PART XV. Allergic Disorder
Chap 133. Allergy and Immunologic Basis of Atopic Disease
#
Allergy
; specific, acquired change
in host reactivity *mediated by an
immunologic mechanism & causing an toward physiologic response
#
*not all antigen are good allergens
#
★Common Characteristics Of Allergens
; protein in part
; acidic with molecular
weight of 10000-70000 daltons
#
Atopy
; hereditary factor
-
expressed as susceptibility to hay fever, asthma, & eczematoid dermatitis
in the families of affected individuals
; ass. with HLA types
; ass. with chromosome 11q13
#
★Immunologic difference in atopy vs non-atopy
; *predisposition to selective synthesis of IgE Ab.to common
environmental Ag.
; defective control of
mediator release or generation
; impaired mediator
inactivation processes
#
ÅType of Immunologic reaction to the reactants
; interaction of humoral Ab.
with Ag.
-
3 forms
/
two occurs on surface of cell an third in extracellular fluid
; interaction of Ag. with
lymphocytes (=cell-mediated or delayed type hypersensitivity)
Type I Hypersensitivity, Mediated By Ige
(=immediate
type or anaphylactic hypersensitivity)
;
occurs on cell surface
;
*circulating basophils and tissue
mast cell
--> sensitized through the
binding of IgE Ab. to their surface receptors
--> allergen interaction
with cell-bound IgE antibody molecules
--> immune tissue injury.
#
Ultimate Outcome Contributing Factors
; broad spectrum of secondary events
involving types of lymphoid cells, inflammatory cells, mediator-producing cells
; soluble products derived
not only from all of these cells but from other tissues(platelets, endothelial
cells) at site of reactions
#
★Reaginic IgE, IgE Reagins, Homocytotrophic Antibodies
; molecules with activities
against specific allergen
; cf) nonspecific IgE
-
found in the serum & tissues of all normal individual
-
*defend against tissue-invasive
parasites
; ass. with HLA-linked immune
response(IR) genes
-
ragweed antigen Ra3 and HLA-A2
-
ragweed antigen Ra5 and HLA-B7
-
rye grass antigen I and HLA-B8
Formation of IgE reagins
㉿Fig.
133-1 을 먼저
이해한 후
본문 숙독
#
IL-1
; activation of presentation
antigen to CD4 (helper T cell) cells
#
*CD4 cells은 TH2로 분화하여 IL-3, IL-4, IL-5,GM-CSF을 합성분비한다.
#
IL-4
; *isotype switching of B-cell에 중요한
역활
-
IgG & IgM --> IgE
-
IgE 합성에 *IL-5(non-isotype
B cell growh factor) & IL-6(non-isotype B cell differentiation factor)도
필요하다.
#
IL-5 & GM-CSF
; induce eosinophil
differentiation
#
IL-3 & IL-4
; mast cell growth factor
#
♥Gamma Interferon
; *inhibit IL-4-dependent IgE synthesis
; *inhibit IL-4 induced expression of low-affinity IgE receptors(CD23)
on B cell
Binding Of Ige Reagins To Mast Cells Or Basophils
;
revisibly or fixed binding to surface receptors of mast cell or basophils
#
receptors(FER)
; involve C4 & C3 domains
of Fc portion of Ig molecule
; nonatopy - 20-50% occupied
by IgE
; atopy - 100% occupied
#
“sensitized”되었다고 말한다.
Events After Allergen-IgE Reagins Bindings
#
Biochemical Reation
; activation of
methyltransferase, phospholipid methylation, Ca++ influx, activation of phospholipid
diacylglycerol cycle
--> fusion of mast cell
granules with plama membrane
--> release of active
substances(chemical mediators)
#
Tissue reation by mediator-binding tissue receptor
; reversible
; mast cell, basophils not
lysed
; *no participation of complement system
; early phase - 6~8hr
; late phase - 12~48hr
#
Interaction of Cytokines with endothelial cell
; activated by IL-1
-->
upregulation of endothelial adhesion molecules(eg, E-selectin, ICAM-1, VCAM-1)
; activated by IL-4
-->
upregulation of VCAM-1.
; *lecitin-binding regions of selectins interacts with ligands on
leukocytes
-->
rolling over endothelial cells
-->
interacts with *integrins, ICAM-1,
VCAM-1
-->
arrest leukocytes
-->
facilitate movement out of vasculatures
#
*Ligand For VCAM-1
; *very late activation antigen-4
#
ÅHistamine이 일으키는
생체 반응 3가지
; increased capillary
permeability
; increased capillary
dilatation
; axon reflex stimulation
--> familiar wheal &
flare reaction
#
★Examples
; ragweed hay fever,
anaphylactic reaction to insect venom, food-induced urticaria, allergic
conjunctivitis or rhinitis
Type II Hypersensitivity (Cytotoxic) Interaction
;
occur on cell surface
;
*IgG or IgM reacts with allergens
;
*activates complement system
#
Examples
; transfusion of incompatible
RBC
- recipient's isohemagglutinin
(Ab. directed against determinants
on the surface of RBC) react
with the incompatible cells
-->
complement system activation
-->
sequential action of complement proteins
-->
Iysis cell
; drug-induced immune
hemolytic anemia
Type III Immunopathologic
Mechanism
;
*occurs in extracellular space
;
Ag-Ab. complex
--> lodge in the filtering
organs of body(kidney,lung)
--> infiltrate the wall of
small blood vessels
--> *activation of complement cascade
--> release of
biologically active substance
-->
chemotaxis for PMN leukocytes
--> *phagocytosis of complex
-->
release of basic protein & proteolytic enzymes from damage tissue
#
Different Ab도 관여
; leakiness of capillaries
-->
toxic complex의 축적을 용이하게 한다.
#
Examples
; *serum sickness, immune complex pericarditis or arthritis,
glomerulonephritis
Type IV Cell-Mediated Or Delayed-Type
Hypersensitivity
;
innteraction of Ag.with specifically sensitized T Iymphocyte
--> macrophage와
cytotoxic cell이 중요한 역할을 하는 것으로만 알려져 있다.
#
Examples
; *contact allergy, tuberculin reactivity, GVHD, tissue,
transplantation reaction, infiltrative hypersensitivity lung ds
1331.1 Chemical Mediators Of Alleric Reactions & Mechanisms Of
Realse
#
★Mast cell & basophils involved condition
; *IgE mediated reaction, chronic inflammatory disorders, rheumatoid
arthritis, parasitic infection
#
♥Activator Of Mast Cell
; cross-linking of
receptor-bound IgE Ab. by multivalent specific Ag.
; purified Ab to IgE receptor
; *complement system (C3a, C5a)
;
kinins
; *neutrophil-derived lysosomal basic
protein
;
lymphokines
#
★Biochemical Reaction Resulting Fusion Of Granule To Plasma
Membrane
; change in membrane
phospholipid metabolism
-
methylation and activation of phospholipases
-
generation of phospholipid by-products
--> leading to extrusion
of mast cell granules
#
Biochemical Reaction during Mediator Release
; activation of serine
esterase
;
utilization of intracellular energy store
;
calcium influx or remobilization of intracellular calcium
; change
in the mast cell cytoskeleton
#
♨Preformed Mediators
; histamine, eosinophil
chemotactic factor , HMV-NCF, heparin, arylsulfatase B, trypsin, chymotrypsin,
inflammatory factors
#
♨Newly performed mediators
;
♥Table 133-1
#
★Early phase에 관여하는 Mediators
; histamine, ECF, other
chemotactic factors
#
★Early & Late Phase에 관여하는 Mediators
; heparin, arylsulfatase B,
enzyme such as trypsin, chymotrypsin, inflammatory factors
#
★cAMP
; increase in intracellular
conc.
-->
inhibition of release of mediators from mast cell
; prostaglandin E &
beta-adrenergic agonist
-->
increase in cAMP
Factors Not Mast Cell-derived That Participate in Immediate-Type
Hypersensitivity Diseases
★Eosinophil- Derived Molecule
; eosinophil major basic
protein (MBP)
; eosinophil peroxidase (EPO)
; eosinophil-derived
neurotoxin (EDN)
; eosinophil cationic protein
(ECP)
#
Eosinophil Major Basic Protein (MBP)
; destruction of airway
epithelium을 야기하여 bronchial hyperresponsiveness발생&
basophil에서 histamine release자극
->
wheal & flare rx야기
eg)
asthma, atopic dermatitis, chronic urticaria
Kinins
-
amplifier & effector property
:chemotaxis, increased vascular
permeability, & smooth m.
contraction
bradykinin - the most important product
of kinin system
potent contractile effect on smooth m., increased vascular permeability&
dilates peripheral arteioles
(특히 cold urticaria시 증가)
stimulate pain receptor
kinin
generation & amplification
:
activation of Hageman factor (factor X11) - initial step
--activated
by tissue injury from IgG aggregates & immune complex
-
converts prekallikrein to kallikrein
-
kallikrein digest high molecular wt. kininogen to liberate
vasoactive peptide bradykinin
Platelet-Activating Factor (PAF)
synthesized
by vascular endothelial cell, monocytes, macrophage, neultrophil. eosinophil
& platelet
poten inducer of increased vascular
permeability
bronchial
hyperresponsiveness in normal subject
late
phase reaction 야기
Type I Hypersensitivity Reaction
#
♨Early Phase Reaction
; 10-30 min
;
d/t release of performed & newly synthetized mast cell mediators
;
vasodilation, edema from increased vascular permeability, smooth m.
constriction (bronchoconstriction), mucus production
; treated with antihistamine
& mast cell memb. stabilizer
#
♨Late-Phase Reaction
; 4-8 hr
; recruitment of inflammatory
cell
-
eosinophil, neutrophil, lyrnphocyte located in the perivascular space
; erythema, edema,
induration, hyperirritability to rechallenge with allergen
; contribute to
hyperresponsiveness in allergic children with asthma, rhinitis & atopic
dermatitis
; poorly respond to
antihistamine or bronchodilator but may respond to coriticosteroids
Serotonin ( 5-hydrotytryptamine)
:
vasoactive amine
smooth m. contraction & increased
vascular permeability
90% of body stores; G-I tract
human mast cell내에는 거의 없음.
diarrhea in carcinoid syndrome
induce bronchoconstriction in asthmatics
but not in normal subjects
#
certain components of complement system have activities that may contrbute to
allergic reaction
1) aggregated IgE can
initiate alternative pathway in vitro
2) C3a, C5a induce mediator
release from basophil, mast cell
-->
wheal & flare reaction
3) C2 mediate angioedema in
hereditory angioedema
#
★Anaphylatoxin
; *C3a, C5a을 말함
; chemotactic activity도 가지고 있음.
