TRAINING MANUAL CONTENTS CONTENTS PART I: ALLERGY GENERAL CONCEPTS 1. INTRODUCTION TO ALLERGY .................................................................................. 3 1.1 Definition .................................................................................................................... 3 1.2 History ....................................................................................................................... 3 1.3 Epidemiology .............................................................................................................. 4 2. ANATOMY OF THE RESPIRATORY SYSTEM ............................................................ 6 2.1 Upper respiratory tract .............................................................................................. 6 2.2 Nose and paranasal sinuses ...................................................................................... 7 2.3 Pharynx ...................................................................................................................... 7 2.4 Larynx ........................................................................................................................ 8 2.5 Ear .............................................................................................................................. 8 3. ANATOMY OF THE SKIN AND FUNCTIONS .................................................................. 9 3.1 Introduction ................................................................................................................ 9 3.2 Skin structure and functions ..................................................................................... 9 3.2.1 Epidermis ............................................................................................................ 10 3.2.2 Dermis ................................................................................................................. 10 3.2.3 Hypodermis ......................................................................................................... 11 3.2.4 Skin adnexa ........................................................................................................ 11 3.2.5 Sensory receptors in the skin ............................................................................. 11 3.2.6 Blood distribution in the skin .............................................................................. 11 3.2.7 Biological functions of the skin .......................................................................... 11 4. SKIN LESIONS AND INFLAMMATION ...................................................................... 13 4.1 Introduction ................................................................................................................ 13 4.2 Inflammatory process in the skin .............................................................................. 13 4.2.1 Vascular mechanisms of skin inflammation ....................................................... 13 4.2.2 Cellular mechanisms of skin inflammation ......................................................... 13 4.2.3 Lesion repair ....................................................................................................... 14 4.3 Skin lesions ................................................................................................................ 15 4.3.1 Primary lesions ................................................................................................... 15 4.3.2 Secondary lesions ............................................................................................... 16 5. THE IMMUNE SYSTEM ............................................................................................ 20 5.1 Non-specific immunity ............................................................................................... 20 5.2 Specific immunity ...................................................................................................... 20 5.2.1 Humoral immunity ............................................................................................... 21 5.2.2 Cell mediated (cellular) immunity ...................................................................... 21 5.2.3 Primary and secondary immune response .......................................................... 22 6. THE HYPERSENSITIVITY REACTION (ALLERGY) ..................................................... 24 6.1 Types of allergic reactions ......................................................................................... 24 6.1.1 Early allergic reaction ......................................................................................... 24 6.1.2 Late allergic reaction (allergic inflammation) .................................................... 25 7. ALLERGIC RHINITIS ................................................................................................. 27 7.1 Traditional classification ........................................................................................... 27 7.2 ARIA classification ..................................................................................................... 29 7.3 Allergic rhinitis and quality of life.............................................................................. 30 7.4 Allergic rhinitis diagnosis........................................................................................... 32 7.4.1 Clinical history and physical examination .......................................................... 32 7.4.2 Physical examination .......................................................................................... 33 For internal use only CONTENTS 7.4.3 Allergy tests ....................................................................................................... 33 7.5 Treatment of allergic rhinitis...................................................................................... 34 7.5.1 Allergen avoidance.............................................................................................. 34 7.5.2 Immunotherapy ................................................................................................... 35 7.5.3 Drug therapy ....................................................................................................... 35 7.5.3.1 First-generation antihistamines .................................................................. 36 7.5.3.2 Second-generation antihistamines ............................................................. 37 7.5.3.3 Adverse reactions of antihistamines .......................................................... 40 8. URTICARIA .............................................................................................................. 42 8.1 EAACI/GA2LEN/EDF/WAO definition ........................................................................ 42 8.2 EAACI/GA2LEN/EDF /WAO classification ............................................................... 43 8.2.1 Acute urticaria .................................................................................................... 43 8.2.2 Chronic urticaria ................................................................................................. 43 8.3 Treatment of urticaria ................................................................................................ 45 8.3.1 Identification and elimination/avoidance of the stimulus ................................. 45 8.3.2 Symptomatic pharmacological treatment .......................................................... 45 8.3.3 Treatment of urticaria according to EAACI/GA2LEN/EDF/WAO guidelines ...... 45 9. OTHER ALLERGIC SKIN CONDITIONS – INSECT BITE PRURIGO ............................. 47 PART II: PRODUCT PROFILE 1. PHARMACOLOGICAL PROPERTIES OF RUPATADINE .............................................. 53 1.1 Chemical structure .................................................................................................... 53 1.2 Pharmacodynamics .................................................................................................... 53 1.2.1 Mode of action .................................................................................................... 54 1.2.2 Antihistamine activity ......................................................................................... 54 1.2.3 Anti-PAF activity ................................................................................................. 58 1.2.4 Anti-inflammatory and antiallergic activity ........................................................ 63 1.2.5 Anticholinergic effects ....................................................................................... 65 2. RUPATADINE PHARMACOKINETIC PROPERTIES .................................................... 66 2.1 Absorption and distribution ........................................................................................ 67 2.2 Metabolism and excretion ......................................................................................... 67 2.3 Pharmacokinetics in children .................................................................................... 67 2.4 Elderly population ..................................................................................................... 68 3. RUPATADINE EFFICACY PROFILE IN ALLERGIC RHINITIS .......................................... 70 3.1 Seasonal allergic rhinitis (SAR) ................................................................................. 71 3.1.1 Dose-finding studies ..........................................................................................