**5. Mast cell membrane stabilising drugs**

Applied topically, these drugs are very useful in mild and moderate AR, as they lack systemic effects and are very well tolerated. To achieve effectiveness, appropriate application methods must be used so that an even distribution of the medication is achieved, especially if there is abundant rhinorrhoea (Okuda et al, 1985). The main drugs being used are:

#### **5.1 Disodium cromoglycate**

Derived from the natural chromone Khellin, disodium cromoglycate (DSCG) is extracted from the *Ammi visnaga* plant, and was synthesised by Fisons (Cox, 1967).

It is a dual chromone joined by a flexible chain. The chromone chain has a hydrogen atom substituted by a sodium atom. It is a white powder that is barely water-soluble.

It is administered by inhalation because it is absorbed poorly orally. It has a plasma half-life of 80 minutes, and it reaches maximum levels in 20 minutes.


Treatment of Allergic Rhinitis:

secretions.

**6. Vasoconstrictors (α-adrenergics)** 

may make them increase the dose.

less than 1 year of age is dangerous.

over twice the recommended time period (Graf & Juto, 1995).

due to its antioxidant properties (Westerveld et al, 1995).

used once a day, preferably at night (Yoo et al, 1997).

and pseudoephedrine (Stubner et al, 2001).

effects on nitric oxide synthase activity (Westerveld et al, 2000)

ARIA Document, Nasal Lavage, Antihistamines, Cromones and Vasoconstrictors 75

with placebo. The efficacy of NAAGA compared to placebo (*P*<.001) and to cromolyn sodium (*P*<.03) was demonstrated. Terfenadine was used as a rescue medication, requiring

Vasoconstrictors are sympathomimetic drugs may act on α-receptors, causing vasoconstriction, or on β-receptors (vasodilation). The use of α-adrenergics in rhinitis is based on its ability to cause vasoconstriction, reducing blood flow in vessels and reducing

They are widespread in Spain, and should not be administered without medical supervision. Those that are used topically are imidazole derivatives: oxymetazoline, naphazoline and xylometazoline. They should not be administered for more than 7 days as their prolonged use causes the onset of a rebound effect by secondary hyperaemia. This effect occurs a few hours after administration and may be interpreted by the patient as a sign of illness, which

Vasoconstrictors have a significant effect on nasal obstruction, but continued use may cause drug-induced rhinitis, creating a dependence on nasal drops. Administration to children

Based on their study, Graf and Juto recommended avoiding the use of oxymetazoline in nasal spray for more than 10 days due to it causing hyperreactivity in the nasal mucosa, thus increasing susceptibility to histamines (Graf & Juto, 1994). These authors showed the lack of rebound with xylometazoline in nasal spray, when used at the recommended dosage, even

In the same time, other authors demonstrated the benefit of oxymetazoline above all, and xylometazoline somewhat less, in the topical treatment of nasal inflammation of rhinitis,

Graf et al, in a study of oxymetazoline, benzalkonium chloride and placebo in nasal spray, found that prolonged use (more than recommended) induced an increase in nasal hyperreactivity and the feeling of nasal obstruction, developing into secondary druginduced rhinitis. This may be related to the presence of benzalkonium in decongestant nasal sprays, which can produce or exacerbate drug-induced rhinitis (Graf & Hallen, 1996). Other authors performed a 4 to 8-week study with oxymetazoline and showed that it was safe, if

Moreover, it was confirmed that oxymetazoline and xylometazoline were beneficial in the treatment of upper respiratory tract inflammation, due to their dose-dependent inhibitory

Stubner studied the efficacy of cetirizine associated with pseudoephedrine, comparing it to xylometazoline at 0.1% in nasal spray. With the exception of nasal obstruction, which improved quickly with xylometazoline nasal spray, the rest of the rhinitis symptoms (mainly the reduction of nasal secretions) clearly improved with the combination of anti-Hl

greater use for placebo than for NAAGA (*P*<.0001) (Althaus & Pichler, 1994).

histamines and eosinophil/neutrophil chemotactic factors. It has no effect on basophils (Okuda et al, 1985). It increases the intracellular level of cyclic AMP, inhibiting phosphodiesterase and regulating the calcium retention mechanism.


The dose is 20-40 mg every 6 hours in each nostril. Therapeutic non-compliance with the dosage is the main cause for the lack of spectacular results.

It is effective in the treatment of AR, especially in patients with high IgE (Okuda et al, 1985). It works to prevent sneezing and rhinorrhoea, but not obstruction.

DSCG performs better than placebo in studies on pollen-sensitized patients. In a doubleblind study that included 104 patients and took place over 6 weeks, authors found significant improvement with minimal side effects (Handelman et al, 1977).

It is important to note that during administration:


#### **5.2 Nedocromil sodium**

A pyrano quinoline dicarboxylic acid, nedocromil sodium has a half-life of 90 minutes, and is eliminated by the liver and kidneys. It acts extracellularly because it does not pass through the lipid membranes due to its physicochemical properties. It acts by blocking the chloride channels that are responsible for cellular activity. It inhibits the release of histamine, leukotriene C4, prostaglandin D2 and chemotactic factors.

Although its mechanism of action is similar to DSCG, nedocromil sodium acts on other types of cells: eosinophils, neutrophil, macrophages, platelets and monocytes (Kaulbach et al, 1992).

Side effects are rare, similar to those of DSCG, although nausea, vomiting, dizziness and headaches have been reported. It is administered by inhalation in doses of 4 mg twice a day. This lower frequency of administration is an advantage over DSCG. Studies demonstrated its clinical efficacy in allergic rhinitis.

#### **5.3 N-acetylaspartylglutamate acid**

The magnesium salts of N-acetylaspartylglutamate (NAAGA) acid are effective in the treatment of seasonal allergic rhinitis.

Althaus performed a multicentre double-blind study for 4 weeks in pollen-allergic patients. Sixty-three patients were treated with NAAGA, 63 others with cromolyn sodium and 64 with placebo. The efficacy of NAAGA compared to placebo (*P*<.001) and to cromolyn sodium (*P*<.03) was demonstrated. Terfenadine was used as a rescue medication, requiring greater use for placebo than for NAAGA (*P*<.0001) (Althaus & Pichler, 1994).
