Zusammenfassung
Hintergrund: Histamin ist der zentrale Mediator der allergischen Sofortreaktion der Nasenschleimhaut.
Antihistaminika gehören zu den am meisten verordneten Therapien bei allergischer Rhinitis.
Methoden: Über eine Literaturrecherche in der Datenbank der National Library of Medicine wurden
aktuelle Daten zur Wirkung von Histamin und Antihistaminika bei der allergischen Rhinitis
erhoben.
Ergebnisse: Histamin vermittelt seine Wirkungen über 4 unterschiedliche Histaminrezeptoren. Über
H1-Rezeptoren auf trigeminalen Nervenfasern werden nasaler Juckreiz, Niesen und, über
einen parasympathischen Reflexbogen, nasale Hypersekretion ausgelöst. Aktivierung
von H1-Rezeptoren auf Endothelzellen bewirkt deren Kontraktion. Folge ist der Austritt
von Blutplasma in das Gewebe, es entwickelt sich ein Schleimhautödem. Über H2-Rezeptoren
führt Histamin zur Relaxation glatter Muskelzellen, wodurch sich die Blutfülle nasaler
Sinusoide erhöht. Dies bedingt eine Volumenzunahme der Nasenschleimhaut. Über periphere
H3-Rezeptoren moduliert Histamin die neurogene Entzündungsreaktion und über H4-Rezeptoren
beeinflusst es Immunzellen. Orale Antihistaminika der 2. Generation hemmen die Histaminwirkung
am H1-Rezeptor. Dadurch werden vorrangig die Symptome nasale Hypersekretion sowie
Juck- und Niesreiz reduziert. Außerdem hemmen sie H1-Rezeptor vermittelte entzündungsfördernde
Mechanismen.
Schlussfolgerung: Aufgrund ihres günstigen Nebenwirkungsprofils und ihrer guten Wirksamkeit bieten
sich orale Antihistaminika der 2. Generation zur Behandlung leichterer Formen der
saisonalen allergischen Rhinitis an.
Abstract
Background: Histamine is a key mediator of the allergic immediate reaction. Antihistamines belong
to the most frequently used treatment modalities in allergic rhinitis.
Methods: The National Libraray of Medicine was searched for current data of the effects of
histamine and antihistamines in allergic rhinitis.
Results: Histamine acts on 4 different histamine receptors. Activation of H1-receptors on
nasal trigeminal nerve fibers transmits nasal itch and sneezing. Nasal hypersecretion
is mainly mediated by an trigeminal-parasympathetic reflex. Activation of H1-receptors
results in contraction of nasal endothelial cells with consecutive plasma extravasation
and edema formation. Histamine also activates H2-receptors on smooth muscle cells
surrounding nasal capacitance vessels. They transmit muscle relaxation, increased
blood content and an enlarged volume of nasal mucosa. Via peripheral H3-receptors,
histamine modulates neurogenic inflammation and via H4-receptors functions of immune
cells. Oral second generation antihistamines inhibit histamine dependent activation
of nasal H1-receptors. They mainly reduce nasal itch, sneezing, and hypersecretion.
In addition, allergy related activity impairment is reduced resulting in improved
physical and mental performance. Second generation antihistamines reduce proinflammatory
effects mediated by H1-receptors, however, drug concentrations necessary for mast
cell stabilization as observed in vitro are not reached in vivo. Oral second generation
antihistamines are readily absorbed and reduce allergy symptoms for approximately
24 hours, allowing convenient once daily medication. Modern antihistamines are generally
safe; tachyphylaxis, tolerance or rebound has not been observed.
Conclusion: Due to their minimal adverse effects and efficient symptom reduction oral second
generation antihistamines are particularly useful for the treatment of less severe
intermittent forms of nasal allergy.
Schlüsselwörter
Histamin · Nasenschleimhaut · Antihistaminika · allergische Rhinitis
Key words
Histamine · nasal mucosa · histamine H1 antagonists, non-sedating · rhinitis
Literatur
- 1
Rasp G.
Therapie der allergischen Rhinitis.
Laryngorhinootologie.
1993;
72
373-378
- 2
Albegger K.
