Help answering a pimp question.

[VJWDO]

I was asked today why you would give Benadryl to a patient who was experiencing extrapyramidal effects while taking Phenergan. So either I missed this in med school or this is somewhat obscure. Any help would be appreciated.

VJWDO MSIII

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[VincentAdultman]

I was asked today why you would give Benadryl to a patient who was experiencing extrapyramidal effects while taking Phenergan. So either I missed this in med school or this is somewhat obscure. Any help would be appreciated.

VJWDO MSIII

Phenergan (promethazine) is an antipsychotic....it blocks dopamine. When you do that, it produces an imbalance between dopamine and ach. The benadryl is an anticholinergic, so you in effect restore balance between the two neurotransmitters.

I hope I got it right.

 

[StickMe]

Hmmm, Benadryl has less Anticholinergic effects than Phenergan. According to my notes, +++ vs. ++++ like that means anything.

 

[Arsenic]

Hmmm, Benadryl has less Anticholinergic effects than Phenergan. According to my notes, +++ vs. ++++ like that means anything.

i hate it when i see that in my notes too.

 

[Idiopathic]

Phenergan (promethazine) is an antipsychotic....it blocks dopamine. When you do that, it produces an imbalance between dopamine and ach. The benadryl is an anticholinergic, so you in effect restore balance between the two neurotransmitters.

I hope I got it right.

Clinically, phenergan is an antihistaminic, competing at H1. Perhaps the antihistaminic property of benadryl competes with that of phenergan at this site as well as others.

 

[SurgONC]

Promethazine blocks both dopamine AND histamine. I think Pompacil has got it right.

 

[s42brown]

Diphenhydramine (Benadryl) -- Anticholinergic medications help restore balance between dopaminergic and cholinergic neurotransmission. Dopaminergic transmission is decreased by neuroleptic drugs.

Emedicine to the rescue.

 

[bigfrank]

Keep it simple -- this the wards. Phenergan blocks DA, which is counteracted by Antihistamines that will block ACh.

 

[TheAyatollah]

Keep it simple -- this the wards. Phenergan blocks DA, which is counteracted by Antihistamines that will block ACh.

Yo BigFrank. Where did you get that avatar. Is it from the space telescope?

 

[tupac_don]

I was asked today why you would give Benadryl to a patient who was experiencing extrapyramidal effects while taking Phenergan. So either I missed this in med school or this is somewhat obscure. Any help would be appreciated.

VJWDO MSIII

Yea b/c its an anticholinergic agent in addition to being a histamine blocker. Cogentin is typically used, but can use benadryl.

 

[tupac_don]

Clinically, phenergan is an antihistaminic, competing at H1. Perhaps the antihistaminic property of benadryl competes with that of phenergan at this site as well as others.

Last time I checked phenergan was an antiemetic.

 

[bigfrank]

Yo BigFrank. Where did you get that avatar. Is it from the space telescope?

It's some NASA Photograph (authentic) that was some star collapse or something -- I'm not really sure; I'm no astronomer. It was circulated in emails as a hoax a few years ago as being "the eye of God photographed by NASA."

I thought it was pretty cool, as it has various interpretations/implications.

 

[Syranope2]

Last time I checked phenergan was an antiemetic.

high levels of dopamine can also lead to nausea/vomiting, so a drug that lowers DA will decrease N/V.

 

[Idiopathic]

Last time I checked phenergan was an antiemetic.

It is, but its also a tranquilizer/CNS depressant, which is why people seek it in the ER (you know, "intractable N/V, allergic to compazine, reglan, etc.") Since phenergan and benadryl have similar anticholinergic properties, the use of one to counteract the dyskinetic effects of the other doesnt make much sense, even though we know that is the mechanism for most rx of neuroleptic induced dyskinesia. My theory is that the histamine must be involved somewhere, since everything is in a balance until disrupted, and that disruption (of, dopamine, ACh, etc.) is what causes the end result.

By the way, phenergan has about 1/10th the dopamine blocking strength of thorazine.

 

[Idiopathic]

high levels of dopamine can also lead to nausea/vomiting, so a drug that lowers DA will decrease N/V.

I think that the -trons (zofran, etc) are the only drugs that decrease N/V through this pathway, since they act on receptors 5-HT3 in the medulla....but maybe thats serotonin, now that I think about it. Regardless, the antiemetic effects of phenergan are nearly totally dependent on anti-ACh activity.

 

[Sugar72]

I think that the -trons (zofran, etc) are the only drugs that decrease N/V through this pathway, since they act on receptors 5-HT3 in the medulla....but maybe thats serotonin, now that I think about it. Regardless, the antiemetic effects of phenergan are nearly totally dependent on anti-ACh activity.

The trons act at the chemoreceptor trigger zone AND at the vagal afferent receptor ( i think they are enterochromaffin cells - not sure about the cell type though).
not that this info has anything to do with the OP's question! I just think it is interesting that the -trons act in the gut and in the medulla.