Chapter 134. Diagnosis
General and Specific Method of Diagnosis
Allergy History
Å병력조사의 중요성을
설명하고, 중점적으로
알아보아야할 4가지
;
nature of inquiries into possible causes of sympom
- detailed history fo “exposure”
to potential allergens
Seasonal Symptom
eg) pollen
perenial Sx eg) houst dust
house dust mites - house dust에서 주
allergen
occurs at the
end of summer because high humidity favors
mites proliferation
Relationship Between Symptom And Where They Occur
pollen;
outdoor에서 더 흔함
allergy to fungi - worsening of
symptoms in a damp, musty
Association Between Symptom And Certain Activities
소아에서 strenous exercise후
coughing or wheezing->asthma
provocatin of coughing by
laughter, crying or exposure to smoke
or specific odors suggests the
bronchial hyperresponsiveness
characteristic of asthma
Nature Of Sx
intermittent recurrent,dry or cough
productive clear mucus
-> asthma
cf) chronic persistent cough productive
purulent sputum
-> bronchiectasis or cystic fibrosis
Allergic Rhinitis
-> chronic or recurrent clear nasal
discharge
sneezing or conjunctival
itching & injection with excessive tearing
Vernal conjunctivitis
-intense
conjunctival itching asso. with photophobia and a viscid, white
conjunctival
discharge
Any Beneficial Or Adverse Effects Of Previous
Treatment
이전 치료의 부작용과 advantage에 대한 병력 중요
Immediate Fhx
eg)
atopic dermatitis
Phsical Examination
1)
Height & Weight
2)
pulsus paradoxus --acute asthma시 airway obstruction의
severity index.
(20mmHg이상->moderate or severe aw
obstruction)
그외 cystic fibrosis
heart failure
cardiac tamponade
3)
cyanosis; SaO2 <85%
4)
supraclavicular & intercostal retraction
5)
flaring of alae nasi
6)
dyspnea
7)
mouth breathing
8)
allergic shiners - dark discolaration of lower eyelid
9)
allergic salute - habitual wiping of the running nose
10)Dennie
lines .(Dennie-Morgan folds) - wrinkle beneath the lower eyelids. all rhinitis,
asthma, atopic dematitis
11)digitai
clubbing - comparison of the depth of the index finger at the base of the nail
with its depth at the distal interphalangeal joint (Table 134-1)
normal : depth at the base -
smaller
12)Inspection
of skin
atopic dermititis - erythematous
maculopapular eruption, fine scaling, or weeping&
oozing with excoriation due to frequent scratching
Urticaria lesion - cholinergic
urticaria, angioedema, dermographism
contact dematitis
13)
Exam of eye
allergic conjunctivitis : excessice
tesring, periorbital edema
vernal conjunctivitis : tenacious
ropy,mucoid conjunctival discharge
14)
nasal mucosa : pale,blue or pink
15)
Exam of chest : A-P diameter증가
In Vitro Tests
Total Eosinophil Count
;
diurnal rhythm & intermittent
- highest in the early
morning
- *2-3번의 검사를
해서 eosinophilia로
진단한다.
;
*more accurate than PBS
;
normal - 250-700/mm3
;
*in allergic condition, not exceed
15-20%
- rarely 35% in allergic
children
;
♨DDx
- drug hypersensitivity,
rheumatologic disorders, pemphigus, dermatitis herpetiformis, inherited
eosinophilia, allergic bronchopulmonary spergillosis, various
malignancy(leukemia, lymphoma, Hodgkin disease), eosinophilic fascitis, toxic
oil syndrome, eosinophilic-myaligia syndrome(associated with L-tryptophan)
;
♨very high eosinophil count
- parasitic infection with *tissue-invading helminths(Toxocara,
trichinosis, Echinococcus, Ascaris), malaria, hypereosinophilic
syndrome
ÅEosinophilia Of Respiratory
Secretion : 의의 설명
; hansen stain - eosin-methylene blue stain
;
smear of nasal secretions or bronchial mucus
;
*suggest diagnosis
;
*allergic rhinitis - 5-l0% eosinophil
in nasal secretion
;
*bronchial asthma - eosinophil in
bronchial mucus
♨Total IgE Content Of Serum : 진단적 가치
;
variable in age
- Table 134-2
;
usually higher than normal
- DDx 해야 한다. Table 134-1
- atopy라 하여 반드시 증가하지는
않는다.
;
*very low level이면 excluding atopic disease
- atopy라 하여도
very low level일 수도 있다.
;
increased total IgE during infancy
- suggest the likelihood of
subsequent development of atopic disease
Radioallergosorbent Test (RAST)
;
Ag.-specific IgE concentrations in serum
;
good correlation with medical histories, provocation tests, leukocyte histamine
release tests, allergy skin testing
;
*less sensitive than skin testing
Leukocyte Histamine Release Test
detect
specific IgE Ab. attached to the surfaces of peripheral bl. basophils by
measuring the amount of histamine released in response to challenge with Ag.
Histamine분비량은
allergen양에 따라 다르며 cell내의
total histamine의 percentage를 반영.
Skin
test가 더 sensitive
In Vivo Tests
ÅSkin Testing : 종류, 방법, 특징
;
important tool in Dx of IgE mediated sensitivity
#
종류
; prick/puncture skin testing
; intradermal skin testing
; patch skin testing - late
phase 검사
#
positive intradermal reaction
; *at least 5 mm of induration plus surrounding erythema, occuring 15
mm after injection of Ag.
; immediate wheal & flare
reation peak in 15-30min
; *indicate presence of specific IgE Ab on mast cell
; *allergen에 노출시
반드시 Sx을
가진다는 것을
가리키는 것은
아니다.
#
*positive puncture skin test
correlate better than more sensitive intradermal tests with specific IgE Ab
& appearance of clinical symptom
Å위양성과 위음성을
찾은 방법과
이들의 유발
조건
#
Pseudopositive
; histamine & normal
saline control
; irritant materials in
extracts
; improper technique -->
nonimmunologic hitamine release
#
Pseudonegative
; ★drugs
medication
-
adrenergic drug (epinephrine & ephedrine) at least 12 hr withhold
-
antihistamine at least 72 hrs
-
*hydroxyzine for 5 days
-
*astemizole for 2 month
; corticosteroid
-
*no appreciable inhibitory effect on
IgE-mediated reaction
-
*systemic corticosteroids for 1yr
-->
suppress cutaneous reactivity to codein(but not to histamine)
:
suggesting suppresion of histamine release
Provocation Testing
Å실시하는 이유
; skin test results가
clinical sympton on natural exposure과 일치하지 않을 경우
; 진단이 불확실한 경우
; 면역 치료에 사용할
allergen선택을 위해
#
종류
; mucous membrane provocation
testing
; bronchial challenge testing
; bronchial provocation
testing with methanecholine or histamine
; oral provocation test
Chapter 135. Principles of Treatment
#
Å4 Principle Of Successful Management Of Allergic Disorders
1. avoidance of allergens or
irritants
2. pharmacologic therapy
3. immunotherapy
(hyposensitization or desensitization)
4 prophylaxis
#
avoidance to house dust mites
; *household humidity < 50%
ÅProphylaxis
;
high allergenic potential individuals의 screening
- *infants born into families with strong histories of hay fever,
asthma. or atopic dermatitis
- *cord blood IgE level > 1.3 lU/mL, elevated serum IgE levels,
eosinophilia during infancy
--> recommend
breast-feeding for *at least 6 mo
avoid
foods of highly allergenic potential such as eggs, cow milk, wheat, fish,
citrus fruit and peanut butter
nursing
mother should avoid highly allergenic foods in her diet
;
avoidance of environmental exposure for sensitized & asthma patients
135.1 Pharmacologic Therapy
♨Adrenergics : 아드레날린 계열의 약물을 분류, 각각의 약리작용 및 부작용
#
α-receptor : excitatory
; vasoconstriction
;
reduces edema of nasal mucous membranes through vasoconstriction & decrease
the permeability of venules & capillaries
#
α-receptor
;
alpha 1 - contract vascular & airway smooth m.
; alpha 2 -
#
β-receptor : inhibitory
; bronchodilation, smooth m.
relaxation
#
β-receptor
;
beta1 - equal affinity for epinephrine & norepinephrine
;
beta2
-
10-fold higher affinity for epinephrine than NE
-
*beta2-selective agonist
:
isoetharine, metaproterenol,
terbutaline, albuterol, fenoterol, bitolterol, pirbuterol, salmeterol
-
*effective bronchodilation in asthma
without significant increase in HR
-
*S/E : skeletal m.tremor,
glycogenolysis, hypokalemia
#
Adrenergic Drug종류
1) catecholamines
;
Epi, isoetharine, isoproterenol, bitolterol
;
rapidly inactivated by enzymes in GI tract & liver
;
*limited to injection, inhalation,
topical application
2) noncatecholamines
;
ephedrine, pirbuterol, procaterol, fenoterol
;
relatively weak β-stimulant activity, frequently
S/E
;
*S/E - insomia, irritbility, headache
3) newer noncatecholamines
;
★terbutaline, albuterol, salmeterol, metaproterenol
;
*relativiely selective activity on β-2 receptors and less cardiovascular effects
;
longer duration than ephedrine
-
salmeterol
/
*very long acting
/
inhalation of a single dose --> 12hr bronchodilatation
:
inhibit both immediate & late-phase reactions
:
inhibit allergen induced bronchial hyper-responsiveness
;
*inhalation시 lower dose로 몇배의
효과와 부작용의
최소화로 가능한한 aerosol administration
#
★Autoantibodies Against β2-Receptors
; asthma, CF, a few normal 에서 발견
; ass. with β-adrenergic
hyporesponsiveness
-->
tolerance & desensitization
; no serious therapeutic
implications
#
★Adverse Side Effects
; skeletal m. tremor, cardiac
stimulation, worsening of hypoxemia, headache. insomnia, increased airway
obst., irritability, nausea, vomiting. epigastric pain, flushing,
tolerance(subsensitivity, refractoriness)
#
Nebulization에도 불구하고 bronchoconstriction발생할 때 고려해야 할 점
; ★Benzalkonium
chloride
-
*preservative in most albuterol &
metaproterenol nebulization solutions
-
occasionally bronchoconstriction
-
metered-dose inhalers으로 대치
; ★Metabisulfite
-
stabilizing agents in solution for nebulization
-
bronchoconstriction
♨Theophylline : 작용기전, 부작용, 투여시 주의사항
;
use fo both chronic & acute asthma
#
♥Mode Of Action
; adenosine antagonism
; effect on calcium flux
across cell membrane
; prostaglandins antagonism
; release of or synergistic
interactions with beta adrenergic agonist
; enhancement of binding of
cAMP to a cAMP-binding protein
#
♥Effects
1. bronchodilation by
relaxing bronchial smooth m.
