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Arquivos Brasileiros de Oftalmologia 2007To compare the cardiovascular and mydriatic effects of 2.5% and 10.0% phenylephrine. (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
To compare the cardiovascular and mydriatic effects of 2.5% and 10.0% phenylephrine.
METHODS
A case-control, randomized, crossover clinical trial study. We monitored heart rate (HR), blood pressure (BP) and mydriasis in healthy volunteers aged 18-45 years after the instillation of 2.5% and 10.0% phenylephrine in two different occasions.
RESULTS
The sample comprised 28 healthy volunteers, 17 male and 11 female, with a mean age of 26.5 years. No changes in heart rate and systolic blood pressure were observed. No significant variation of the mean diastolic blood pressure was found after 1, 5, 10 and 30- minute instillation of 2.5% phenylephrine. However, with 10.0% phenylephrine, there was an increase in mean diastolic blood pressure after five and ten minutes, followed by a drop after 30 minutes, which was not statistically significant. Mydriasis was more marked in both eyes with a statistically significant difference after instillation of 10.0% phenylephrine.
CONCLUSIONS
The mydriatic effect was greater with 10.0% phenylephrine than with 2.5% phenylephrine and the difference was statistically significant. No statistically significant difference was found in relation to cardiovascular effects in both phenylephrine concentrations.
Topics: Adolescent; Adult; Blood Pressure; Female; Heart Rate; Humans; Male; Middle Aged; Mydriatics; Phenylephrine; Prospective Studies; Pupil; Statistics, Nonparametric; Time Factors
PubMed: 18235907
DOI: 10.1590/s0004-27492007000600014 -
British Journal of Pharmacology Jul 2017Agonists acting at GPCRs promote biased signalling via Gα or Gβγ subunits, GPCR kinases and β-arrestins. Since the demonstration of biased agonism has implications...
BACKGROUND AND PURPOSE
Agonists acting at GPCRs promote biased signalling via Gα or Gβγ subunits, GPCR kinases and β-arrestins. Since the demonstration of biased agonism has implications for drug discovery, it is essential to consider confounding factors contributing to bias. We have examined bias at human α -adrenoceptors stably expressed at low levels in CHO-K1 cells, identifying off-target effects at endogenous receptors that contribute to ERK1/2 phosphorylation in response to the agonist oxymetazoline.
EXPERIMENTAL APPROACH
Intracellular Ca mobilization was monitored in a Flexstation® using Fluo 4-AM. The accumulation of cAMP and ERK1/2 phosphorylation were measured using AlphaScreen® proximity assays, and mRNA expression was measured by RT-qPCR. Ligand bias was determined using the operational model of agonism.
KEY RESULTS
Noradrenaline, phenylephrine, methoxamine and A61603 increased Ca mobilization, cAMP accumulation and ERK1/2 phosphorylation. However, oxymetazoline showed low efficacy for Ca mobilization, no effect on cAMP generation and high efficacy for ERK1/2 phosphorylation. The apparent functional selectivity of oxymetazoline towards ERK1/2 was related to off-target effects at 5-HT receptors endogenously expressed in CHO-K1 cells. Phenylephrine and methoxamine showed genuine bias towards ERK1/2 phosphorylation compared to Ca and cAMP pathways, whereas A61603 displayed bias towards cAMP accumulation compared to ERK1/2 phosphorylation.
CONCLUSION AND IMPLICATIONS
We have shown that while adrenergic agonists display bias at human α -adrenoceptors, the marked bias of oxymetazoline for ERK1/2 phosphorylation originates from off-target effects. Commonly used cell lines express a repertoire of endogenous GPCRs that may confound studies on biased agonism at recombinant receptors.
