The nasal airways response in normal subjects to oxymetazoline spray: randomized double-blind placebo-controlled trial.
AIMS: The effects of a single dose of oxymetazoline nasal spray on nasal patency have been compared with placebo using three separate measuring systems in normal subjects. METHODS: The study was a placebo-controlled, randomised double-blind crossover trial. Subjects without ear, nose or throat disease and with resting nasal airways resistance >0.15 Pa s cm-3 were selected so that a fall in airways resistance could be detected. Nasal airways resistance (NAR) was measured by NR6-2 rhinomanometer. Acoustic rhinometry (SR-2000 rhinometer) provided the sum of the minimum cross-sectional areas (tMCA) and volume (tVOL) of the left and right nasal cavities. Symptoms of congestion were assessed on a visual analogue scale (CON, range 0-100). Measurements were made for 60 min before and for 120 min after bilateral administration of oxymetazoline nasal spray (0.9 mg) or placebo (0.9% saline). Crossover occurred 7-21 days later. Results for all measures were analysed as change from average baseline value by trapezoidal AUC, and statistical significance was tested by 2-way anova. RESULTS: NAR, tMCA, tVOL and CON did not change after placebo, but NAR and CON fell and tMCA and tVOL increased significantly at all timepoints after oxymetazoline. NAR_AUC, tVOL_AUC, tMCA_AUC were significantly different between placebo and oxymetazoline (P<0.001) as was CON_AUC (P=0.012). The day-to-day intraindividual repeatability of baseline NAR tMCA and tVOL was <10%. CONCLUSIONS: Normal subjects can be used to detect the effects of nasally vasoactive drugs with a variety of complementary systems, with the advantages of easy subject recruitment and low variability. (+info)
Nasal airflow dynamics: mechanisms and responses associated with an external nasal dilator strip.
The adhesive external nasal dilator strip (ENDS) is widely advocated for prevention of snoring and promotion of nasal breathing during exercise. In the present study, the effects of the ENDS on nasal airflow resistance (Rn) in normal subjects were examined and factors determining individual responses to the ENDS explored. Using posterior rhinomanometry, 20 healthy Caucasian adults (10 males, 10 females; age: 18-56 yrs) were studied during quiet tidal breathing and voluntary hyperpnoea with (ENDS) and without (control) ENDS and with a placebo strip (placebo) before and after application of a topical nasal decongestant (oxymetazoline hydrochloride). During tidal breathing, only nine subjects showed a significantly (p<0.05) decreased inspiratory and/or expiratory Rn with the ENDS ("responders"). During the control, inspiratory Rn (at 0.4 L x s(-1)) was higher in "responders" than "nonresponders" (3.28+/-0.16 versus 2.60+/-0.08 cmH2O x L(-1) x s; p=0.04). The effects of nasal decongestant and the ENDS were additive. During voluntary hyperpnoea, inspiratory Rn (at 1.0 L x s(-1)) and the hysteresis of the inspiratory transnasal pressure/flow curve were decreased with the ENDS in most subjects. It is concluded that the external nasal dilator strip influences nasal airflow dynamics by both dilation of the nasal valve and stabilization of the lateral nasal vestibule walls and may be more effective in subjects with a high resting nasal airflow resistance. (+info)
Inhibition of nitric oxide synthase by nasal decongestants.
The nasal decongestants oxymetazoline and xylometazoline are frequently used in the topical treatment of rhinitis and sinusitis. As nitric oxide (NO) is thought to play a role in inflammation of the upper respiratory tract, the aim of this study was to examine the in vitro effects of these compounds on the activity and the expression of NO producing enzymes, including the inducible form of NO synthase (iNOS) and the constitutive isoform of NO synthase (cNOS). Experiments concerning the effects of both compounds on enzymatic activity and enzyme induction of iNOS were performed in a lipopolysaccharide (LPS) induced rat alveolar macrophage cell line (NR8383) using the Griess assay and the 3H-citrulline assay respectively. The effects on cNOS were examined in fresh rat synaptosomes using the 3H-citrulline assay. The direct scavenging properties of both compounds were investigated using a amperometric NO sensor. Oxymetazoline and xylometazoline were shown to have a dose dependent inhibitory effect on total iNOS activity indicated by nitrite/nitrate formation in the Griess assay. This effect was found to be due to an inhibition of induction of the enzyme rather than inhibition of the enzyme activity, as was investigated in two separate experiments using the 3H-citrulline assay. Inhibition of cNOS was moderate and in the same order of magnitude as the inhibition of enzymatic iNOS activity. Direct scavenging of NO could not be detected. As constitutive nitric oxide synthase activity is thought to serve beneficial physiological functions, and exaggerated inducible nitric oxide synthase activity may cause exacerbation of the inflammatory process, pharmacological treatment influencing the nitric oxide generating system should focus on inhibition of inducible nitric oxide synthase alone. The specific characteristics of these decongestants in vitro suggests suitability for this application and may indicate an additional beneficial effect in the treatment of upper respiratory tract inflammation. (+info)
Phenylpropanolamine and the risk of hemorrhagic stroke.