2. increases concentration of
endogenous catecholamine in the circulation
3. enhance the contractility
of the fatigued diaphragm
4. inhibit both immediate
& late-phase asthmatic response to allergic challenge
5. sometimes reduce bronchial
hyperresponsiveness
#
*therapeutic & toxic effect 모두 serum concentration과 연관되어
있다.
; *serum level of toxic effect - 20 ug/mL 이상
; *measurement of serum theophylline concentration
-
*15-min method : excellent result
-
*saliva collection : 60% in serum
Pharmachokinetics
★Table
135-1, 135-2
#
종류
; rapidly absorbed formula
; slow-release (SR) formula
-
TheoDur tablets, Slo-bid Gyrocaps, TeoDur Sprinkle, Uniphyl, Teolair-SR
#
*식사에 의한
영향을 받는다.
; *RAF 는 no effect
; *SRF 는 accelerated or delayed
-
TheoDur tablets or Slo-bid Gyrocaps
/
peak serum conc.이 늦어지지만, no effect on
bioavailability
-
TheoDur Sprinkle
/
50% bioavailability 감소
-
Uniphyl
/
double absorption rate
; *TheoDur tablets or Slo-bid Gyrocaps을
제외한 SRF는
식전 60분에
투여하는 것을
원칙
#
peak serum concentrations
; most SRF는
4-6hr after administration
; SRF가
RAF보다 no fluctuations
-
*12hr interval로
투여시에는 있을
수 있으므로 8hr interval로 투여를
원칙
Pharmacodynamics
;
logarithmic relationship between theophylline bronchodilator effect and serum
concentration
- *5-20 ug/mL
Toxicity
#
Symptom & sign of acute intoxication
; variable
-
nausea, insomnia, irritability, tremor, headache, seizure & death
; Gl symptoms
-
*N/V, hematemesis, cramping
-
*ealiest sign & precede the more
serious CNS manifestation
; disturbance in cardiac rate
-
tachycardia, arrhythmia(APC, VPC), hypotension
-
*serious toxicity때
흔히 나타난다.
; hypokalemia, hyperglycemia,
ataxia, hallucanations.
#
Treatment of intoxication
; induce emesis or gavage
; *activated charcoal
-
*also remove serum theophylline
-
ipecac을 사용할 경우에는 emesis가 일어날 때까지
charcol투여를 delay
; nonabsorbed saline
cathartics
; peritoneal dialysis
; hemoperfusion using a
specially prepared column
-
*method of choice
; diazepam for seizure
; propranolol for hypotension
or supraventricular or ventricular arrhythmia
; lidocaine for ventricular
tachycardia
; ranitidine for gastric
acid-induced emesis
#
chronic theophylline use
; subtle behavioral change
-
hyperactivity & sleep disturbance
-
no adverse effect on congnitive function.
Antihistmine
#
3 Histamine Receptors
; H1, H2, H3 receptors
#
H1-Receptor Blocker
; initially used in treatment
of allergic disorders
#
*Combination of Hl & H2
Antagonist
; beneficial some patients
with *chronic urticaria,
anaphylactoid reaction(e.g., IV contrast media)
#
H2-Receptor Blocker
; cimetidine, ranitidine
; *inhibit delayed-type hypersensitivity skin response
-->
suggesting modulation of CMI
#
♨Classification : 투여시 주의사항
1) First Generation
Antihistamines
Type
I - ethylenediamines
Type
II - ethanolamine
Type
III - alkylamine
Type
IV - piperazine
Type
V - piperidines
Type
VI - phenothiazines
2) Hydroxyzine
3) Second Generation
Antihistamines
;
*terfenadine, astemizole, loratadine,
cetirizine(active metabolite of hydroxyzine)
#
2nd generation antihistaminse의 특징
; effective suppressing sign
& symptoms of allergic rhinitis
;
do not cross the BBB - less sedative effect
#
Antihistamine의 chemical classification은
no functional significance
; *except) cyproheptadine - antiserotonine activity
#
Bioavailability
; rapidly absorbed through GI
tract
; onset of action within 30
min
; peak plasma concentration
within 1hr
; complete absorption within
4hr
; mostly metabolized in liver
; *little correlation between serum concentration and therapeutic
effect in tissue
-
suppressing the wheal & flare response over 24hr
-
chloropheniramine
/
mean serum half-life of 13.7hr but significant suppression of clincial symptom
as long as 30hr
-
*cholorpheniramine, bromopheniramine,
hydroxyzine
/
*twice or even once a day
more effective in preventing than in
reversing the action of histamine
#
♥Allergy(Asthma)에서
Antihistamine을 선택하지
않는 이유
; act as competitive
antagonists
-
less potent in antagonizing effect of histamine
; lung에서
allergic reaction은 histanine보다는
bronchoconstriction을 야기하는 다른 mediator가 관련
#
*소아에서
asthma의 course에
이롭지도 해롭지도
않다
#
★Adverse Effects
1) exocrine secretion
2) CNS
;
sedatives
;
drowsiness
;
1st generation에 흔함.
3) cardiovascular system
;
1st & 2nd generation 모두 나타날 수 있다.
;
prolongation of QT interval, ventricular tachycardia, cardiac arrest
;
*loratadine은
아직 보고되지
않았다.
4) anticholinergic effect
;
excitation, nervousness, tachycardia, palpitations, dryness of the mouth,
urinary retention, constipation
5) others
;
seizures, skin eruptions, blood dyscrasias, fever, neuropathy
#
★Increased risk for adverse effects
; impaired hepatic function
; concurrent treatment of
inhibitor of cytochrome P450enzyme
-
Erythromycin, macrolide AB, ketoconazole, itraconazole
#
antihistamine은 CNS depressants와 병용해서 사용하면 않됨
Cromolyn Sodium (Disodium Cromoglycate)
;
disodium salt of 1,3,-bis(2-carboxychromon-5-yloxy)-2-hydroxypropane
;
chemical analog of drug khellin
;
투여 방법
- powder(Intal) with special
turboinhaler, Spinhaler
- 1%(20mg/ml) solution for
neubulization
- metered-dose
inhaler(800ug/actuation)
#
ÅIndication
; *pricipally in asthma for prophylaxis
-
*20mg two to four times each day by
Spinhaler or nebulization
-
*1.6mg two to four times each day by
metered-dose inhaler
; allergic rhinitis
; aphthous ulcer, food
allergy, systemic mastocytosis, ulcerative collitis, chronic procitis
#
ÅAction Mechanism & Effect
; *no bronchodilator effect
; *no antimediator or antiinflammatory effect
1) prevent both Ab-mediated
& non-Ab-mediated mast cell degranulation & mediator- release
;
due to block Ag-stimulated calcium transport across the the mast cell memhrane
;
due to regulation of phosphorylation of mast cell protein
;
due to weak phosphodiesterase inhibitor activity
;
*no effect on basophils or cutaneous
mast cells
2) reduce airway hyperrectivity
; unknown mechanism
3) prevent late-phase asthmatic responses
4) inhibit bronchocontriction produced by nonimmunologic stimuli
;
due to directly neural control of airway by inhibiting reflex
bronchoconstriction through *inhibition of
transmission of neural impulses by myelinated afferent nerve fibers
# *▲Great Value Of Cromolyn Sodium
; allergic or extrinsic asthma
#
★Side Effect
; extremely low incidence
; dry throat, transient
bronchoconstriction
-
*▲frequently
-
due to inhalation of dry powder not
intrinsic effect of drug
; rare - urticaria,
angioedema, pul. eosinophilia
Nedrocromil sodium
antiallergic
& antiinflammatory activity를 가짐
new
agent that inhibit early- & late-phase responses after Ag. challenge
#
action
1.
inhibit release of mediator from human lung mast cells &
supresses activation of neutrophil.
macrophage.
2.
inhibit bronchoconstrictive effects of exercise
#
Adverse effect
unpleasant taste. coughing,
sorethroat,headache,nausea, rhinitis
Lodoxamide tromethamine
:mast
cell stabilizer more effective than cromolyn sodium in allergic
ocular disease
Ix;
2세 이상에서 vernal
keratoconjunctivitis, vernal conjunctivitis,
vernal keratitis.
adverse
effect; burning or sttringing
Corticosteroids
;
*▲potent
drugs available for treatment of allergic disorder
#
bioavailability of prednisone
; 80% of oral dose
; interconversion to
prednisolone(active form)
; peak plasma conc. at 1-2hr
; little effect of liver
disease or renal insufficiency
#
bioavailability of prednisolone
; effect within 2hr
-
fall in eosinophil. lymphocyte
;
maybe delaye effect 6-8 hr or longer
-
hyperglycemia, improvement in pul. function in asthamatics
-
reflect the indirect mechanism of action of glucocorticoid
#
Step Leading To Activity
1) simple diffusion through
the cell membrane
2) binding to cytosol
glucocorticoid receptors
3) translocation of the
steroid-receptor complex to the nucleus
4) binding of the complex to
chromatin, which affects nuclear gene expression
5) subsequent synthesis of
messenger RNA & protein with enzyme activity
#
phenobarbital & phenytoin
; increase steroid clearance
#
ÅAnti-Inflammatory Actions Of Glucocorticoids Result From
1) alteration in leukocyte
number & activity
;
redistribution
;
suppression of migration to sites of inflammation
;
decreased response to mitogens
;
decreased cytotoxicity
;
suppression of delayed hypersensitivity responses in the skin
2) surppression of mediator
release
;
decreased histamine synthesis & release
;
decreased synthesis of prostaglandine & other product of arachidonic acid
metabolism
3) enhanced response to
agents that increase cAMP
;
PGE3, histamine via H2 receptor
4) enhanced response to
catecholamine
;
increased systhesis of beta-adrenergic receptor
;
increased availability of epinephrine due to decreased extraneuronal uptake of
catecholamine
#
chronic administration
; reduce total Ig
concetration
Topical steroid
;
direct local effect
- decreased inflammation,
edema, mucus production, vascular permiability & mucosal IgE level
- less accumulation of
neutrophil, eosinophils, basophils, mast cells
- attenuation of airway
hyper-responsiveness
;
reduce early-& late-phase reaction
- *systemic steroid는 late-phase eaction을
주로 inhibition
#
Complication of Inhaled steroid
;
oropharyngeal candidiasis, dysphonia
; suppression of H-P-A axis
at high dose
#
Growth Impairment
; more than 400ug at total
daily dose
; *depend on dosage and duration
; possible normal height
after discontinuation
4)
long-term use Cx
- mc adverse effects: suppression of
linear growth
- Post. subcapsular cataracts
- osteoporosis, hypertension, DM,
cushingoid habitus, infection(disseminated varicella or Pneumocystis
carinii),pancreatitis, gastritis, myopathy.