Symptomatische Therapie der allergischen Rhinitis.
Laryngorhinootologie.
1990;
69
613-620
- 3
Bousquet J, van Cauwenberge P, Khaltaev N.
Allergic rhinitis and its impact on asthma.
J Allergy Clin Immunol.
2001;
108
147-334
- 4
Klimek L, Eggers G.
Olfactory dysfunction in allergic rhinitis is related to nasal eosinophilic inflammation.
J Allergy Clin Immunol.
1997;
100
158-164
- 5
Wilken J A, Berkowitz R, Kane R.
Decrements in vigilance and cognitive functioning associated with ragweed-induced
allergic rhinitis.
Ann Allergy Asthma Immunol.
2002;
89
372-380
- 6
Marshall P S, O’Hara C, Steinberg P.
Effects of seasonal allergic rhinitis on selected cognitive abilities.
Ann Allergy Asthma Immunol.
2000;
84
403-410
- 7
Marshall P S, O’Hara C, Steinberg P.
Effects of seasonal allergic rhinitis on fatigue levels and mood.
Psychosom Med.
2002;
64
684-691
- 8
Vuurman E F, van Veggel L M, Uiterwijk M M, Leutner D, O’Hanlon J F.
Seasonal allergic rhinitis and antihistamine effects on children’s learning.
Ann Allergy.
1993;
71
121-126
- 9
Burton W N, Conti D J, Chen C Y, Schultz A B, Edington D W.
The impact of allergies and allergy treatment on worker productivity.
J Occup Environ Med.
2001;
43
64-71
- 10
Blaiss M S.
Cognitive, social, and economic costs of allergic rhinitis.
Allergy Asthma Proc.
2000;
21
7-13
- 11
Howarth P H.
Mediators of nasal blockage in allergic rhinitis.
Allergy.
1997;
52
12-18
- 12
Gerth van Wijk R, Mulder P G, Dieges P H.
Nasal provocation with histamine in allergic rhinitis patients: clinical significance
and reproducibility.
Clin Exp Allergy.
1989;
19
293-298
- 13
Bisgaard H, Olsson P, Bende M.
Effect of leukotriene D4 on nasal mucosal blood flow, nasal airway resistance and
nasal secretion in humans.
Clin Allergy.
1986;
16
289-297
- 14
Okuda M, Watase T, Mezawa A, Liu C M.
The role of leukotriene D4 in allergic rhinitis.
Annals of Allergy.
1988;
60
537-540
- 15
Doyle W J, Boehm S, Skoner D P.
Physiologic responses to intranasal dose-response challenges with histamine, methacholine,
bradykinin, and prostaglandin in adult volunteers with and without nasal allergy.
J Allergy Clin Immunol.
1990;
86
924-935
- 16
Wang D Y, Hanotte F, DeVos C, Clement P.
Effect of cetirizine, levocetirizine, and dextrocetirizine on histamine-induced nasal
response in healthy adult volunteers.
Allergy.
2001;
56
339-343
- 17
Austin C E, Foreman J C.
Acoustic rhinometry compared with posterior rhinomanometry in the measurement of histamine-
and bradykinin-induced changes in nasal airway patency.
British Journal of Clinical Pharmacology.
1994;
37
33-37
- 18
Numata T, Konno A, Yamakoshi T, Hanazawa T, Terada N, Nagata H.
Comparative role of peptide leukotrienes and histamine in the development of nasal
mucosal swelling in nasal allergy.
Ann Otol Rhinol Laryngol.
1999;
108
467-473
- 19
Mizutani N, Nabe T, Imai A, Sakurai H, Takenaka H, Kohno S.
Markedly increased nasal blockage by intranasal leukotriene D4 in an experimental
allergic rhinitis model: contribution of dilated mucosal blood vessels.
Jpn J Pharmacol.
2001;
86
170-182
- 20
Howarth P, Walsh S, Robinson C.
The comparative nasal effects of prostaglandin D2 in normal and rhinitic subjects.
Adv Prostaglandin Thromboxane Leukot Res.
1991;
21A
449-452
- 21
MacGlashan D, Jr.
Histamine: A mediator of inflammation.
