anaphylaxis screening and protection program...

12/6/2012

© 2012 by the American Pharmacists Association. All rights reserved. 1

1

Anaphylaxis

Screening

and

Protection Program

Development and Support

This webinar was developed by the

American

Pharmacists Association and supported by

an independent educational grant from

Mylan Specialty L. P.

Speakers and Disclosures

Philip Johnston, PharmD

Professor and Dean

Belmont University College of Pharmacy

Elisa Greene, PharmD

Assistant Professor, Pharmacy Practice

Belmont University College of Pharmacy

The speakers and APhA’s education staff declares no conflicts of

interest or financial interests in any product or service mentioned in this

activity, including grants, employment, gifts, stockholdings, and

honoraria. For complete staff disclosures, please see the Education and

Accreditation Information section at www.pharmacist.com.

12/6/2012


Accreditation Information

The American Pharmacists Association is accredited by the Accreditation Council for

Pharmacy Education as a provider of continuing pharmacy education (CPE). This activity,

Anaphylaxis Screening and Protection is approved for 1.5 hours of CPE credit (0.15

CEUs). The ACPE Universal Activity Number assigned by the accredited provider is

0202-0000-12-255-L04-P for pharmacist and 0202-0000-12-255-L04-T for technicians.

To obtain CPE credit for this activity, participants will be requires to actively participate in

the entire webinar and complete an online evaluation and assessment located at

www.pharmacist/com/live-activities by November 27, 2012. Instructions and an

attendance code will be provided at the completion of the webinar.

Target audience: Pharmacist and Technicians

ACPE Activity Type: Knowledge-based

Learning Level: 2

Initial Release Date: November 13, 2012

Define the term “anaphylaxis,” list common symptoms, and identify key

elements of anaphylaxis treatment.

Name factors that increase a person’s risk of experiencing anaphylaxis as

well as factors that increase the severity of anaphylaxis.

Describe the elements of a comprehensive strategy for preventing and

treating episodes of anaphylaxis in the community setting.

Explain the appropriate use of epinephrine auto-injectors and identify errors

commonly made by patients.

Summarize the usual components of an emergency action plan for an

individual patient at risk of anaphylaxis.

Learning Objectives for Technicians

Only 1 does of epinephrine should be used to

reverse a severe allergic reaction or anaphylaxis

event?

True

False

http://www.pharmacist/com/live-activities



12/6/2012


When should an epinephrine autoinjector be

replaced?

a.If it was obtained more than 6 months ago.

b.If it will expire before the patient can return to the

pharmacy for a replacement.

c.After it has expired.

d.It does not need to be replaced unless it has been

used.

Side effects of epinephrine include:

a.Palpitations and difficulty breathing

b.Dizziness and lightheadedness

c.Leg weakness

d.Nausea

Roy Petrey is a 32-year-old male with a history of

allergic reactions

Through trial and error, he has eliminated multiple

possible causes, such as dust, grass, and animal

dander

The most recent incident included complete body

rash, facial swelling, and bronchospasm

Introduction to Patient Case

12/6/2012


Definition

◦ “A severe and sometimes fatal allergic reaction that is

characterized by hives, itching, respiratory difficulty, and

shock; this condition requires immediate medical attention”

◦ “A severe, life-threatening, generalized or systemic

hypersensitivity reaction that is characterized by rapidly

developing life-threatening airway and/or breathing and/or

circulation problems usually associated with skin and

mucosal changes”

Anaphylaxis Overview

Highly likely when any one of the following 3 criteria are

fulfilled:

◦ 1. Acute onset of an illness (minutes to several hours)

with involvement of the skin, mucosal tissue, or both

(e.g., generalized hives, pruritus or flushing, swollen

lips-tongue-uvula) AND AT LEAST ONE OF THE

FOLLOWING

A. Respiratory compromise

B. Reduced Blood Pressure or symptoms of end-organ

dysfunction

Clinical Criteria for Diagnosis of

Anaphylaxis

◦2. Two or more of the following that occur rapidly after

exposure to a likely allergen for that patient (minutes to

several hours):

A. Involvement of the skin-mucosal tissue

B. Respiratory compromise

C. Reduced BP or associated symptoms

D. Persistent gastrointestinal symptoms


Anaphylaxis

12/6/2012


◦3. Reduced blood pressure after exposure to known

allergen for that patient (minutes to several hours):

