Food allergy lecture for clinical pharmacist student
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Penatalaksanaan Alergi Makanan Pada Anak
Prof DR Dr ARIYANTO HARSONO SpA(K)
Lab/SMF Ilmu Kesehatan AnakFK Unair/RSUD Dr. Soetomo
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Pendahuluan
• The American Academy of Allergy and Immunology– Alergi Makanan : Reaksi imunologi yang
menyimpang terhadap makanan, sebagian besar reaksi ini melalui reaksi hipersensitifitas tipe I
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Food Hypersensitivity: reaksi terhadap makanan dengan dasar reaksi tipe II, III, IV
Food Intolerance: reaksi terhadap makanan dengan dasar reaksi non imunologi
Contoh: Toksik Metabolik Idiosinkrasi
3Prof DR Dr Ariyanto Harsono SpA(K)
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Patofisiologi
• Alergen Makanan– Protein, glikoprotein, polipeptida– BM > 18.000 dalton– tahan panas– tahan enzim proteolitik
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Prof DR Dr Ariyanto Harsono SpA(K)
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patofisiologi
• Pada ikan : alergen M• Pada telur : ovomucoid• Pada susu : betalaktoglobulin (BLG)
alfalaktalbumin (ALA) bovin serum
albumin (BSA) bovin gama globulin (BGG)
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Cow's milk -caseins Whey
-Casein,-Casein-Casein-Casein -Lactoglobulin-Lactalbumin
Exposure of allergen
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patofisiologi
• Pada kacang tanah : Arachin Conarachin
• Pada permunian : Peanut I Glicoprotein
180.000 dalton
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patofisiologi
• Pada udang : – alergen I (21.000 dalton)– alergen II (200.000 dalton)
• Pada gandum :– albumin– pseudoglobulin– euglobulin
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1. Genetic: Atopy2. Exposure
3. Mucosal Barrier
Immunology Paradigm
Factors Of Allergy Development
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Prof DR Dr Ariyanto Harsono SpA(K)
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a, b, c, d : HLA DRe : HLA DMf : HLA DM CIITA
Genetic
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patofisiologi
• Paparan awal– sel yang berperan
• sel penyaji antigen• sel T• sel B
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Macrophage are abundant in the lamina propria of the villi.Function:1.Phagocytosis2.Immune regulation by cytokines release3.APC
Goblet Cells
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Aktivasi sel-selImuno-kompeten•Sel T•Sel B•Sel Mast•Sel Langer- hans
Aktivasi sel-selstruk-tural
•Sel endotel•Sel epitel
Aktivasi dan Rekruitmen
•Sel Mast•Eosinofil•Neutrofil
•Basofil
Pelepasan mediator
Kerusakan epitel
Stimulasi neural
Dilatasi & peningkatan
permeabilitas vaskulerl
Bronkokonstriksi
Perbaikan epitel
•Proliferasi fibroblast
•Deposisi kolagen•Hipertropi/
hiperplasia otot polos
•Ekspansi vaskuler
Penyempitan saluran nafas
bawah
Symptom alergi
Bronkus hiper-reaktif
ALERGEN
A B C D EImunopatologi alergi
Airway remodelling
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SpA(K)
Trigger
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Macam Reaksi
• Reaksi tipe cepat (Rapid onset reaction)• Reaksi tipe lambat (Delayed onset Reaction)• Target organ:
– Mengenai 1 atau lebih organ tertentu– Contoh :
• Paru : asma bronkial• Hidung : rinitis alergika• Kulit : urtikaria, dermatitis atopik• Kardiovaskuler : renjatan anafilaktik
17Prof DR Dr Ariyanto Harsono SpA(K)
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VACCINATION
ACTIVATIONANTIGEN SPECIFIC B
CELL
GENERATION OF MEMORY
ACTIVATED CD4
+ Th-2 CELL IL-4
DIFFERENTIATION& AFFINITY
MATURATION
ANTIBODY SECRETING PLASMA CELLS
ANTIGEN PROCESSING &PRESENTATION
MHC Class II B CELL IMMUNOGLOBULINE
T CELL RECEPTOR ANTIGEN
B CELL
IL-5,IL-13
Cow’s Milk Protein
Cow’s Milk epitope
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Granule contents:Histamine,TNF-
Proteases, Heparin Lipid mediators:Prostaglandins
Leukotrienes
Cytokine production:Specifically IL-4, IL-13
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IgGIgG mediated: Kolik, Protein loosing enteropathy, Gastro-intestinal haemorrhageProf DR Dr Ariyanto Harsono SpA(K)
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Unsoluble allergen
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IgMIgM mediated: Kolik, Protein loosing enteropathy, Gastro-intestinal haemorrhage
Prof DR Dr Ariyanto Harsono SpA(K)
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Unsoluble allergen
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Prof DR Dr Ariyanto Harsono SpA(K)
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paparan awal...