J Allergy Clin Immunol.
2003;
112
53-59
- 22
Boyce J A.
Mast cells: beyond IgE.
J Allergy Clin Immunol.
2003;
111
24-32
- 23 Nilsson G, Costa J J, Metcalfe D D.
Mast cells and basophils. In: Gallin JI, Snyderman R (Hrsg.) Inflammation - basic principles and clinical
correlates. Philadelphia, PA; Lippincott Williams & Wilkins 1999: 97-117
- 24
Marone G, Granata F, Spadaro G, Genovese A, Triggiani M.
The histamine-cytokine network in allergic inflammation.
J Allergy Clin Immunol.
2003;
112
83-88
- 25
Ash A S, Schild H O.
Receptors mediating some actions of histamine.
Br J Pharmacol.
1966;
27
427-439
- 26
Black J W, Duncan W A, Durant C J, Ganellin C R, Parsons E M.
Definition and antagonism of histamine H2-receptors.
Nature.
1972;
236
385-390
- 27
Arrang J M, Garbarg M, Schwartz J C.
Auto-inhibition of brain histamine release mediated by a novel class (H3) of histamine
receptor.
Nature.
1983;
302
832-837
- 28
Hill S J, Ganellin C R, Timmerman H, Schwartz J C, Shankley N P, Young J M. et al
.
International Union of Pharmacology. XIII. Classification of histamine receptors.
Pharmacol Rev.
1997;
49
253-278
- 29
Leurs R, Blandina P, Tedford C, Timmerman H.
Therapeutic potential of histamine H3 receptor agonists and antagonists.
Trends Pharmacol Sci.
1998;
19
177-183
- 30
Raible D G, Lenahan T, Fayvilevich Y, Kosinski R, Schulman E S.
Pharmacologic characterization of a novel histamine receptor on human eosinophils.
Am J Respir Crit Care Med.
1994;
149
1506-1511
- 31
Oda T, Morikawa N, Saito Y, Masuho Y, Matsumoto S.
Molecular cloning and characterization of a novel type of histamine receptor preferentially
expressed in leukocytes.
J Biol Chem.
2000;
275
36 781-36 786
- 32
Akdis C A, Blaser K.
Histamine in the immune regulation of allergic inflammation.
J Allergy Clin Immunol.
2003;
112
15-22
- 33
Milligan G, Bond R A, Lee M.
Inverse agonism: pharmacological curiosity or potential therapeutic strategy?.
Trends Pharmacol Sci.
1995;
16
10-13
- 34
Leurs R, Church M K, Taglialatela M.
H1-antihistamines: inverse agonism, anti-inflammatory actions and cardiac effects.
Clin Exp Allergy.
2002;
32
489-498
- 35 Simons F ER.
Antihistamines. In: Adkinson NF, Middleton E, (Hrsg.) Middleton’s allergy - principles & practice. St.
Louis; Mosby 2003: 834-869
- 36
Shelton D, Eiser N.
Histamine receptors in the human nose.
Clinical Otolaryngology.
1994;
19
45-49
- 37
Togias A.
H1-receptors: localization and role in airway physiology and in immune functions.
J Allergy Clin Immunol.
2003;
112
60-68
- 38
Togias A, Proud D, Kagey-Sobotka A, Norman P, Lichtenstein L, Naclerio R.
The effect of a topical tricyclic antihistamine on the response of the nasal mucosa
to challenge with cold, dry air and histamine.
J Allergy Clin Immunol.
1987;
79
599-604
- 39
Mygind N.
Nasal inflammation and anti-inflammatory treatment. Semantics or clinical reality.
Rhinology.
2001;
39
61-65
- 40
Konno A, Togawa K, Fujiwara T.
The mechanisms involved in onset of allergic manifestations in the nose.
Eur J Respir Dis.
1983;
64
155-166
- 41
Baroody F M, Wagenmann M, Naclerio R M.
Comparison of the secretory response of the nasal mucosa to methacholine and histamine.
J Appl Physiol.
1993;
74
2661-2671
- 42
Hirata N, Takeuchi K, Ukai K, Jin C, Yoshida T, Sakakura Y.
