-
Drugs in R&D Mar 2018Topical α-adrenergic agonist therapy has been developed to treat the persistent erythema of rosacea patients. Brimonidine and oxymetazoline are both topical...
BACKGROUND
Topical α-adrenergic agonist therapy has been developed to treat the persistent erythema of rosacea patients. Brimonidine and oxymetazoline are both topical α-adrenergic agonists.
OBJECTIVES
The objective of this in vitro safety pharmacology study was to compare the potential safety profiles of brimonidine and oxymetazoline.
METHODS
Brimonidine and oxymetazoline underwent pharmacological profiling with a standard panel of 151 assays, including α-adrenergic receptors and 5-hydroxytryptamine (5-HT) receptors. A valvular interstitial cell (VIC) proliferation assay was performed with oxymetazoline hydrochloride.
RESULTS
Brimonidine was highly selective for the α adrenergic receptors, specifically α, whereas oxymetazoline was found to be much less selective and was highly active against a wide range of targets. Negligible activity was observed with brimonidine at the 5-HT receptor, whereas oxymetazoline had significant 5-HT receptor agonist activity and caused proliferation of mitral VICs in vitro.
CONCLUSION
As the 5-HT receptor is potentially involved in drug-induced valvulopathy, the benefit/risk ratio should be carefully considered, especially in patients with cardiovascular disease or other comorbidities.
Topics: Administration, Topical; Adrenergic alpha-Agonists; Biological Assay; Brimonidine Tartrate; Cell Proliferation; Cells, Cultured; Heart Valves; Humans; Oxymetazoline
PubMed: 29374829
DOI: 10.1007/s40268-018-0227-y -
Lasers in Surgery and Medicine Jan 2020Oxymetazoline, an α-1A agonist, is approved by the United States Food and Drug Administration (FDA) for treatment of persistent facial erythema associated with rosacea...
BACKGROUND AND OBJECTIVE
Oxymetazoline, an α-1A agonist, is approved by the United States Food and Drug Administration (FDA) for treatment of persistent facial erythema associated with rosacea and induces vasoconstriction by interacting with α receptors. The objective of our study was to study the microvascular effects of oxymetazoline and pulsed dye laser (PDL).
MATERIALS AND METHODS
A dorsal window chamber was surgically installed on 20 mice. Each animal was assigned to one of four experimental groups: saline alone, oxymetazoline alone (10 μl applied once daily × 7 days), saline + PDL (saline applied 5 minutes before PDL irradiation [10 mm spot, 1.5 ms pulse duration, 7 J/cm delivered to epidermis]), or oxymetazoline + PDL (10 μl oxymetazoline applied 5 minutes before PDL and then once daily × 7 days). Brightfield and laser speckle imaging were performed for 7 days to monitor vascular architectural and functional changes.
RESULTS
We observed persistent blood flow in all of the saline-only and oxymetazoline-only experiments. A higher rate of vascular shutdown was observed with oxymetazoline + PDL (66.7%) compared with saline + PDL alone (16.7%). Oxymetazoline application increased venule diameter at 5 minutes post-application and decreased both arteriole and venule diameters at 60 minutes post-application.
CONCLUSION
The combination protocol of oxymetazoline + PDL induces persistent vascular shutdown observed 7 days after irradiation. This result may be associated with the acute vascular effects of oxymetazoline. Oxymetazoline + PDL should be evaluated as a treatment for cutaneous vascular disease, including rosacea and port wine birthmarks. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.
Topics: Adrenergic alpha-Agonists; Animals; Lasers, Dye; Low-Level Light Therapy; Mice; Mice, Inbred C3H; Microcirculation; Oxymetazoline; Skin
PubMed: 31758568
DOI: 10.1002/lsm.23186 -
Journal of the American Academy of... Jun 2018Limited treatments are available for persistent erythema of rosacea.
BACKGROUND
Limited treatments are available for persistent erythema of rosacea.