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patofisiologi
• Patologi yang timbul disebabkan :– intereksi antar sel– mediator – sitokin
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patofisiologi
• Paparan selanjutnya mulai berperan
– limfosit T– netrofil– eosinofil
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Paparan selanjutnya
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Mast Cells and basophiles involve in allergic reaction in the context of antigen-IgE complex
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Physiologic barriers Block penetration of ingested antigens: Epithelial cells Glycocalyx Intestinal microvillus membrane structure Tight junctions joining adjacent enterocytes Intestinal peristalsisBreak down ingested antigens: Salivary amylases and mastication Gastric acid and pepsins Pancreatic enzymes Intestinal enzymes Intestinal epithelial cell lysozyme activity
Immunologic barriers Block penetration of ingested antigens: Antigen-specific s-IgA in gut lumen Clear antigens penetrating gastrointestinal barrier: Serum antigen-specific IgA and IgG Reticuloendothelial system
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Intestinal Epithelial Cells (IECs)
Central regulatory role in *Determining allergen absorption*Pattern of uptake of ingested Ag*Function as APC
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Mucosal immunoglobulins
S-IgA: Non inflammatoryMucosal protection
S-IgM similar to PlasmaIgM, activates complement and phagocytes
IgG: Neutralization, potentially inflammatory, Activates Complement and phagocytesIgE: Adverse hypersensitivity states, parasite expulsion
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IgA
Immunological BarrierThe role of B Cells
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Component (SC)
Dimeric
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mAb-IgA
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mAb-SC
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Development of Cow’s Milk AllergyEarly introduction of food antigens • stimulate production of IgE • IgE-mediated response to an allergen
– result of a series of molecular & cellular interactions
– Involving APC, T cells and B cells.
APCs present epitope• MHC class II molecules to T cells; peptide-MHC complex. • "first signal" leads to:
– T-cell proliferation, differentiation– initiation of "second"signal
These cells and their products
• interact with B-cells bearing appropriate antigen-specific receptors
• isotype switching • generation of antigen-
specific IgE.
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IgE in Relation to Cow’s Milk Allergy
• In atopic children– early antigenic exposure ->
IgE production – sensitisation of mast cells
• gastro-intestinal • respiratory tracts.
• IgE production starts early – primary immune response to food – continue even when the allergen is
avoided by an elimination diet.
• Food IgE-antibody concentrations:– increase to individual peak levels and
thereafter decline– sensitised through breast-milk to foods their
mother have eaten
This explains • infants already react to their first intake of
cow's milk formula• Infants with onset of allergic to one food,
also at high risk of developing allergy to other foods.
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once IgE response to cow’s milk protein is initiated
Prevention of food allergy using hypoallergenic milk formula in the first
trimester of life is very important, because:
it progresses throughout the infant life sensitisation to other food allergen may
develop
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Immunoglobulin Other Than IgE
IgG, IgM1. Anaphylactoid
2. Malabsorption.
3. Protein Losing Enteropathy
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Induction of Oral ToleranceT-cells regulation: 1.Intra Epithelial Lymphocytes: extrathymically derived, have limited TCR repertoir, capable of recognizing common microbiologic Ags, and demonstrate predominantly cytolytic functions
2.Lamina Propria Lymphocytes: thymicaly derived, contributes to limiting TCR/CD3-mediated signals in the mucosa.
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M Cell
Epithelial Cell
Intra EpithelialLymphocyte
Lamina PropriaLymphocyte
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IEL
LPL
CD3
Anergy/Tolerance
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Infiltrasi eosinofil...
