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Background Maternal hypotension occurs in up to 80% of parturients during cesarean section (CS) under spinal anesthesia. Phenylephrine, a direct-acting α-1 agonist, has been widely recommended for the prevention of hypotension. We evaluated the efficacy and safety of phenylephrine infusion to prevent hypotension in obese and non-obese patients during cesarean section. Methods One hundred forty-one patients were included in this single-arm study. Patients received prophylactic phenylephrine infusion at a rate of 50 µg/min-1 immediately after spinal local anesthetic injection until delivery. Hypotension was defined as a systolic blood pressure <100 mmHg or <20% of baseline. The primary outcome was the incidence of hypotension. Results The incidence of hypotension was 17%. The median and interquartile range (IQR) of the number of hypotensive episodes was 0 (0-0). It was observed that 79.1% of the patients had hypotension in the first six minutes. Reactive hypertension and bradycardia occurred in 20.5 and 12.7% of the patients, respectively. In addition, there was a higher incidence of bradycardia in pregnant women with a body index mass of < 30 kg/m-2. Patients with baseline systolic blood pressure <120 mmHg had a threefold increased risk of hypotension. The incidence of nausea and vomiting was 13.4 and 2.8%, respectively. The incidence of an Apgar score <7 at the first minute was 2.8%, and no neonates presented an Apgar score <7 at the fifth minute. A pH of <7.2 occurred in 6.3% of the neonates. All neonates had no sequelae and were discharged together with their mothers. Conclusion The prophylactic infusion of phenylephrine 50 µg/min-1 is safe and demonstrates efficacy in reducing maternal hypotension providing adequate maternal hemodynamic stability during CS under spinal anesthesia.
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Aim: To compare pupil dilation achieved by a single microdose versus two microdoses of tropicamide-phenylephrine fixed combination (TR-PH FC) delivered by the Optejet®. Patients & methods: In this assessor-masked, crossover, noninferiority study, 60 volunteers underwent two treatment visits and received either one (â¼8 µl) or two sprays (â¼16 µl) of TR-PH FC to both eyes in randomly assigned order. Results: At 35 min postdose, mean change in pupil diameter was 4.6 mm and 4.9 mm following one or two sprays, respectively. The estimated treatment group difference was -0.249 mm (standard error: 0.036; 95% CI: -0.320, -0.177). No adverse events were reported. Conclusion: A single microdose was noninferior to two microdoses of TR-PH FC and achieved clinically significant mydriasis in a timely manner. Clinical Trial Registration: NCT04907474 (ClinicalTrials.gov).
Pupil dilation efficacy and efficiency were evaluated using microdosing via the Optejet®. The Optejet® is a new ophthalmologic drug device that utilizes piezoelectric technology to deliver a fine, controlled, horizontal microdroplet spray with precise volume (â¼8 µl), spray pattern and velocity. A single spray versus two sprays of tropicamide-phenylephrine fixed combination (TR-PH FC) were administered to both eyes anesthetic free. Efficacy and safety were evaluated at specific time intervals. The primary end point was the mean change in pupil diameter at 35 min compared with baseline. At 35 min, clinically relevant dilation was observed, with a mean change of 4.55 mm ± 0.68 for one spray and 4.88 ± 0.60 for two sprays. The treatment group difference of one spray of TR-PH FC was noninferior to two sprays (p < 0.001). Rapid dilation was observed at 15 min, and the proportions of eyes that achieved a pupil diameter of ≥6.0 mm were 74% and 83% of patients at 15 min with one spray and two sprays, respectively. The mydriatic agent was well tolerated with the delivery system even in the absence of topical anesthetic, with no ocular or system adverse events reported. Mydriasis is a vital component of routine eye healthcare, and the current standard-of-care mydriatic eye drops potentially have limitations, including contamination, spillage and burning/stinging. Delivery of a mydriatic with the Optejet® may improve patient care flow in the clinical office setting.
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Midriáticos , Pupila , Humanos , Soluções Oftálmicas , Tropicamida , FenilefrinaRESUMO
Venoms from tarantulas contain low molecular weight vasodilatory compounds whose biological action is conceived as part of the envenomation strategy due to its propagative effects. However, some properties of venom-induced vasodilation do not match those described by such compounds, suggesting that other toxins may cooperate with these ones to produce the observed biological effect. Owing to the distribution and function of voltage-gated ion channels in blood vessels, disulfide-rich peptides isolated from venoms of tarantulas could be conceived into potential vasodilatory compounds. However, only two peptides isolated from spider venoms have been investigated so far. This study describes for the first time a subfraction containing inhibitor cystine knot peptides, PrFr-I, obtained from the venom of the tarantula Poecilotheria regalis. This subfraction induced sustained vasodilation in rat aortic rings independent of vascular endothelium and endothelial ion channels. Furthermore, PrFr-I decreased calcium-induced contraction of rat aortic segments and reduced extracellular calcium influx to chromaffin cells by the blockade of L-type voltage-gated calcium channels. This mechanism was unrelated to the activation of potassium channels from vascular smooth muscle, since vasodilation was not affected in the presence of TEA, and PrFr-I did not modify the conductance of the voltage-gated potassium channel Kv10.1. This work proposes a new envenomating function of peptides from venoms of tarantulas, and establishes a new mechanism for venom-induced vasodilation.
