Siti Kemala Sari

Bagian Farmakologi dan Teraupetik

Universitas Islam Sumatera Utara
2010
Ana = away from

Phylaxis = protection

Anaphylactic Shock occurs when a patient

becomes sensitized to a substance from
previous exposures.
Anaphylactic Shock is the most severe type of
allergic reaction
 Systemic allergic reaction

Affects body as a whole

Multiple organ systems may be involved

Onset generally acute

Manifestations vary from mild to fatal

 Antibiotics and other drugs
Foods (nuts, eggs, shellfish)
Allergen extracts (allergy shots)
Hymenoptera stings (bees, wasps)
Hormones (insulin)
Aspirin
Blood products
Preservatives (sulfiting agents)
Triggers
Common causes: Drugs causing anaphylaxis

Foods Antibiotics (especially penicillin)

Bee and wasp stings Anaesthetic agents
Drugs Aspirin
Latex rubber NSAIDS
IV Contrast media
Opioid analgesics
Foods reported as triggers

Peanuts 8
Fish
Shellfish
Eggs
Milk
Rare Causes:
Sesame, Pulses etc Note:
Others Anaphylaxis may be worse in
Exercise those on beta blockers 9
Semen
Vaccines
 35%55% of anaphylaxis is caused by food allergy

6%8% of children have food allergy

1%2% of adults have food allergy

Incidence is increasing

Accidental food exposures are common and

unpredictable
 Children and adults (usually not outgrown):
Peanuts (Beware Atrovent)
Tree nuts
Shellfish
Fish
Additional triggers in children (commonly outgrown):
Milk
Egg
Soy
Wheat
 0.5%5% (13 million) Americans are
sensitive to one or more insect venoms
Incidence is underestimated
Incidence increasing due to fire ants and
Africanized bees
Incidence rising due to more outdoor activities
At least 40100 deaths per year
 Hymenoptera
Bees
Wasps
Yellow jackets
Hornets
Fire ants
Geographical
Honeybees, yellow jackets most common in
East, Midwest, and West regions of US
Wasps, fire ants most common in Southwest
and Gulf Coast
 Normal: Local pain, erythema, mild
swelling
Large local: Extended swelling, erythema
Anaphylaxis: Usual onset within 1520
minutes
Cutaneous: urticaria, flushing, angioedema
Respiratory: dyspnea, stridor
Cardiovascular: hypotension, dizziness, loss of
consciousness
30%60% of patients will experience a
systemic reaction with subsequent stings
 Uniphasic
Biphasic
Recurrence up to 8 hours later
Different in Peds
Descriptions and perceptions are different

Protracted
Hours to days
 biphasic anaphylaxis is defined as return of symptoms after
resolution of initial symptoms, without subsequent allergen exposure
usually, symptoms return within 1 to 8 hours (sometimes longer)
up to 20% of anaphylactic reactions are biphasic
patients with biphasic anaphylaxis may require more epinephrine to
control initial symptoms
in protracted anaphylaxis, symptoms may be continuous for 5-32 hrs

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

 Cellular infiltrates: 3 to 6 hours (LPR)
Eosinophil
CysLTs, GM-CSF,
Histamine IL-4, IL-6 TNF-, IL-1, IL-3, PAF,
ECP, MBP

Allergen
3 to 6 hours Basophil
Histamine,
(CysLTs, PAF, CysLTs, Return
IL-5) TNF-, IL-4, IL-5, IL-6
of
Monocyte Symptoms
PGs CysLTs CysLTs, TNF-,
PAF, IL-1
Proteases

Mast cell Lymphocyte

IL-4, IL-13, IL-5,
IL-3, GM-CSF
EPR 15 min
(Early-Phase Reaction)
Did you ever have a severe allergic reaction:
To any food?

To any medicine?

To an insect sting?

To latex?

Side effect or allergic reaction?

That caused breathing trouble? Severe hives and

swelling? Severe vomiting or diarrhea? Dizziness?

That required you to go to the hospital?
Antigen the foreign protein that when
taken into the body stimulates/formulates
specific protective proteins called
antibodies.
Antibody a protein produced in the
body to response to a specific antigen
(foreign protein) tot destroy or inactivate
the antigen. (IgE)
Coronary vasoconstriction
Bronchoconstriction
Vascular permeability
Intestinal smooth muscle contraction
Dysrhythmias: sinus tach, a-fib, AV, and IVCD
 Antigen (allergen)
exposure
Antigen

Plasma cells
produce IgE antibodies Plasma cell
against the allergen

IgE

Mast cell with

IgE antibodies fixed IgE
attach to mast antibodies
cells
and basophils Granules
containing
histamine
 More of Antigen
same allergen
invades body

Allergen combines

with IgE attached to

Mast cell granules
.


release contents

mast cells and

after antigen binds

basophils,

with IgE antibodies

which triggers

degranulation and

release

of histamine and other

Histamine and

chemical mediators other mediators

 Skin: Flushing, pruritus,
urticaria, angioedema
Upper respiratory:
Congestion, rhinorrhea
Lower respiratory:
Bronchospasm, throat or
chest tightness,
hoarseness, wheezing,
shortness of breath,
cough
 Gastrointestinal tract:
Oral pruritus
Cramps, nausea,
vomiting, diarrhea
Cardiovascular system:
Tachycardia,
bradycardia,
hypotension/shock,
arrhythmias, ischemia,
chest pain
 Pale, diaphoretic skin
Tachycardia
Hypotension
Difficulty breathing
Urticaria
Swelling of face or neck
Stridor, barking or wheezing
Syncope
 Based on clinical simptom