Topics: Adrenergic alpha-1 Receptor Agonists; Animals; CHO Cells; Cells, Cultured; Cricetulus; Dose-Response Relationship, Drug; Humans; Imidazoles; Methoxamine; Norepinephrine; Phenylephrine; Receptors, Adrenergic, alpha-1; Structure-Activity Relationship; Tetrahydronaphthalenes
PubMed: 28444738
DOI: 10.1111/bph.13837 -
British Journal of Clinical Pharmacology Jan 2007The aim of this review was to investigate the rationale for replacing the nasal decongestant pseudoephedrine (PDE) with phenylephrine (PE) as a means of controlling the... (Review)
Review
The aim of this review was to investigate the rationale for replacing the nasal decongestant pseudoephedrine (PDE) with phenylephrine (PE) as a means of controlling the illicit production of methamphetamine. A literature search was conducted in electronic databases and use of textbooks. Restrictions have been placed on the sale of PDE in the USA in an attempt to control the illicit production of methamphetamine. This has caused a switch from PDE to PE in many common cold and cough medicines. PE is a poor substitute for PDE as an orally administered decongestant as it is extensively metabolized in the gut and its efficacy as a decongestant is unproven. Both PDE and PE have a good safety record, but the efficacy of PDE as a nasal decongestant is supported by clinical trials. Studies in the USA indicate that restricting the sale of PDE to the public as a medicine has had little impact on the morbidity and number of arrests associated with methamphetamine abuse. Restricting the sale of PDE in order to control the illicit production of methamphetamine will deprive the public of a safe and effective nasal decongestant and force the pharmaceutical industry to replace PDE with PE, which may be an ineffective decongestant. Restrictions on sales of PDE to the public may not reduce the problems associated with methamphetamine abuse.
Topics: Amphetamine-Related Disorders; Ephedrine; Humans; Methamphetamine; Nasal Decongestants; Phenylephrine
PubMed: 17116124
DOI: 10.1111/j.1365-2125.2006.02833.x -
Anesthesiology Apr 2015
Topics: Anesthesia, Spinal; Blood Pressure; Cesarean Section; Female; Humans; Monitoring, Intraoperative; Norepinephrine; Phenylephrine; Pregnancy
PubMed: 25654435
DOI: 10.1097/ALN.0000000000000602 -
Clinics (Sao Paulo, Brazil) 2023The authors investigated changes in vascular reactivity in rats following pilocarpine-induced status epilepticus.
OBJECTIVE
The authors investigated changes in vascular reactivity in rats following pilocarpine-induced status epilepticus.
METHOD
Male Wistar rats weighing between 250g and 300g were used. Status epilepticus was induced using 385 mg/kg i.p. pilocarpine. After 40 days the thoracic aorta was dissected and divided into 4 mm rings and the vascular smooth muscle reactivity to phenylephrine was evaluated.
RESULTS
Epilepsy decreased the contractile responses of the aortic rings to phenylephrine (0.1 nM-300 mM). To investigate if this reduction was induced by increasing NO production with/or hydrogen peroxide L-NAME and Catalase were used. L-NAME (N-nitro-L arginine methyl ester) increased vascular reactivity but the contractile response to phenylephrine increased in the epileptic group. Catalase administration decreased the contractile responses only in the rings of rats with epilepsy.
CONCLUSIONS
Our findings demonstrated for the first time that epilepsy is capable of causing a reduction of vascular reactivity in rat aortas. These results suggest that vascular reactivity reduction is associated with increased production of Nitric Oxide (NO) as an organic attempt to avoid hypertension produced by excessive sympathetic activation.
Topics: Rats; Male; Animals; Vasoconstrictor Agents; NG-Nitroarginine Methyl Ester; Rats, Wistar; Catalase; Pilocarpine; Phenylephrine; Aorta, Thoracic; Status Epilepticus; Nitric Oxide
PubMed: 37099815
DOI: 10.1016/j.clinsp.2023.100195 -
Turkish Journal of Medical Sciences Apr 2022Irisin, a newly identified exercise-derived myokine, has been found involved in a peripheral vasodilator effect. However, little is known regarding the potential...
BACKGROUND
Irisin, a newly identified exercise-derived myokine, has been found involved in a peripheral vasodilator effect. However, little is known regarding the potential vascular activity of irisin, and the mechanisms underlying its effects on vascular smooth muscle have not been fully elucidated. This study was aimed to investigate the effects of irisin on vascular smooth muscle contractility in rat thoracic aorta, and the hypothesis that protein kinase C (PKC) may have a role in these effects.
METHODS
Isometric contraction-relaxation responses of thoracic aorta rings were measured with an isolated organ bath model. The steady contraction was induced with 10 µM phenylephrine (PHE), and then the concentration-dependent responses of irisin (0.001-1 µM) were examined. The time-matched vehicle control (double distilled water) group was also formed. To evaluate the role of PKC, endothelium-intact thoracic aorta rings were incubated with 150 nM bisindolylmaleimide I (BIM I) for 20 min before the addition of 10 µM PHE and irisin. Also, a vehicle control group was formed for dimethyl sulfoxide (DMSO).
