Intranasal Sodium Cromoglycate Research Articles

Fetal Safety of Drugs Used in the Treatment of Allergic Rhinitis

Allergic rhinitis is the most common allergic disease. Pharmacological interventions are often not used in pregnancy because of alarming information in drug labels and patient information, even when evidence for safety exists.Low-risk therapies could include immunotherapy, intranasal sodium cromoglycate (cromolyn sodium), beclometasone, budesonide and first-generation antihistamines. In a meta-analysis examining the safety of first-generation antihistamines in pregnancy, 200 000 first trimester exposures failed to show increased teratogenic risk. Loratadine is the most studied second-generation antihistamine (with a total patient cohort of 2147 women who were exposed) and does not appear to increase the risk of major congenital malformations; however, it has not been as well studied as the earlier antihistamines. Since desloratadine is the principal metabolite of loratadine, it can be assumed that a similar safety profile would fit for desloratadine as was described for loratadine although no direct human studies have been done. Decongestants have not been conclusively proven to affect the fetal outcome and may be used for short-term relief when no other safer alternatives are available. Intranasal corticosteroids have not been associated with an increase in congenital malformations in humans. Based on efficacy and the fact that there would be little systemic absorption, they can be considered a first-line treatment over oral antihistamines, decongestants and mast cell stabilisers; however, the number of controlled trials in pregnancy is limited. Intranasal corticosteroids are associated with minimal systemic effects in adults and are the most effective therapy for allergic rhinitis. Benefit-risk considerations must, therefore, be done but favour their first-line use during pregnancy. Because fetal safety is paramount, recommendations should be based both on the safety of the drugs during pregnancy and the comparative efficacy of the agent in the treatment of the underlying condition. This review exemplifies the fact that there are many safe treatment options for the clinician when dealing with allergic rhinitis during pregnancy.

Intranasal Fluticasone Propionate

The intranasal corticosteroid fluticasone propionate is an effective agent for the treatment of rhinitis, demonstrating potent local anti-inflammatory activity and little, if any, systemic activity. Intranasal fluticasone propionate has shown clinical efficacy similar to that of other intranasal corticosteroids, including beclomethasone (administered at up to a 2-fold higher dosage than fluticasone), budesonide, flunisolide and triamcinolone acetonide, and provides greater relief from nasal symptoms (including nasal blockage) than antihistamine agents and intranasal sodium cromoglycate. Its efficacy in the treatment of seasonal allergic rhinitis and perennial allergic and nonallergic rhinitis has been demonstrated in large well-controlled studies in which the drug maintained adequate control of symptoms when administered in a once daily dose of 200 micrograms. In addition, fluticasone propionate has shown similar efficacy to that of beclomethasone in the treatment of nasal polyps; however, its use in the postoperative setting requires further investigation. Intranasal fluticasone propionate is well tolerated in the majority of patients, the incidence of adverse events being similar to that seen with placebo. Pharmacoeconomic analyses indicate that intranasal fluticasone propionate is significantly more cost-effective than the antihistamines terfenadine and loratadine. Overall quality of life was improved to a similar extent by fluticasone propionate and beclomethasone. In conclusion, recent clinical experience has confirmed that intranasal fluticasone propionate is a convenient, effective and well tolerated alternative to other intranasal corticosteroids and antihistamines for the treatment of rhinitis when administered once daily.

The effect of inhaled and intranasal sodium cromoglyeate on symptoms of upper respiratory tract infections

Summary Background A well established drug for the treatment of asthma and allergy, sodium cromoglycale, was found in open trials to be useful as a symptomalic treatment for upper respiratory tract infections. Objective To compare the efficacy of inhaled and intranasal sodium cromoglyeate and matching placebos on the symptoms of upper respiratory tract infections. Methods Adult subjects with symptoms of runny nose, throat pain, or cough for less than 24 h were recruited. They were treated for 7 days using a randomized, double‐blind, placebo‐controlled, group comparative design. The medication given was: sodium cromoglyeate dry powder 20mg per inhalation in spincaps; sodium cromoglycate aqueous nasal spray delivering 5.2mg per dose; or matching placebo as dry powder and nasal spray. One spincap and one spray per nostril were taken every 2h during waking hours on days 1 and 2 and then four times daily on days 3–7. Severity of nine symptoms (general malaise, body aches and pains, chills and shivering, snzeening, nasal running, nasal blocking, sore throat, cough and voice disturbance) was recorded twice daily by subjects on diary cards, using a scale of 0 (absent) to 3 (severe). Results The sludy was conducted between February and April 1993. One hundred and eighteen patients aged 21–63 years (mean 41 years) were included. Symptoms resolved faster (P < 0.001) and the severity in the last three days of treatment was significantly less in patients treated with sodium cromoglycate than with placebo (P < 0.05‐day 5; P < 0.01‐day 6; P < 0.001‐day 7). Side‐effects were local and mild and did not differ between the treatment groups. Conclusion Sodium cromoglyeate administered both by inhalation and intranasally is an effective treatment for the symptoms of upper respiratory tract infection. Its combined safety and efficacy would make it an acceptable form of treatment for these conditions.