Expression and localization of histamine H2 receptor messenger RNA in human nasal
mucosa.
J Allergy Clin Immunol.
1999;
103
944-949
- 43
Okayama M, Baraniuk J N, Hausfeld J N, Merida M, Kaliner M A.
Characterization and autoradiographic localization of histamine H1 receptors in human
nasal turbinates.
J Allergy Clin Immunol.
1992;
89
1144-1150
- 44
Howarth P.
Clinical nasal decongestant activity with oral antihistamines.
Clinical Experimental Allergy Reviews.
2002;
2
101-106
- 45
Bockman C S, Zeng W.
Histamine receptor type coupled to nitric oxide-induced relaxation of guinea-pig nasal
mucosa.
Auton Autacoid Pharmacol.
2002;
22
269-276
- 46
Imai A, Nabe T, Mizutani N, Sakurai H, Takenaka H, Kohno S.
Involvement of nitric oxide in pollen-induced biphasic nasal blockage in sensitised
guinea pigs.
Eur J Pharmacol.
2001;
423
63-70
- 47
Silkoff P E, Roth Y, McClean P, Cole P, Chapnik J, Zamel N.
Nasal nitric oxide does not control basal nasal patency or acute congestion following
allergen challenge in allergic rhinitis.
Ann Otol Rhinol Laryngol.
1999;
108
368-372
- 48
Maniscalco M, Sofia M, Carratu L, Higenbottam T.
Effect of nitric oxide inhibition on nasal airway resistance after nasal allergen
challenge in allergic rhinitis.
Eur J Clin Invest.
2001;
31
462-466
- 49
Dear J W, Ghali S, Foreman J C.
Attenuation of human nasal airway responses to bradykinin and histamine by inhibitors
of nitric oxide synthase.
Br J Pharmacol.
1996;
118
1177-1182
- 50
Havas T E, Cole P, Parker L, Oprysk D, Ayiomamitis A.
The effects of combined H1 and H2 histamine antagonists on alterations in nasal airflow
resistance induced by topical histamine provocation.
J Allergy Clin Immunol.
1986;
78
856-860
- 51
Secher C, Kirkegaard J, Borum P, Maansson A, Osterhammel P, Mygind N.
Significance of H1 and H2 receptors in the human nose: rationale for topical use of
combined antihistamine preparations.
J Allergy Clin Immunol.
1982;
70
211-218
- 52
Wood-Baker R, Lau L, Howarth P H.
Histamine and the nasal vasculature: the influence of H1 and H2-histamine receptor
antagonism.
Clin Otolaryngol.
1996;
21
348-352
- 53
Mizutani N, Nabe T, Sasaki K, Takenaka H, Kohno S.
Nasal hyperresponsiveness to histamine induced by repetitive exposure to cedar pollen
in guinea-pigs.
Eur Respir J.
1999;
14
1368-1375
- 54
American Academy of Allergy and Immunology .
The use of antihistamines in patients with asthma.
J Allergy Clin Immunol.
1988;
82
481-482
- 55
Gonzalez M, Estes K.
Pharmacokinetic overview of oral second-generation H1 antihistamines.
International Journal of Clinical Pharmacology and Therapeutics.
1998;
36
292-300
- 56
Lacour M, Sterkers O.
Histamine and betahistine in the treatment of vertigo: elucidation of mechanisms of
action.
CNS Drugs.
2001;
15
853-870
- 57
Stoll W.
Otogener Schwindel. Differenzierung und Therapie.
Laryngorhinootologie.
1993;
72
311-315
- 58
Liu Q, Horio Y, Fujimoto K, Fukui H.
Does the [3H]mepyramine binding site represent the histamine H1 receptor? Re-examination
of the histamine H1 receptor with quinine.
J Pharmacol Exp Ther.
1994;
268
959-964
- 59
Benavides J, Schoemaker H, Dana C, Claustre Y, Delahaye M, Prouteau M. et al .
In vivo and in vitro interaction of the novel selective histamine H1 receptor antagonist
mizolastine with H1 receptors in the rodent.
Arzneimittelforschung.
1995;
45
551-558
- 60
Henz B M.
The pharmacologic profile of desloratadine: a review.
