Allergy and inflammation
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- Lynne Griffith
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1 and inflammation 1
2 Allergic population hyper-producers of IgE consistently increasing western societies: ~20% of general population 2
3 Allergic population 3
4 Allergic triggers 4
5 Allergic triggers abnormal over-reaction to normal exposures 5
6 Allergic reactions basophils, blood cells tissue cells 6
7 Allergic reactions 7
8 Allergic symptoms food allergies mouth/pharynx itching abdominal pain nausea, vomiting BP respiratory symptoms dermatological symptoms airborne allergies runny nose mucus production sneezing itching eyes, nose, throat watering eyes conjunctivitis 8
9 Allergy types/presentations allergic rhinitis inflammation of nasal mucous membranes allergic conjunctivitis atopic eczema/contact dermatitis anaphylactic reaction (shock) asthma 9
10 Allergic rhinitis local exposure to allergen (inhaled) interaction with mast cells release of hisatmine, leukotrienes, chemotactic factors local edema, cellular infiltration, mucosal thickening signs and symptoms of allergic rhinitis sneezing, nasal irritation, watery nose, congestion 10
11 Allergic rhinitis allergic rhinitis asthma 11
12 Non-pharmacological Tx 12
13 Non-pharmacological Tx avoiding/minimizing exposure to allergen immunotherapy = desensitization ( IgE, IgG) 13
14 H 1 -recpetor blockers (antihistamines) α-adrenergic agonists (AAAs) intranasal corticosteroids (INCs) cromolyn/nedocromil leukotriene modifiers 14
15 H 1 -recpetor blockers (antihistamines) α-adrenergic agonists (AAAs) intranasal corticosteroids (INCs) cromolyn/nedocromil leukotriene modifiers 15
16 H 1 -recpetor blockers (antihistamines) block histamine binding to H 1 receptors most effective vs. sneezing and watery nose ineffective vs. congestion oral/nasal administration 1 st generation: additional anticholinergic properties and CNS ADEs 2 nd generation: less anticholinergic/cns ADEs, longer action 16
17 H 1 -recpetor blockers (antihistamines) - 1 st generation chlorpheniramine (Ahiston, Acamol-Tsinun, Dexamol-Cold ) diphenhydramine (various combination products) hydroxizine (Otarex ) anticholinergic properties: - sedation, drowsiness, dry mouth/eyes, urinary hesitance CNS effects (lipophillic): - memory, confusion, motor function 17 - children, rare: stimulation
18 H 1 -recpetor blockers (antihistamines) - 2 nd generation cetirizine (Zytrec, Histazine ) loratadine (Lorastine ) desloratadine (Aerius ) metabolites: less CNS ADEs than parent? fexofenadine (Telfast ) (terfandine metabolite) azelastine (Rhinolast ) - spray (antiinflammatory: vs. congestion; rapid onset: rescue ; bitter taste) 18
19 H 1 -recpetor blockers (antihistamines) - 2 nd generation lesser anticholinergic effects (dry eyes) less CNS penetration (lipophobic): less/non-sedating less effective against congestion (vs. INCs) 19
20 H 1 -recpetor blockers (antihistamines) α-adrenergic agonists (AAAs) intranasal corticosteroids (INCs) cromolyn/nedocromil leukotriene modifiers 20
21 α-adrenergic agonists (AAAs) nasal decongestants, sympathomimetics phenylephrine (combinations: Alnase, Vibrocil, Sinaf ) oxymetazoline (Alrin, Rhinoclir ) xylometazoline (Otrivin ): long-acting pseudoephedrine (Sinufed, various combinations), 21
22 α-adrenergic agonists (AAAs) vasoconstrictors: reduce edema, congestion mostly intranasal use (pseudoephedrine - oral) pseudoephedrine: additional beta-agonist effect: bronchial relaxation, HR AAA phenylephrine xylometazoline pseudoephedrine duration 0.5-4hr 10hr 6-8hr frequency 4-6/day 2/day 2-4/d 22
23 α-adrenergic agonists (AAAs) ADEs: limited with intranasal administration; potential: - CNS effects: headache, insomnia, excitability - BP, HR - local effect: dryness, irritation, itching PD DDIs (low probability with local administration) 23
24 α-adrenergic agonists (AAAs) high dose/prolonged use down-regulation of local α 1 receptors loss of pharmacological effect rebound congestion 24 rhinitis medicamentosa
25 H 1 -recpetor blockers (antihistamines) α-adrenergic agonists (AAAs) intranasal corticosteroids (INCs) cromolyn/nedocromil leukotriene modifiers 25
26 Intranasal corticosteroids (INCs) fluticasone (Flixonase, Allegro ) mometasone (Nasonex ) budesonide (Nasocort ) betamethasone (Betnesol ) 2 nd generation 1 st generation 3 rd generation 26
27 Intranasal corticosteroids (INCs) inhibition of allergic inflammation advanced INCs (mometasone, fluticasone): lipophilicity systemic bioavailability (<2%) systemic adverse effects 27
28 Intranasal corticosteroids (INCs) inhibition of allergic inflammation 1998 meta-analysis: significantly greater relieve of congestion, nasal discharge, sneezing, nasal itch, postnasal drip, and total nasal symptoms than oral antihistamines. ADEs: - systemic - rare - local - irritation, itching, dryness, burning sensation once-daily: prefer at night 28
29 H 1 -recpetor blockers (antihistamines) α-adrenergic agonists (AAAs) intranasal corticosteroids (INCs) cromolyn/nedocromil leukotriene modifiers 29
30 Cromolyn/nedocromil mast-cell stabilizers effective only as prevention/prophylaxis - prior to allergy season - prior to exposure to known allergen in mild cases may be corticosteroid-sparing (young children) frequent dosing required (3-4/day) main advantage: safety (children, pregnancy, elderly) 30
31 H 1 -recpetor blockers (antihistamines) α-adrenergic agonists (AAAs) intranasal corticosteroids (INCs) cromolyn/nedocromil leukotriene modifiers 31
32 Leukotriene modifiers mainly effective vs. congestion useful in patients - intolerant of intranasal administration - with concomitant asthma 32
33 Therapeutic considerations INCs usually 1 st -line: superior efficacy vs. all symptoms antihistamines ineffective vs. congestion 2 nd -generation ( non-sedating ) safer than 1 st generation AAAs for short-term use only cromolyn ineffective for acute relief leukotriene modifiers: limited data combination products 33
34 Therapeutic considerations - special populations population 1 st -line 2 nd -line 3 rd line children <3yr cromolyn 2 nd -gen. AH INC concomitant asthma leukotriene modifier elderly INC 2 nd -gen. AH pregnancy cromolyn 2 nd -gen. AH (budesonide?) AH - antihistamine; INC - intranasal corticosteroid 34
35 Pharmacotherapy allergy DRUGS FOR EXAM chlorpheniramine loratadine oxymetazoline pseudoephedrine (fluticasone) (cromolyn) (montelukast) 35
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