6. Histamine Endogenous Vasoactive Amine • Mediates the increase in capillary permeability associated with the contraction of endothelial cells in postcapillary venules that occurs with mild injuries • Released from granules in mast cells, basophils, and platelets • Degranulation is usually a localized event in response to acute insult, therefore inflammation remains site specific Gartner and Hiatt. “Color Textbook of Histology” Second Ed. 2001
7. Histamine Histamine Receptor Subtypes Katzung. “Basic and Clinical Pharmacology.” 9th edition. 2004 Eosinophils, neutrophils, CD4 T-cells H 4 Presynaptic: brain, neurons H 3 Gastric mucosa, cardiac muscle, mast cells, brain H 2 Smooth muscle, endothelium, brain H 1 Distribution Receptor subtype
15. Allergic Rhinitis Co-morbidities and Associated Findings • Asthma • Otitis Media • Sinusitis Reduced Quality of life: • sleep disturbance • impaired cognitive function • depression and anxiety “ Pharmacotherapy of allergic rhinitis: a pharmaco-economic approach.” Allergy 2009: 64: 85: 9 5
16. Allergic Rhinitis Burden-of-illness • $2-5 billion USD annually in direct costs • $5-9 billion USD annually in indirect costs “ The economic burden of allergic rhinitis: a critical evaluation of the literature.” Reed SD, Lee TA, McCrory DC. Pharmacoeconomics . 2004;22(6):345-61. Review.
23. Chronic Idiopathic Urticaria A Difficult Disease To Treat “ I've had Chronic Idiopathic Urticaria for 6 years and its not going away, but getting worse. I've been to so many doctors and specialists! All these doctors do the same tests and they tell me the same thing ‘there is no cure and nothing we can do.’” http://answers.yahoo.com/question/index?qid=20080928142252AA64Xyf
31. Treatment Options Pharmacotherapy for Allergic Rhinitis Well-controlled clinical trials have shown the efficacy and safety of pharmacotherapy : • Intranasal corticosteroids • Oral or intranasal antihistamines • Oral antihistamine/decongestant combinations • Intranasal ipratropium • Intranasal cromolyn (42) • Oral montelukast Online.statref.com
32. Treatment Options Pharmacotherapy for Allergic Rhinitis Well-controlled clinical trials have shown the efficacy and safety of pharmacotherapy: • Oral antihistamines
34. Treatment Options Pharmacotherapy for CIU The cornerstone of treatment for Chronic Idiopathic Urticaria is antihistamines: • Oral antihistamines Online.statref.com
38. Antihistamine Pharmacology 1st Generation Diphenhydramine ( Benadryl ) - inverse agonist at H 1 receptor - anticholinergic - antiemetic, sedative, hypnotic - treatment for RA, hives - cheap, effective, available - significant drowsiness “ Lippincott’s Illustrated Review: Pharmacology.” Harvey and Champe Eds. 4th edition. 2009
39.
40. Antihistamine Pharmacology 2nd Generation Cetirizine ( Zyrtec ) - racemic compound - treatment for allergies, hay fever, angioedema, and urticaria - available OTC - less CNS effects than 1st generation antihistamines - mild drowsiness www.wikipedia.org/cetirizine
41. Antihistamine Pharmacology “ Heritage” - Following administration of hydroxyzine, a 1st generation antihistamine, the major metabolite in the blood is cetirizine - Cetirizine is a racemic mixture of dextrocetirizine and levocetirizine
44. Antihistamine Pharmacology Levocetirizine - While both cetirizine and hydroxyzine possess high affinity at the H 1 receptor, the R-configured levocetirizine has much slower dissociation rate from the H 1 receptor than R-hydroxyzine, making it an insurmountable antagonist. - Levocetrizine and cetirizine have longer half-lives, and can be administered once daily. “ Physicochemical, pharmacological and pharmacokinetic properties of the zwitterionic antihistamines cetirizine and levocetirizine.” Curr Med Chem. 2008;15(21):2173-91.