Allergy.
2001;
56 (Suppl 65)
7-13
- 61
Frossard N, Benabdesselam O, Purohit A, Mounedji N, Pauli G.
Activity of ebastine (10 and 20 mg) and cetirizine at 24 hours of a steady state treatment
in the skin of healthy volunteers.
Fundam Clin Pharmacol.
2000;
14
409-413
- 62
Frossard N, Melac M, Benabdesselam O, Pauli G.
Consistency of the efficacy of cetirizine and ebastine on skin reactivity.
Ann Allergy Asthma Immunol.
1998;
80
61-65
- 63
Purohit A, Melac M, Pauli G, Frossard N.
Twenty-four-hour activity and consistency of activity of levocetirizine and desloratadine
in the skin.
Br J Clin Pharmacol.
2003;
56
388-394
- 64
Purohit A, Melac M, Pauli G, Frossard N.
Comparative activity of cetirizine and mizolastine on histamine-induced skin wheal
and flare responses at 24 h.
Br J Clin Pharmacol.
2002;
53
250-254
- 65
Purohit A, Duvernelle C, Melac M, Pauli G, Frossard N.
Twenty-four hours of activity of cetirizine and fexofenadine in the skin.
Ann Allergy Asthma Immunol.
2001;
86
387-392
- 66
Purohit A, Duvernelle C, Melac M, Benabdesselam O, Pauli G, Frossard N.
Consistency and efficacy of cetirizine (10 mg) versus ebastine (20 mg) at 4 h on skin
reactivity.
Eur J Clin Pharmacol.
1999;
55
589-592
- 67
Grant J A, Danielson L, Rihoux J P, DeVos C.
A double-blind, single-dose, crossover comparison of cetirizine, ebastine, epinastine,
fexofenadine, terfenadine, and loratadine versus placebo: suppression of histamine-induced
wheal and flare response for 24 h in healthy male subjects.
Allergy.
1999;
54
700-707
- 68
Simons F E, McMillan J L, Simons K J.
A double-blind, single-dose, crossover comparison of cetirizine, terfenadine, loratadine,
astemizole, and chlorpheniramine versus placebo: suppressive effects on histamine-induced
wheals and flares during 24 hours in normal subjects.
J Allergy Clin Immunol.
1990;
86
540-547
- 69
Juhlin L.
A comparison of the pharmacodynamics of H1-receptor antagonists as assessed by the
induced wheal-and-flare model.
Allergy.
1995;
50
24-30
- 70
Denham K J, Boutsiouki P, Clough G F, Church M K.
Comparison of the effects of desloratadine and levocetirizine on histamine-induced
wheal, flare and itch in human skin.
Inflamm Res.
2003;
52
424-427
- 71
Bousquet J, Czarlewski W, Cougnard J, Danzig M, Michel F B.
Changes in skin-test reactivity do not correlate with clinical efficacy of H1-blockers
in seasonal allergic rhinitis.
Allergy.
1998;
53
579-585
- 72
Braunstein G, Malaquin F, Fajac I, Melac M, Frossard N.
Inhibition of histamine-induced nasal obstruction by cetirizine in allergic rhinitis.
Br J Clin Pharmacol.
1992;
33
445-448
- 73
van Steekelenburg J, Clement P A, Beel M H.
Comparison of five new antihistamines (H1-receptor antagonists) in patients with allergic
rhinitis using nasal provocation studies and skin tests.
Allergy.
2002;
57
346-350
- 74
Crawford W W, Klaustermeyer W B, Lee P H, Placik I M.
Comparative efficacy of terfenadine, loratadine, and astemizole in perennial allergic
rhinitis.
Otolaryngol Head Neck Surg.
1998;
118
668-673
- 75
Baroody F M, Lim M C, Proud D, Kagey-Sobotka A, Lichtenstein L M, Naclerio R M.
Effects of loratadine and terfenadine on the induced nasal allergic reaction.
Arch Otolaryngol Head Neck Surg.
1996;
122
309-316
- 76
Bousquet J, Lebel B, Chanal I, Morel A, Michel F B.
Antiallergic activity of H1-receptor antagonists assessed by nasal challenge.