#
㉿Considerations
In The Systemic Use Of Corticosteroids
1) when given in equivalent
anti-inflammatory doses, available drugs *do
not differ qualitavely in anti-inflammatory effects
;
adverse effects are related to dose, dosing interval. & duration of
treatment
;
oral administration
-
predenisone, prednisolone
;
iv administration
-
methylprednisolone, hydrocortisone
2) when corticosteroid
therapy is initiated, *sufficient
amount should be given in 3-4 divided doses to bring the disease under
control
;
whenever possible, alternate-day regimens using
-
prednisone & prednisolone every 48hr
-
single dose between 6:00 and 8:00 a.m.
;
adult data
-
single dose at 3:00 p.m.
-
better control of asthma esp. nocturnal asthma
3) short-term steroid therapy
(<7 days) suppress the pituitary-adrenal axis only briefly and *can be stopped abrouptly without
tapering dose
Additional Pharmacologic Agents
(1)
anticholinergic agent having antimuscarinic activity
adjuvant aerosol therapy로 이용
atropine sulfate, ipratropium
bromide
bronchodialtor effect - not as
great as sympathomimetic agents
(2)
ketotifen, benzocyclohepatathiophine
antihistamine with mast
cell-stabilizing property
leukotriene antagonism
inhibit IgE-dependent medidator
release.
attenuate platelet activating
factor-induced bronchoconstriction
(3)
calcium channel blocking agent, nifedipine
block bronchoconstriction due to
allergy, exercise, PGF2, LT C4 & D4, cold air,
histamine, methacholine
(4)
methotrexate
135.2 Immunotherapy
♨Immunologic Change
1)
appearance of Ab of the lgG class
; blocking or Ag-binding Ab
; ultimate titer is related
to the quantity of extract injected
-
but does *not correlate with clinical
change
2)
*inhihit histamine release from
leukocytes (basophils)
; ★“desensitized”
; unknown basis
; *not related to titers of Ig E or Ig G
3)
change in ratios of helper to suppressor T cell
; *increase in antigen-specific suppressor T-cell
4)
inhibit the late-phase asthmatic response
Studies Of Efficacy
#
고려해야 할점
; cost of immunotherapy
; inconvenience
; the possibility of the
disease worsening
; the risk of inducing
anaphylaxis
#
★효과가
인정된 Allergens
; *ragweed, grass, tree pollen, house dust mite, Alternaria, maountain
cedar, Clasdosporium, cat allergen
#
효과가 인정되지 않은 allergens
; danders (dog, horse), most
molds, bacterial vaccines, occupational allergens, synthetic Ag, whole-insect
extracts, food extracts
#
*multiple allergen 을
가진 경우에는 not effective
Indications, Materials, And Procedure
#
ÅIndication
1) allergic rhinitis
2)
IgE-mediated asthma
3)
allergy to stinging insect
#
*atopic dermatis & food allergy는 not effective
#
♥Candidate For A Trial Of Immunotherapy
;
good correlation between symptom and inhalant allergen that cannot be avoided
; evidence o IgE-mediated
allergy
- either skin test or in
vitro test
;
disabling symptom are not easily controled with medication
#
Extracts
; *▲common used extracts -
aqueous extracts
single injection에
1O가지 이내의 allergen이 포함되어야
함
high-dose therapy는 allergen의 수가 적을때 효과적
children tolerate the same doses as adult
#
failure to see a local reaction at any time의 의미
1. the pt. is not allergic to the constituents
of the extract
2. the extract is inactive
#
Procedures
1) conventional methods
2) “rush” methods
3) perennial methods
#
Beneficial Results
; *6개월 이후에
나타남
#
★Duration Of Treatment
; *치료후 3년동안
의미있는 증상의
호전을 보이면
치료를 중단할
수 있다.
; *치료를 계속해도 2년내 증상의
호전이 없는
경우에는 치료를
중단해야 한다.
Precaution And Adverse Reactlons
;
*obsevation for at least 20min after
each injection
;
*no short- or long-term adverse
effects except for consitutional symptoms
Respiratory Allergy
respiratory
tract - most frequently affected by allergic disorders during childhooa
Chap 136. Allergic Rhinitis
#
seasonal allergic rhinitis, seasonal pollinosis,& hay fever
-
a symptom complex seen in children who have become sensitized to wind-borne pollens of
trees, grasses, & weed
#
increasing prevalence with age
#
ragweed hay fever is rare before 4-5yr
#
perennial allergic rhinitis
#
*Indoor Inhalant Allergens
; *▲often
; house dust, feathers,
allergens or danders of household pets, mold spores
#
Prognosis
; not good
; *only 10% symptom free after 8-11 yr
; *19% asthma or wheezing
Pathophysiology
Ag.
are deposited on the nasal mucosa
-
water-soluble Ag. diffuse into the epithelium
-
in genetically predisposed atropic individual, initiate the production or local IgE
-
IgE stimulated release of mast cell mediators, synthesis of new mast cell mediators
-
subsequent recruitment of neutrophil, eosinophil. basophil, & lymphocyte
-
early & late-phase reaction
-
mucus, edema, inflammation, pruritus & vasodilation
delayed
inflammation: nasal hyperresponsiveness to nonspecific stimuli야기
Diagnosis
#
symptoms & signs
; paroxysmal sneezing
; watery & profuse
rhinorrhea
#
★Local Findings
; bilateral nasal obstruction
due to boggy edema of the membrane
; redundant mucosa is piled
up on the floor of the nose
; bluish mucous membrane
; clear nasal discharge
#
itching of the nose, palate, pharynx & ears
#
eye
; itching, redness, tearing
-- causing severe symptoms
#
★Characteristic mannerisms
; *rabbit nose & allergic salute
; *allergic shiner
-
dark circles under the eyes
-
due to venous stasis result from edematous nasal mucous membrane
; mouth breathing
#
*fever - bacterial sinusitis, otitis
media합병시
#
nasal smear
; best prepared
; eosinophilis
Differential Diagnosis
1.
eosinophilic non-allergic rhinitis
adult에 common
serum IgE - normal, skin test - negative
2.
primary nasal mastocytosis
perennial nasal blockage &
rhinorrhea
mast cell in smear, skin test - negative
3,
neutrophilic (infectious) rhinitis
early years of childhoodo에 common
4,
vasomotor rhinitis
5
기타 nasal obst. 을 야기하는 원인
unilat.
choanal atresia, septal deviation, adenoidal hypertrophy encephalocele, nasal
polyposis
-
in ciliary dyskinesia, immunologic deficiency
#
Triad asthma : syndrome of nasal polyp. asthma. & aspirin intolerance
foreign
body : foul-smelling, unilat. purulent or blood-tinged
purulent nasal
discharge
malignancy
: persistent bloody nasal discharge
#
benign nasopharyngeal fibroma (angiofibroma)
; nasal obst. with epistaxis
in late childhood or early early
adolescence
Treatment
1.
avoidance of exposure to suspected allergens or irritants
2.
immunotherapy who can't avoid inhalant allergens
3,
drug therapy
Avoidance
Drug Therapy
#
Antihistamines
; useful in seasonal allergic
rhinitis
;
nasal itching, sneezing, & rhinorrhea : well controlled
; *use nonsedating antihistamines (astemizole, loratdine, terfenadine)
#
Decongestant
; troublesome nasal
obstruction있을때 사용
; pseudoephedrine,
phenylpropranolamine
-
alone or combination with antihistamines
-
short-term use
; ※97
decongestants 장기간 사용시
생기는 질환과
치료법
-
rhinitis medicamentosa
-
progressively severe nasal obstruction due to rebound vasodilation
-
Treatment
/
complete cessation of use medicated nose drops
/
substitution of mose drops of physiological saline solution
#
Cromolyn Nasal Solution
useful in both perennial & seasonal allergic rhinitis
prophylactically
#
Corticosteroid
; *▲effective as topical
use
; beclomethasone(vancenase or
beconase) budesonide(rhinocort), flunisolide(nasalide), fluticasone(flonase)
; used in resistant to
antihistamine-decongestant therapy
; no systemic absorption,
candidiasis & mucosal atrophy are not
problem
*
persistent neutrophilic (infectious) rhinitis
-
2 WK course of broad-spectrum AB.(amoxicillin)
nasal irrigation - with Water Pik
device
Chapter 137. Asthma
;
*▲frequent
admitting diagnosis in children
#
★Incidence
; 10-15% of boys and 7-10% of
girls during childhood
; before puberty - male 2배
;
after " - same
#
ÅDefinition
; diffuse, obstructive lung
disease with
1)
hyperreactivity of the airways to a variety of stimuli and
2)
a high degree of reversibility of the obstructive process, which may occur
either spontaneously or as a result of treatment
# reactive airway disease
;
wheezy bronchitis,
viral-associated wheezing, & atopic related asthma
#
alternative designation
; chronic desquamating
eosinophilic bronchitis
#
hyperresonsiveness
; bronchoconstriction after
exposure to exercise, strong odor or irritant fumes (sulfur dioxide, tabacco
smoke, cold air & histamine, parasymptomatics ( eg.methacoline)
#
acute decrease in airway irritability
; beta-receptor agonist,
theophylline, anticholinergics, cromolyn, steroid
#
inheritance
; *one affected parent : 25% risk
; *both "
"
: 50% risk
; *not universally present amon monzygotic twins
Epidermiology
#
onset
; 30 % of pt : 1세 경
;
80-90 % pt : 4 ~5세 이전
; relationship of age of
onset to Px :uncertain.
