THE CHOICE OF DRUGS IN THE MANAGEMENT OF ALLERGY DISEASES Zakiudin Munasir

Allergen Avoidance and Environmental Control Pharmacotherapy Immunotherapy Step 1 Step 2 Step 3 Step-wise management of allergic diseases

Church MK, Journal WAO May/June 2004

Antihistamin Ditemukan akhir 1930, digunakan dalam klinik thn 1940 Struktur menyerupai histamin  menempati reseptor histamin  menghambat efek histamin

Antihistamines Block histamine receptor Stabilise mast cell membrane Reduce Mediator release ICAM-1 expression Eosinophil recuitment

Church MK, Journal WAO May/June 2004

Antihistamine Generation I (classic) : Chlorpheniramine maleat,diphenhydramine (sedative,anticholinergic effect) Generation II: cetirizine,loratadine Generation III: levo-cetirizine, des-loratadine (less sedative, no anti cholinergic, antiinflammation effect)

Cetirizine Potent and specific AH Second generation H1 receptor antagonist, active metabolite of carboxylic acid of first generation H1 antihistamine, hydroxyzine Not metabolized through cytochrome P450, excreted in large amount in urine

Cetirizine Antiinflammation effect, inhibits eosinophil migration induction in the skin of atopic patient.atopik (invivo ) Decreases ICAM-1 receptor in nasal epithel. Controls persistent minimal inflammation

Dosis < 2 tahun : 2 x 0,25 mg/ KgBB perhari > 2 tahun : 1 x 0,25 mg/KgBB perhari

LORATADIN Loratadin dapat menghambat pelepasan histamin invivo dan invitro Loratadin dapat menghambat pelepasan histamin dari basofil yang diinduksi anti IgE dan kalsium ionofor pada rinitis alergika Efektivitas sebanding dengan terfenadin tetapi lebih aman Beberapa studi membuktikan loratadin tidak mempunyai efek samping bermakna, terutama thd SSP dan jantung

Dosis 2 – 5 tahun5 mg/hari 1x 6 tahun – dewasa10 mg/hari 1x Pasien dg gangguan fungsi hati dan ginjal, diberikan dosis yg sama selang sehari Tidak harus diberikan setelah makan

Corticosteroids Mucus secretion Vascular permeability/oedema Mediator release Cytokine production Inflammatory infiltrate/activation Langerhan cells in epithelium

Glucocorticoid inhibits The production of the major RV receptor, ICAM-1 Van de Stolpe et al. Am J Respir Cell Mol Biol 1995

Relative Potencies and Equivalent Doses of Representative CorticosteroidsCompound Antiinflamatory potency Na + - Retaining potency Duration of action Equivalent dose, mg Cortisol11S20 Cortisone0.80.8S25 Fludrocortisone10125I + + Prednisone40.8I5 Prednisolone40.8I5 6α-methylprednisolone50.5I4 Triamnicolone50I4 Betamethasone250L0.75 Dexamethasone250L This agent is not used for glucocorticoid effects (Schimmer BP, Parker KL. Adrenocorticotropic hormone, adrenocortical steroids and their synthetic analogs, inhibitor of the synthesis and actions of adrenocortical hormones; Goodman & Gilman’s the pharmacological basis of theurapeutics, 2001)

Symptomatic drugs Bronchodilator : B 2 agonists Phosphodiesterase inhibitors

Bronchodilator & Vasoconstrictor Adrenaline/ Nor epinephrine HCL Ephedrine

Decongestant Pseudoephedrine: stereoisomer of ephedrine but less potent

Mast cell stabilizers Ketotifen Generation II AH Sodium cromoglycate B 2 agonist + phosphodiesterase inhibitor combination

LEUKOTRIEN RECEPTOR ANTAGONIST Montelukast Zafirlukast

Antileukotrien (leukotrien modifyer) Cysteinil - leukotrien 1 receptor antagonist (montelukast, pranlukast dan zafirlukast) dan inhibitor 5- lipoxygenase (zileuton) Modify leukotrien effect : Small bronchi dilatation, control cough, improve lung function, control respiratory tract inflamation and prevent asthma exacerbation.

ANTI IgE ( Omalizumab)

Indication: Refractory treatment with high dose glucocorticoid inhalation Can be given add-on in patient after received glucocorticoid and Long-acting β2 - agonist inhalation

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