Pharmacology, particle deposition and drug administration techniques of intranasal corticosteroids for treating allergic rhinitis

Abstract

This review presents an overview of the available literature regarding intranasal corticosteroids (INCs) for the treatment of allergic rhinitis (AR). Various treatment options exist for AR including INCs, antihistamines and leucotriene antagonists. INCs are considered to be the most effective therapy for moderate-to-severe AR, as they are effective against nasal and ocular symptoms and improve quality of life. Their safety has been widely observed. INCs are effective and safe for short-term use. Local adverse events are observed but generally well-tolerated. The occurrence of (serious) systemic adverse events is unlikely but cannot be ruled out. There is a lack of long-term safety data. INC may cause serious eye complications. The risk of INCs on the hypothalamic-pituitary-adrenal axis, on bone mineral density reduction or osteoporosis and on growth in children, should be considered during treatment. Pharmacological characteristics of INCs (e.g. the mode of action and pharmacokinetics) are well known and described. We sought to gain insight into whether specific properties affect the efficacy and safety of INCs, including nasal particle deposition, which the administration technique affects. However, advances are lacking regarding the improved understanding of the effect of particle deposition on efficacy and safety and the effect of the administration technique. This review emphasizes the gaps in knowledge regarding this subject. Advances in research and health care are necessary to improve care for patients with AR.

FIGURE 1

Flowchart for the treatment of allergic rhinitis based on Table 1., , ,

FIGURE 2

Mode of action of glucorticoids (GCs) —three mechanisms. (A) After diffusion across the cell membrane, GCs bind to the glucocorticoid receptor (GR). The GC/GR complex is translocated to the nucleus and binds to the DNA GC/GR complex (genomic activation). This increases the transcription of genes that encode for anti‐inflammatory proteins (transactivation) and suppresses the transcription of genes that encode for pro‐inflammatory and immune proteins (transrepression). (B) By dissociation of the GC/GR complex, GC signalling through membrane‐associated receptors and second messengers is activated (nongenomic activation). (C) The GC/GR complex interacts with other transcription factors, such as nuclear factor‐κB. This prevents the production of inflammatory proteins.

FIGURE 3

Administration technique and deposition pattern. In the figure, the possible variations in the instruction steps prior to, during and after administration of an INC spray are displayed, which affect the deposition pattern of INC particles. The instructions steps include instructions regarding blowing and rinsing the nose prior to administration, instructions regarding the head position, the spray position, the depth of the spray into the nostril, closing the contralateral nostril and the droplet‐size distribution determined by the nasal airflow and the spray velocity during administration and the instruction regarding exhalation after administration. As described in: Section 5.4, from this review, no definitive conclusions regarding which administration technique leads to the desired deposition pattern and highest efficacy can be drawn for all instruction steps. To give insight in how an instruction step can be carried out differently, the figure illustrates the possible variation in these instruction steps. If a variation in the instruction step is possible, two examples of the variation are displayed as illustration a and b. In this figure, no recommendations regarding the correct administration technique according the authors are indicated. For this, we refer to the current standardized Dutch protocol in Table 3.