Chapter 20: Drugs for Tx Allergic Rhinitis DH206: Pharmacology Lisa Mayo, RDH, BSDH Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.

Chapter 18 Outline 1.Histamine 2.Antihistamines 3.Intranasal Corticosteroids

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Chapter 18 Outline 1.Histamine

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Histamine Basics All human synthesize histamine Stored in mast cells in intestinal mucosa Amt released determines person’s response There are 3 types of histamine in human body (next slide)

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Histamine Basics 3 histamine receptors (none have clinical use) 1.H 1 : located on smooth muscle of GI tract, heart, vein, capillaries, bronchi  Vasodilation ( ↓ BP – could lead to hypotension)  Bronchoconstriction  Pain or itching in cutaneous nerve endings (histamine binds to receptors on local sensory nerve endings)  ↑ production of nasal & bronchial mucus 2.H 2 : located on brain, stomach, heart, blood vessels  ↑ gastric acid secretion  Vasodilation 3.H 3 : on mast cells  Stimulation inhibits histamine release

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.

(A): Initial exposure to allergen, IgE produced & binds to mast cells (B) Subsequent exposure: allergen binds to IgE on the mast cell (C) Mast cells release histamine, leukotriene, prostaglandin ↓ cause bronchoconstriction, vasodilation, mucus production ALLERGY RXN

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ Histamine is released largely in part by: a.Macrophages b.Enteroendocrine cells c.Lymphocytes d.Neutrophils e.Mast cells

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ Histamine is released largely in part by: a.Macrophages b.Enteroendocrine cells c.Lymphocytes d.Neutrophils e.Mast cells

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 2.Antihistamines

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Histamine Basics Antihistamines: Block histamine receptors ▫H 1 -blockers used to tx allergic rxns & motion sickness ▫Adverse rxns due to binding of antihistamines on other organs ▫Anaphylactic rxn  Histamine causes more vasodilation & capillary permeability = leads to a further decrease in BP = then shock & cardiac collapse  Which drug do we give to tx? Why? EPIANTIHISTAMINE α 1 -receptors Causes vasoconstriction ( ↑ BP) ß2-receptors Cause bronchodilation Histamine Antagonist Antagonize bronchoconstriction

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ Serotonin is a preferred vasoactive mediator with actions similar to those of: a.Heparin b.Thrombin c.Acetylcholine d.Histamine

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ Serotonin is a preferred vasoactive mediator with actions similar to those of: a.Heparin b.Thrombin c.Acetylcholine d.Histamine

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Relieve S&S of histamine release in body These drugs ONLY effective on H 1 receptors in body (H 2 assoc. with effects in stomach – CH15) ▫Oral ▫Parental ▫Topical creams, lotions, sprays ▫Nasal spray for relief of allergic rhinitis ▫Eye drops for itching, watery eyes Antihistamines (H 1 -Receptor Antagonists)

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. First-generation drugs: adverse rxns related to anticholinergic activity (xerostomia, sedation) Antihistamines (H 1 -Receptor Antagonists) 1 st -Generation Antihistamines Diphenhydramine(Benadryl) Chlorpheniramine(Chlor-Trimeton) Hydroxyzine(Atarax, Vistaril) Dexchlorpheniramine(Prolarmine) Promethazine(Phenergan) Clemastine(Tavist) Dimenhydrinate(Dramamine) Meclizine(Antivert)

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Second-generation drugs ▫Less anticholinergic activity: not as many adverse rxns Antihistamines (H 1 -Receptor Antagonists) 2 nd -Generation Antihistamines Fexofenadine(Allegra) Cetirizine(Zyrtec) Loratadine(Claritin)

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Allegra & Claritin 2 nd gen.

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Antihistamines (H 1 -Receptor Antagonists) ACTIONEFFECTS IN BODYDRUGS Antihistaminic Action Allergy relief Relieve itching Benadryl is most effective Anticholinergic Action Sedation, Dry up secretions Bronchodilation Dilate eyes Relieve vertigo & motion sickness Meclizine(Antivent,Bonine) Promethazine(Phenergan) Dimenhydrinate(Dramamine) Adverse Rxns related to these effects

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Intranasal antihistamines ▫All intranasal’ s usually taken in combo with oral sinus med Antihistamines (H 1 -Receptor Antagonists) Intranasal Antihistamine Azelastine(Astelin)Allergic rhinitis Oxymetazoline(Afrin) Phenylephrine(Sinex) α 1 -antagonist: constrict blood vessels 3-5 days after use – will have re-bound action & symptoms worse than before Olopatadine hydrocholoride(Patanase) Allergic rhinitis Board Alert!

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ Which of the following adverse effects occurs with antihistamines? a.Dry mouth b.Increased salivation c.Dry skin d.Moist skin

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ Which of the following adverse effects occurs with antihistamines? a.Dry mouth b.Increased salivation c.Dry skin d.Moist skin

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ Which of the following antihistamines has anticholinergic effects? a.Loratadine b.Fexofenadine c.Diphenhydramine d.Azelastine

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ Which of the following antihistamines has anticholinergic effects? a.Loratadine b.Fexofenadine c.Diphenhydramine d.Azelastine

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 3.Intranasal Corticosteroids

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Intranasal Corticosteroids Intranasal Corticosteroid Budesonide(Rhinocort) Ciclesonide(Omnaris) Fluticasone propionate(Flonase) Mometasone furoate(Nasonex) Board Alert!