OBJECTIVE
To examine the long-term safety and efficacy of oxymetazoline cream 1.0% in patients with rosacea with moderate-to-severe persistent erythema.
METHODS
Patients applied oxymetazoline once daily for 52 weeks. Safety assessments included treatment-emergent adverse events (TEAEs), skin blanching, inflammatory lesion counts, telangiectasia, disease severity, and rebound effect. Efficacy was assessed by the Clinician Erythema Assessment and Subject Self-Assessment composite score at 3 and 6 hours after the dose on day 1 and at weeks 4, 26, and 52.
RESULTS
Among 440 patients, 8.2% reported treatment-related TEAEs; the most common were application-site dermatitis, paresthesia, pain, and pruritus. The rate of discontinuation due to adverse events (mostly application-site TEAEs) was 3.2%. No clinically meaningful changes were observed in skin blanching, inflammatory lesions, or telangiectasia. At week 52, 36.7%, and 43.4% of patients achieved a 2-grade or greater composite improvement from baseline in both Clinician Erythema Assessment and Subject Self-Assessment 3 and 6 hours after a dose, respectively. Less than 1% of patients experienced a rebound effect following treatment cessation.
LIMITATIONS
A vehicle-control group was not included.
CONCLUSION
This long-term study demonstrated sustained safety, tolerability, and efficacy of oxymetazoline for moderate-to-severe persistent erythema of rosacea.
Topics: Administration, Cutaneous; Adolescent; Adult; Dose-Response Relationship, Drug; Drug Administration Schedule; Erythema; Facial Dermatoses; Female; Humans; Male; Middle Aged; Oxymetazoline; Patient Reported Outcome Measures; Patient Safety; Prospective Studies; Rosacea; Severity of Illness Index; Skin Cream; Time Factors; Treatment Outcome; United States; Young Adult
PubMed: 29409914
DOI: 10.1016/j.jaad.2018.01.027 -
Biochemical Pharmacology Feb 2018The capacity of G protein-coupled receptors to modulate mechanistic target of rapamycin (mTOR) activity is a newly emerging paradigm with the potential to link cell...
The capacity of G protein-coupled receptors to modulate mechanistic target of rapamycin (mTOR) activity is a newly emerging paradigm with the potential to link cell surface receptors with cell survival. Cardiomyocyte viability is linked to signalling pathways involving Akt and mTOR, as well as increased glucose uptake and utilization. Our aim was to determine whether the α-adrenoceptor (AR) couples to these protective pathways, and increased glucose uptake. We characterised α-AR signalling in CHO-K1 cells co-expressing the human α-AR and GLUT4 (CHOαGLUT4myc) and in neonatal rat ventricular cardiomyocytes (NRVM), and measured glucose uptake, intracellular Ca mobilization, and phosphorylation of mTOR, Akt, 5' adenosine monophosphate-activated kinase (AMPK) and S6 ribosomal protein (S6rp). In both systems, noradrenaline and the α-AR selective agonist A61603 stimulated glucose uptake by parallel pathways involving mTOR and AMPK, whereas another α-AR agonist oxymetazoline increased glucose uptake predominantly by mTOR. All agonists promoted phosphorylation of mTOR at Ser2448 and Ser2481, indicating activation of both mTORC1 and mTORC2, but did not increase Akt phosphorylation. In CHOαGLUT4myc cells, siRNA directed against rictor but not raptor suppressed α-AR mediated glucose uptake. We have thus identified mTORC2 as a key component in glucose uptake stimulated by α-AR agonists. Our findings identify a novel link between the α-AR, mTORC2 and glucose uptake, that have been implicated separately in cardiomyocyte survival. Our studies provide an improved framework for examining the utility of α-AR selective agonists as tools in the treatment of cardiac dysfunction.
