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ROLE OF ANTIHISTAMINE IN MAST CELL-ASSOCIATED DISEASE PowerPoint Presentation

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Description : Histamine regulating : maturation and activation of leukocyte directing migration to target site modulating function of monocyte, T cells, macrophages, neutrophils, eosinophils, B cells, and dendritic cells

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Published on : Sep 07, 2020 | Views : 1077 | Downloads : 3

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JOURNAL READING Supervisor : Prof. Dr. Teti H. S. Madiadipoera, dr., Sp. THT-KL (K), FAAAAI Presenter : Eveline Sabrina Ranti, dr Otorhinolaryngology Head and Neck Surgery Departement Medical Faculty Padjajaran University Hasan Sadikin Hospital 2020
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INTRODUCTION
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Allergic disease allergic asthma Allergic rhinitis Pruritus atopic dermatitis Mast cell histamine  axial player in stimulating the development of allergic-related inflammatory disease INTRODUCTION 3 Thangam EB, Jemima EA, Singh H, Baig MS. The Role of Histamine and Histamine Receptors in Mast Cell-Mediated Allergy and Inflammation : The Hunt for New Therapeutic Targets. 2018;9(August) COMPLEX INTERACTION Between several inflammatory cells, in response to various allergic stimuli
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Histamine regulating : maturation and activation of leukocyte directing migration to target site modulating function of monocyte, T cells, macrophages, neutrophils, eosinophils, B cells, and dendritic cells Histamine receptors exert its biological impacts INTRODUCTION 4 Thangam EB, Jemima EA, Singh H, Baig MS. The Role of Histamine and Histamine Receptors in Mast Cell-Mediated Allergy and Inflammation : The Hunt for New Therapeutic Targets. 2018;9(August) H1R, H2R, H3R, H4R
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Mast Cells : Source of Histamine Histamine regulates plethora of pathophysiological and physiological processes (gastric acid secretion, inflammation, vasodilation, bronchoconstriction) 5 Monticelli S and Leoni C. Epigenetic and transcriptional control of mast cell responses F1000Research 2017 Thangam EB, er al.. The Role of Histamine and Histamine Receptors in Mast Cell-Mediated Allergy and Inflammation : The Hunt for New Therapeutic Targets. 2018;9(August)
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Role of Histamine in Allergic Disease Creditos, 1998, Allergic Rhinitis and Asthma
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Simon FER, et al. J Allergy Clin Immunol 2011;128:1139-50. Antiinflammatory Effects of Antihistamines
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HISTAMINE RECEPTORS AND ROLE IN ALLERGIC INFLAMMATION
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Thangam EB, Jemima EA, Singh H, Baig MS. The Role of Histamine and Histamine Receptors in Mast Cell-Mediated Allergy and Inflammation : The Hunt for New Therapeutic Targets. 2018;9(August)
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Increase vascular permeability 10 The H1-Receptor Thangam EB, Jemima EA, Singh H, Baig MS. The Role of Histamine and Histamine Receptors in Mast Cell-Mediated Allergy and Inflammation : The Hunt for New Therapeutic Targets. 2018;9(August) Enhance immune response Contraction of smooth muscle of respiratory tract Skin pruritus
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Secretion of Gastric Acid Relaxation of airway, and induce mucus production Increase Vascular Permeability Activation of Immune System 11 The H2-Receptor Thangam EB, Jemima EA, Singh H, Baig MS. The Role of Histamine and Histamine Receptors in Mast Cell-Mediated Allergy and Inflammation : The Hunt for New Therapeutic Targets. 2018;9(August)
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The H3-Receptor 12 Associated with rhinitis homeostatic regulation of energy levels, sleep-wake cycle Homeostatic regulation of cognition Thangam EB, Jemima EA, Singh H, Baig MS. The Role of Histamine and Histamine Receptors in Mast Cell-Mediated Allergy and Inflammation : The Hunt for New Therapeutic Targets. 2018;9(August)
