistamines/ anticholinergics? That just happens to be one scenario where antihistamines are better? Likewise, could dopamine antagonist antiemetics (since the dopamamine antagonism is what accounts for the superior antiemetic effect in Promerhazine) be used to treat nausea and vomiting from vertigo/motion sickness/inner ear disorders as well?
     
  28. OP
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    NurseDude1966

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    So Mepyramine is stronger than Diphenhydramine even though it has weaker anticholinergic properties?

    What are some of the stronger antihistamine antiemetics?
     
  29. spacecowgirl

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    [​IMG]

    Multiple pathways = multiple drugs and drugs often have multiple targets. We almost never used prometh for N/V in favor of 5HT3 antagonists (Zofran) in my hospital. You can see above 5HT3 have many sites of importance in the pathway, which is why they work so well. And for CINV, 5HT3 of NK1 (Emend). Or both. Occasionally we did use prometh, as well as diphen but that was usually when a sedating effect was also desired, which is not the case for PONV when you are already giving sedating meds and wanting someone to wake up in the PACU. And then there is this side effect of prometh.
    [​IMG]

    So for the vestibular causes of N/V - antimuscarinics like scopolamine or mixed antimusc/antihist like dimenhydrinate, meclizine work. In the stomach, 5HT3, in the CTZ dopamine antagonists like haloperidol, droperidol, prometh work but are limited by side effects.

    It's not all about affinity for receptors = most potent agent for XYZ. It's about multiple and complementary sites of action, off-target effects, toxicity limitations like the pic above, side effects, etc.
     
    #29 spacecowgirl, Feb 12, 2019
    Last edited: Feb 13, 2019
  30. Rouelle

    PhD Pharmacist 7+ Year Member

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    And the SDN Award for Excellence in Education goes to....
     
  31. OP
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    NurseDude1966

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    Thank you for this visual! So as the poster above stated, the reason promethazine is more effective of an antiemetic than other antihistamines is because of the fact that it also works on the dopamine receptors and some other sites?
     
  32. BidingMyTime

    BidingMyTime Lost Shaker Of Salt
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    I have never met a nurse who was so single-mindedly focused on a subject that will have little relevance to her career (although I have met people in other careers like this....this is just the first nurse.) This has been an interesting discussion. I don't think I've ever heard of mepyramine (if I did, it was in med chem class and quickly forgotten, I've never heard it as a drug people would actually take.) And now, I plan to promptly forget all about it, because nobody is going to actually take mepyramine...but never mind me, carry on with the discussion for the nursing student's curiosity.
     
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  33. zelman

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    Feminine pronouns for “Nursedude”? Come on now. Don’t be nurses=girls&doctors=boys-ing in this day and age.
     
  34. OP
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    NurseDude1966

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    I already stated it was curiosity
     
  35. CetiAlphaFive

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    How dare they right?

    It is the C U R R E N T Y E A R
     
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  36. BidingMyTime

    BidingMyTime Lost Shaker Of Salt
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    99% of the time I use s/he here when referring to someone of unknown gender, kudo's to you for catching me the one time my coffee hasn't kicked in and I missed the /.
     
  37. CetiAlphaFive

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    @zelman is trying to force us to pretend three emperor has amazing clothes on.

    A person that assumes "doctor" refers to a male is right over 70% of the time.
    Someone who assumes "nurse" refers to a female is right 90% of the time.

    The fact that it is the current year does not change these facts
     
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  38. zelman

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    Their username is literally “male nurse”. You are right that those assumptions make sense without other contextual clues, but that is not the case here.
     
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  39. CetiAlphaFive

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  40. zelman

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    So why can’t we use OTC Oxytrol patches instead of scopolamine patches for motion sickness?
     
  41. lgrw16

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    Looks like you have a ton of responses already, but just wanna say thanks - and that I appreciate you consulting pharmacy! Some health systems don’t have the best nursing–pharmacy relationships (we just don’t know just how much each other really contribute, nursing is on the front line whereas pharmacy’s often in the basement) and even other providers/prescribers forget about how useful our training can be.

    Congrats on entering into nursing school and best of luck on your future endeavors. I wish all students could be as inquisitive and curious as you!
     
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  42. OP
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    NurseDude1966

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    Thank you very much! I know it seems like I'm being over the top but sometimes I just like to understand the rationale for lets say using one med in a particular class as opposed to another in that same class.
     
  43. spacecowgirl

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    Side benefit - fewer pee stops. IDK though, maybe it's not potent enough for vestibular effects?
     
  44. zelman

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    FYI: There is often no real rationale. Why is Indomethacin the be-all-end-all NSAID for gout? Because that's what we've been using since we started using NSAIDs for gout, and no other reason.
     
    BidingMyTime and owlegrad like this.
  45. lgrw16

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    That’s great that you go above and beyond! I’m like that too, I want to know the etiology and patho of every disease state I’m treating. It makes learning the drugs much, much easier and I feel more prepared/well-rounded.

    Don’t get too hung up on pharmacology tho - as a user above mentioned, sometimes there IS no rationale. Usually it’s the way it is bc that’s just the way it’s been done for decades and there’s no research (or not enough) to allow us to treat in other ways. It can be so frustrating sometimes
     
    penichillin likes this.
  46. CetiAlphaFive

    2+ Year Member

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    [​IMG]
     
  47. spacecowgirl

    15+ Year Member

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    Pupil dilation? I don't get it.

    I once had sinus surgery and I had a scop patch and opioids. My pupils were like WTF do we do here? So one was pinpoint and one was huge. Looked like I had a TBI.
     

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