A. Infants and children: low systolic blood pressure (age specific)

or >30% decrease in systolic blood pressure

B. Adults: systolic blood pressure of <90 mm Hg or >30%

decrease from that person’s baseline


Anaphylaxis

Overall incidence

◦ Estimates range widely

◦ Up to 49.8 per 100,000 person years

◦ Up to 10.5-70 per 100,000 person years in those <19

years

Compare to colorectal cancer ◦ 52.7 per 100,000 person years (males)

◦ 39.7 per 100,000 person years (females)

Anaphylaxis Incidence

Admissions rate for anaphylactic shock

◦ 3.8 cases per 100,000 hospital admissions

Emergency room visits ◦ 71% of patients present to ED or urgent care

◦ Of these, only 11% required hospitalization

Inpatients

◦ 1 in 3,000 inpatients in US has an anaphylactic reaction

Anaphylaxis Statistics

12/6/2012


Ages

◦ Peak occurrence: 15-55 years

◦ Mean age 29 years, highest rates in <20 years

Gender ◦ 56% female

Epinephrine prescriptions

◦ More in men if <15 years

◦ More in women if >15 years


Season

◦ Peak: July-Sept (stings)

Geographic region ◦ More in North/East vs South/West

Deaths

◦ 1,443-1,503 deaths per year (0.002%)


Anaphylaxis: IgE mediated

◦ First exposure: sensitization

◦ Subsequent exposure: release of inflammatory mediators

(e.g., histamine, cytokines)

Anaphylactoid: Non-IgE mediated ◦ May occur after first exposure

Pathophysiology

Note: Distinction not recommended

because presentation and treatment

are identical

12/6/2012


Most commonly peanuts, milk, eggs, tree nuts,

shellfish, soy, fish, wheat, sesame seed

Usually immediate although may be delayed or

return

Common Triggers: Food

Antibiotics

◦ Penicillin most common medication cause

NSAIDs or ASA ◦ 2nd most common

◦ May be med specific

Other medications

◦ Radio contrast media

◦ IV anesthetics

◦ Opioid analgesics

◦ Omalizumab

All patients should have epinephrine Rx

Common Triggers: Medications

Insect venom

◦ Most commonly Hymenoptera order – honeybees,

bumblebees, sweat bees, yellow jackets, hornets, wasps,

ants

Latex

Exercise

Idiopathic

Autoimmune

Other Common Triggers

12/6/2012


Food 33.2%

Insect sting 18.5%

Medication 13.7%

Contrast 0.5%

Other known 9 %

Unknown 25.1%

Incidence

Typical

◦ Exposure to trigger

May not be identified

◦ Rapid onset of symptoms

◦ Resolves within minutes to hours

Spontaneous or with medical attention

Less likely

◦ Delayed onset

◦ Prolonged duration

◦ Biphasic reaction

Clinical Presentation

May vary

between people

and between

episodes!

Most frequently encountered signs/symptoms

◦ Mucocutaneous 94%

◦ Respiratory 88%

◦ Gastrointestinal 22%

◦ Cardiovascular 21%

Early signs/symptoms ◦ Flushing

◦ Urticaria

Clinical Presentation

12/6/2012


Recurrence after remission of initial symptoms

◦ Maximum incidence 20%

◦ Variable severity

◦ Difficult to predict

◦ May require second dose

Increased likelihood with: ◦ Delay in epinephrine

◦ Inadequate epinephrine

◦ Need for large amounts of epinephrine

Biphasic Reactions

Mucocutaneous Respiratory Cardiovascular Gastrointestinal Other

Pruritis Congestion Hypotension Nausea Weakness

Flushing Sneezing Vascular collapse Vomiting Dizziness

Angioedema Bronchospasm Shock Abdominal cramps

Urticaria Upper respiratory

obstruction •Dyspnea

•Stridor

•Wheezing

•Throat tightness

•Aphonia

Arrest Diarrhea

Arrhythmias

Syncope or pre-

syncope

Chest pain

Increased vascular

permeability

◦ Diffuse urticaria 51.2%

◦ Local angioedema 48.8%

◦ Dyspnea 48.8%

◦ Pruritis 48.3%

◦ Throat tightness/fullness 39.8%

◦ Flushing 38.4%

◦ Tachycardia 35.6%

◦ Wheezing/bronchospasm 26.5%

◦ Emesis 18.0%

◦ Local urticaria 17.1%

Most Common Symptoms

12/6/2012


Dyspnea/difficulty breathing 48.8%

Intra-oral angioedema 15.6%

Hypotension 12.3%

Oro/hypo-pharyngeal edema 10.9%

Arrhythmia 6.6%

Syncope 6.6%

Diffuse angioedema 6.2%

Cyanosis 5.2%

Laryngeal edema 4.3%

Shock 1.0%

Severe Symptoms

RP has determined that his most recent allergic

reaction was actually anaphylaxis ◦ Skin testing has revealed an allergy to beef protein

