Orale Antihistaminika der 2. Generation bei allergischer Rhinitis

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

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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.