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The H4 - receptor 13 upregulates the expression of FcεRI on mast cells expression of various pro-inflammatory cytokine and chemokines Thangam EB, Jemima EA, Singh H, Baig MS. The Role of Histamine and Histamine Receptors in Mast Cell-Mediated Allergy and Inflammation : The Hunt for New Therapeutic Targets. 2018;9(August)
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Two-state model of the Histamine H1 receptor Simons FER. Advances in H 1 -Antihistamines . N Engl J Med. 2004;351(21):2203–17.
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Molecular Basis of Action of Histamine and Antihistamines Bakker RA, et al (2000) Constitutive activity of the histamine H1 receptor reveals inverse agonism of histamine H1 receptor antagonists Simons FER, Akdis CA. (2011) Histamine and H1-antihistamines
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Characteristic of Histamine Receptors Simons FER. Advances in H 1 -Antihistamines . N Engl J Med. 2004;351(21):2203–17.
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Antihistamine and Clinical Use Simons FER, Simons KJ. Histamine and H1-antihistamines: Celebrating a century of progress. J Allergy Clin Immunol [Internet]. 2011;128(6):1139-1150.e4.
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ROLE OF ANTIHISTAMINE IN MAST CELL-ASSOCIATED DISEASE
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H1-anthistaminecetirizine, mizolastine  treatment mast cell activated diseases H2R selective antihistaminesCimetidine, ranitidine reduce gastric acid secretion H3R antihistaminesthioperamide, clobenpropit, BF2. 649, PF-03654746, JNJ-17216498, and MK 0249. selective H4R antihistamineJNJ 7777120  inflammation and pruritus 19 ANTIHISTAMINE Thangam EB, Jemima EA, Singh H, Baig MS. The Role of Histamine and Histamine Receptors in Mast Cell-Mediated Allergy and Inflammation : The Hunt for New Therapeutic Targets. 2018;9(August)
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Antihistamines Generation First Generation Sedating antihistamines Poor H1 receptor selectivity Act on muscarinic receptors  anticholinergic effect Cross blood brain barrier E.g. Diphenhydramine, chlorpeniramine Second Generation Non sedating antihistamines Improved H1 receptor selectivity Widely tissue distribution Minimal CNS penetration Absence or decreased sedation Anti-allergic & anti-inflammatory properties Longer half life (once daily) E.g. cetirizine, loratadine. New Second Generation Have been developed from existing agent (second generation, active stereoisomer or metabolit) Non sedating antihistamines More effective vs 2nd gen Less side effect vs 2nd gen E.g.. levocetirizine, Desloratadine, fexofenadine Bousquet J. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008. Allergy.2008:63(S86): 53-72
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CLINICAL TRIALS TARGETING HISTAMINE RECEPTORS
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CLINICAL TRIAL JNJ 39758979, a potent and selective H4R antagonist, has shown impressive results in different allergic inflammatory diseases such as dermatitis, asthma, pruritus, and arthritis The combination therapy of H4R antagonist and the H1R antihistamine, cetirizine, showed a more beneficial effect in the treatment of pruritus as compared with H1R alone 23 Thangam EB, Jemima EA, Singh H, Baig MS. The Role of Histamine and Histamine Receptors in Mast Cell-Mediated Allergy and Inflammation : The Hunt for New Therapeutic Targets. 2018;9(August)
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24 Conclusion andFuture Prospective The research on histamine pathway underscore the importance of histamine in allergic inflammation through its effects on the H1R and H4R. There appears to be some overlap in function between H1R and H4R Suggest the combination both H4R and H1R antagonists may provide a potential benefit in the treatment of various allergic and inflammatory diseases. Thangam EB, Jemima EA, Singh H, Baig MS. The Role of Histamine and Histamine Receptors in Mast Cell-Mediated Allergy and Inflammation : The Hunt for New Therapeutic Targets. 2018;9(August)
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