RP has been educating himself about trigger

avoidance but is worried and fearful about future

episodes of anaphylaxis

RP calls and asks if you can talk him through what

might happen if he needs to be treated again

The Case of Mr. Petrey

First line therapy

◦ Epinephrine first and always!

Management of Acute Anaphylaxis

http://www.epipen.com/about-epipen [Accessed 08/31/2012]

http://www.auvi-q.com/ [Accessed 09/13/12]

http://www.epipen.com/about-epipen



http://www.auvi-q.com/

12/6/2012


Second-line therapy

◦ Antihistamines

Symptomatic for urticaria, angioedema and pruritis

May use H1 + H2

◦ Systemic corticosteroids

May prevent protracted or biphasic reaction


Sample Regimen:

Diphenhydramine 25-50 mg

Ranitidine 300 mg

Methylprednisolone 1-2 mg/kg

*or equivalents

Third-line therapy

◦ Bronchodilators

◦ Supportive measures

Oxygen

Fluid resuscitation

Vasopressors

Glucagon

Positioning

◦ Remain recumbent (unless vomiting/SOB prevents)

◦ Legs elevated

It is not recommended to induce vomiting


Observe patient after initial event

◦ Recommended: 8 hours

◦ Longer if more severe

◦ Caution in patients with reactive airway disease

More fatalities

At discharge ◦ Prescription: epinephrine auto-injector

◦ Education: avoidance if trigger known

◦ Follow-up: notify PCP/refer to allergist


12/6/2012


That was awful—am I ever going to have to do it

again?

You really want me to give myself a shot?


Access

◦ Epinephrine auto-injector is not available

◦ Not prescribed

◦ Not on their person

◦ Not able to use epinephrine auto-injector

◦ Regulatory restrictions (schools, day care. etc.)

Fear

◦ Needle

◦ Adverse effects

Denial

◦ Recognition of reaction

◦ Severity of reaction

Behavioral Barriers

“I had plenty of auto-injectors available, but that time the

symptoms were different…it wasn’t until we got into the car

(that) I suddenly thought, ‘no, this is the same thing.’”

“I thought I was having an asthma attack; I thought if I had

anaphylactic shock I would be throwing up, because that’s

what I did when I was little.”

“I didn’t realize that I could use it if I was just going into the

reaction. You don’t know if you should take it now or wait until

it develops and see how it goes. Are you bad enough to use it,

that’s the big issue…”

Behavioral Barriers

12/6/2012


Self-education

◦ Food labels

“May contain”

◦ Eating out

◦ Travel

Vigilance

Parental role ◦ Educating child on trigger avoidance

◦ Reinforcement

◦ Gradual hand over of responsibility/management to

adolescent

Overcoming Barriers

Psychosocial Impact

“I think if you have experienced an anaphylactic

shock and you know what it’s like. Very, very

frightening…the second time he had an

anaphylactic reaction he hardly ate for 6 months.”

—Parent of child with anaphylaxis

“Quite a lot of my friends go and kiss boys and

things and it’s kind of awkward for me because I’ll

have to kind of ask have you eaten nuts. And you

can’t really do that in a club…”

Psychosocial Impact

12/6/2012


After discussing treatment of acute anaphylaxis,

RP feels reassured and is confident he can

overcome any of the barriers he is facing

He asks if he is at high risk for experiencing a

future episode—if so, is there anything he can do

to prevent it?