RESULTS
Irisin exerted the vasorelaxant effects at concentrations of 0.01, 0.1, and 1 µM compared to the control group (p < 0.001). Besides, PKC inhibitor BIM I incubation significantly inhibited the relaxation responses induced by varying concentrations of irisin (p: 0.000 for 0.01 µM; p: 0.000 for 0.1 µM; p: 0.000 for 1 µM). However, DMSO, a solvent of BIM I, did not modulate the relaxant effects of irisin (p > 0.05).
DISCUSSION
In conclusion, physiological findings were obtained regarding the functional relaxing effects of irisin in rat thoracic aorta. The findings demonstrated that irisin induces relaxation responses in endothelium-intact thoracic aorta rings in a concentration-dependent manner. Furthermore, this study is the first to report that irisin-induced relaxation responses are regulated probably via activating signaling pathways implicating PKC.
Topics: Animals; Aorta, Thoracic; Endothelium, Vascular; Fibronectins; Phenylephrine; Protein Kinase C; Rats; Signal Transduction; Vasodilator Agents
PubMed: 36161624
DOI: 10.55730/1300-0144.5340 -
PloS One 2023Alpacas (Vicugna pacos) have physiologic adaptations to live at high altitude. These adaptations may result in unexpected responses to changes in cardiac performance and...
Alpacas (Vicugna pacos) have physiologic adaptations to live at high altitude. These adaptations may result in unexpected responses to changes in cardiac performance and blood pressure during general anesthesia. There are few studies evaluating cardiovascular variables in anesthetized alpacas. The purpose of this study was to report cardiovascular performance in anesthetized mature alpacas during normotension, hypotension, and hypertension using ultrasound dilution and echocardiography. Six adult alpacas, 3 females and 3 castrated males, weighing 62.6 to 88.7 kg were anesthetized and maintained with isoflurane and placed in right lateral recumbency. Each alpaca underwent ultrasound dilution and echocardiography measurements during three cardiovascular phases, normotension, hypotension via increased isoflurane concentration, and hypertension via phenylephrine infusion. Variables were analyzed with a Friedman test and a post hoc Dunn's test when significant. A p < 0.05 was used for significance. Cardiac output, cardiac index, systemic vascular resistance, stroke volume, total ejection fraction, left ventricular internal diameter during diastole, and total stroke volume indexed to body weight were greater for hypertension compared to hypotension. Total ejection fraction, stroke volume, and left ventricular ejection time were greater for hypertions compared to normotension. There was no difference between ultrasound dilution and echocardiography determined cardiac output measurements within each cardiovascular phase. Phenylephrine appeared to have increased ventricular performance and/or increased preload in anesthetized, mature alpacas. For detecting change in cardiovascular status in anesthetized alpacas, ultrasound dilution and echocardiography may be useful.
Topics: Animals; Male; Female; Adult; Humans; Blood Pressure; Camelids, New World; Isoflurane; Hypotension; Phenylephrine; Hypertension; Echocardiography; Cardiac Output
PubMed: 37036882
DOI: 10.1371/journal.pone.0284299 -
Pharmaceutical Research Feb 2015Identify an orotopical vehicle to deliver an α-adrenergic vasoconstrictor to submucosal vasculature that is readily palatable to cancer/bone marrow transplant patients...
PURPOSE
Identify an orotopical vehicle to deliver an α-adrenergic vasoconstrictor to submucosal vasculature that is readily palatable to cancer/bone marrow transplant patients that suppresses chemo-radiotherapy-associated oral mucositis.
METHODS
A [(3)H] norepinephrine ligand binding assay was developed to quantify receptor binding in hamster oral mucosa. Vehicle components (alcohols, polyols, cellulose, PVP) were tested versus [(3)H] norepinephrine binding. Vehicle refinement was also done to mask phenylephrine bitter taste and achieve human subject acceptance. The optimized vehicle was tested with α-adrenergic active agents to suppress radiation-induced oral mucositis in mice.
RESULTS
The ligand binding assay quantified dose- and time-dependent, saturable binding of [(3)H] norepinephrine. An ethanol:glycerol:propylene glycol:water (6:6:8:80) vehicle provided the best delivery and binding. Further vehicle modification (flavoring and sucralose) yielded a vehicle with excellent taste scores in humans. Addition of phenylephrine, norepinephrine or epinephrine to the optimized vehicle and painting into mouse mouths 20 min before 19 Gy irradiation conferred significant suppression of the weight loss (P < 0.001) observed in mice who received oral vehicle.
