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Author Topic: Why antihistamines won't stop anaphylaxis  (Read 18140 times)

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Offline AdminCM

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Offline admin rebekahc

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Re: Why antihistamines won't stop anaphylaxis
« Reply #1 on: September 19, 2011, 09:18:21 AM »
lilpig99
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Posted: 08.08.2011 at 09:43:33


Thought this was a good explanation of why benadryl doesn't stop anaphylaxis from occurring. (I never thought it did, but never could recall exactly *why*. DS's reaction got me thinking yesterday.)
 
Quote:

Antihistamines: Drugs that combat the histamine released during an allergic reaction by blocking the action of the histamine on the tissue. Antihistamines do not stop the formation of histamine nor do they stop the conflict between the IgE and antigen. Therefore, antihistamines do not stop the allergic reaction but protect tissues from some of its effects. Antihistamines frequently cause mouth dryness and sleepiness. Newer "non sedating" antihistamines are generally thought to be somewhat less effective. Antihistamine side effects that very occasionally occur include urine retention in males and fast heart rate.
 


http://www.medicinenet.com/epinephrine_with_chlorpheniramine_allergy_kit/glossary.htm


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Offline admin rebekahc

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Re: Why antihistamines won't stop anaphylaxis
« Reply #2 on: September 19, 2011, 09:19:59 AM »
CMdeux
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Posted: 08.09.2011 at 02:29:32


I'm going to add a few additional references to this thread. (Great idea to start this topic, Lilpig!)
 
http://en.wikipedia.org/wiki/Anaphalaxis

A surprisingly thorough discussion of the pathophysiology (ie-- the biochemical mechanism) of anaphylaxis, with very good citations throughout.
 
I'll also keep looking for the graphical overview of anaphylaxis that I know that I've seen at some point. It was excellent as an overview of the process, and did a terrific job of showing the points at which various pharmacological interventions must act.
 
Once mast cell degranulation occurs, anaphylaxis is about surviving that process. Epinephrine, being a potent beta agonist, is unmatched for its ability to help a person maintain an open airway and cardiac sufficiency during an anaphylactic event.

Antihistamines only stop one (early) intermediary among several.


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Offline admin rebekahc

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Re: Why antihistamines won't stop anaphylaxis
« Reply #3 on: September 19, 2011, 09:21:26 AM »
CMdeux
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Posted: 08.09.2011 at 03:29:31


A terrific resource:

J Allergy Clin Immunol. 2010 February; 125(2 Suppl 2): S73S80.


from that article about Ige, Mast Cells, Basophils and Eosinophils:

Quote
Mast cell activation through FcεR1 is central to the pathogenesis of allergic diseases, including anaphylaxis, allergic rhinitis, and allergic asthma. Activation of FcεR1 by polyvalent allergen recognized by bound IgE leads to the initiation of an immediate hypersensitivity reaction, as well as a late-phase reaction. The immediate reaction is determined by pre-formed mediators and rapidly synthesized lipid mediators and results in: erythema, edema, and itching in the skin; sneezing and rhinorrhea in the upper respiratory tract; cough, bronchospasm, edema, and mucous secretion in the lower respiratory tract; nausea, vomiting, diarrhea, and cramping in the gastrointestinal tract; and hypotension. Late phase reactions are mediated by cytokines and chemokines and can occur 624 hours after the immediate reaction. Late phase reactions are characterized by edema and leukocytic influx and may play a role in persistent asthma.

This is why, characteristically, biphasic reactions occur to begin with-- and why they tend to differ markedly from initial phase reactions in terms of clinical features.  They resist treatment because most of the treatment for allergic reactions is about those 'released' mediators (not the 'synthesized' ones that are more dominant in late-phase reactions). 

The entire article, while technically challenging for the lay reader, is WELL WORTH THE EFFORT.  It goes a long way toward explaining why the signalling pathways that produce anaphylaxis are so difficult to shut down.  For one thing, there are a LOT of them, there are a tremendous variety of mediators released (all possessing unique physiological signalling of their own), and many of the individual pathways contain feedback loops that amplify responses once activation occurs.


<sigh>  But I'm still looking for my figure that shows the activation of the system by an allergen docking with IgE.


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Offline admin rebekahc

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Re: Why antihistamines won't stop anaphylaxis
« Reply #4 on: September 19, 2011, 09:23:02 AM »
CMdeux
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Posted: 08.09.2011 at 04:43:02


08.09.2011 at 04:41:25, CMdeux wrote:
Quote
PERFECT.

Chapter 17: Immunology: HYPERSENSITIVITY REACTIONS  Dr. Jaffar, USC school of medicine


A very good introduction that is also very thorough in terms of its coverage of the mediators involved in anaphylaxis.  Really perfect for understanding the process involved.  (At least as far as it has been elucidated thus far-- there is some thought that much food anaphylaxis might be basophil-mediated rather than mast-cell mediated, which would explain the absense of serum tryptase in so many of those patients.)



I will cross-post this into the twin thread, too.




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Offline CMdeux

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Re: Why antihistamines won't stop anaphylaxis
« Reply #5 on: January 01, 2015, 09:43:48 PM »
Adding since I got motivated to find that elusive figure again.

http://www.medscape.com/viewarticle/780614_7

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Offline CMdeux

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Resistance isn't futile.  It's voltage divided by current. 

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Offline CMdeux

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Re: Why antihistamines won't stop anaphylaxis
« Reply #7 on: January 01, 2015, 09:55:30 PM »
Generally excellent-- particularly the figure, which nicely lays out why a Ni allergy has no bearing on being food allergic (or not).
http://philschatz.com/anatomy-book/contents/m46566.html

Resistance isn't futile.  It's voltage divided by current. 

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