Topics: Animals; CHO Cells; Calcimycin; Calcium; Cricetinae; Cricetulus; Gene Expression Regulation; Glucose; Glucose Transporter Type 4; Myocytes, Cardiac; Norepinephrine; Phosphorylation; Prazosin; Rats; Receptors, Adrenergic, alpha-1; Signal Transduction; TOR Serine-Threonine Kinases
PubMed: 29175420
DOI: 10.1016/j.bcp.2017.11.016 -
Advanced Biomedical Research 2023Considering the high prevalence of tonsillectomy in children and concerns of postoperative management, this study was conducted with the aim of evaluating the effects of...
BACKGROUND
Considering the high prevalence of tonsillectomy in children and concerns of postoperative management, this study was conducted with the aim of evaluating the effects of oxymetazoline on bleeding, cough, and sore throat in children undergoing tonsillectomy.
MATERIALS AND METHODS
The current double-blind clinical trial study was conducted on 88 tonsillectomy candidate patients. These patients were randomly divided into two groups. In the first group, oxymetazoline 0.05% nasal spray (OXY group) and in the second group, distilled water spray (Control group) was prescribed as one puff in each nostril immediately after anesthesia induction., the nasal spray was prescribed again in both nostrils at 12 h after tonsillectomy. Then the hemodynamic parameters, post-tonsillectomy hemorrhage (PTH) and sore throat were evaluated.
RESULTS
The mean of the sore throat of children was not significantly different between the two groups in any of the follow-up times ( value >0.05). PTH in recovery and in the ward in the OXY group with the mean of 57.60 ± 71.82 ml and 22.11 ± 22.50 ml, respectively, was significantly lower than the control group (83.50 ± 113.64 ml and 27.52 ± 35.11 ml) ( value < 0.05). Also, the frequency of cough in the ward in the OXY group with 27.3% was significantly lower than the control group with 56.8% ( value = 0.005).
CONCLUSION
Regarding the results of the present study, sore throat and hemodynamic parameters did not change significantly with the administration of oxymetazoline. But this drug has played a significant role in reducing PTH and cough in children.
PubMed: 37694249
DOI: 10.4103/abr.abr_247_22 -
Spartan Medical Research Journal 2022Epistaxis is a common otolaryngologic problem that affects most of the general population. Common risk factors for epistaxis include nasal irritants, nasal/facial oxygen...
INTRODUCTION
Epistaxis is a common otolaryngologic problem that affects most of the general population. Common risk factors for epistaxis include nasal irritants, nasal/facial oxygen use, certain systemic conditions (e.g., hypertension and coagulopathies) and medication use (e.g., anticoagulants and intranasal medications). This study examined risk factors for and management of epistaxis in patients admitted for other medical conditions who developed an episode of epistaxis during their hospital admission.
METHODS
Patients were included in the study if they were older than 18, admitted for medical illnesses other than epistaxis and developed an episode of epistaxis during their admission during calendar year 2020 at the authors' institution's hospitals. Electronic health record data regarding sociodemographic characteristics, common risk factors (e.g. oxygen use, anticoagulant use, history of hypertension) and treatment for epistaxis (e.g. holding anticoagulation therapy, administration of oxymetazoline, nasal cautery, nasal packing) were extracted from each chart. Patients were split into otolaryngologic treatment versus no treatment groups and risk factors were compared between sample subgroups.
RESULTS
A total of 143 sample patients were included, with most common reason for admission being cardiovascular related, 48 (33.6%). Most patients, 104 (72.7%), did not have a previous diagnosis of epistaxis, were positive for anticoagulant use, 106 (74.1%) and were positive for hypertension, 95 (66.4%). Oxygen use showed a significantly decreased risk for intervention (OR 0.45, 95% CI: 0.23-0.894; p = 0.028). Most patients required changes in medical management (e.g., holding anticoagulation or starting nasal saline sprays/emollients).
CONCLUSION
These results demonstrate the common risk factors for epistaxis in patients admitted for other clinical diseases. Identifying at-risk patients for epistaxis at hospital admission can help to initiate measures to prevent epistaxis episodes. Future studies are needed to study epistaxis risk factors and identify effective preventative measures for epistaxis among hospital populations.
