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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 -
American Family Physician Jun 2018
Topics: Administration, Cutaneous; Adrenergic alpha-Agonists; Erythema; Humans; Oxymetazoline; Rosacea; Skin Cream
PubMed: 30216014
DOI: No ID Found -
JAMA Ophthalmology Nov 2020Treatment of acquired blepharoptosis (ptosis) is currently limited to surgical intervention.
IMPORTANCE
Treatment of acquired blepharoptosis (ptosis) is currently limited to surgical intervention.
OBJECTIVE
To examine the efficacy and safety of oxymetazoline hydrochloride, 0.1%, ophthalmic solution (oxymetazoline, 0.1%) in participants with acquired ptosis.
DESIGN, SETTING, AND PARTICIPANTS
This pooled analysis of 2 randomized, double-masked, placebo-controlled, multicenter phase 3 clinical trials included participants 9 years and older with acquired ptosis and superior visual field deficit. The 2 studies were conducted across 16 and 27 sites in the United States. Patients were enrolled from May 2015 to April 2019. Analyses for the individual trials were initiated after database lock and completed on September 6, 2017, and May 16, 2019. Pooled analysis was completed on August 25, 2019.
INTERVENTIONS
Participants (randomized 2:1) received oxymetazoline, 0.1%, or vehicle, self-administered as a single drop per eye, once daily, for 42 days.
MAIN OUTCOMES AND MEASURES
The primary efficacy end point was change from baseline in the number of points seen on the Leicester Peripheral Field Test, a test to detect superior visual field deficits due to ptosis, on days 1 (6 hours after instillation) and 14 (2 hours after instillation). The secondary end point, change from baseline in marginal reflex distance 1, was assessed at the same time points.
RESULTS
In total, 304 participants were enrolled (mean [SD] age, 63.8 [13.8] years; 222 women [73%]). Overall, 97.5% (198 of 203) of participants receiving oxymetazoline, 0.1%, and 97.0% (98 of 101) of participants receiving vehicle completed the studies. Oxymetazoline, 0.1%, was associated with a significant increase in the mean (SD) number of points seen on the Leicester Peripheral Field Test vs vehicle (day 1: 5.9 [6.4] vs 1.8 [4.1]; mean difference, 4.07 [95% CI, 2.74-5.39]; P < .001; day 14: 7.1 [5.9] vs 2.4 [5.5]; mean difference, 4.74 [95% CI, 3.43-6.04]; P < .001). Oxymetazoline, 0.1%, also was associated with a significant increase in marginal reflex distance 1 from baseline (mean [SD]: day 1: 0.96 [0.89] mm vs 0.50 [0.81] mm; mean difference, 0.47 mm [95% CI, 0.27-0.67]; P < .001; day 14: 1.16 [0.87] mm vs 0.50 [0.80] mm; mean difference, 0.67 mm [95% CI, 0.46-0.88]; P < .001). Treatment-emergent adverse events (TEAEs) occurred in 31.0% (63 of 203) of participants receiving oxymetazoline, 0.1%, and 35.6% (36 of 101) of participants receiving vehicle. Among participants receiving oxymetazoline, 0.1%, with a TEAE, 81% (51 of 63) had a maximum TEAE intensity of mild, and 62% (39 of 63) had no TEAE suspected of being treatment related.
CONCLUSIONS AND RELEVANCE
Oxymetazoline, 0.1%, was associated with positive outcomes and was well tolerated in phase 3 trials after instillation at days 1 and 14, demonstrating its potential promise for the treatment of acquired ptosis, although further study is needed to elucidate the clinical relevance of these findings beyond 6 weeks.
Topics: Adolescent; Adrenergic alpha-Agonists; Adult; Aged; Aged, 80 and over; Blepharoptosis; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Ophthalmic Solutions; Oxymetazoline; Treatment Outcome; Visual Fields; Young Adult
PubMed: 33001144
DOI: 10.1001/jamaophthalmol.2020.3812 -
Diseases of the Colon and Rectum Feb 2019Topical α-agonists contract the internal anal sphincter muscle; therefore, they may serve as treatment for fecal incontinence. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Topical α-agonists contract the internal anal sphincter muscle; therefore, they may serve as treatment for fecal incontinence.
OBJECTIVES
The aim of this study was to investigate the effect of the α-agonist oxymetazoline 1.0% on fecal incontinence in patients with spinal cord injury.
DESIGN
This was a double-blind, crossover study. Before randomization, all patients underwent a 1-day, open-label anal manometry and pharmacokinetic study.
SETTINGS
The study was conducted at the Department of Internal Medicine, Semmelweis University, Hungary.
PATIENTS
Nineteen patients were enrolled into a randomized double-blind, placebo-controlled clinical trial with 2 arms: placebo for 4 weeks followed by oxymetazoline for 4 weeks, or vice versa, with an interval 2-week washout period, in a crossover trial design. Treatment order was randomly assigned, and fecal incontinence was captured with daily diaries.
MAIN OUTCOME MEASURES
The primary outcome measured was the number of fecal incontinence episodes in the 8 and 12 hours after drug administration.