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Gejala klinik
organ sasaran• Kulit• saluran napas• saluran cerna
• Mata• telinga• kardiovaskuler
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Target Organ
IgE-mediated disorder Non IgE-mediated disorder
Skin
Gastro-intestinal
Respiratory Tract Multi-system
Urticaria and angioedemaAtopic Dermatitis
Oral Allergy SyndromeGastrointestinal anaphylaxisAllergic eosinophilic gastroenteritis Asthma; Allergic Rhinitis Food-induced anaphylaxisFood associated, exercise-induced anaphylaxis
Atopic DrmatitisDermatitis Herpetiformis
ProctocolitisEnterocolitisAllergic eosinophilic- gastroenteritisEnteropathy syndromeCeliac Disease
Heiner Syndrome
Clinical Manifestation
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Target organ Unusual Clinical manifestation
•Skin
•ENT
•Respiratory
•Gastrointestinal
•Multi system
Vasculitis; Fixed Skin Eruption
Chronic Serous Otitis Media
Chronic Pulmonary disease (Heiner Syndrome)Hypersensitivity pneumonitis
Constipation; Gastroesophageal reflux
Irritability/Sleeplessness in infants; Arthropathy;Nephropathy; Thrombocytopenia
Unusual Clinical Manifestation
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Diagnosis
• Anamnesis• pemeriksaan fisik• laboratorium• uji eliminasi provokasi
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diagnosis
• Step 1 : eliminasi– eliminasi diet– minimal diet 1 (modified Rowe’s diet 1)– minimal diet 2 (modified Rowe’s diet 2)– egg & fish free diet– his own’s diet
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Diagnosis...
Step 2
• Provokasi :-DBPCFC -Open Challenge
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Penatalaksanaan
• “The mainstay of treatment of allergic disease is avoidance of allergen”
• allergen yang ditemukan dg uji eliminasi provokasi harus disingkirkan sebaik mungkin
• desensitisasi tidak dilakukan
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Diet Eliminasi 1. Elimination Diet2. Minimal Diet 13. Minimal Diet 24. Egg and Fish free
diet5. His own Diet
Prof DR Dr Ariyanto Harsono SpA(K) 66
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Diet Eliminasi
1. Elimination Diet2. Minimal Diet 13. Minimal Diet 24. Egg and Fish free
diet5. His own Diet
Prof DR Dr Ariyanto Harsono SpA(K) 67
Elimination Diet (BSTIK)Alergen utama yang harus dipantang selama 3 mingguBuahSusuTelurIkan Kacang
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Diet Eliminasi 1. Elimination Diet2. Minimal Diet 13. Minimal Diet 24. Egg and Fish free
diet5. His own Diet
Makanan hipoalergenik yang diperbolehkan:
Nasi(Beras) Daging sapi Kelapa Kedelai Sayur Wortel Bawang Gula, garam
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Diet Eliminasi
1. Elimination Diet2. Minimal Diet 13. Minimal Diet 24. Egg and Fish free
diet5. His own Diet
Makanan hipoalergenik lain yang diperbolehkan:
Kentang Daging kambing Jagung Kacang merah Sayur Wortel Bawang Gula, garam
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Diet Eliminasi 1. Elimination Diet2. Minimal Diet 13. Minimal Diet 24. Egg and Fish free
diet5. His own Diet
Diet ini digunakan untuk gejala alergi pada kulit.
Telur Ikan dipantang selama 3
minggu
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Diet Eliminasi
1. Elimination Diet2. Minimal Diet 13. Minimal Diet 24. Egg and Fish free
diet5. His own Diet
Diet ini digunakan untuk gejala alergi hirupan pada saluran nafas, pada uji kulit debu rumah dan tungau positif, anamnesa positif. Makanan yang disebutkan oleh pasien sendiri yang dipantang selama 3 minggu
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Makanan Pengganti
BuahSusuTelurIkan Kacang
Sayur Kentang Wortel Nasi Teh Susu Formula HA/Soya Kue mangkok, lapis, bikang Daging sapi, hati,paru, otak. Tahu, tempe, kecap
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PENATALAKSANAANPencegahan PrimerPencegahan SekunderPencegahan Tertier (Therapy)
ImunoterapiDietPharmalogic therapy
Beta-2 agonis Xanthine derivativeCorticosteroidAntagonist H1 generasi II
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PENATALAKSANAANPencegahan PrimerPencegahan SekunderPencegahan Tertier (Therapy)
ImunoterapiDietPharmalogic therapy
Beta-2 agonis Xanthine derivativeCorticosteroidAntagonist H1 generasi II
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Kehamilan = “Th2-disease”
*Anti-oksidan
*Hindari asap rokok
*Probiotik trimester terakhir kehamilan
Pencegahan Primer: Masa Kehamilan
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• ASI Eksklusif• Diet eliminasi untuk
ibu• Formula HA• Tunda makanan padat
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Pencegahan Primer dengan susu Formula
FORMULA H.A.
Partially hydrolyzed formulas: BUBUR SUSU
BISKUIT SUSU
XX
77Prof DR Dr Ariyanto Harsono SpA(K)
BISKUIT/BUBUR SUSU HA V
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PENATALAKSANAANPencegahan PrimerPencegahan SekunderPencegahan Tertier (Therapy)
ImunoterapiDietPharmalogic therapy
Beta-2 agonis Xanthine derivativeCorticosteroidAntagonist H1 generasi II
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Pencegahan Sekunder dengan susu Formula
FORMULA E.H.A.
