Local field potential power spectra and locomotor activity following treatment with pseudoephedrine in mice.

The efficacy of pseudoephedrine (PSE) as a nasal decongestant has been well­demonstrated; however, PSE is strictly prescribed as a control substance due to its controversial psychostimulant effects. Although standard stimulatory drugs increase exploratory behavior and stimulate the dopamine system, the exact effects of PSE on locomotion and electrical activity in the striatum have not been determined. This study aimed to examine and compare the locomotor activities, local field potential (LFP) and sleep­wake patterns produced by PSE and morphine, which is a standard drug used to promote psychomotor activity. Male Swiss albino mice were anesthetized and implanted with an intracranial electrode into the striatum. Animals were divided into four groups, which received either saline, PSE or morphine. Locomotor activity and LFP signals were continuously monitored following pseudoephedrine or morphine treatment. One­way ANOVA revealed that locomotor count was significantly increased by morphine, but not PSE. Frequency analyses of LFP signals using fast Fourier transform also revealed significant increases in spectral powers of low­ and high­gamma waves following treatment with morphine, but not PSE. Sleep­wake analysis also confirmed significant increases in waking and decreases in both non­rapid eye movement and rapid eye movement sleep following morphine treatment. Sleep­wakefulness did not appear to be disturbed by PSE treatment. These findings indicate that acute PSE administration, even at high doses, does not have psychostimulatory effects and may be relatively safe for the treatment of non­chronic nasal congestion.

Safety of the use of xylometazoline nasal spray in young children undergoing lacrimal surgery: an observational study.

PURPOSE: It is common practice to prepare the nasal mucosa with decongestant in children undergoing lacrimal surgery. Xylometazoline 0.05% (Otrivine) nasal spray is commonly used. It has been reported to cause cardiovascular side effects. In the absence of formal guidelines on the safety of the use of nasal decongestants in children, we reviewed our practice to answer the question: How safe is preoperative use of xylometazoline in children undergoing lacrimal surgery? To our knowledge, this is the first study to address the potential side effects of the use of xylometazoline preoperatively in children undergoing lacrimal surgery. METHODS: This was a retrospective analysis of medical notes of children undergoing lacrimal surgery with the use of preoperative intranasal xylometazoline 0.05% over a 5-year period. RESULTS: Twenty-nine children, age 1-6 years (mean 3 years), underwent lacrimal surgery under general anesthesia with preoperative use of intranasal xylometazoline. Topical intranasal 1:10,000 adrenaline was used during surgery in all patients. All children were found to have uneventful surgery and recovery from anesthesia. CONCLUSIONS: Xylometazoline 0.05% intranasal use for prelacrimal surgery was found to be effective and safe. Addition of sympathomimetic topical adrenaline (1:10,000) did not impose any risks. The type of general anesthesia may influence the cardiovascular side effects anecdotally recorded during xylometazoline use.

Topical glucocorticoid reduces the topical decongestant-induced histologic changes in an animal model nasal mucosa.

OBJECTIVES/HYPOTHESIS: To investigate the histologic consequences of simultaneous nasal glucocorticosteroid and xylometazoline HCl administration in the rabbit nasal mucosa. STUDY DESIGN: Prospective randomized study. METHODS: Twenty New Zealand male rabbits were randomly placed into three groups: group I, control (n = 6); group II, xylometazoline HCl (n = 8); or group III, xylometazoline HCl-fluticasone furoate (n = 6). Group I received no treatment. Groups II and III received two intranasal puffs of xylometazoline HCl 0.5 mg/mL twice daily or two puffs of xylometazoline HCl 0.5 mg/mL twice daily plus one puff of 27.5 µg fluticasone furoate twice daily to each nostril (110 µg), respectively. At the end of 3 weeks, the rabbits were sacrificed. The mucosa of the nasal cavities was excised. Specimen sections (5 µm) were stained with hematoxylin and eosin, mucicarmine, and Gomori one-step trichrome and were examined under a light microscope. The presence of edema, congestion, inflammatory cell infiltration, nasociliary loss, epithelial and nerve-ending degeneration, and goblet cell increase were evaluated semiquantitatively (grades 0-3). RESULTS: Statistically significant differences were detected between groups II and III in terms of edema, congestion, inflammatory cell infiltration, nasociliary loss, and epithelial degeneration (P = .006, P = .049, P = .015, P = .014, and P = .049, respectively). Nerve-ending degeneration, goblet cell increase, and quantitative goblet and neutrophil cell counts did not yield statistically significant differences between groups II and III (P = .137, P = .580, P = .770, and P = .616, respectively). CONCLUSIONS: The combined simultaneous intranasal administration of xylometazoline HCl and fluticasone furoate appears to be beneficial in minimizing the long-term usage-associated congestion, edema, inflammatory cell infiltration, epithelial degeneration, and nasociliary loss in the rabbit model nasal mucosa.

Oxymetazoline ototoxicity in a chinchilla animal model.

OBJECTIVE: To investigate possible ototoxic effects of a one-time application of oxymetazoline drops in a chinchilla animal model with tympanostomy tubes. Study Design. A prospective, controlled animal study. SETTING: The Research Institute of the Montreal's Children Hospital, McGill University Health Centre. SUBJECTS AND METHODS: Ventilation tubes were inserted in both ears of 12 animals. One ear was randomly assigned to receive oxymetazoline drops (0.5 mL). The contralateral ear did not receive any drops, serving as a control ear. OUTCOME MEASURES: Distortion product otoacoustic emissions were measured bilaterally for a wide range of frequencies (between 1 and 16 kHz) before and 1 day after the application of oxymetazoline in the experimental ears. Two months later, the animals were sacrificed and all cochleae were dissected out and processed for scanning electron microscopy. RESULTS: In this established chinchilla animal model, the measured distortion product otoacoustic emission amplitudes and the morphological appearance on scanning electron microscopy were similar for both control and experimental ears. CONCLUSION: Oxymetazoline did not cause ototoxicity in a chinchilla animal model 2 months after a single application via a tympanostomy tube.