J Allergy Clin Immunol.
1988;
82
881-887
- 77
Persi L, Demoly P, Harris A G, Tisserand B, Michel F B, Bousquet J.
Comparison between nasal provocation tests and skin tests in patients treated with
loratadine and cetirizine.
J Allergy Clin Immunol.
1999;
103
591-594
- 78 Simons K J, Simons F ER.
Clinical pharmacology of H1 antihistamines. In: Simons FER (Hrsg.) Histamine and H1-antihistamines in allergic disease. New York;
Marcel Dekker 2002: 141ff
- 79
Bousquet J, Chanal I, Skassa-Brociek W, Lemonier C, Michel F B.
Lack of subsensitivity to loratadine during long-term dosing during 12 weeks.
J Allergy Clin Immunol.
1990;
86
248-253
- 80
Murray J J, Nathan R A, Bronsky E A, Olufade A O, Chapman D, Kramer B.
Comprehensive evaluation of cetirizine in the management of seasonal allergic rhinitis:
impact on symptoms, quality of life, productivity, and activity impairment.
Allergy Asthma Proc.
2002;
23
391-398
- 81
Wiseman L R, Faulds D.
Ebastine. A review of its pharmacological properties and clinical efficacy in the
treatment of allergic disorders.
Drugs.
1996;
51
260-277
- 82
Wilson A M, Haggart K, Sims E J, Lipworth B J.
Effects of fexofenadine and desloratadine on subjective and objective measures of
nasal congestion in seasonal allergic rhinitis.
Clin Exp Allergy.
2002;
32
1504-1509
- 83
Nayak A S, Schenkel E.
Desloratadine reduces nasal congestion in patients with intermittent allergic rhinitis.
Allergy.
2001;
56
1077-1080
- 84
Horak F, Stubner U P, Zieglmayer R, Harris A G.
Effect of desloratadine versus placebo on nasal airflow and subjective measures of
nasal obstruction in subjects with grass pollen-induced allergic rhinitis in an allergen-exposure
unit.
J Allergy Clin Immunol.
2002;
109
956-961
- 85
van Cauwenberge P, Wang D.
Antihistamines and nasal blockage.
Allergy.
1997;
40
35-38
- 86
Wang D, Clement P, Smitz J.
Effect of H1 and H2 antagonists on nasal symptoms and mediator release in atopic patients
after nasal allergen challenge during the pollen season.
Acta Otolaryngol.
1996;
116
91-96
- 87
Ciprandi G, Tosca M A, Ricca V, Passalacqua G, Riccio A M, Bagnasco M. et al .
Cetirizine treatment of rhinitis in children with pollen allergy: evidence of its
antiallergic activity.
Clin Exp Allergy.
1997;
27
1160-1166
- 88
Ciprandi G, Ricca V, Tosca M A, Landi M, Passalacqua G, Canonica G W.
Continuous antihistamine treatment controls allergic inflammation and reduces respiratory
morbidity in children with mite allergy.
Allergy.
1999;
54
358-365
- 89
Simons F E, Silver N A, Gu X, Simons K J.
Clinical pharmacology of H1-antihistamines in the skin.
J Allergy Clin Immunol.
2002;
110
777-783
- 90
Marone G.
Milestones in the biology and pharmacology of histamine H1-receptor antagonists.
Allergy.
1997;
34
7-13
- 91
Gelfand E W, Appajosyula S, Meeves S.
Anti-inflammatory activity of H1-receptor antagonists: review of recent experimental
research.
Curr Med Res Opin.
2004;
20
73-81
- 92
Bensch G W, Nelson H S, Borish L C.
Evaluation of cytokines in nasal secretions after nasal antigen challenge: lack of
influence of antihistamines.
Ann Allergy Asthma Immunol.
2002;
88
457-462
- 93
Di Lorenzo G, Gervasi F, Drago A, Esposito Pellitteri M, Di Salvo A, Cosentino D.
et al .
Comparison of the effects of fluticasone propionate, aqueous nasal spray and levocabastine
on inflammatory cells in nasal lavage and clinical activity during the pollen season
in seasonal rhinitics.