BACKGROUND: Phenylpropanolamine is commonly found in appetite suppressants and cough or cold remedies. Case reports have linked the use of products containing phenylpropanolamine to hemorrhagic stroke, often after the first use of these products. To study the association, we designed a case-control study. METHODS: Men and women 18 to 49 years of age were recruited from 43 U.S. hospitals. Eligibility criteria included the occurrence of a subarachnoid or intracerebral hemorrhage within 30 days before enrollment and the absence of a previously diagnosed brain lesion. Random-digit dialing identified two matched control subjects per patient. RESULTS: There were 702 patients and 1376 control subjects. For women, the adjusted odds ratio was 16.58 (95 percent confidence interval, 1.51 to 182.21; P=0.02) for the association between the use of appetite suppressants containing phenylpropanolamine and the risk of a hemorrhagic stroke and 3.13 (95 percent confidence interval, 0.86 to 11.46; P=0.08) for the association with the first use of a product containing phenylpropanolamine. All first uses of phenylpropanolamine involved cough or cold remedies. For men and women combined, the adjusted odds ratio was 1.49 (95 percent confidence interval, 0.84 to 2.64; P=0.17) for the association between the use of a product containing phenylpropanolamine and the risk of a hemorrhagic stroke, 1.23 (95 percent confidence interval, 0.68 to 2.24; P=0.49) for the association with the use of cough or cold remedies that contained phenylpropanolamine, and 15.92 (95 percent confidence interval, 1.38 to 184.13; P=0.03) for the association with the use of appetite suppressants that contained phenylpropanolamine. An analysis in men showed no increased risk of a hemorrhagic stroke in association with the use of cough or cold remedies containing phenylpropanolamine. No men reported the use of appetite suppressants. CONCLUSIONS: The results suggest that phenylpropanolamine in appetite suppressants, and possibly in cough and cold remedies, is an independent risk factor for hemorrhagic stroke in women. (+info)
Adult rhinosinusitis: diagnosis and management.
Rhinosinusitis can be divided among four subtypes: acute, recurrent acute, subacute and chronic, based on patient history and a limited physical examination. In most instances, therapy is initiated based on this classification. Antibiotic therapy, supplemented by hydration and decongestants, is indicated for seven to 14 days in patients with acute, recurrent acute or subacute bacterial rhinosinusitis. For patients with chronic disease, the same treatment regimen is indicated for an additional four weeks or more, and a nasal steroid may also be prescribed if inhalant allergies are known or suspected. Nasal endoscopy and computed tomography of the sinuses are reserved for circumstances that include a failure to respond to therapy as expected, spread of infection outside the sinuses, a question of diagnosis and when surgery is being considered. Laboratory tests are infrequently necessary and are reserved for patients with suspected allergies, cystic fibrosis, immune deficiencies, mucociliary disorders and similar disease states. Findings on endoscopically guided microswab culture obtained from the middle meatus correlate 80 to 85 percent of the time with results from the more painful antral puncture technique and is performed in patients who fail to respond to the initial antibiotic selection. Surgery is indicated for extranasal spread of infection, evidence of mucocele or pyocele, fungal sinusitis or obstructive nasal polyposis, and is often performed in patients with recurrent or persistent infection not resolved by drug therapy. (+info)
Anesthetic considerations for orthognathic surgery with evaluation of difficult intubation and technique for hypotensive anesthesia.
Orthognathic surgery is carried out to improve facial appearance and/or to improve malocclusion. Usually, patients are young and healthy. However, they may have airway problems. Reinforced silicone low-pressure, high-volume endotracheal tubes and p-xylometazoline (Otrivin) for nasal vasoconstriction reduces problems due to the endotracheal tubes. A head-up position with ventilator and monitoring equipment at the foot end helps the surgeons as well as the surgery. Surgeons may be the cause of endotracheal tube problems. Bleeding is a major problem that may be encountered and is reduced by induced hypotension. During osteotomies, severe bradycardia may occur and may even lead to cardiac arrest. In the early postoperative period, bleeding may be a problem. Later ulceration at the tip of the nose and on the buttocks may be seen if preventive measures are not carried out. (+info)
Comparison of the clinical efficacy of standard and mucoadhesive-based nasal decongestants.
AIMS: To compare two xylometazoline 0.1% preparations: reference commercial solution (RS) and test mucoadhesive solution (TS). METHODS: Twenty subjects with perennial allergic rhinitis (age range 18-69 years, 5 atopic, 7 men) applied randomly in turn TS and RS for 5 days in a double-blind crossover clinical trial. Nasal airflow resistance (NAR), nasal symptoms (6 grade scoring), frequency of application (times/day), and side-effects were recorded. RESULTS: Mean ratio TS/RS of areas under the resistance/time curves for NAR +/- 90% CI: 3.56 +/- 0.92; mean TS-RS differences +/- 95% CI: for congestion: -1.12 +/- 0.59, for frequency of application: -1.10 +/- 0.20. Subjects experienced fewer side-effects with TS. CONCLUSIONS: A mucoadhesive solution with a decongestant had a greater and longer lasting effect on nasal congestion in subjects with perennial allergic rhinitis than the commercially available decongestant solution. It also caused fewer side effects. (+info)
The stability of oxymetazoline hydrochloride in aqueous solution.
The kinetics of the hydrolysis reaction of oxymetazoline hydrochloride in aqueous solution at three temperatures (343 K, 353 K, 363 K), over the pH-range 0.5-12.5 and ionic strength 0.5 has been investigated. The changes of concentration of oxymetazoline hydrochloride were followed by the HPLC method with UV detection. In the pH range from 0.45 to 12.50, the hydrolysis of oxymetazoline consists of hydrolysis of oxymetazoline molecules catalyzed by hydrogen ions, spontaneous hydrolysis of the dissociated and undissociated oxymetazoline molecules. A minimal rate of the hydrolysis oxymetazoline was observed to occur in the pH range from 2.0 to 5.0. Thermodynamic parameters of the reaction: energy, entropy and enthalpy of activation and the frequency factor for the specific rate constants were determined. (+info)