RESULTS
Resting anal pressure increased in response to oxymetzoline (25.2%). The change in the mean fecal incontinence episodes per month (12 hours post drug application) favored oxymetazoline over placebo: 26.3 (SD ±28.4) versus 36 (SD ±39.8) (p = 0.021). When only nongas episodes were included, the mean number of episodes decreased from 10.1 (+4.3) to 6.3 (±2.1) fecal incontinence episodes per month (p = 0.022). No difference was observed in adverse events between treatment and placebo periods. All pharmacokinetic samples were below the detection limit.
LIMITATIONS
The study was limited by the small number of participants.
CONCLUSIONS
In this study, oxymetazoline gel presented a clear clinical beneficial effect accompanied by a favorable safety and tolerability profile. Results of the pharmacokinetic analysis indicate that the clinical benefit was mainly due to a local effect of oxymetazoline. Future studies are planned to investigate higher doses of oxymetazoline for this indication. See Video Abstract at http://links.lww.com/DCR/A797.
Topics: Administration, Rectal; Administration, Topical; Adrenergic alpha-Agonists; Adult; Cross-Over Studies; Double-Blind Method; Fecal Incontinence; Female; Humans; Male; Manometry; Middle Aged; Oxymetazoline; Pressure; Spinal Cord Injuries; Treatment Outcome; Young Adult
PubMed: 30451757
DOI: 10.1097/DCR.0000000000001265 -
Dermatologic Surgery : Official... Feb 2021
Topics: Hemostasis, Surgical; Humans; Mohs Surgery; Nasal Mucosa; Nose Neoplasms; Oxymetazoline; Vasoconstrictor Agents
PubMed: 31809355
DOI: 10.1097/DSS.0000000000002272 -
The Journal of Pharmacology and... Feb 2006The nasal decongestant oxymetazoline effectively reduces rhinitis symptoms. We hypothesized that oxymetazoline affects arachidonic acid-derived metabolites concerning...
The nasal decongestant oxymetazoline effectively reduces rhinitis symptoms. We hypothesized that oxymetazoline affects arachidonic acid-derived metabolites concerning inflammatory and oxidative stress-dependent reactions. The ability of oxymetazoline to model pro- and anti-inflammatory and oxidative stress responses was evaluated in cell-free systems, including 5-lipoxygenase (5-LO) as proinflammatory, 15-lipoxygenase (15-LO) as anti-inflammatory enzymes, and oxidation of methionine by agglomerates of ultrafine carbon particles (UCPs), indicating oxidative stress. In a cellular approach using canine alveolar macrophages (AMs), the impact of oxymetazoline on phospholipase A(2) (PLA(2)) activity, respiratory burst and synthesis of prostaglandin E(2) (PGE(2)), 15(S)-hydroxy-eicosatetraenoic acid (15-HETE), leukotriene B(4) (LTB(4)), and 8-isoprostane was measured in the absence and presence of UCP or opsonized zymosan as particulate stimulants. In cell-free systems, oxymetazoline (0.4-1 mM) inhibited 5-LO but not 15-LO activity and did not alter UCP-induced oxidation of methionine. In AMs, oxymetazoline induced PLA(2) activity and 15-HETE at 1 mM, enhanced PGE(2) at 0.1 mM, strongly inhibited LTB(4) and respiratory burst at 0.4/0.1 mM (p < 0.05), but did not affect 8-isoprostane formation. In contrast, oxymetazoline did not alter UCP-induced PLA(2) activity and PGE(2) and 15-HETE formation in AMs but inhibited UCP-induced LTB(4) formation and respiratory burst at 0.1 mM and 8-isoprostane formation at 0.001 mM (p < 0.05). In opsonized zymosan-stimulated AMs, oxymetazoline inhibited LTB(4) formation and respiratory burst at 0.1 mM (p < 0.05). In conclusion, in canine AMs, oxymetazoline suppressed proinflammatory reactions including 5-LO activity, LTB(4) formation, and respiratory burst and prevented particle-induced oxidative stress, whereas PLA(2) activity and synthesis of immune-modulating PGE(2) and 15-HETE were not affected.
Topics: Animals; Arachidonic Acid; Carbon; Cells, Cultured; Dogs; Lipoxygenase Inhibitors; Macrophages, Alveolar; Nasal Decongestants; Oxidative Stress; Oxymetazoline; Particle Size; Phagocytosis; Respiratory Burst; Zymosan
PubMed: 16221739
DOI: 10.1124/jpet.105.093278 -
Lancet (London, England) Aug 1984
Topics: Child; Child, Preschool; Humans; Imidazoles; Infant; Infant, Newborn; Oxymetazoline
PubMed: 6146886
DOI: 10.1016/s0140-6736(84)92712-0 -
Paediatric Anaesthesia Oct 2013Oxymetazoline nasal spray is not FDA approved for use in children less than 6 years; however, its safety and efficacy are widely accepted, and it is in widespread use in...