Clin Exp Allergy.
1999;
29
1367-1377
- 94
Taborda-Barata L, Jacobson M, Walker S, Njuki F, Ying S, Randev P. et al .
Effect of cetirizine and prednisolone on cellular infiltration and cytokine mRNA expression
during allergen-induced late cutaneous responses.
Clin Exp Allergy.
1996;
26
68-78
- 95
Sienra-Monge J J, Gazca-Aguilar A, Del Rio-Navarro B.
Double-blind comparison of cetirizine and loratadine in children ages 2 to 6 years
with perennial allergic rhinitis.
Am J Ther.
1999;
6
149-155
- 96
Simons F E, Johnston L, Simons K J.
Clinical pharmacology of the H1-receptor antagonists cetirizine and loratadine in
children.
Pediatr Allergy Immunol.
2000;
11
116-119
- 97
Simons F E.
Prospective, long-term safety evaluation of the H1-receptor antagonist cetirizine
in very young children with atopic dermatitis. ETAC Study Group. Early Treatment of
the Atopic Child.
J Allergy Clin Immunol.
1999;
104
433-440
- 98
Spicak V, Dab I, Hulhoven R, Desager J P, Klanova M, De Longueville M. et al .
Pharmacokinetics and pharmacodynamics of cetirizine in infants and toddlers.
Clin Pharmacol Ther.
1997;
61
325-330
- 99
Pariente-Khayat A, Rey E, Dubois M C, Vauzelle-Kervroedan F, Pons G, d’Athis P. et
al .
Pharmacokinetics of cetirizine in 2- to 6-year-old children.
Int J Clin Pharmacol Ther.
1995;
33
340-344
- 100
Ten Eick AP, Blumer J L, Reed M D.
Safety of antihistamines in children.
Drug Saf.
2001;
24
119-147
- 101 Schatz M.
H1-antihistamines in pregnancy and lactation. In: Simons FER (Hrsg.) Histamine and H1-antihistamines in allergic disease. New York;
Marcel Dekker 2002: 421ff
- 102
Loebstein R, Lalkin A, Addis A, Costa A, Lalkin I, Bonati M. et al .
Pregnancy outcome after gestational exposure to terfenadine: A multicenter, prospective
controlled study.
J Allergy Clin Immunol.
1999;
104
953-956
- 103
Einarson A, Bailey B, Jung G, Spizzirri D, Baillie M, Koren G.
Prospective controlled study of hydroxyzine and cetirizine in pregnancy.
Ann Allergy Asthma Immunol.
1997;
78
183-186
- 104
Moretti M E, Caprara D, Coutinho C J, Bar-Oz B, Berkovitch M, Addis A. et al .
Fetal safety of loratadine use in the first trimester of pregnancy: a multicenter
study.
J Allergy Clin Immunol.
2003;
111
479-483
- 105
Diav-Citrin O, Shechtman S, Aharonovich A, Moerman L, Arnon J, Wajnberg R. et al .
Pregnancy outcome after gestational exposure to loratadine or antihistamines: a prospective
controlled cohort study.
J Allergy Clin Immunol.
2003;
111
1239-1243
- 106 Yap Y G, Camm A J.
Potential cardiac toxicity of H1-antihistamines. In: Simons FER (Hrsg.) Histamine and H1-antihistamines in allergic disease. New York;
Marcel Dekker 2002: 389ff
- 107
Mann R D, Pearce G L, Dunn N, Shakir S.
Sedation with “non-sedating” antihistamines: four prescription-event monitoring studies
in general practice.
Bmj.
2000;
320
1184-1186
- 108
Leynaert B, Neukirch F, Demoly P, Bousquet J.
Epidemiologic evidence for asthma and rhinitis comorbidity.
J Allergy Clin Immunol.
2000;
106
201-205
- 109
Polzehl D, Keck T, Riechelmann H.
Analyse der Effektivität der subkutanen Immuntherapie mit Hausstaubmilbenextrakten
bei Erwachsenen mit allergischer Rhinitis und/oder Asthma bronchiale.
Laryngorhinootologie.
2003;
82
272-280
- 110
Nielsen L P, Dahl R.