#
★Most Severely Affected Chiidren
; *wheezing onset during the 1st yr of life, family history of asthma,
other allergic diseases esp. atopic dermatitis
; steroid 투여와 관계없이
growth retardation (+)
; 지속적인
PFT이상
#
Prognosis
; generally good
;
depend on growth in the cross-sectional diameter of the airway
; *50% of asthmatic children
-
*free of symptom within 10-20 yr
-
common recurrence
miId
asthma with onset between 2yr & puberty
: remission rate 50% & 5% develop
severe dis,
severe
asthma : 95% become adult asthmatics
과거 20년 동안 asthma의 빈도와
mortality가 증가
#
★Risk Factor For Occureance Of Asthma
1) poverty, black race
2) *maternal age <20 yr at birth
3) BW < 2500gm
4) maternal smoking
5) small home house (<8
roomes)
6) large family size (> 6
members)
7) intense allergenic
exposure in infancy
8) frequent URI in childhood
#
★Risk Factor For Death From Asthma
1) underestimation of the
severity of the illness
2) delay in implementation of
appropriate treatment
3) underuse of bronchodialtor
& steroid
4) black race
5) noncompliance with
recommendations for treatment
6) Psychosocial dysfunction
& stress
7) sedation
8) excessive allergenic
exposures
#
★▲high risk for fatal astma
; *sudden, severe airway obstruction
; *chronic steroid-dependent asthma
Pathophysiology
#
ÅAirway Obstruction In Asthma Are Due To
1. bronchoconstriction
2. hypersecretion of mucus
3. mucosal edema
4. cellular infiltration
5. desquamation of epithelial
& inflammatory cell
various
stimuli
-
inhaled allergens: dust mite, pollen, soybean or caster bean
protein
vegetable protein
viral infection
cigarette smoke
air pollutants
odors
drugs: NSAID, beta-receptor antagonists,
metabisulfite. tartrazine
cold air
exercise
#
pathology of severe asthma
; bronchoconstriction,
bronchial smooth m. hypertrophy, mucus g1. hypertrophy, mucosal edema,
infiltration of inflammatory cell, desquamation
#
pathognomonic findings
1. Charcot-Leyden crystals
(eosinophil membrane)
2. Curschmann spirals
(bronchial mucus cyst)
3. Creolar bodies
(desquamated epithelial cells)
#
immune responses
early - result in bronchoconstriction
treatable with beta2-receptor agonists
maybe prevented by mast cell stabilizing agent (cromolyn)
late - occurs 6-8 hr later, produce a
continued state of airway
hyperresponsiveness with inflammatory cell infiltration
treated
& prevented by steroids
prervented
by cromolyn
Pathophysiology. (Fig. 137-1)
Obstruction : most severe during
expiration
-> hyperinflation
-> decreased compliance
-> increased work of
breathing
& *
increased transpulmonary pressure.
->
further narrowing & premature closure of some aw.
during expiration
& *
increased intrathoracic pressure-> venous return방해
-> C.O 감소 ->pulsus paradoxus.
->
mismatching V/P
->alveolar
hypoventilation.
-> PaO2감소,
PaCO2증가
-> metabolic &
respiratory acidosis
acidosis
& hypoxia->pul. vasoconstriction
->
damage to Type II alveolar cell.
->
atelectasis 유발.
Etiology
#
*astham is a complex disorder
involving autonomic, immunologic, infectous, endocrine, psychologic factors
varying degrees in different individuals
#
Control Of The Airway Diameter
; balance of neural &
humoral forces
; neural factor
-
bronchoconstriction
/
vagal sensory ending
-
bronchial m. relaxation
/
*vasoactive intestinal peptide(VIP)
:
*dominant neuropeptide in maintaining
airway potency
; humoral factor :
-
bronchodilation - endogenous catecholamine acting on β-receptor
-
bronchoconstriction - histamine,leukotrienes, locally produced adenosine
#
※89
Szentivany theory
1. abnormal β-adrenergic
receptor-adenylate cyclase fuction with deceased adrenergic responsiveness.
2. hyporesponsiveness to β-agonist
;
deceased number of β-adrenergic receptors on
leukocytes
3. increased cholinergic
activity in the airway
Immunologic Factors
Å병인론적인 분류
#
Extrinsic or Allergic Asthma
; follows exposure to
environmental factors
;
increase of total IgE & specific IgE against allergen
#
Intrinsic Asthma
; clinically similar asthma
;
no evidence of IgE involvement
-
low level of IgE, negative skin test
; *▲often 1st 2yr of life
and in older adult (late-onset asthma)
#
viral agents
; *▲important infectious
triggers of asthma
-
through stimulation of afferent vagal receptor of cholinergic system
; *early in life - respiratory syncytial virus & parainfluenza
virus
-
RSV respiratory disease는 no wheezing
; *older chiId - rhinovirus
; influenza virus - important
with increasing age
Endocrine Factors
worsening - pregnancy, menses, esp,
premenstrually or maybe at
menopause, thyrotoxicosis
improving - at puberty
Psychologic Factors
emotional or behavioral disturbances가
asthma attack의 severity보 다는 poor control과 관련
Clinical Manifestations
; attack
acute episode : by exposure to
irritants, allergens or
simple chemicals
due to smooth m. spasm in large airway
slower onset : by viral respiratory
infection
at night: airway patency 가장 감소하므로
attack이 잘 일어남
; cough : nonproductive early
in the course of attack
wheezing
: extreme resp. distress시 없을 수 있음
tachypnea
& dyspnea uith prolonged expiration:hunched
-over. tripod-like posture
use
of accessory m. of respiration : abd. m. 사용시 abd. pain complaint
cyanosis
hyperinflation
of chest
barrel
chest deformity : a sign of chronic, unremitting airway obst. of severe asthma
; clubbing of finger
-
rare
-
*suggest other cause of chronic obst.
lung dis. such as cystic fibrosis
tachycardia
& pulsus paradoxus
low
grade fever, fatique
Harrison
sulci - recurrent sever retraction으로.
Diagnosis
#
highly suggestive signs
; recurrent episodes of
coughing & wheezing
-
esp. if aggrevated or triggered by exercise, viral infection, inhaled allergens
#
insufficient flow rate, mild airway obstruction, unrecognizable caretakers
-->
persistent coughing without history of wheezing
; PFT을 실시함으로
진단에 도움이 된다.
-
before and after methacholine or bronchodilator
-
before and after exercise
#
improvement following bronchodilator therapy도 진단에 도움이 된다.
Laboratory Evaluation
1)
eosinophilia of the blood & sputum
; blood eosinophilia
-
more than 250-400 cells/mm3
; sputum
-
eosin-methylene blue stain : numerous eosinophil
2)
IgE level
3)
allergy skin test
4)
RAST(radioallergosorbent test)
5)
inhalation bronchial challenge test
; skin testing에 의한
allergen에 대해 임상적으로 의심스러울때에만 실시한다.
-
이유
/
provoke late-phase asthmatic response
/
procedure is time consuming
/
only single allergen is tested
6)
methacholine provocation testine
; asthma의 진단이 의심스러울때
; *metachoiline or histamine의
bronchoconstrictive effect에 대한
hyperresponsiveness를 test
; abnormal baseline pul.
function시 금기
7)
exercise test
; *characteristlc response against exercise
-
running for 1-2 min : often cause bronchodilation
-
prolonged strenuous exercise : bronchoconstriction when breathing dry, cold air
; Treadmill running at
3-4miles/hr up a 15% at least 6min
-->
airway obstruction in mostly asthma
; measurement of PFT before
& after exercise
-
decrease PFR or FEV1 of at least 15%
; withhod drugs
-
bronchodilator & cromolyn : 8 hr
-
theophylline : 12-24 hr
8)
Roentgenogram of the chest
;
exclusion위해 필요
; hyperinflation.
; atelectasis : 6%, esp. Rt.
middle lobe
; ♥indication
of repeated chest roentgenogram during exacerbation
-
fever
-
peumothorax 의심시
-
tachypnea greater than 60 beats/min
-
tachycardia of more than 160 beats/min
-
localized rales or wheezing, or decreased breath sounds
9)
pulmonary function test
; useful in
1)
assessing the degree of airway obst. & the disturbance in gas exchange
2)
measuring response of the airways to inhaled allergen & chemical or
exercise (bronchial provocation test)
3)
assessing the response to therapeutic agents
4)
evaluating the long-term course of the disease
; *▲valuable when made
before & after administration of aerosol bronchodilator
-
*aerosol therapy후 PFR or FEV1이 최소 10%이상 증가시 asthma를 강력히
의심
ÅTable
137-1
; increase : TLC. RV,FRC
; decreaes : VC, FVC, FEV1,
PFR, FEF25-75
10)
determination of arterial blood gas & pH
ÅDifferential Diagnosis
1.
congenital malformations (of the resp. cardiovascular, GI systems)
2.
foreign bodies in the airway or esophagus
3.
infectious bronchiolitis
4,
cystic fibrosis
S.
immunologic deficiency diseases
6.
hypersensitivity pneumonitis
7,
allergic bronchopulmonary disease
8.
rare condition
; endobronchial Tbc, fungal
dis., bronchial adenoma
ÅTable
137-2
Asthma In Early Life
;
Symptoms of obstructive airway disease
- 30% younger than 1yr
- 50-55% younger than 2yr
;
※89
antomic & physiologic pecularities of early life predispose to obstructive
airway disease
1) decreased amount of smooth
m. in the peripheral airways
-->
less support
2) mucous gl. hyperplasia,
increase intraluminal mucus production
3) disproportionately narrow
peripheral airway up to 5yr
-->
decrease conductance & vulnerable to dis. affecting the small airway
4) decreased static elastic
recoil of the young lung
-->
early airway closure & mismatching ventilation & perfusion and
hypoxemia
5) highly compliant rib cage
& mechanicallly disadvantageous angle of insertion of diaphragm to rib
cage(horizontal).