Previous episode: greatest predictor of future event

◦ Within 10 years:

◦ Median 395 days

◦ Range 7 days to 13 years later

Atopic history: present in 54%-60% of patients ◦ i.e. Asthma, allergic rhinitis, atopic dermatitis, hives

◦ More likely if food-induced or idiopathic

Identifying Patients at Risk

Patient age

Concomitant disease states ◦ Asthma

◦ Allergies to anaphylaxis-causing substances

◦ Heart Disease

Medications

◦ Beta blockers, alpha blockers (block epinephrine activity)

◦ ACE inhibitors, ARBs (may interfere with endogenous

compensatory responses)

Identifying Patients with Increased

Severity

12/6/2012


Identify and avoid patient-specific triggers

Manage relevant comorbidities

Assess benefits, risks of concurrent meds

Assess need for prophylactic therapy ◦ Trigger not identified or not avoidable

◦ Consider:

H1 and/or H2 antagonist

Leukotriene modifier

Corticosteroids

Consider immunomodulation ◦ Venom-induced anaphylaxis

Preventing Anaphylaxis

ACE inhibitors

ARBs

Beta blockers

Alpha blockers

Cocaine

Amphetamines

Tricyclic antidepressants

Monoamine oxidase inhibitors

Epinephrine Drug Interactions

Has RP eliminated all possible allergens to protect

himself from future episodes of anaphylaxis?

What education does RP require to be prepared for

the future? ◦ Hint: He has never used an epinephrine auto-injector

What are the elements of a complete

emergency plan?


12/6/2012


Also known as adrenaline

Mechanism of action ◦ Alpha and beta adrenergic agonist

Therapeutic effects

◦ Vasoconstriction

◦ Bronchodilation

◦ Decreased mucosal edema

◦ Decreased release of mast calls, basophils, tryptase,

histamine

◦ Increased myocardial output and contractility

Autoinjectable Epinephrine

Adverse effects

◦ Anxiety

◦ Tremor

◦ Headache

◦ Difficulty breathing

◦ Palpitations (could be drug or disease)

Contraindications ◦ None!


Delivery systems

◦ EpiPen

◦ Auvi-Q

◦ No longer marketed: Twinject, Adrenaclick

Available in 0.15 mg or 0.3 mg doses ◦ Weight-based dosing:

If 10-25 kg: give 0.15 mg

If >25 kg: give 0.3 mg

Route of administration: intramuscular


12/6/2012


Site of administration: anterior lateral thigh

◦ Inject through clothing

May repeat every 5-15 minutes

If in doubt, administer!

13% required >2 doses


Both doses are available as auto-injections

◦ EpiPen – Yes Auvi-Q – Yes

Needle left exposed after auto-injection

◦ EpiPen – Yes Auvi-Q – No

Second dose can be saved and used later

◦ EpiPen – Yes Auvi-Q - Yes

Trainer device is included

◦ EpiPen – Yes Auvi-Q - Yes

Autoinjectable Epinephrine Comparison

[NOTE

Autoinjector Administration Technique

1

2

3

4

12/6/2012


Common adverse effects

◦ Anxiety

◦ Tremors

◦ Pallor

◦ Tachycardia

10 seconds may feel like eternity

Should feel improvement within 5-10 minutes

What to Expect After Administration

You receive a call from an EMT en route to the

emergency room with RP, who appears to be having an

acute cyanotic episode ◦ The EMT has found the pharmacy telephone number on a

prescription for a metered dose inhaler in RP’s hand

The EMT asks you what other medications RP is getting

and if you have a history that would help them manage

RP

On questioning you find that they do not know of RP’s

history of anaphylaxis!


The EMT determines that RP has already self

administered an epinephrine auto-injector

Based on patient reaction and vital signs, the EMT

administers an additional dose (0.3mg) of

epinephrine en route to the nearest ED

RP is given supportive treatment and kept for

observation, but makes a full recovery


12/6/2012


RP arrives in your pharmacy and asks for you by name

He shakes your hand and thanks you for “saving his life” during

his recent ambulance ride

You assure him that you are happy to assist and that keeping

all of his records in one pharmacy helped his chances of

having a complete medication history available for the EMT

RP states that he will always keep his emergency action plan

on his person, and needs to acquire an emergency ID bracelet


Emergency action plan

◦ Information necessary for urgent care

◦ Instructions for family, others

Emergency preparedness ◦ Medical alert bracelet

◦ Vigilance and education

Emergency Action Plan

Practice Improvements

◦ Keep all brands of epinephrine necessary for your

clientele

◦ Keep emergency plan forms for patient education

◦ Offer patients a method of purchasing a medical

emergency identification

◦ Consider collaborative drug therapy management

agreement with allergist of primary care physician

◦ Administer epinephrine and call 911 in patient presenting

with anaphylaxis

Tips for Pharmacists

12/6/2012


Educate!

