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Author Topic: How epinephrine works to stop Anaphylaxis  (Read 18814 times)

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Offline AdminCM

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Re: How epinephrine works to stop Anaphylaxis
« Reply #1 on: September 19, 2011, 09:24:28 AM »
lilpig99
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Posted: 08.08.2011 at 01:12:47


EpiPen and EpiPen Jr auto-injectors both contain the active ingredient adrenaline, which is a hormone produced naturally by the body. It is given by injection to treat a life-threatening allergic reaction called anaphylactic shock. (NB. Adrenaline is also sometimes referred to as epinephrine.)
 
Adrenaline is released by the adrenal glands in times of stress. It prepares the body when extra energy or exertion is needed, making the body more able to deal with life-threatening situations.
 
Anaphylatic shock is a severe allergic reaction that can be triggered by a drug or food allergy, or by an insect bite. A severe reaction of this type can include the following symptoms: itching of the skin, a raised rash (like a nettle rash), swelling of your lips, tongue, throat, hands and feet, flushing, weak pulse, tightening of the chest, difficulty in breathing, fall in blood pressure and in some cases loss of consciousness.
 
Adrenaline reverses the symptoms of anaphylaxis by acting on alpha and beta adrenergic receptors in the body.
 
Alpha receptors are found on the walls of blood vessels. When adrenaline stimulates these receptors this causes the blood vessels to narrow, which stops the blood pressure from falling too low. It also redirects blood to vital organs like the heart and brain.
 
Beta receptors are found in the heart and lungs. When adrenaline stimulates these receptors this relaxes and opens the airways, making breathing easier. It also stimulates the heart, making it beat faster and stronger.
 
Adrenaline also relieves itching, hives and swelling.

http://www.netdoctor.co.uk/medicines/100000940.html

Last Edited by lilpig99 08.08.2011 at 01:14:05


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Re: How epinephrine works to stop Anaphylaxis
« Reply #2 on: September 19, 2011, 09:25:55 AM »
CMdeux
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Posted: 08.09.2011 at 12:47:43


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.)


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Re: How epinephrine works to stop Anaphylaxis
« Reply #3 on: September 19, 2011, 09:26:37 AM »
lakeswimr
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Posted: 08.09.2011 at 01:18:37


CM, I thought that epinepherine actually *does* stop or reverse ana in most cases. There are quite a few that require several doses and some that require additional interventions but many times one epi or two actually *does* stop or reverse ana.
 
I know in my son's case that is what has happened. He was having ana, got the epi and almost instantly all symptoms were totally gone and did not return. Of course he had to go to the ER, etc but he didn't require any further treatment.
 

Lisa - CT, USA
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Re: How epinephrine works to stop Anaphylaxis
« Reply #4 on: September 19, 2011, 09:28:16 AM »
CMdeux
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Posted: 08.09.2011 at 02:21:27
 

Anaphylaxis itself pretty much can only be 'steered' with pharmacology and other resuscitative interventions.

Mostly, from a physiological standpoint, the point of interventions is to allow the person to survive it.  Generally (aside from unusually protracted anaphylaxis) the entire thing is over and done with in a few minutes to a few hours.

Once mast cell degranulation occurs (often pretty early on) all you can do is manage symptoms-- and the thing is that initially, it may not be clear just how bad they'll become as a result of that massive dump of second messengers (histamine, leukotrienes, etc. etc.).  That's where a beta-agonist like epinephrine comes into things-- it's supportive, and there is absolutely nothing better at maintaining open airways and cardiac sufficiency under those conditions.

Believe it or not, I was coming back to both of these threads to post this link-- the pathophysiology section of the article is particularly thorough and well-referenced:

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

I know that I have seen a graphic of the mast-cell/IgE-antigen second messenger cascade at some point, and I'll keep looking.  It's really much more clear where various pharmacological agents impact the pathway when seeing it all at once like that.

Last Edited by CMdeux 08.09.2011 at 02:23:49


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Re: How epinephrine works to stop Anaphylaxis
« Reply #5 on: September 19, 2011, 09:31:22 AM »
lilpig99
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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.)

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?

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


Last Edited by lilpig99 08.09.2011 at 03:23:23


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Re: How epinephrine works to stop Anaphylaxis
« Reply #6 on: September 19, 2011, 09:32:50 AM »
CMdeux
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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): 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.


Last Edited by CMdeux 08.09.2011 at 03:42:21


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Re: How epinephrine works to stop Anaphylaxis
« Reply #7 on: September 19, 2011, 09:34:26 AM »
CMdeux
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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


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Re: How epinephrine works to stop Anaphylaxis
« Reply #8 on: September 19, 2011, 09:36:03 AM »
CMdeux
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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).


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.


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


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Re: How epinephrine works to stop Anaphylaxis
« Reply #9 on: September 19, 2011, 09:37:36 AM »
CMdeux
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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


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Re: How epinephrine works to stop Anaphylaxis
« Reply #10 on: March 08, 2014, 04:56:01 PM »
I'm adding this excellent (if basic) overview of anaphylaxis and treatment:

Anaphylaxis




Notice-- epinephrine, epinephrine, epinephrine...   :yes:



How to use an epinephrine autoinjector



Also very good.
« Last Edit: March 08, 2014, 05:20:26 PM by CMdeux »
Resistance isn't futile.  It's voltage divided by current. 

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Offline LinksEtc

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Re: How epinephrine works to stop Anaphylaxis
« Reply #11 on: March 08, 2014, 07:45:44 PM »

Anaphylaxis



Notice-- epinephrine, epinephrine, epinephrine...   :yes:



At about 6:48, they seem to emphasize salbutamol for breathing symptoms.  They mention that if epi already given, that would help also ..... but, they don't seem to stress that epi also must be given  :-/ 

Again at 12:05.

They define ana as more than 1 body system.  What if just breathing issues?

Thoughts?



« Last Edit: March 08, 2014, 07:59:10 PM by LinksEtc »


Offline CMdeux

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Re: How epinephrine works to stop Anaphylaxis
« Reply #13 on: March 08, 2014, 09:31:28 PM »

Anaphylaxis



Notice-- epinephrine, epinephrine, epinephrine...   :yes:



At about 6:48, they seem to emphasize salbutamol for breathing symptoms.  They mention that if epi already given, that would help also ..... but, they don't seem to stress that epi also must be given  :-/ 

Again at 12:05.

They define ana as more than 1 body system.  What if just breathing issues?

Thoughts?


I'm thinking that this is assuming an environment where intubation and IV push EPI are both options, honestly-- so it's not really a "first-aid" kind of thing.

And there's not really a reason why straight-up bronchodilation wouldn't be a thing in that particular setting. 
Resistance isn't futile.  It's voltage divided by current. 

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