How epinephrine works to stop Anaphylaxis

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admin rebekahc:
lilpig99
Member
Posted: 08.09.2011 at 03:12:35

08.09.2011 at 03:11:05, Guest wrote:
--- Quote --- 08.09.2011 at 12:47:43, CMdeux wrote:
--- Quote ---VERY important to understand something which is implied (but not directly stated) in the above--

epinephrine treats the SYMPTOMS of anaphylaxis, making them more survivable.

It doesn't "stop" or "reverse" the underlying cause of the systemic allergic cascade-- ergo, emergency medical aid is STILL AN ABSOLUTE REQUIREMENT after using epinephrine, because medical providers have additional tools for supporting a person who is experiencing anaphylaxis. (Steroids, intravenous fluids for volume depeletion, additional antihistamines and other second-messenger agonists/antagonists.)
--- End quote ---

That's kind of why I chose 'works to stop' instead of 'stops anaphylaxis'.

Do you think I should edit the title of this thread...Or is it best to leave it for simplicity's sake?
--- End quote ---

Maybe: 'why epinephrine can help keep you alive until anaphylaxis is over'

« Last Edited by lilpig99 08.09.2011 at 03:23:23 »

"Those of us who were bewitched by his eloquence on the campaign trail chose to ignore some disquieting aspects of his biography: that he had accomplished very little before he ran for president." ~ Drew Westen, a professor of psychology at Emory University, on Obama, New York Times.

admin rebekahc:
CMdeux
Moderator1
Posted: 08.09.2011 at 03:31:15

I'd leave it. Because it is what most people (even many physicians and medical personnel) believe, and functionally, it amounts to the same thing for laypersons. :yes:

ETA: I do wonder, however, if a lack of understanding the pathophysiology of anaphylaxis is what leads ER docs to release patients too soon, though. :-/ Because really, there is a REASON for that six hour observation window.

From the other thread, I'm cross-posting this one:
A terrific resource:

J Allergy Clin Immunol. 2010 February; 125(2 Suppl 2): S73–S80.

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 6–24 hours after the immediate reaction. Late phase reactions are characterized by edema and leukocytic influx and may play a role in persistent asthma.
--- End quote ---

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.

« Last Edited by CMdeux 08.09.2011 at 03:42:21 »

"To travel hopefully is a better thing than to arrive." -Robert Louis Stevenson

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admin rebekahc:
CMdeux
Moderator1
Posted: 08.09.2011 at 03:47:11

Oh, here is a good find!

http://download.journals.elsevierhealth.com/pdfs/journals/0091-6749/PIIS0091674905027235.pdf

The Journal of Allergy and Clinical Immunology Volume 117, Issue 2 , Pages 391-397, February 2006

This is an article which has DETAILED discussion of how to properly treat anaphylaxis, with the rationale for each intervention clearly given. :yes:

(I'm very pleased with that find! )

Another really terrific article:

The Journal of Allergy and Clinical Immunology Volume 110, Issue 3 , Pages 341-348, September 2002; "Anaphylaxis, a review of causes and mechanisms"

On that last one, the discussion of how histamine modulates nitric oxide is of particular interest-- and we've SEEN how well a large dose of antihistamine can work to prevent that vasodilatory response. It just doesn't always. :-/

« Last Edited by CMdeux 08.09.2011 at 03:56:17 »

"To travel hopefully is a better thing than to arrive." -Robert Louis Stevenson

USA

admin rebekahc:
CMdeux
Moderator1
Posted: 08.09.2011 at 04:16:44

http://journals.lww.com/waojournal/Fulltext/2008/07002/Epinephrine__The_Drug_of_Choice_for_Anaphylaxis_A.1.aspx#P34

Explains why there is NO substitute for epinephrine. :yes:

--- Quote ---Respiratory compromise and cardiovascular collapse cause most fatalities (28, 34).
--- End quote ---

This is why epinephrine is SO effective as a life-saving drug. It counteracts precisely those two-- killer-- symptoms of anaphylaxis. :)

--- Quote ---Increased vascular permeability during anaphylaxis can shift up to 35% of intravascular fluid to the extravascular space within 10 minutes.(35) The intrinsic compensatory response to anaphylaxis (endogenous epinephrine and other catecholamines, as well as angiotensin II, endothelin-1, etc) also influences the extent of clinical manifestations and, when adequate, may be lifesaving independent of medical intervention, which sometimes contributes to diagnostic and therapeutic confusion.
--- End quote ---

This goes a long way to explaining, I hope, why it can STILL be anaphylaxis and the person can STILL have recovered spontaneously, or survived without proper intervention. This, however, is what we would, in technical terms, call-- DUMB LUCK. Just to be clear. BTDT-- I have that teeshirt. Thankfully, I still have my child along with it. :heart:

« Last Edited by CMdeux 08.09.2011 at 04:30:11 »

"To travel hopefully is a better thing than to arrive." -Robert Louis Stevenson

USA

admin rebekahc:
CMdeux
Moderator1
Posted: 08.09.2011 at 04:41:25

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 (about antihistamines), too.

« Last Edited by CMdeux 08.09.2011 at 04:43:56 »

"To travel hopefully is a better thing than to arrive." -Robert Louis Stevenson

USA