The effect of inhaled and intranasal sodium cromoglycate on symptoms of upper respiratory tract infections

The effect of inhaled and intranasal sodium cromoglycate on symptoms of upper respiratory tract infections

The effect of topical sodium cromoglycate on intranasal histamine challenge in allergic rhinitis

Topical sodium cromoglycate is used to treat allergic diseases of the upper and lower airways. To investigate its mechanisms of action, intranasal histamine challenge was used in nine subjects with perennial allergic rhinitis. After a preliminary day where subjects' reactivity thresholds (D100) for histamine were determined, intranasal sodium cromoglycate was administered in a double-blind, placebo-controlled fashion. Graded (D100/3, D100, D100X3), sequential challenges were performed on days 1 and 21 of each course, and responses measured by changes in nasal airway resistance, sneezes, secretion volume and secretion content: total protein, lysozyme and mucin. After a single dose of sodium cromoglycate, there was no change in resistance, but secretion volumes fell significantly (3.12 ml/5 min c.i. 2.83-3.4; placebo 3.61, c.i. 3.32-3.90: P = 0.026). After a 3-week-course, there was a significant fall in resistance (4.29 cm H2O/l/s, c.i. 3.85-4.72; placebo 5.45, c.i. 5.01-5.88: P < 0.0001). No change in other parameters was observed. Thus, in perennial allergic rhinitis, intranasal sodium cromoglycate has both short- and long-term effects on nasal reactivity to histamine challenge. Acutely, there is a reduction in nasal lavage fluid volume which may be the result of reduced irritant receptor activity. After a 3-week course, there is a reduction in nasal resistance responses, a possible anti-inflammatory effect.

Intranasal fluticasone propionate. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in allergic rhinitis.

Fluticasone propionate is a potent topical anti-inflammatory corticosteroid with low systemic activity. Available pharmacodynamic data are only preliminary; however, large placebo- and drug-controlled clinical studies involving almost 4000 patients with seasonal allergic rhinitis and 1500 with perennial allergic and nonallergic rhinitis have confirmed the efficacy of intranasal fluticasone propionate in the control of nasal symptoms. Fluticasone propionate generally demonstrated similar efficacy compared with intranasal beclomethasone dipropionate, flunisolide acetonide and oral astemizole and better or a trend towards better efficacy compared with oral loratadine, terfenadine, cetirizine and intranasal sodium cromoglycate (cromolyn sodium) against nasal symptoms. The incidence of adverse effects in association with intranasal fluticasone propionate appears to be comparable to that observed with placebo; the most frequently reported effects are nasal dryness/burning, epistaxis and headache. Consistent with its minimal systemic availability, intranasal fluticasone propionate in a dosage of up to 4 mg/day does not cause adrenal suppression. Thus, based on early data from large clinical trials, fluticasone propionate administered once daily offers an effective and convenient treatment option in patients with seasonal and perennial allergic rhinitis, and is distinguished by its low oral bioavailability.

Exposure of hay fever subjects to an indoor environmental grass pollen challenge system.

A new indoor nasal allergen challenge system has been developed which allows subjects with hay fever to be exposed to pre-determined concentration of grass pollen grains in the immediate environment. Thirteen subjects were exposed during the winter months to an atmosphere containing approximately 1000 grains/m3 for 30 min. No changes in nasal airway patency or symptoms of nasal congestion were recorded. It was necessary to increase the pollen concentration to approximately 9000 and 35 000 grains/m3 in two subjects and six subjects respectively, before a positive response was recorded. This response was reproducible in all subjects. Administration of intra-nasal sodium cromoglycate before exposure significantly inhibited the decrease in nasal airway patency and when administered 1 min before exposure totally abolished symptoms of nasal congestion. This new challenge system may therefore be used as an in vivo screen to assess the potential therapeutic value of drugs in hay fever under controlled conditions.

Beclomethasone dipropionate. A reappraisal of its pharmacodynamic properties and therapeutic efficacy after a decade of use in asthma and rhinitis.

Inhaled beclomethasone dipropionate is now well established in the management of asthma. Studies conducted over the last decade, and since the drug was previously reviewed in the Journal, have confirmed that inhaled beclomethasone dipropionate 400 to 800 micrograms daily can reduce the need for oral maintenance corticosteroids in the majority of asthmatic patients requiring such therapy, and that increasing the dosage to 2000 micrograms daily may provide additional clinical benefit in some patients unresponsive to usual therapeutic dosages. Follow-up over a period of several years has confirmed that the initial response to inhaled beclomethasone can be maintained in most patients. Recent studies indicate that beclomethasone dipropionate 400 micrograms daily is equally effective when administered in 2 or 4 divided doses in patients with stable asthma, but it is likely that the lower frequency of administration will be less effective when the asthma is unstable. Recent studies have established the usefulness and good tolerability of intranasal beclomethasone dipropionate in the treatment of perennial and seasonal rhinitis, where the drug has been shown to be more effective than intranasal sodium cromoglycate and similar in efficacy to flunisolide. Nasal polyps decrease in size during continuous treatment with intranasal beclomethasone dipropionate, but enlarge again during periods of respiratory infection. After a decade of treatment with inhaled and intranasal beclomethasone dipropionate, there is no evidence that the drug damages the tracheobronchial lining or the nasal mucosa. Thus, the initial promise of beclomethasone dipropionate has been fulfilled. It has had an important role in asthma therapy over the past decade, which will continue into the future.