PubMed: 36128022
DOI: 10.51894/001c.37760 -
Indian Journal of Otolaryngology and... Dec 2008To compare the efficacy and tolerability of Oxymetazoline 0.05 % plus Dexpanthanol 5% versus Xylometazoline 0.1 % nasal drops in patients with nasal congestion due to...
AIMS
To compare the efficacy and tolerability of Oxymetazoline 0.05 % plus Dexpanthanol 5% versus Xylometazoline 0.1 % nasal drops in patients with nasal congestion due to allergic rhinitis and following nasal surgery.
METHODS
An investigator-blind, randomized, controlled, phase IV clinical trial conducted in 100 patients with acute allergic rhinitis or patients post-nasal surgery. Patients received either Oxymetazoline 0.05% with Dexpanthanol 5% (OD) or Xylometazoline 0.1% (XO) nasal drops.
RESULTS
Relief from nasal congestion was significantly better in the OD group then in the XO group (mean nasal scores 1.24 vs 1.86). Significantly more improvement in sneezing and decrease in nasal discharge was seen in the OD group than the XO group. Nasal irritation in the OD group was significantly less as compared to XO group (0.38 v/s 1.12 on second day and 0.10 vs 0.36 on the fourth day). The recovery time for OD group was 1.08 hours, which was significantly (46 min) lesser than that of the XO group. Rebound congestion was significantly less in OD as compared to XO group (6.25% vs 82.98%). 93.75% of the physicians in the OD group and 51.28% in XO group reported response to therapy as good to excellent. 95.83% patients in the OD group and only 52.91% patients in the XO group rated tolerability to therapy as good to excellent.
CONCLUSION
Oxymetazoline and dexpanthenol combination has a better efficacy, shorter recovery time, causes lesser rebound congestion and has better tolerability than xylometazoline.
PubMed: 23120592
DOI: 10.1007/s12070-008-0125-7 -
Journal of Pharmacological Sciences Jul 2009The nasal decongestant oxymetazoline (OMZ) exhibits anti-oxidative and anti-inflammatory properties (I. Beck-Speier et al., J Pharmacol Exp Ther. 2006;316:842-851). In a...
The nasal decongestant oxymetazoline (OMZ) exhibits anti-oxidative and anti-inflammatory properties (I. Beck-Speier et al., J Pharmacol Exp Ther. 2006;316:842-851). In a follow up study, we hypothesized that OMZ generates pro-resolving lipoxins being paralleled by production of immune-modulating prostaglandin E(2) (PGE(2)) and anti-inflammatory 15(S)-hydroxy-eicosatetraenoic acid [15(S)-HETE] and depletion of pro-inflammatory leukotriene B(4) (LTB(4)). Human neutrophils (PMN) were chosen as the cellular system. The effect of OMZ on these parameters as well as on respiratory burst activity and oxidative stress marker 8-isprostane was analyzed in unstimulated and co-stimulated PMN by ultrafine carbon particles (UCP) or opsonized zymosan (OZ), respectively. In unstimulated cells, OMZ induced formation of PGE(2), 15(S)-HETE, and LXA(4). The levels of LTB(4) and 8-isoprostane were not affected, whereas respiratory burst activity was drastically inhibited. In UCP- and OZ-stimulated control cells, all parameters were elevated. Here, OMZ maintained the increased levels of PGE(2), 15(S)-HETE, and LXA(4), but substantially suppressed levels of LTB(4) and 8-isoprostane and inhibited the respiratory burst activity. These findings suggest a switch from the pro-inflammatory eicosanoid class LTB(4) to the pro-resolving LXA(4). Since LXA(4) is most relevant in returning inflamed tissue to homeostasis, OMZ is postulated to terminate rhinitis-related inflammation, thus contributing to shortening of disease duration.
Topics: Carbon; Cell Survival; Dinoprost; Eicosanoids; Humans; In Vitro Techniques; Lipoxins; Nasal Decongestants; Neutrophils; Oxymetazoline; Respiratory Burst; Zymosan
PubMed: 19609065
DOI: 10.1254/jphs.09012fp -
Journal of Advanced Pharmaceutical... 2022Metered-dose nasal sprays (MDNS) are the most widely used for treating rhinitis. Medicinal preparations in the pharmaceutical market vary in their characteristics. To...