Extensively hydrolyzed formulas:
BUBUR SUSU
BISKUIT SUSU
XX
79Prof DR Dr Ariyanto Harsono SpA(K)
BISKUIT SUSU/Bubur susu HA X
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Prevensi Sekunder dengan susu Formula
Soy formulas:BUBUR SUSU
BISKUIT SUSU
XX
80Prof DR Dr Ariyanto Harsono SpA(K)
BISKUIT SUSU/BUBUR SUSU HA X
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Prevensi Sekunder dengan susu Formula
Amino Acids:BUBUR SUSU
BISKUIT SUSU
XX
81Prof DR Dr Ariyanto Harsono SpA(K)
BISKUIT SUSU/BUBUR SUSU HA X
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PENATALAKSANAANPencegahan PrimerPencegahan SekunderPencegahan Tertier (Therapy)
ImunoterapiDietPharmalogic therapy
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Penatalaksanaan…..
• Eliminasi makanan setelah uji provokasi
• Diberi petunjuk makanan pengganti
– Pengganti Susu Sapi:
• Susu formula hidrolisat kasein
• Susu formula hidrolisat whey
• Susu formula kedelai
– Pengganti Buah: sayur
– Pengganti telur, ikan, ayam: daging sapi/kambing
• Jika diet tidak bisa dilaksanakan harus diberi pengobatan simtomatis
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PENATALAKSANAANPencegahan PrimerPencegahan SekunderPencegahan Tertier (Therapy)
ImunoterapiDietPharmacologic therapy
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penatalaksanaan
• Tujuan penatalaksanaan– frekuensi serangan– intensitas serangan– penggunaan obat– hari bolos sekolah– kualitas hidup
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penatalaksanaan
• Makanan pengganti (substitusi)– susu : formula hidrolisat whey
formula hidrolisat kasein formula kedelai
– buah : sayur– telur/ikan : daging sapi
daging kambing tahu tempe
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penatalaksanaan
• Makan direstoran tidak aman• Dianjurkan melakukan “label reading”• pada bayi, ibu juga harus ikut eliminasi
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penatalaksanaan
• Farmakoterapi– tidak bisa menggantikan eliminasi alergen– mengurangi gejala ringan tapi menutupi gejala
awal kulit
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Obat-obatan dan yang digunakan untuk mengobati alergi dapat dibagi menjadi kelompok besar:
1. Obat yang menghambat aktivitas bahan kimia yang dilepaskan dalam tubuh selama reaksi alergi: - antihistamin dan antagonis leukotriene;
2. Obat yang mengendurkan otot di saluran udara dari paru-paru, atau mengecilkan jaringan padat, atau membalikkan efek dari bahan kimia yang dilepaskan selama reaksi alergi: - bronkodilator, dekongestan dan epinefrin; anti acetylchloline
3. Obat-obatan yang mencegah aktivasi sel yang terlibat dalam reaksi alergi: - agen anti-alergi: kromolin, ketotifen
4. Obat yang memiliki efek yang lebih umum dalam mengurangi peradangan: - kortikosteroid;
5. Terapi yang memodifikasi respon imun: - imunoterapi alergen. Prof DR Dr Ariyanto Harsono
SpA(K)89
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penatalaksanaan
• Cromolin, nedocromil– penggunaan pada asma
• asma ringan• asma latihan• gejala GI• dermatitis atopi
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penatalaksanaan
• Glukokortikoid – digunakan pada penderita alergi makanan
dengan gejala• asma• rinitis alergika• anafilaksis
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penatalaksanaan
• Beta adrenergik agonis– beta 2 agonis
• untuk asma– epinefrin
• untuk renjatan anafilaksis
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penatalaksanaan
• Metilxantin– sebagai bronkodilator
• Antagonis kolinergik– untuk pengobatan tambahan pada penderita
dengan gejala asma, rinitis alergika
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penatalaksanaan
• Leukotrien antagonis: Montelukast, Zafirlukast– untuk gejala asma
• kombinasi dengan xantin dan beta 2 agonis
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penatalaksanaan
• H1 reseptor antagonis • Generasi II
– efek samping CNS ( - )– dapat digunakan mulai 6 bulan– dapat digunakan dalam jangka lama – efektif untuk
• urtikaria kronik• rinitis alergika• dermatitis atopik• asma ringan