-->
increase diaphragmatic work of breathing
6) decreased numbers of
fatigue-resistant skeletal m. fiber in the diaphragm
-->
poorly maintain high work output
7) deficient collateral
ventilation with the pores of Kohn & the Lambert canals deficient in
numbers & size
#
bronchiolitis
asthma와 Clinical,
roentgenographic, blood gas finding이 유사.
DDx 1. RSV에 의해 생후 6개월에
peak 득히 cold weather months
2. 2차,
3차 재발은 드물다.
3. epinephrine에 대한 반응
: favorable response in asthma
4. onset of Sx이 더
typical
previously well infants or young children
cold, rhinorrhea, irritability, cough, tachypnea, wheezing,
Sx이 빨리
progress.
#
Infancy에서 asthma와 감별할 질환
1.
resp. infection with virus or chlamydia
bacterial inf. 은
rare
2.
cystic fibrosis or immunologic deficiency
child with recurrent episode of coughing
& wheezing asso. with bacterial inf.이 있는
경우 반드시 검사 요.
3.
chronic aspiration due to swallowing dysfunction or gastroesophageal reflux
4.
obliterative bronchiolitis
5,
bronchopulmonary dysplasia
Food
allergy와 obst. Sx.과의 관계는
controversial하고 positive skin test for
IgE-mediated sensitivity to food는 unusual하지만 의심스러운 food를 일시적으로 제거
->3주뒤 challenge :confirm된 Food allergy는 적어도
6개월간 제외
#
Important predictor of subsequent obst. airway problems
1.
several episode of obst. airway disease
2.
Hx of asthma, hay fever, or atopic dermatitis in family
3.
eczem
4.
eosinophilia greater than 400 cells/mm3, esp 700 cell/mm3이상
& high serum IgE
conc.
Treatment
# Basic consepts
; avoiding allergens
; improving bronchodilation
; reducing mediator-induced inflammation
ÅFig. 137-2 ~ 137-4
Avoidance
; nonspecific irritants
-
tobacco smoke, smoke from woodburnig stoves, fumes from kerosene heaters to
strong odors such as wet paint and disinfectants
; icecold drinks, rapid
changes in temperature & humidity
; humidity not exceed 50%
Pharmacologic Therapy
;
*mainstay of treatment of asthma
;
O2 supply by mask or nasal prongs at 2-3L/min
;
epinephrine
- *0.01 ml/kg of the aqueous of the 1:1,000(1mg/ml)
- repeat once or twice at
interval 20min
- upper limit 0.3 ml
;
terbutaline
- selective beta2-agonist,
- *0.01 ml/kg of the aqueous of 1:1,000(1mg/ml)
- no peripheral
vasoconstriction, longer duration up to 4hr
- upper limit 0.25ml
;
inhalation of bronchodilator aerosol
- *rapid effective
- ※90,94 장점
/
less drug is given than would be required by the subcut. route
/
unpleasant side effect of injected drug s are avoided
/
more effectve than epinephrine in reversing bronchoconstriction despite airway
obstruction
- albuterol (ventolin)
/
a dose of 0.15 mg/kg (max. 5 mg),
/
0.05-0.15mg/kg repeat at interval 20-30min until response is adequate
/
available as 0.5% solution (5mg/ml) with 2-3ml normal saline
/
nebulization with oxygen at 6 L/min
;
Aminophylline
- epinephrine or bronchodilator
aerosol에 ineffective시 사용.
- *a dose of 5mg/kg for 5-15min but no more than 25mg/min
- *dose of 1mg/kg increase serum level by about 2ug/ml
-
beta2-aerosol therapy와 병행
/
little additional benefits
/
helpful in severe airway obstruction, less than maximal treatment with inhaled β2-adrenergic
agonists
;
steroid
- indication
/
corticosteroid dependent case
/
corticosteroid in recent past
- borderline cases
/
입원하지 못하고 귀가를 해야하는 환아의 경우를 말함
/
prednisone decreasing dose over 5-7days로 처방
- reduce the relapse &
hospitalization rates
;
relapse
- 15-20% hospitalized
- *10-20% relapse within 10days
Status Asthmaticus
;
clinical diagnosis
- continuous state having
significant respiratory distress despite treatment
- *increasingly severe asthma that is not responsive to drugs that are
usually effective
Table 137-3 Factors associated with risk of severe statrus asthmaticus
※92 Treatment
;
ICU care
;
carefully minitoring
- bseline CBC &
electrolyte
-
cardiac monitoring
- ABGA
#
Oxygen supply
; *continuously by nasal prong or mask
; 2-3 L/min
; *optimal oxygenation
-
*PaO2 : 70-90 mm Hg, SaO2 > 92%
; mist tent - should not be
used
#
Fluid & Electrolyte Balance
;
cause of dehydration
-
inadequate fluid intake
- insensible water loss due to tachypnea
- diuretic effect of theophylline
; *no more than 1-1.5 times maintenance level
; *Indication Of Bicarbonate
-
arterial pH < 7.3
-
metabolic acidosis
-
serum Na < 145 mEq/L
-->
1.5-2 mEq/kg, every 4-6 hr
; β2-adrenergic
agents의 사용으로 hypokalemia를 초래 할 수 있으므로
potassium add.
#
bronchodilator sympathomimatic aerosol therapy
; continued
#
aminophylline
;
4-5 mg/kg lV over 20 min, every 6 hr
or
5 mg/kg IV loading, followed by constant infusion in a dose of 0.75-1.25 mg/kg/hr
; TDM
-
*steady state 12-15 ug/mL
-
if every 6-hr regimen
/
1 hr after IV injection & just before the next dose
-
if constsnt infusion
/
1, 6, 12, 24 hr as a basis for dose adjustment
/
6, 12hr after any change dosage
/
every 24hr while iv theophylline
;
different starting dose at age
-
0.5mg/kg/hr at 1-6mo
-
1mg/kg/hr at 6-11mo
-
1.2-1.5 mg/kg/hr at 1-9yr
-
0.9 mg/kg/hr over 10yr
#
Terbutaline
; 0.01 mg/kg(maximum 0.3mg)
sc
; 10 ug/kg bolus, 0.4-0.6
ug/kg/min continuous infusiion increasing by 0.2ug/kg/min to 3-6 ug/kg/min) iv
#
treatment with antimuscarinic such as atropine suifate
; combination with nebulized
beta-agonist
-
more effective than alone
#
ipratropium bromide : nebulization
#
Corticosteroid
; *methylprednisolone(solu-medrol) 1-2mg/kg every 6 hr
; ※87 Effect
-
improve oxygenation
- decrease airway obst.
- shorten the time needed for recovery
#
mechanical ventilation
;
volurne-cycled ventilator with short inspiratory & long expiratory times,
10- to15-mL/kg tidal volume, 8-15 breaths/min,
; peak pressure 60 cm HzO
;
goals : 1. improve oxygenation
2.
maintain PCO2 between 40-60 mm Hg
3.
avoid barotrauma
; recovery phase, PEEP to
prevent atelectasis
; sedation of non-ventilated
pt : should be avoid
Daily Management Of The Asthmatic Child
Mild Asthma
; exacerbations
-
up to twice each week
; decrese of PEFR
-
not more than 20%
; not severe & respond to
bronchodilator treatment within 24-48hr
; *medication is not required between attack
; good school attendance,
good exercise tolerance
; no hyperinflation of chest,
CXR - essentially normal
; PFT - mild, reversible
airway obst.
Moderate Asthma
; more frequently than mild
asthma
; cough & mild wheezing
between more severe exacerbation
; impaired school attendance,
diminished exercise tolerance
; lose sleep at night, esp.
during exacerbation
; medication
-
*continuous bronchodilator therapy
-
*continuous treatment with cromolyn,
nedocromil or inhaled steroid to reverse bronchial hyper-responsiveness
Severe Asthma
; daily wheezing & more
frequent & more severe exacerbation
; recurrent hospitalization
; interrupted sleep by
asthma, poor excercise tolerance
; chest deformities due to
chornic hyperinflation
; bronchodilator treatment
required continuously & regular systernic or aerosol of steroid
Treatment
Children With Miid Asthma
; should receive
bronchodilator medication only when symptomatic.
; satisfactorlly with
adrenergic drug, preferably by aerosol.
; theophylline may be added.
when indicated
*
Exercise-induced asthma
prevented by inhalation of
adrenergic drug immediately before
exercise -most effective
inhaldtion of cromolyn or
nedocromil
Children With Moderate Asthma
; two inhalations of
adrenergic aerosol every 4-6 hr or two inhalations of salmetrol every 12hr
; theophylline may be added
-
begin with 14-16 mg/kg/24hr : safest
; cromolyn powder inhaled 4
times a day from a Spinhaler or cromolyn aerosol
; nedocromil
; steroid
-
early use on symptom onset
-
1-2 mg/kg/24 hr, discontinue as quickly as possible
Children With Severe Asthma
#
steroid alternate-day basis
; steroid alternate-day
therapy
-
intense daily therapy : short-acting steroid(prednisone,prednisolone) for
5-7days
-->
and then alternative -day regimen
-
12yr-old boys
/
60mg, 40mg, 30mg, 20mg, 10mg /24hr over 5days
-->
20mg/24hr alternate-day at 6:00-8:00am
-->
reduced by 5mg/dose at 10-14days interval
-->
usually 5-10mg on alternate-days
; *concurrent therapy with aerosol adrenergic drug, theophylline, or
cromolyn
#
Inhalational Corticosteroids
; *alternative to use of oral corticosteroids
; aerosol more effective than
oral steroid
; beclomethasone
#
Various factors may exacerbate asthma or rnake the disease
difficult to treat :
1.
gastroesophageal reflux
2.
allergic bronchopulmonary aspergillosis
3.
nonsteroidal antiinflammatory agents
4.
pregnancy
5.
sinusitis- treatment with antibiotics, intranasal steroid, & oral or topical decongestant
for 3 wks
-> may improve bronchoconstriction as well as sinusitis
#
Prevention of Death from Asthma
reasons for increase in mortality
1.
increased prevalence of asthma
2.
increased indoor air pollution, emphasis on energy conservation
3.
delay in implementation of appropriate treatment for acute
asthma
4.
lack of access or utilization of medical care, including preventive care
5.
over-reliance of bronchodilator inhalers leading to delayed treatment with steroids
or other
therapy
6.
unavailability of epinephrine for pt unable to use inhalers effectiveiy
7.
inappropriate use of the metered dose inhaler & failure to provide contnuity of care
or education
#
사망을 초래할 수 있는 위험인자.