Metered-dose nasal sprays (MDNS) are the most widely used for treating rhinitis. Medicinal preparations in the pharmaceutical market vary in their characteristics. To identify the most effective drug, it is necessary to compare the preparations regarding various parameters. The purpose of the research was to compare oxymetazoline MDNS of different brands regarding their dispersion qualities. To that end, nine oxymetazoline sprays available in the Russian market were chosen and analyzed considering their dynamic characteristics and the spraying dispersion composition. The research was conducted with the shadow photography method, the selection of which was justified by its simplicity, the possibilities for detecting the spray jet composition, the process of its formation in dynamics, and the possibility for measuring droplets of all forms. Momentary images of spray activation phases, as well as an averaged image of 100 shots of the spraying main phase, were obtained. According to a range of characteristics, such as spraying duration, a cone angle and cone structure, all the preparations were grouped into three categories. It was found out that the sprays from Group 2 had the best dynamic rates of dispersion, with Vicks Sinex having the best results. Regarding the distribution of particles of different size, the most optimal composition was found for the drugs from Group 2, particularly, Vicks Sinex and Afrin preparations. Hence, Vicks Sinex spraying regimen and microsprayer design were found the most effective for delivering the medicinal substance to the destination.
PubMed: 35223438
DOI: 10.4103/japtr.japtr_240_21 -
British Journal of Pharmacology Jan 1984Oxymetazoline demonstrated a pronounced organ selectivity, when compared to noradrenaline, by being a potent full agonist in rat anococcygeus muscle and a partial... (Comparative Study)
Comparative Study
The relative contribution of affinity and efficacy to agonist activity: organ selectivity of noradrenaline and oxymetazoline with reference to the classification of drug receptors.
Oxymetazoline demonstrated a pronounced organ selectivity, when compared to noradrenaline, by being a potent full agonist in rat anococcygeus muscle and a partial agonist in rat vas deferens. Responses of rat anococcygeus muscles to oxymetazoline were relatively more sensitive to antagonism by phenoxybenzamine (Pbz) an alkylating alpha-adrenoceptor antagonist. Therefore, although oxymetazoline was more potent than noradrenaline in this tissue, after Pbz (0.3 microM for 10 min), the responses to oxymetazoline were completely inhibited while those to noradrenaline were only partially inhibited. Schild analysis with phentolamine, corynanthine, prazosin and yohimbine indicated no alpha-adrenoceptor heterogeneity within the rat anococcygeus muscle or between this tissue and rat vas deferens. Measurement of agonist Kd values and Schild analysis of oxymetazoline antagonism of responses to noradrenaline (after alkylation) confirmed the homogeneity of alpha-adrenoceptors with respect to these two agonists. The above profiles of activity would be predicted if oxymetazoline had a higher affinity but lower efficacy than noradrenaline. Experimentally this was confirmed when it was found that oxymetazoline had 5 times the affinity but 0.2 to 0.3 times the efficacy of noradrenaline. These results serve as a caveat to the use of selective receptor desensitization and/or selective receptor alkylation (or protection from alkylation) as means of differentiating drug receptors. Theoretical modelling and these experimental results indicate that high affinity/low efficacy agonists are much more sensitive to receptor coupling. The implications for therapeutic selectivity could be important in that high affinity/low efficacy agonists theoretically have a much greater potential for organ selectivity.
Topics: Animals; Imidazoles; In Vitro Techniques; Male; Muscle, Smooth; Norepinephrine; Organ Specificity; Oxymetazoline; Phenoxybenzamine; Rats; Rats, Inbred Strains; Receptors, Adrenergic, alpha; Receptors, Drug; Vas Deferens
PubMed: 6322891
DOI: 10.1111/j.1476-5381.1984.tb10753.x