Efficacy and mechanism of action of 1st versus 2nd generation antihistamines

[arctica]

I've gotten some conflicting advice from docs over the years about antihistamines, and I was wondering if you guys could help sort it out.

I have bad allergies. An allergist recommended that I take both Benadryl and Zyrtec together (plus other Rx drugs), while another advised me to double up on the Zyrtec and forget about the Benadryl. Does Benadryl (or the combination) have any advantages over Zyrtec alone (assuming you're not trying to get to sleep)? Do they act in an entirely analogous fashion and on the same receptors (minus Zyrtec crossing the BBB less readily)? Benadryl seems subjectively more effective to me at OTC dosages, but maybe I am imagining things.

Another question regarding antihistamines...a pharmacist recommend Dramamine for nausea caused by some other medications I was taking at the time. I know that Dramamine works specifically for motion sickness, but does it work for other types of nausea as well? I haven't found anything that seems truly effective for nausea short of Zofran and weed, but the availability, cost, and safety of OTC antihistamines certainly seem preferable to either. Would Benadryl or Zyrtec have similar effects, or would Zyrtec not have these properties because it doesn't cross the BBB as well? Are the anti-nausea effects caused by effects on the brain or effects on the histamine receptors of other systems?

Thanks in advance!

 

[Hammilton]

I'm pretty sure that because nausea is caused via central means the zyrtec won't work for nausea.

 

[arctica]

Thanks Hammilton, that was my suspicion as well.

 

[sekio]

Diphenhydramine doesn't appear to be very effective as a central antinausea medication for e.g. chemotherapy, but it does work for stuff like vertigo, motion sickness and occasionally food posionings. Gravol (dimenhydrinate) is basically diphenhydramine plus caffeine and is marketed as motion sickness/antinauseant medication. It is certainly better than nothing if you don't have access to newfangled antiemetics or cannabis.

The second-generation antihistamines which don't cross BBB are not effective antinauseants for the reason Hammilton said, they need to make it into the brain.

People even use very low doses of scopolamine for motion sickness/space adaption sickness... perhaps it is a muscarinic effect of some sort at work.

refs
http://www.ncbi.nlm.nih.gov/pubmed/1955741
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2426995/

 

[arctica]

Thanks seiko! From an anti-allergy efficacy perspective, do you know how Benadryl and Zyrtec compare? Is there likely any benefit from combining the two versus taking a larger dose of one or the other?

Cannabis does a pretty good job controlling nausea for me and it's readily available where I live. It seems that docs are more cautious handing out scripts for stuff like compazine and Zofran, probably because of the potential side effects (like QT prolongation), but I still have a couple stashed away just in case. I hear that Zofran is now being tested as an antipsychotic, especially for psychosis related to advanced cases of Parkinson's, despite no effects on 5HT2A or dopamine, which is interesting. Also, Zofran apparently doesn't work well for motion sickness, which surprises me, because it seems to work like a champ otherwise.

Diphenhydramine doesn't appear to be very effective as a central antinausea medication for e.g. chemotherapy, but it does work for stuff like vertigo, motion sickness and occasionally food posionings. Gravol (dimenhydrinate) is basically diphenhydramine plus caffeine and is marketed as motion sickness/antinauseant medication. It is certainly better than nothing if you don't have access to newfangled antiemetics or cannabis.

The second-generation antihistamines which don't cross BBB are not effective antinauseants for the reason Hammilton said, they need to make it into the brain.

People even use very low doses of scopolamine for motion sickness/space adaption sickness... perhaps it is a muscarinic effect of some sort at work.

refs
http://www.ncbi.nlm.nih.gov/pubmed/1955741
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2426995/

 

[5HToInfinity]

For the record, later generation antihistamines such as fexofenadine may show increased BBB permeability when combined with Piracetam. Maybe this could facilitate anti-emetic action?

 

[ebola?]

People even use very low doses of scopolamine for motion sickness/space adaption sickness... perhaps it is a muscarinic effect of some sort at work.

Indeed, it is my understanding too that anti-cholinergics are known to be anti-emetics too, so dramamine should be superior to any second generation anti-histamine due to both increased central activity and reduced selectivity. Honestly, though, these don't hold a candle to low-dose cannabis for this purpose.

ebola

 

[arctica]

Does anyone know why some drugs (scopolamine, Dramamine) seem to be effective for motion sickness but less so for food poisoning/chemo-induced nausea, while the opposite is true for other drugs (Zofran)? Is it the difference between working on the vestibular system versus the area postrema(?) Wikipedia implies that the area postrema lies outside the BBB:

http://en.wikipedia.org/wiki/Vomiting

Receptors on the floor of the fourth ventricle of the brain represent a chemoreceptor trigger zone, known as the area postrema, stimulation of which can lead to vomiting. The area postrema is a circumventricular organ and as such lies outside the blood–brain barrier; it can therefore be stimulated by blood-borne drugs that can stimulate vomiting or inhibit it.

I suppose this makes all sorts of sense if you're trying to detect if your body has been poisoned by something that doesn't necessarily cross the BBB, but then why don't the 2nd generation antihistamines seem to have an effect?

Wikipedia also notes that there are many inputs, including:

The vestibular system, which sends information to the brain via cranial nerve VIII (vestibulocochlear nerve), plays a major role in motion sickness, and is rich in muscarinic receptors and histamine H1 receptors.

If I recall correctly, the vestibular system has it's own system analogous to the BBB, so I'm guessing that's the difference. Maybe the antihistamines/scopolamine work on the vestibular system and Zofran works on the area postrema? Does anyone know by what mechanism cannabis works?

 

[ebola?]

The majority of serotonergic receptors are located in the gut, so Zofran is pharmacologically specifically targeted toward the signals that induce nausea with food poisoning (and to a reduced extent chemotherapy).

ebola

 

[Dr.Albrecht D.O]

As a Dr I would give Trimethobenzamide . It works by decreasing the signals in the brain that lead to vomiting.
And 100mg of benadryl

 

[endotropic]

As a Dr I would give Trimethobenzamide . It works by decreasing the signals in the brain that lead to vomiting.
And 100mg of benadryl

I've never heard of that drug before. It has the same substitution pattern as mescaline, yet apparently no serotonergic effects. How very strange.