BACKGROUND
Oxymetazoline nasal spray is not FDA approved for use in children less than 6 years; however, its safety and efficacy are widely accepted, and it is in widespread use in children prior to procedures that may lead to epistaxis. We report a case of intraoperative oxymetazoline toxicity in a 4-year-old boy that led to a hypertensive crisis. While examining the possible causes for this problem, we became aware that the method of drug delivery led to an unanticipated overdose. The position in which the bottle is held causes pronounced variation in the quantity of oxymetazoline dispensed.
METHODS
To examine the impact that bottle position has on the volume delivered, we measured the volume of oxymetazoline dispensed with the bottle in the upright and inverted position. We also measured the volume of a drop of oxymetazoline dispensed from the bottle. Because an additional source of oxymetazoline exposure is from packing the nares with surgical pledgets, we analyzed the volume of oxymetazoline absorbed by each pledget.
RESULTS
Squeezing the bottle in the upright position results in a fine spray of fluid that averaged 28.9 ± 6.8 μl and was largely independent of effort. This volume is nearly identical to the measured volume of a drop of oxymetazoline, which was 30 μl. However, squeezing the bottle in the inverted position resulted in a steady stream of fluid, and the volume administered was completely effort dependent. Multiple tests in the inverted position demonstrated an average volume of 1037 ± 527 μl, with a range of 473-2196 μl. Lastly, the volume of oxymetazoline absorbed by each surgical pledget was 1511 ± 184 μl.
DISCUSSION
Our testing indicates that bottle position during oxymetazoline administration can cause up to a 75-fold increase in intended drug administration.
Topics: Administration, Inhalation; Administration, Intranasal; Blood Pressure; Child; Child, Preschool; Drug Overdose; Equipment Failure; Humans; Hypertension; Male; Nasal Decongestants; Oxymetazoline; Radiography, Dental
PubMed: 23679077
DOI: 10.1111/pan.12192 -
The Annals of Otology, Rhinology, and... Sep 1995The purpose of this study was to determine if use of an intranasal vasoconstrictor (oxymetazoline) could be used to effectively treat epistaxis, avoiding nasal packing....
The purpose of this study was to determine if use of an intranasal vasoconstrictor (oxymetazoline) could be used to effectively treat epistaxis, avoiding nasal packing. The charts of 60 patients who presented to the emergency room with the diagnosis of epistaxis and who required medical management were reviewed. Sixty-five percent of these patients were successfully managed with oxymetazoline as their sole therapy. An additional 18% were managed successfully with silver nitrate cautery in combination with oxymetazoline. In only 17% of patients was it necessary to use nasal packing as treatment for epistaxis after an initial attempt with oxymetazoline alone or in combination with silver nitrate failed. These data suggest that pharmacologic management may be adequate in the majority of patients with epistaxis, thus avoiding the need for nasal packing with its associated complications.
Topics: Adult; Cautery; Drug Administration Schedule; Epistaxis; Female; Humans; Male; Middle Aged; Oxymetazoline
PubMed: 7661519
DOI: 10.1177/000348949510400906 -
Biochimica Et Biophysica Acta.... Dec 2017In LNCaP cells that stably express α-adrenergic receptors, oxymetazoline increased intracellular calcium and receptor phosphorylation, however, this agonist was a weak...
In LNCaP cells that stably express α-adrenergic receptors, oxymetazoline increased intracellular calcium and receptor phosphorylation, however, this agonist was a weak partial agonist, as compared to noradrenaline, for calcium signaling. Interestingly, oxymetazoline-induced receptor internalization and desensitization displayed greater effects than those induced by noradrenaline. Phorbol myristate acetate induced modest receptor internalization and minimal desensitization. α-Adrenergic receptor interaction with β-arrestins (colocalization/coimmunoprecipitation) was induced by noradrenaline and oxymetazoline and, to a lesser extent, by phorbol myristate acetate. Oxymetazoline was more potent and effective than noradrenaline in inducing ERK 1/2 phosphorylation. Mass spectrometric analysis of immunopurified α-adrenergic receptors from cells treated with adrenergic agonists and the phorbol ester clearly showed that phosphorylated residues were present both at the third intracellular loop and at the carboxyl tail. Distinct phosphorylation patterns were observed under the different conditions. The phosphorylated residues were: a) Baseline and all treatments: T233; b) noradrenaline: S220, S227, S229, S246, S250, S389; c) oxymetazoline: S227, S246, S381, T384, S389; and d) phorbol myristate acetate: S246, S250, S258, S351, S352, S401, S402, S407, T411, S413, T451. Our novel data, describing the α-AR phosphorylation sites, suggest that the observed different phosphorylation patterns may participate in defining adrenoceptor localization and action, under the different conditions examined.
Topics: Calcium Signaling; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Humans; MAP Kinase Signaling System; Mass Spectrometry; Norepinephrine; Oxymetazoline; Phosphorylation; Protein Kinase C; Proteolysis; Receptors, Adrenergic, alpha-1; Tetradecanoylphorbol Acetate
PubMed: 28888989
DOI: 10.1016/j.bbamcr.2017.09.002