 

[tupac_don]

It is, but its also a tranquilizer/CNS depressant, which is why people seek it in the ER (you know, "intractable N/V, allergic to compazine, reglan, etc.") Since phenergan and benadryl have similar anticholinergic properties, the use of one to counteract the dyskinetic effects of the other doesnt make much sense, even though we know that is the mechanism for most rx of neuroleptic induced dyskinesia. My theory is that the histamine must be involved somewhere, since everything is in a balance until disrupted, and that disruption (of, dopamine, ACh, etc.) is what causes the end result.

By the way, phenergan has about 1/10th the dopamine blocking strength of thorazine.

Yea intractable N/V would fall under the category of antiemetic.

 

[tupac_don]

It is, but its also a tranquilizer/CNS depressant, which is why people seek it in the ER (you know, "intractable N/V, allergic to compazine, reglan, etc.") Since phenergan and benadryl have similar anticholinergic properties, the use of one to counteract the dyskinetic effects of the other doesnt make much sense, even though we know that is the mechanism for most rx of neuroleptic induced dyskinesia. My theory is that the histamine must be involved somewhere, since everything is in a balance until disrupted, and that disruption (of, dopamine, ACh, etc.) is what causes the end result.

By the way, phenergan has about 1/10th the dopamine blocking strength of thorazine.

Yea and it is the anticholinergic effect. Look it up.

 

[bigfrank]

I'm rusty.

 

[Idiopathic]

Yea intractable N/V would fall under the category of antiemetic.

i dont recall anyone arguing with you, but if all you know about phenergan is that its an antiemetic, then you are sorely underprepared.

 

[Idiopathic]

Yea and it is the anticholinergic effect. Look it up.

What exactly are you referring to, the antiemetic props or the rx for dyskinesia? I agree with you that the antiACh is the main player for the antiemetic properties, but I think that since benadryl and phenergan have similar ACh profiles, the answer for the latter must come from somewhere else.

I also referenced this in my subsequent post to the one quoted.

 

[sdn1977]

I'll throw my 2 cents in here also. I haven't read recent pharmacy literature on the actual mechanisms, so newer info may be available. However, D2 receptor blockers like promethazine change the ratio of dopamine to ACH in the basal ganglia. The higher the ratio, the greater the risk of acute dystonia. Whether diphenhdramine actually changes the affinity of promethazine for the receptor (as it does for histamine on H-receptors) or if thru its own mechanisms (histamine itself is a neurotransmitter & works on H3 receptors in the CNS), it does increase the ACH & changes this ratio, thus reducing the extrapyramidal effects. However, its really not completely clear because we do know that D2 receptor affinity decreases with age, which is why the elderly are at reduced risk of acute dystonic reactions & the mechanism explanations do not seem to hold up well for all the six neurologic syndromes associated w/antipsychotics - acute dystonic reactions, akathisia,parkinsonian syndrome, neuroleptic malignant syndrome, perioral tremor & tardive dyskinesia. Also...we aren't really sure what role the balance between serotonin & dopamine plays in this because akathisia can occur w/ SSRIs & they have weak affinity for dopamine neuronal uptake, D2 & H1receptors. Again, there is probably newer info, but thats what I learned.


Also...promethazine's extrapyradimal effects are due to actions in the basal ganglia...its antiemetic effects are due to actions in the CTZ in the medulla (as another poster pointed out) - different receptors w/ different affinities. Due to its chemical structure, in pharmacology it is thought of as an antipsychotic (altho not used for this today), but it can also be classified as an antiemetic; antihistamine; potentiator for analgesics, sedatives & general anesthetics.

 

[Dr.MISHKA D.O.]

I am very disappointed Idiopathic. You are no longer my hero, you have been replaced by corpsmanup. Good day sir!

Straight from the PDR
"Phenergan is a phenothiazine derivative, which differs structurally from the potent antipsychotic phenothiazines........it is thought this configuration is responsible for its relative low amount of dopamine antagonism properties."
"phenergan is a H1 receptor blocker" - therby its antiemetic effects.
uses include;
alergic rhinitis
sedation
antiemetic
therapeutic adjunct to analgesics
prevention of motion sickness
Other

While Phernegan is much lower in D blocking than say compazine or haldol I say the same principal of using benadryl or cogentin with dystonia from haldol/typical antipsychotic use applies. Decreasing Dopamine causes a relative (or actually?) increase in ACH which we know is a transmitter in Motor system. Thus it makes sense you would get dystonia (or muscle tightness activated at a central level - - see example of tetnus at a peripheral level) Therfore decreasing this increased ACH with a anticcholinergic decreases the s/s (i.e - EPS symptoms).

For examples of EPS symptoms see video of Idiopathic dancing

Best wishes

The Mish