1.
resp. failure with hypercarbia
2.
loss of consciousness due to asthma
3.
psychosocial dysfunction in the pt or family - judgement & compliance에 장애
Chater 138. Atopic Dermatitis (=Infantile or Atopic Eczema)
;
inflammatory skin disorder characterized by erythema, edema, intense pruritus.
exudation, crusting, scaling
- acute stage :
intraepidermal vesiculation (spongiosis)
;
subsequently to develop allergic rhinitis & asthma
ÅImmunologic
Abnormalities
# increased serum IgE conc.
;
80% of patients
;
5- to 10- fold
;
*related to severity or extent of
dermatitis
;
not always increased in affected patients
;
maybe related to *deficiency of IgE
isotype-specific suppressor T-cell function
# high rates of spotaneous
basophil histamine release
# ※82 impairment of cell-mediated immunity
;
absence of the reaction of delayed hypersensitivity upon intradermal skin
testing with certain testing
;
inability to be sensitized with potent contact sensitizers
;
diminished proliferative response of lymphocytes to mitogens (e.g. phytohemagglutinin)
;
variable phagocytic & chemotactic defects of monocytes & neutrophils
#
★Hyperreactive Skin Of Atopic Dermatitis
; ♨white
dermographism
-
light mechanical stroke
-->
within *1 min in a white line
with a surrounding blanched area
; abnormal rates of cooling
& warming in response to temperature change
-
particularly in flexural areas
; paradoxical response occur
to injection of various pharmacologic agents such as histamine, acetylcholine,
nicotinic acid ester
-
*blanching rather than erythma
; 원인
-
autonomic imbalance로 생각함
/
그이유는 decreased adrenergic response in
lymphocytes & granulocytes
Clinical Manifestation.
;
2-8% of children
;
typically occurs in 3 stages with fairly distinctive features
- 1기
: 생후 2개월에서 2년
- 2기
: 2년에서 10년
- 3기
: 사춘기와 성인
In Infancy
;
*▲often
;
usually during the first 2-3 mo of life
- sometimes delayed until 2nd
or 3rd yr
- 60% by 1yr, 90% by 5yr
;
earliest lesion
- erythematous weepy patches
on the cheeks
with
subsequent extension to remainder of the face, neck, wrist, hand, abdomen,
extensor aspects of extremities
;
erythmatous flush
--> marked pruritus
--> *scratching : major role of production of typical skin lesion
--> weeping & crusting
--> secondary infection
;
*coincides with introduction of
certain foods, esp. cow's milk, soy, peanuts, fish, egg
- 50-90%
- 20-30% hypersensitivity to
one or more of six common allergens
During Childhood
;
remission at 3-5yr
;
mostly less prominent by 5 yr
;
in some, mild to moderate eczema in antecubital and popliteal fossae, on wrist,
behind ears, on face & neck
;
after 5yr
- *common involvement of antecubital and popliteal
- extensor surf. maybe
involved
;
with increasing age, drying & thickening of the skin
;
mask of atopic dermatitis
- whitish hue as increased
capillary permeability
- edema & blanching of
surrounding tissue due to dilatation
#
★▲Poor Condition
; *severe dermatitis, family histories of atopic dermatitis,
associated asthma or allergic rhinitis, onset before 1yr, in female
Diagnosis
support
Dx
-increased pruritus & characteristic
lesion
-Family history of asthma, hay fever, or
atopic dermatitis
-elevated serum IgE conc. & reaginic
Ab. to a variety of foods & inhalants
-eosinophilia
-demonstration of white dermographism
㉿Table
138-1
★Table
138-2
ÅDifferential Diagnosis
1)
♥Seborrheic Dermatitis
- cradle cap : typically begin on the
scalp
- eyebrow and eyelids with
greasy
- *shorter course & respose much more
rapidly to treatment
2)
scabies
-
location 으로 감별
/
begin with large papule on the upper back
with vesicle on the palm & sole
3)
primary irritant dermatitis
4)
allergic contact dermatitis
5)
infectious eczematoid dermatitis
6)
ichthyosis
7)
PKU
8)
acrodermatitis enteropathica
9)
histiocytosis X
10)
primary immunologic deficiency dis.-Wiskott-Aldrich syndrome
X-linked agammaglobulinemia
Complicatlons
1)
★Secondary Infection
; bacterial or viral
; staphylococcus &
beta-hemolytic streptococci
-
Å▲common bacteriae
;
herpes simplex virus
-
*Kaposi varicelliform eruption
; common wart
; molluscum contagiosum
2)
keratoconus d/t rubbing of the eyelid
3)
cataract - *rare in childhood
Treatment
#
control of environmental precipitants of itch-scratch-itch cycle
; avoidance of ingestant,
injectant, contactant(wool) & atmospheric factors
-
avoidance of extreme termperature
/
warm climate & moderate humidity : optimal
-
avoidance of sweating
/
exposure to sunlight & salt water : of benefit
-
avoidance of wool
/
smooth-textured cotton
-
avoidance of soap & detergent
/
bath oil & other creams
/
soaking in tepid water for 30min two or three times each day followed by gentle
drying and application within 3min of ointment base(Aquaphor) or cream
base(Acid Mantle)
/
nondrying cleansing agent such as Cetaphil
/
nonlipid lotion
-
minimum bathing
-
avoidance food aggrevating itching
/
정확한 검사를 통하여 회피
/
reintroduction within 2-4yr
#
Food Allergen Sensitization을 줄이기 위한 방법
1. breast milk feeding
2. delaying the introduction
of solid food until after 6 mo of life
3. breast-feeding mother
should avoid high risk food
#
Local Therapy
; *mainstay of management
1) wet dressing
;
Burow solution 1:20
-
antipruritic & anti-inflammatory effect
2) topical corticosteroid
lotion or creams
3) itching control
;
*almost impossible to manage during
infancy & early childhood
;
cutting fingernail
;
*difficut to control with drugs
-
both sedative & antihistamine activity
/ *diphenhydramine (Benadryl), hydroxyzine (Atatax, Vistaril),
promethazine (Phenergan)
/
*▲value
-
aspirin
#
infection control
; if infection(acute weeping
or crusting)
-->
systemic AB
-
EM or cephalexin
/
prudent choice
; local AB
-
*little therapeutic value
-
*exception) Mupirocin(Bactroban)
#
after the acute phase subsided
; topical steroid cream &
ointment of great value
; 0.1% topical triamcinolone
acetonide ointment often useful
#
after improvement
; less potent corticosteroid
#
potent topical steroid는 face에 금기
; *0.5 or 1 % hydrocortisone이 적당
#
systemic corticosteroids
; avoided except severely
affected patients
#
*Topical Coal Tar Preparations
; Estar gel(Westwood) and
psoriGel(Owen)
-
effective & more acceptable
#
experimental therapy
; interferon gamma,
cyclosporine, chinese herb
Table 138-3
Prognosis
;
resolution occurs within 5yr usually.
Chapter 139. Urticaria-Angioedema(Hives)
Clinical Manifestations
urticaria
(or hive)
-
characterized by usually well-circumscribed but sometimes
coalescent. localized, or generalized
erythematous raised skin
lesion
usually resolve within 48hr
intensely pruritic or itch little
chronic urticaria - 6주 이상지속시
Angioedema
(angioneurotic edema)
-
deeper layer of skin or submucosa & subcut. or other tissue를 involve
-
urticaria와 구별점
:
common target organ : upper resp. tr. GIT
Incidence
female>
male
Pathogenesis
(1)
interaction of Ag. with mast cell
or basophil-bound IgE Ab.
: principal noncytotoxic mechanism
- histamine release
- vasodilatation, increased
vascular permeability, stimulate axon
reflex
- typical wheal & flare
reaction
- leukotriene release
- edema of IgE-mediated
reaction
(2)
complement system activation
C3a & C5a
-
act as anaphylatoxin & trigger histamine release from mast cell & basophil by direct action on the cell surf.,
independent of Ab.
(3)
plasma kinin-forming system of the coagulation scheme
: bradykinin - increase vascular
permeability
Etiology
★Table
139-1
Differential Diagnosis
allergy
skin test is generally not helpful except when specific drug or food allergy
are identified
#
TMC cause of urticaria : drug & food
#
Chronic urticaria의 원인은 10%에서만
identify.
# cholinergic urticaria
wheal 1-2 mm in diameter
surround by erythema
frequently involve skin of the neck
cause : exercise
hot showers
anxiety
viral infection . hepatitis, infectious mononucleosis
전형적인 hives가 자발적으로
erythema multiforme의 lesion으로 변하면 drug allergy의 sign이 될 수 있다.
#
Urticaria pigmentosa : Systemic mastocytosis
#
adult에선 urticaria가
malg.나 collagen-vascular disorder와 관련
#
cold urticaria : mc form caused by physical factor
- exposure to cold & confined to the
exposed part of body
- 2 forms : priamry acquired form & familial
type.
- systemic ds와 관련
: cryoglobulinemia, cryofibrinogenemia,
cold-agglutinin ds, 2ndary syphilis.
#
Hereditary angioedema ;life-threatening form
#
Exercise-induced anphylaxis
Treatment
(1)
antihistamine
hydroxyzine(atarax)
- most effective for control of urticaria,
0.5 mg/kg
diphenhydramine
- 1.25 mg/kg
(2)
epinephrine - 1:1000, 0.01 ml/kg, max 0.3 ml
(3)
corticosteroid
-
urticaria를 조절하기 위해서는 다량이 필요해 부작용 유발 가능
cholinergic
& chronic urticaria : hydroxyzine
prophylactic
agent for cold urticaria : cyproheptadine (periactin)
Chapter 140. Anaphylaxis
Definition
;
acute, potentially life-threatening reactions caused by release of mediators
from mast cells & basophils
;
*interaction of allergen with
specific, cell-bound Ig E
ÅEtiology
;
대부분 drugs, food, hymenoptera venom
allergy
★Table
140-1
ÅPathogenesis
#
IgE-mediated anaphylactic sensitivity to an Ag.