Careful history to identify possible causes

Can be confirmed by serum tryptase

Specific for mast cell degranulation
Remains elevated for up to 6 hours

Other labs to rule out other diagnoses

Refer to allergist for specific testing

 Allergists can identify specific causes by:
Skin tests/RAST
Foods
Insect venoms
Drugs
Challenge tests
Foods
NSAIDs
Exercise
RECOGNISE THE PROBLEM

GET HELP

ABC
Place patient in Trendelenburg position.
Establish and maintain airway.
Give oxygen via nasal cannula as needed.
Place a tourniquet above the reaction site
(insect sting or injection site).
Epinephrine (1:1000) 0.1-0.3 ml at the site of
antigen injection
Start IV with normal saline.
Corticosteroids
Decrease immune response
Methylprednisolone 125mg IV
Hydrocortisone 5-10 mg/kg IV

Antihistamines
Diphenhydramine 0.5 mg/kg IV
Cimetidine 2-5 mg/kg IV
Famotidine

Intubation if needed
Pada dosis tinggi mempengaruhi reseptor

Dominasi reseptor menyebabkan peningkatan

resistensi perifer peningkatan tekanan darah.

Dijantung epinefrin mengaktiasi reseptor 1 pada

otot jantung efek inotropik dan kronotropik

positif memperkuat kontraksi dan mempercepat
relaksasi curah jantung bertambah tapi kerja
jantung dan pemakaian oksigen juga bertambah.
Pemberian epinefrin IV dengan cepat (pada

hewan) menaikkan tekanan darah yang cepat

dan berbanding langsung dengan besarnya
dosis.
Naiknya tekanan darah akibat perangsangan

pada jantung dan kontriksi arteriol kulit,

mukosa dan ginjal serta kontriksi vena.
Pemberian peroral , epinefrin tidak mencapai

dosis terapi karena sebagian besar epinefrin

dirusak oleh enzim COMT dan MAO yang banyak
terdapat pada dinding usus dan hati.
Pada pemberian SC terjadi absorpsi yang

lambat oleh karena vasokonstriksi lokal,

dipercepat dengan masage tempat suntiakan.
Pada pemberian IM absorpsi terjasi lebih cepat.
Epinefrin stabil dalam darah

Metabolisme terjadi di hati oleh enzin COMT

dan MAO
Efek samping: perasaan takut, gelisah, khawatir,

tegang, nyeri kepala berdenyut, tremor, lemah,pucat,

sukar bernafas dan palpitasi. Gejala akan mereda
setelah istirahat.
Epinefrin dapat menyebabkan perdarahan

subarachnoid vasodilator : nitrit atau natriun

nitropusid
Dikontraindikasikan pada penderita yang memakai

bloker non selektif.

Epinephrine has the ability to reverse many of the
effects of histamine release. This is accomplished by:
Constricts arteries
Dilates Bronchioles
Increases Heart Rate
Increases Blood Pressure
Use with caution
Always useful in True Anaphylaxis
IM 0.3-0.5 ml 1:1000 dilution
Contraindications
Hypovolemia shock- correct volume deficit
Use with caution in coronary insufficiency
Dose
Cardiac arrest
1 mg IVP q 3-5 min
2.5 times the normal dose if via ETT
Contraindications
Hypovolemia shock- correct volume deficit
Use with caution in coronary insufficiency
Dose
Cardiac arrest
1 mg IVP q 3-5 min
2.5 times the normal dose if via ETT
Dose
Drips
Mix 1 mg ampule in 500 ml (2 mcg/ml) and infuse at
1-2 mcg/min titrate to desired response
Anaphylactic reaction
Mild- 0.3-0.5 mg (1:1000) IM
Severe- 1-2 ml (1:10000) slow IV
Epinephrine:

Dose:
Adults 0.5 1 mg IM repeated at 5 min intervals if no imp

Children:

> 12 years : up to 500 micrograms IM (0.5 mL 1:1000 solu

250 micrograms if child is small or prepubertal

6 - 12 years: 250 micrograms IM (0.25 mL 1:1000 solution)

>6months-6years: 120 micrograms IM (0.12 mL 1: 1000

< 6 months: 50 micrograms IM (0.05 mL, absolute accuracy

Note:

IV use is hazardous and should only be used by those trai

IM means deep IM (thigh, buttock or deltoid)
Immediate treatment with
epinephrine imperative
No contraindications in
anaphylaxis
Failure or delay associated with
fatalities
IM may produce more rapid,
higher peak levels vs SC
Must be available at all times
Administer one injection from the Epi Pen
In upper arm or lateral thigh
Delivers a smaller dose (0.3 mg) than the ALS
dosage, and should be used only by BLS units
* EpiPen 2-Pak was launched in April
2001
How to Hold
Form a fist around the
center of the unit
Pull off gray activation cap

How to Use
Hold black tip near outer
thigh (always apply to thigh)

Count to 10
Swing and jab into outer
thigh. Hold in place and
count to 10
EpiPen /EpiPen Jr:
Directions for Use
Chlorpheniramine

H1 blockers should be used in all anaphylactic reactions

They counteract the histamine release from mast cells

Their use should come after epinephrine or if reaction is

Dose

Adult 10-20 mg IM or IV
Side effects

Sedative effect
Hydrocortisone

Still some discussion as to its usefulness still recommen

Effects are not useful until about 3-4 hours after administ

May help prevent biphasic or protracted attacks

Useful in anaphylaxis in those with asthma

Dose 100 - 500mg IM or IV

Important points to note:

Adrenaline is underused

Adrenaline reverses nearly all anaphylactic reactions

Other supportive measures include

Oxygen
Salbutamol 10

IV Fluids
Monitoring