Trapping of adrenergic decongestant drugs into cellular endomembrane compartments: toxicological and pharmacological consequences.

Rhinitis of allergic and viral origin is often self-treated by patients with locally applied vasoconstrictor decongestant drugs. In turn, prolonged use of these agents produce an inflammatory condition termed rhinitis medicamentosa. Cationic drugs are sequestered into cells via various mechanisms, including mitochondrial concentration and V-ATPase-driven trapping in vacuoles that swell by an osmotic mechanism. We hypothesized that receptor-independent endomembrane sequestration of topically applied concentrated alpha-adrenoceptor agonists (decongestants, mydriatics) could contribute to their toxicity and prolonged duration of action. The morphological and functional effects of phenylephrine and xylometazoline on rabbit aortic smooth muscle cells were examined and their possible sequestration evaluated using the contractility of rabbit aorta rings. Synthetic agonists produced V-ATPase-dependent cell vacuolization (prevented by bafilomycin A1; xylometazoline 250 microM, phenylephrine 2.5 mM). V-ATPase-mediated cytotoxicity was slow (24 h; phenylephrine only, 5-10 mM); a rapid xylometazoline-induced cytotoxicity (> or =500 microM, 4 h) correlated to mitochondrial functional alterations. Xylometazoline had slower contraction and relaxation kinetics than the other alpha-adrenoceptor agonists in the aorta; bafilomycin pre-treatment influenced its kinetics (accelerated contraction and relaxation) and concentration-effect relationship (potentiation). V-ATPase-driven sequestration contributed to a component of the tissue reservoir of both phenylephrine and xylometazoline as assessed by aortic rings contracted with the concentrated agonists and subsequently washed. Phenylephrine and xylometazoline caused the V-ATPase-dependent cytopathology at a fraction of the usual topical concentrations; this form of sequestration influenced the toxicity and pharmacology of individual agents.

[The tolerability of nasal drugs with special regard to preservatives and physico-chemical parameters]. / Die Verträglichkeit von Nasalia unter besonderer Berücksichtigung des Einflusses von Konservierungsmitteln und physikalisch-chemischen Parametern.

BACKGROUND: Recent technical developments allow preservative-free nasal drug application in multi-dose systems. New pharmaceutical formulations for better tolerable nasal sprays are now possible and consequently reformulations introduced to the market. Therefore, a representative and systematic overview on comparable products is mandatory. METHODS: Marketed nasal products in the indication groups: decongestants, antiallergics, care and wound-healing, hormones and saline solutions were tested for their cytotoxic properties according to DIN EN 30 993 - 5, pH, and osmolality. RESULTS: In all indication groups reformulation to preservative-free application resulted in significant increase of cell growth and reduction of cytotoxicity. Physico-chemical galenic properties are of considerable importance too. With decongestants tolerability is dependant on the concentration of the active compound. CONCLUSIONS: Our data lead to the conclusion that preserved nasal sprays are obsolete, when preservative-free alternatives are available. Attention should be paid to galenic properties and dosage of the active.

Treatment of rhinitis medicamentosa with fluticasone propionate--an experimental study.

The efficacy of fluticasone propionate aqueous nasal spray (0.05% w/w) in the treatment of rhinitis medicamentosa has been studied in an animal model (guinea pig). Rhinitis medicamentosa was induced through the instillation of 0.05% naphthazoline nitrate (Privine) for 8 weeks. Fluticasone propionate nasal spray was then administered to the animals for 2 weeks. The spray successfully cleared the interstitial edema which is the pathologic hallmark of rhinitis medicamentosa. The study suggests that fluticasone propionate nasal spray can be beneficial in the treatment of patients with rhinitis medicamentosa.

A new nasal decongestant, A-57219: a comparison with oxymetazoline.

2-(4-Amino-3,5-dichlorobenzyl)imidazoline hydrochloride (A-57219), has alpha 1-agonist/alpha 2-antagonist activity and was more effective and long-acting than oxymetazoline on canine nasal mucosa, in-vitro and in-vivo. Upon intranasal administration to dogs, the compound was devoid of systemic effects up to a concentration 1000 times that needed for local decongestant effect (1.65 micrograms, atomized from a 1 microgram mL-1 solution) suggesting limited mucosal absorption. After nasal administration to rats for 15 days at a concentration 1000 times greater than that required for nasal decongestion, no mucosal tissue toxicity or systemic effects were seen.

Effects of topical nasal decongestants on the cilia of a chicken embryo tracheal organ culture system.

There is little physiologic data concerning the possible toxicity of nasal decongestants on respiratory cilia. Consequently, a chicken embryo tracheal organ culture system was employed to study the effect on ciliary activity of various preparations and concentrations of the following medications: tetrahydrozoline hydrochloride (Tyzine), xylometazoline hydrochloride (Otrivin), Dristan, Sinex, NTZ oxymetazoline hydrochloride (Afrin), naphazoline hydrochloride (Privine), and phenylephrine (Neosynephrine). Only two dilutions of injectable phenylephrine 0.25% and 0.10% produced essentially no ciliotoxicity when compared to the cilia in control cultures. All the other topical nasal medications in the concentrations tested possessed some toxicity for cilia. The use of these medications should be tempered with the warning of possible cilia damage.