Comparison of intranasal corticosteroids and antihistamines in allergic rhinitis:
a review of randomized, controlled trials.
Am J Respir Med.
2003;
2
55-65
- 111
Weiner J M, Abramson M J, Puy R M.
Intranasal corticosteroids versus oral H1 receptor antagonists in allergic rhinitis:
systematic review of randomised controlled trials.
British Medical Journal.
1998;
317
1624-1629
- 112
Borish L.
Allergic rhinitis: systemic inflammation and implications for management.
J Allergy Clin Immunol.
2003;
112
1021-1031
- 113
Moinuddin R, deTineo M, Maleckar B, Naclerio R M, Baroody F M.
Comparison of the combinations of fexofenadine-pseudoephedrine and loratadine-montelukast
in the treatment of seasonal allergic rhinitis.
Ann Allergy Asthma Immunol.
2004;
92
73-79
- 114
Kernan W N, Viscoli C M, Brass L M, Broderick J P, Brott T, Feldmann E. et al .
Phenylpropanolamine and the risk of hemorrhagic stroke.
N Engl J Med.
2000;
343
1826-1832
- 115
Wilson A M, Orr L C, Coutie W J, Sims E J, Lipworth B J.
A comparison of once daily fexofenadine versus the combination of montelukast plus
loratadine on domiciliary nasal peak flow and symptoms in seasonal allergic rhinitis.
Clin Exp Allergy.
2002;
32
126-132
- 116
Mygind N, Dahl R, Bisgaard H.
Leukotrienes, leukotriene receptor antagonists, and rhinitis.
Allergy.
2000;
55
421-424
- 117
Tonnesen P, Mygind N.
Nasal challenge with serotonin and histamine in normal persons.
Allergy.
1985;
40
350-353
- 118
Pipkorn U, Andersson M.
Topical dermal anaesthesia inhibits the flare but not the weal response to allergen
and histamine in the skin-prick test.
Clin Allergy.
1987;
17
307-311
- 119
Sicherer S H, Eggleston P A.
EMLA cream for pain reduction in diagnostic allergy skin testing: effects on wheal
and flare responses.
Ann Allergy Asthma Immunol.
1997;
78
64-68
1 Es ist deswegen bei anaphylaktischen Reaktionen sinnvoll, neben einem HR1-Antagonisten
einen HR2-Antagonisten wie z.B. Cimetidin oder Ranitidin zu geben.
2 Der gewohnte Sprachgebrauch „Antagonist“ wird in diesem Beitrag beibehalten.
3 Solche Substanzen sind z. B. Makrolidantibiotika (Erythromycin, Roxithromycin, Clarithromycin)
und Imidazol-Fungostatika (Ketoconazol, Itraconazol).
4 Es stehen nur wenige Daten zu tatsächlich erreichten Gewebekonzentrationen von HR1-Rezeptorantagonisten
zur Verfügung. In Hautbiopsien wurden nach mehrtägiger Applikation von Fexofenadin
3 × 60 mg/die Gewebekonzentrationen um 500 ng/g und nach Gabe von Loratadin 1 × 10
mg/die Gewebekonzentrationen um 200 ng/g erreicht [89]. Dies entspricht in etwa 0,5
- 1 μmol/l. Eine 50 %-Reduktion der Histaminfreisetzung aus Mastzellen durch HR1-Antagonisten
in vitro beobachtet man bei Konzentrationen zwischen 10 und 50 μmol/l [21].
5 Ausreichende Erfahrungen beim Menschen liegen nicht vor. Der Tierversuch erbrachte
keine Hinweise auf embryotoxische/teratogene Wirkungen.
6 Es wurden keine Anzeichen von Teratogenität in Reproduktionsstudien an Tieren beobachtet.
Sowohl fetotoxische Wirkungen als auch solche auf die männliche oder weibliche Fertilität
zeigten sich bei Abwesenheit maternal toxischer Effekte nicht.
7 Ausreichende Erfahrungen über die Anwendung beim Menschen liegen nicht vor.
Prof. Dr. Herbert Riechelmann
Univ.-HNO-Klinik Ulm
Prittwitzstraße 43 · 89075 Ulm