CONCLUSION
We identified a highly efficient vehicle for the topical delivery of phenylephrine to the oral mucosa of both hamster and human subjects. This will enable its testing to suppress oral mucositis in an upcoming human clinical trial.
Topics: Administration, Topical; Adrenergic Agonists; Animals; Cricetinae; Drug Delivery Systems; Humans; Mice; Mouth Mucosa; Phenylephrine
PubMed: 25079392
DOI: 10.1007/s11095-014-1477-1 -
British Journal of Anaesthesia Apr 1995We have investigated the effects of phenylephrine alone and combined with prostaglandin E1 (PGE1) on ventriculo-arterial matching during halothane anaesthesia in dogs....
We have investigated the effects of phenylephrine alone and combined with prostaglandin E1 (PGE1) on ventriculo-arterial matching during halothane anaesthesia in dogs. The ratio of left ventricular end-systolic elastance (Ees) to effective arterial elastance (Ea) was used as an index of ventriculo-arterial matching. In group 1 (n = 7), measurements were performed at control, 1.5% halothane, halothane+phenylephrine 1-10 micrograms kg-1 min-1, and halothane+phenylephrine+PGE1 0.2-1.0 or 1.0-2.0 micrograms kg-1 min-1. In group 2 (n = 5), dobutamine 2 and 5 micrograms kg-1 min-1 was infused during halothane anaesthesia. Halothane 1.5% decreased mean arterial pressure (MAP), cardiac output and Ees. Phenylephrine restored MAP, but further decreased cardiac output. The decrease in Ees produced by halothane was reversed by phenylephrine. PGE1 increased cardiac output and reversed the increases in Ea and Ea/Ees during phenylephrine infusion. Dobutamine also reversed halothane-induced decreases in MAP, cardiac output and Ees, and improved Ea/Ees. Our results indicate that combined use of PGE1 with phenylephrine can eliminate the vasoconstrictive property of phenylephrine, resulting in an improvement in ventriculo-arterial matching.
Topics: Alprostadil; Anesthesia, General; Animals; Blood Pressure; Cardiac Output; Dogs; Drug Synergism; Female; Halothane; Heart; Heart Rate; Male; Myocardial Contraction; Phenylephrine; Vasodilator Agents
PubMed: 7734265
DOI: 10.1093/bja/74.4.438 -
Anesthesiology Sep 1984To investigate the central nervous system circulation during spinal anesthesia, local spinal cord blood flow (SCBF) and cerebral blood flow (CBF) were measured...
To investigate the central nervous system circulation during spinal anesthesia, local spinal cord blood flow (SCBF) and cerebral blood flow (CBF) were measured simultaneously by the hydrogen clearance technique following subarachnoid lidocaine, phenylephrine, or a combination of both. The mean control values of SCBF and CBF were 22.4 +/- 7.9 ml X 100 g-1 X min-1 and 53.1 +/- 12.0 ml X 100 g-1 X min-1, respectively, in dogs lightly anesthetized with halothane. The subarachnoid administration of lidocaine solutions (1, 2, 3, and 5%), 1 ml, failed to produce statistically significant changes in SCBF (P greater than 0.05). Whereas, when phenylephrine (0.1, 0.2, 0.3, and 0.5%), 1 ml, was injected into the spinal subarachnoid space, SCBF decreased significantly with concentrations greater than 0.2% (P less than 0.05). When a mixture of lidocaine (24 mg) and phenylephrine (1 mg) was administered into the subarachnoid space, SCBF decreased significantly and returned to control within 60-90 min. CBF did not change significantly with any of the injections, remaining within less than +/- 12% of control. Dextrose solutions in water (5 and 7.5%), which were used for dilution of the drugs, did not affect either SCBF or CBF. These results indicate that local spinal cord blood flow can be affected significantly during spinal anesthesia when phenylephrine is added to the local anesthetic solution. However, the circulatory effects of drugs injected into the spinal subarachnoid space appear to be restricted to the local spinal cord per se and do not involve other parts of the CNS.
Topics: Anesthesia, Spinal; Animals; Blood Gas Analysis; Blood Pressure; Cerebrovascular Circulation; Dogs; Drug Combinations; Heart Rate; Hydrogen-Ion Concentration; Lidocaine; Phenylephrine; Regional Blood Flow; Spinal Cord
PubMed: 6476432
DOI: 10.1097/00000542-198409000-00002