◦ patients, parents, teachers, and others

46% of people contacted friend or family member first when

they had severe reactions

Counsel on secondary treatments and preventive measures,

as necessary

Teach proper use, storage and administration of epinephrine

Review product insert/instructions with patients

Avoid excessive heat or cold

Remind about intramuscular injection

Replace if submersed in water

Inspect regularly for changes in color or clarity


Alleviate patient fears

◦ Provide necessary, patient specific information

◦ Assure them this is a manageable situation

◦ Address psychosocial barriers

Help resolve access barriers ◦ Physician collaboration for initial prescription

◦ Second prescription for keeping at school or work

◦ Prescription renewal/expiration reminders


Provide support

◦ Offer to help complete the patient emergency plan

Suggest who should be informed and trained

◦ Give the patient your contact information for follow up

information with a copy for his/her primary care provider

◦ Call the patient if an incident has occurred recently

◦ Keep specialist contact information available


12/6/2012


◦ Educate close contacts

◦ Check expiration date on epinephrine

◦ Know and avoid triggers

◦ Recognize symptoms

◦ Carry self-injectable epinephrine at all times

◦ Use epinephrine early and correctly

◦ Seek medical care after epinephrine use

Patient Steps for Successful Management

Only 1 does of epinephrine should be used to

reverse a severe allergic reaction or anaphylaxis

event?

True

False

When should an epinephrine autoinjector be

replaced?

a.If it was obtained more than 6 months ago.

b.If it will expire before the patient can return to the

pharmacy for a replacement.

c.After it has expired.

d.It does not need to be replaced unless it has been

used.

12/6/2012


Side effects of epinephrine include:

a.Palpitations and difficulty breathing

b.Dizziness and lightheadedness

c.Leg weakness

d.Nausea

For more information:

◦ EpiPen: www.myepipen.com

◦ The American College of Allergy, Asthma, and

Immunology:

http://www.acaai.org/allergist/allergies/Anaphylaxis/Pages/

anaphylaxis-patient-tip-sheet.aspx

◦ The Food Allergy and Anaphylaxis Network:

http://www.foodallergy.org/section/education

◦ http://www.foodallergy.org/section/support-groups

Additional Resources

References Akeson N, Worth A. Sheikh A. The psychosocial impact of anaphylaxis on young people and their parents. Clin Exp

Allergy. 2007; 37:1213-20.

Bohlke K, Davis RL, DeStefano F, Marcy SM, Braun MM, Thompson RS, et al. Epidemiology of anaphylaxis among children and adolescents enrolled in a health maintenance organization. J Allergy Clin Immunol. 2004;113:536-42.

Bothnar BS, Lichtenstein LM. Anaphylaxis. NEJM 1991; 324: 1785-90.

Camargo CA, Clark S, Kaplan MS, Lieberman P, Wood RA. Regional differences in EpiPen prescriptions in the United States: The potential role of Vitamin D. J Allergy Clin Immunol 2007;120:131-6.

Campbell RL, Luke A, Weaver AL, St. Sauver JL, Bergstralh EJ, et. al. Prescriptions for selfinjectable epinephrine and follow-up referral in emergency department patients presenting with anaphylaxis. Ann Allergy Asthma Immunol. 2008;101:631-6.

CDC Glossary, www2a.cdc.gov/nip/isd/ycts/mod1/scripts/glossary.asp?item=anaphylaxis accessed: August 29, 2012.

Choo K and Sheikh A. Action plans for the long-term management of anaphylaxis: systematic review of effectiveness. Clinical and Experimental Allergy. 37;1090-1094

Decker WW, Campbell RL, Manivanna V, Luke A, St Sauver JL, Weaver A, et. Al. The etiology and incidence of anaphylaxis in Rochester, Minnesota: A report from the Rochester Epidemiology Project. J Allergy Clin Immunol. 2008;122:1161-5.

Eigenmann PA, Dayer Pastore F, Zamora SA. An Internet-based survey of anaphylactic reactions to foods. Allergy 2001; 56:540-3.