#
Other mechanisms
; *direct effect of causative agent on basophils and mast cells
; *by activation of alternative complement pathyway with
anaphylactoxin
--> 증거
:
decreased factor V & Vlll - DIC 암시
:
*decreased HMW kininogen, C3 & C4
Clinical Manifestations
;
*characterically explosive,
particularly when the antigen is injected
;
*tingling sensation around mouth or
face
--> feeling of warmth,
difficulty in swallowing, tightness in throat or chest
--> apprehension,
weakness, diaphoresis
--> general prutitis
--> flushed
--> urticaria &
angioedema
--> hoarseness,
inspiratory stridor, dysphagia, nasal congestion, itching of eyes, sneezing,
wheezing
--> abdominal cramp,
diarrhea, contraction of uterus and other organ
--> loss of consciousness
--> hypotension, feeble
heart sounds, bradycardia
--> cardioresoiratory
arrest
--> death
;
*cause of death
- *most often acute upper airway obstruction
; *begin
within 30min
--> resolve within a few hours
Treatment
1.
epinephrine 1:1000, 0.01 ml/kg (max, 0.3 ml) -BP; 80mmHg유지
2.
tourniquet above the site
3,
aminophylline, nebulized albuterol; Lower aw obst에 효과.
4.
volume expander for hypotension. CVP측정이 필요
5.
02
6.
antihistamine: diphenhydramine, cimetidine
corticosteroid
- not useful as emergency
may be useful in
preventing the recurrence of symptom during 12-24hr following the acute reaction
contrast
media에 의한 anaphylaxis는 소아에서
less common
prophylactic regimen
1.
prednisone, 50 mg orally every 6 hr for 3 doses, ending 1 hr before procedure
2.
diphenhydramine, 50 mg, given by im 1 hr before procedure
Chapter 141. Serum Sickness
a
characteristic systemic immunologic disorder that follows the administration of
foreign antigenic materials
Etiology
1.
adverse reaction to the serum proteins of the animal in which antitoxin was
prepared
2.
drug allergy - major cause, penicillin
3.
human gamma globulin
4.
hymenoptera stings
Pathogenesis
;
*type III
hypersensitivity."immune complex disease"
-
these complex activate the complement sequence
- promote accumulation of neutrophils
- tissue injury result from liberration
of toxic molecules from the
neutrophils
#
urticaria
-
due to IgE Ab. molecules reacting with horse serum protein
#
joint symptom
-
due to deposition of Ag.-Ab. complex of the IgG & IgM classes
#
Histamine
-facilitates
the deposition of immune complexes through increase in vascular permeability
Clinical Manifestations
; *typically, begin 7-12 days following injection of foreign material
-
may appear as late s 3wk afterward
fever
& malaise, urticaria ; common finding
characteristic
cutaneous lesion
-
faint erythema with a serpiginous border at the margin of palmar or plantar
skin of
the hands, fingers, feet, & toes
-
become pruritic with time
recover
in 7-10 days
; *carditis & glomerulonephritis - rare
; *Guillain-barre syndrome & peripheral neuritis, involving
brachial plexus (C5-C6)
-
*▲serious
complication
Laboratory Manifestations
; marked thrombocytopenia
; ESR ↑
; *C3 & C4 ↓around 10th day
Treatment
; *aspirin & antihistamine
corticosteroid
- severe sx.시 effective
Prevention
skin
test
epinephrine
& antihistamine before beginning injection
Chapter 142. Adverse Reactions To Drugs
Definition
any
unwanted consequence of administration of the agent during or following a
course of therapy
#
2 broad categories : pharmacologic & immunologic mechanisms
#
certain generalities apply to adverse drug reactions
(1)
any organ system may be involved
(2)
children are less often affected than adult
(3)
incidence of reactions increase with the numbers of drug given simultaneously
(4)
certain diseases predispose to adverse drug reaction, esp. those in which
multiple drug
therapy is common.
diseases that affect organ
responsible for absorption. metabolism, or excretion of drug
also increase the likelihood of
adverse reaction
(5)
pharmacokinetic properties of a drug also affect the incidence of adverse
reaction
Classlflcatlon
toxicity - high concentration of drug in
the body due to excessive intake, or to
abnormalities in absorption, metabolism, or excretion of drug
#
intolerance - excessive pharmacologic responses to average drug dosage
#
side effect - undesirable but essentially unavoidable effects of drugs
and largely reflect the fact that a given drug rarely affects only
one
tissue
eg.
theophylline - CNS stimulation
#
secondary effect - those not related to their primary
pharmacologic action
eg.
antibiotic therapy - disturbance of the bacterial flora of the intestine
#
idiosyncracy - sg. & sx. of the reaction are unrelated to the known pharmacologic
properties of the agents
eg. G- 6-PD
deficiency시 primaquine - hemolytic anemia야기
#
allergic drug reactions occur on the basis of recognized models of immune injury
(I)
IgE-mediated reaction
(2)
cytotoxic reactions resulting from hapten binding to cell
membrane & subsequent reaction
with anti-hapten Ab.
(3)
immune complex reaction, activate the complement system
(4)
reaction due to autoAb. formation
(5)
cell-mediated mechanism
#
Penicillin allergy
minor hapten determinants 에 의해 발생
-
penicilloate, penilloate, penicillenate, oxidative product
#
ampicillin rash
not urticarial, 10%,
(urticaria-1%)
infectious mononucleosis,
hyperuricemia 환자의 90%에서 발생
Clinical Manifestations
; cutaneous manifestation
-
*▲common
-
utricaria, exanthematous & eczematoid eruption
; renal or pulmonary diseases
-
rarely occur during childhood
;
phenytoin - interstitial nephritis
; drug fever
-
a child who has received prolonged antimicrobial therapy has
persistent fever without other
cause concornitant rash
Dx. drug D/C후
24-48 시간뒤 fever down
immunologically mediated drug-induced
reactions involving liver,
disorder of granulocytes & platelet
are extremely rare in chiIdren
Risk Factors
# one parent with allergy to antimicrobial drugs
;
*25% of children risk for allergy
rather than 2% in no allergic parents
#
★Other Risk Factors
; dose, route, duration,
frequency
-
large dose
-
topical administration
-
nonoral adminstration
-
frequent, intermittent adminstration
Diagnosis
Treatment Of Drug Reactons
antihistamine
- diphenhydramine, hydroxyzine
epinephrine
corticosteroid
- severe case
Prevention
Capter 143. Insect Allergy
allergic
reactions to insects can cause
(1)
symptoms of resp. allergy due to inhalation of particulate matter
of insect origin
(2)
local cutaneous reactions to insect bites
(3)
anaphylactic reactions to stinging insects
Etitology
Pathogenesis
IgE-mediated
sensitivity to antigenic materials found in the insect bodies stinging insect
venoms contain at least 9 components that contribute to adverse reaction
- vasoactive material : histamine,
acetylcholine. kinins
enzyme : phospholipase A & B.
hyaluronidase
apamine,melittin,formic acid
Clinical Manifestations
rhinitis,
conjunctivitis, asthma
cutaneous
lesion- urticaria(most often) maybe papule,vesicle, erythema
late
sequelae - serum sickness, nephrotic syndrome, vasculitis,
neuritis, encephalopathy
Diagnosis
Treatmemt
#
previous severe or anaphylactic reation to Hymenoptera stings
; equipped with EpiPen or
EpiPen Jr
; wear identification
bracelet(Medic-Alert)
#
Immunotherapy
; children
-
*severe systemic reaction(airway
involvement or hypotension) & positive skin test
-
*not indication with only urticarial
or local reaction
; adolescent & adult
-
positive skin test & non-life-threatening or life-threatening systemic rxn
-
not indication
/
negative skin tests and RAST
Chapter 144. Ocular Allergies
less common in children
mechanism
- IgE-mediated allergy : ragweed hay fever
cell-mediated (delayed hypersensitivity) : contact dermatitis
Eyelids
chronic
staphylococcal infection : major cause of chronic eczema of eyelid
Allergic Conjunctivitis
watery
secretion
purulunt
secretion이라도 eosinophil predominant로
infectious 와 감별
#
vernal conjunctivitis
male : female = 3 : 1
warm climate & during the spring
& summer
2 forms
*palpebral form - cobblestone appearance
*limbal form - Trantas dots : represent accumulation of eosinophil IgE-mediated
sensitivity
immunotherapy - of little value
Chapter 145. Adverse Reactions To Foods
;
*mostly adverse reactions to food
don't have immunologic basis
;
*immunologic test & therapy are
unwarranted
Etiology
allergy
enzyme
deficiency
nonimmunologic
reaction to tyramine, nitrite & monosodium glutamate macromolecules may pass through the
epithelium of the GIT &
gain access to systemic circulation
- secretary Ig.A limit absorption
of intact macromolecules
pt with IgA
deficiency, higher level of Ab. to cow milk
protein & of
immune complex containing milk
#.
a variety of reactions have been reported to follow ingestion of cow milk by
infant &
children
1.
IgE mechanism
2.
Ab. to milk protein, α-lactalbumin, β-lactoglobulin.
& casein
3.
no immunologic mechanism
#
cow milk ingestion
during the 1st yr of life
- vomiting &
watery,blood-streaked,mucoid diarrhea may follow young infant fed large vol.of
whole pasteurized milk
-enteropathy c loss .
recurrent reontgenograohic pul.infiltrate
older infant
-occult fecal blood
loss,recurrent roentgenograpnic pul.infiltrate & multiple precipitating Ab.to cow milk
protein
Diagnosis
-elimination
from the diet for period of 7-10 days of a food causing
difficulty should generally result in in
improvement in sx.
-reintroduction
of the food, within 7 days at most food challenge test
-
skin test - anaphylactic food allergy시 위험
-
RAST
excellent for codfish, egg white, nut,
peanut, peas
poor in cereal, soybean & white
beans
Treatment
foods
most likely to become tolerated uith the passage with time
-
cow milk,eggs & soys
hypersensitivity
to peanut,nut,fish persists for long period