AGORA’ 2016

3° Corso Dermatologia, Immunologia e Allergologia Dermatologica

Antistaminici: pro e controMaria Filomena Caiaffa

Professore di Allergologia ed Immunologia Clinica Presidente di Corso di Laurea di Medicina e Chirurgia

Università di Foggia

AntihistaminesAntihistamines → available since the 1950sH1 receptor antagonistsHistamine → H1 receptors on endothelial cells (the wheal) and on sensory nerves (pruritus) → active conformationAntihistamines → same H1 receptors → inactive conformationEfficacy proportional to receptor occupancy → histamine vs. antihistamine

Simons F. N Eng J Med 351:2203-2217, 2004.

Antihistamines• Chemical Class First generation agents Second generation agents

Alkylamines → Chlorpheniramine(Trimeton)BrompheniramineTriprolidine Acrivastine

Piperazines → OxatomideHydroxyzine Cetirizine(Atarax) Levocetirizine

Ethanolamines → Diphenydramine

Phenotiazines → Promethazine(Farganesse)

Piperidines → Azatadine Astemizole*, Terfenadine*,Ketotifene Bilastine, Ebastine,Ciproeptadine Rupatadine, Loratadine

Fexofenadine

Tryciclic Antidepressant → Doxepin Azelastine

First generation H1-antihistamines

Pronounced anthicolinergic effects and sedative actions on the central nervous system (CNS)

Interactions with alcohol and CNS drugs (analgesics, hypnotics, sedative)Impact on concentration, learning and performance (risk increased in the elderly and children)Side effects most pronounced in Promethazine, Ketotifen, Diphenydramine, Chlorpheniramine (hospital use → premedication in allergic patients)

Penetrate blood-brain barrier and bind to H-1 receptors in the CNS

Zuberbier et al. The EAACI/GA2LEN/EDF/WAO Guideline for the definition, classification, diagnosis, and management of urticaria. : the 2013 definition and update Allergy 69:868-887, 2014.

Second generation H1-antihistamines

Minimum or none sedating effects

Free of anticholinergic effects

Two of earlier second generation drugs astemizole and terfenadine→ cardiotoxic effects → if concomitant administration of erythromycin or ketoconazole

First line → syntomatic treatment for urticaria

Second line → increase dosage up to fourfold (desloratadine, levocetirizine, bilastine, fexofenadine, rupatadine)

Once daily administrationRapid onset and 24 hour duration of action

Zuberbier et al. The EAACI/GA2LEN/EDF/WAO Guideline for the definition, classification, diagnosis, and management of urticaria. : the 2013 definition and update Allergy 69:868-887, 2014.AIFA, 2015

In pregnancy → cetirizine, loratadine

Management of chronic ordinary urticaria: general principles

Continuous treatment with second generation H1-antihistamines Safety data are available for use of several years continuouslyLow sedation antihistamines should be taken regularly – not only when symptoms occurSedative antihistamine e.g. hydroxyzine 25mg before sleep if nocturnal pruritus is a problem (possible impairment of cognitive function the following morning)

Finn AJ, Kaplan A, Fretwell R. J Allergy Clin Immunol 103:1071-1078, 1999.Nelson H, Reynolds R, Mason J. Annals Allergy Asthma Immunol 84:517-522, 2000.LaRosa M, Leonardi S, Marchese G, et. al. Annals Allergy Asthma Immunol 87:48-53, 2001.Zuberbier et al. The EAACI/GA2LEN/EDF/WAO Guideline for the definition, classification, diagnosis, and management of urticaria. : the 2013 definition and update Allergy 69:868-887, 2014.

Management of allergic

rhinitis: general principles

• First line treatment for mild allergic rhinitis

• Effective for Rhinorrhea, Nasal pruritus, Sneezing

• Less effective for Nasal blockage

• Possible additional anti-allergic and anti-inflammatory effect (in-vitro effect > in-vivo effect)

• Minimal or no sedative effects

• Once daily administration

• Rapid onset and 24 hour duration of action

Newer generation oral antihistamines

PlaceboN =201

Fexofenadine 120 mgN =211

Fexofenadine 180 mgN =202

Cetirizine 10 mgN =207

** **

Change frombaseline in

total symptomscore

0

-0.5

-1.0

-1.5

-2.0

-2.5

-3.0

Newer antihistamines are equally effectivein the treatment of allergic rhinitis

Howarth P et al. J Allergy Clin Immunol 1999;104:927

*: <0.05 compared to placeboBaseline symptomsStudy duration

**

Bachert C et al. J Allergy Clin Immunol 2004:114:838

Efficacy of an antihistamine over 6 months inpersistent allergic rhinitis

Sneezing Rhinorrhea Pruritus Nose Pruritus Eyes Congestion

*

*

*

*

*

*

*

*

*

*

*

*

*

1.0

0.8

0.6

0.4

0.2

01 wk

4 wk6 mo 1 wk

4 wk6 mo 1 wk

4 wk6 mo 1 wk

4 wk6 mo 1 wk

4 wk6 mo

meanIndividualsymptom

scoreimprovement

* P<0.05

Levocetirizine, 5 mg, N = 276Placebo, N = 271

Baseline total symptom score: 8.95

Nasal antihistamines

• Azelastine

• Levocabastine

• Olopatadine

Modified from van Cauwenberge P Allergy 2000;55:116-134

Agents and actionsOral

antihistamines

Nasal antihistamines

Cys-LT1 receptor

antagonists

Nasal steroids

Nasal decongestants

Oral decongestants

Nasal ipratrop

ium

Nasal cromon

es

Rhinorrhea + + ++ ++ +++ 0 0 +++ +

Congestion + + + +++ ++++ ++ 0 +

Sneezing ++ ++ ++ +++ 0 0 0 +

Pruritus ++ ++ + +++ 0 0 0 +

Ocular symptoms ++ 0 ++ ++ 0 0 0 0

Onset of action 1 hr 15 min 48 hr 12 hr 5-15

min 1 hr 15-30 min -

Duration 12-24 hr 6-12 hr 24 hr 12-48 hr 3-6 hr 12-24 hr 4-12 hr 2-6 hr

Terapia intranasaleAssociazione antistaminico/corticosteroide

Treatment days

Riduzione di almeno il 50% del TNSSRe

spon

ders (%

) 

Giorni di trattamento

Inizio

FP+AZE

Carr W et al. A novel intranasal therapy of Azelastine with Fluticasone for the treatment of Allergic Rhinitis. J Allergy Clin Immunol 2012;129(5):1282-89

TNSS Total Nasal Symptom Score

Management della rinite allergica

La terapia farmacologica antistaminica è sintomatica

L’Immunoterapia allergenicarappresenta l’unico trattamento

immunomodulatorio antigene-specifico in grado di modificare la storia naturale

della malattia

University of BariMarcello Albanesi Attilio Di GirolamoIrene Fiorino Flavia Frisenda Valentina LaudadioAndrea NicoCarlo PasculliLuigi Macchia

University of FoggiaLuciana d’EliaElena MinennaMaria Luisa TaurinoMaria F. Caiaffa

Polo Biomedico“Emanuele Altomare”