Gallagher M, Worth A, Cunningham-Burley S, Sheikh A. Epinephrine auto-injector use in adolescents at risk of anaphylaxis: a qualitative study in Scotland, UK. Clin Exp Allergy 2011; (41): 869-77.

http://www.myepipen.com

http://www.acaai.org/allergist/allergies/Anaphylaxis/Pages/anaphylaxis-patient-tip-sheet.aspx








http://www.foodallergy.org/section/education

http://www.foodallergy.org/section/support-groups



12/6/2012


Gupta R, Sheikh A, Strachan DP, and Anderson HR. Time trends in allergic disorders in the UK.Thorax 2007; 62: 91-6.

Gupta R, Sheikh A, Strachan DP, and Anderson HR. Burden of allergic disease in the UK: secondary analyses of national databases. Clin Exp Allergy 2004;34:520-6.

Johann-Liang R, Josephs S, and Dreskin SC. Analysis of anaphylaxis cases after vaccination: 10-year review from the national vaccine injury compensation program. Ann Allergy Asthma Immunol. 2011.

Johannes CB, Ziyadeh N, Seeger, Tucker E, Reiter, and Faich G. Incidence of Allergic Reactions Associated with Antibacterial Usei in a Large, Managed Care Organisation. Drug Safety. 2007; 30 (8): 705-13.

Kelso JM. A second dose of epinephrine for anaphylaxis: How often needed and how to carry. J Allergy Clin Immunol. ;17(2): 464-5.

Kemp SF, Lockey RF, Simos FER. Epinephrine: the drug of choice for anaphylaxis. A statement of the World Allergy Organization. Allergy; 2008: 63;1061-70.

Lieberman P. Biphasic anaphylactic reactions. Ann Allergy Asthma Immunol. 2005; 95:217-26.

Lieberman P, Decker W, Camargo CA, O’Connor R, Oppenheimer J, Simons FE. SAFE: a multidisciplinary approach to anaphylaxis education in the emergency department. Ann Allergy Asthma Immunol. 2007;98:519-23.

Lieberman P, Nicklas RA, Oppenheimer J, Kemp SF, Lang D. The diagnosis and management of anaphylaxis practice parameter: 2010 update. J Allergy Clin Immunol 2010; 126:477-80.

Manivannan V, Campbell RL, Bellolio MR, Stead LG, Li JTC, Decker WW. Factors associated with repeated use of epinephrine for the treatment of anaphylaxis. Ann Allergy Asthma Immunol. 2009;103:395-400.

Muelleman RL, Tran TP. Chapter 113: Allergy, hypersensitivity, and anaphylaxis. In: Rosen’s emergency medicine: concepts and clinical practice. 5th ed. St Lousi (MO): Mosby, INC., 2002.

Neugut AI, Ghatak AT, Miller RL. Anaphylaxis in the United States: An Investigation Into Its Epidemiology. Arch Intern Med. 2001; 161:15-21.

References

Pumphrey R. Anaphylaxis: can we tell who is at risk of a fatal reaction? Curr Opin Allergy Clin Immunol 2004;4:285-

90. Resuscitation Council (2008) Emergency treatment of anaphylactic reactions. Guidelines for healthcare providers.

Available at: www.resus.org.uk/pages/reaction.pdf. Accessed: August 24,2012.

Sampson HA, Munoz-Furlong A, Campbell RL, Adkinson NF, Bock SA, Branum A, et. al. Second symposium on the definition and management of anaphylaxis: Summary report - Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J Allergy Clin Immunol. 2006;117:391-7.

Sheikh A and Alves B. Age, sex, geographical and socio-economic variations in admissions for anaphylaxis: analysis of four years of English hospital data. Clinical and Experimental Allergy. 2001; 31: 157106.

Sheikh A, Shehata YA, Brown SGA, Simons FER. Adrenaline (epinephrine) for the treatment of anaphylaxis with and without shock (Review). The Cochrane Library 2012; 4: 1-16.

Simons FER, Peterson S, Black CD. Epinephrine dispensing patterns for an out of hospital population: A novel approach to studying the epidemiology of anaphylaxis. J Allergy Clin Immunol 2002;110:647-51.

Stumpf JL, Shehab N, Patel AC. Safety of Angeiotensin-Converting EnzymeInhibitors in Patients with Insect Venom Allergies. Ann Pharmacother 2006;40:699-703.

Walker S, Sheikh A. Managing anaphylaxis: effective emergency and long-term care are necessary. Clin Exp Allergy 2003; 33:1015-18.

References

http://www.resus.org.uk/pages/reaction.pdf

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