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INTRODUCTION: The aim of this case series was to examine the association between unaided binocular visual acuity for near vision and pupil change after the instillation of a special topical formulation for presbyopia treatment. METHODS: This was a case series consisting of consecutive participants with presbyopia aged 40-70 years who were tested for visual acuity and pupil diameter before and 2 h after instillation of a formulation of pilocarpine and phenylephrine drops (FOV Tears) for presbyopia. Participants underwent subjective refraction, photopic and scotopic pupil diameter measurement and unaided monocular and binocular visual acuity testing by logMAR for distance and near vision both pre- and post-instillation of eye drops. RESULTS: The study enrolled 363 subjects (n = 176 women, 48%) with a mean (± standard deviation) age of 50.4 ± 5.8 years. Mean spherical equivalent (SE) changed significantly (- 0.17 Diopters) after instillation of the FOV Tears formulation (p < 0.001). Post-instillation of eye drops, the scotopic pupil diameter decreased by 0.97 ± 0.98 mm, and the near visual acuity by logMAR improved significantly by nearly two lines (p < 0.01). In the linear regression analyses, age (p < 0.001) and SE pre-drop instillation (p < 0.001) were associated with unaided binocular visual acuity. The changes in photopic pupil diameter and the scotopic pupil diameter were not associated with unaided binocular visual acuity. CONCLUSIONS: The use of the pilocarpine and phenylephrine formulation (FOV Tears) improved binocular visual acuity for near vision in presbyopic patients, and the effect was independent of pupil change.
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ABSTRACT Purpose: This study aimed to evaluate the current practice patterns for assessing and managing upper lid ptosis among members of the Latin American and Spanish societies of Ophthalmic Plastic and Reconstructive Surgery. Methods: An e-mail was sent to invite members of both societies to participate in this anonymous web-based survey. The survey collected data on surgeons' demographics and four other sections: upper lid ptosis preoperative evaluation, surgical preferences, postoperative management, and complications. The frequency and proportions of the responses were then statistically analyzed. Results: The survey was responded by 354 experienced oculoplastic surgeons, 47.7% of whom generally performed more than 20 upper lid ptosis surgeries annually. Of those respondents, 244 (68.9%) routinely check for dry eye preoperatively. Less than half of the respondents (47.4%) perform the phenylephrine test for congenital or acquired ptosis. Mild upper lid ptosis was reported to be usually corrected with conjunctival mullerectomy (43.6%). Severe upper lid ptosis was reported to be usually corrected with frontalis surgery (57%), followed by anterior levator resection, mainly supramaximal resection (17.5%). In cases of severe congenital ptosis, the main reason for surgery was to alleviate the risk of amblyopia (37.3%). An anterior approach was reported to be usually (63.3%) used to manage involutional ptosis associated with dermatochalasis. Common complications comprised undercorrection after levator resection (40%) or frontalis suspension (27.5%). Conclusions: This study reports the current practice patterns among Spanish and Latin American oculoplastic surgeons in upper lid ptosis diagnosis and treatment. Surgeons can use this study data to compare disease management with their colleagues.
RESUMO Objetivo: Avaliar a prática e tratamento da ptose da pálpebra superior por membros das sociedades latino-americanas e espanhola de Cirurgia Plástica Ocular. Métodos: Os membros das referidas sociedades foram convidados por e-mail para responder a um questionário eletrônico garantindo o anonimato. O questionário constou de dados demográficos do cirurgião e outras quatro seções: avaliação pré-operatória da ptose da pálpebra superior, preferências cirúrgicas, conduta pós-operatória e complicações. Estatística descritiva foi utilizada para análise da frequência e proporções percentuais. Resultados: Trezentos e cinquenta e quatro experientes cirurgiões oculoplásticos dos quais 47,7% realizam mais de 20 cirurgias de ptose da pálpebra superior por ano responderam ao questionário. Na avaliação pré-operatória, 68,9% realizam testes para olho seco, mas o teste da fenilefrina é feito por menos da metade dos entrevistados (47,4%). A ptose da pálpebra superior leve geralmente é corrigida por conjuntivo-mullerectomia (43,6%), a ptose da pálpebra superior grave por cirurgia do músculo frontal (57%) ou ressecção da aponeurose do levantador via anterior, principalmente usando a supramáxima (17,5%). O principal motivo para operar a ptose congênita grave é o risco de ambliopia (37,3%). A ptose involucional associada à dermatocálase costuma ser corrigida pela via anterior (63,3%). Hipocorreção é complicação comum após a ressecção da aponeurose do levantador (40%) ou suspensão ao frontal (27,5%). Conclusões: As práticas atuais dos cirurgiões oculoplásticos espanhóis e latino-americanos para diagnóstico e tratamento de ptose da pálpebra superior foram relatadas. Os dados apresentados podem ser usados para comparar a abordagem dos cirurgiões com a de seus pares.
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ABSTRACT Purpose: To evaluate the effect of pupil dilation on intraocular pressure in preterm and term newborns. Methods: This prospective study involved 55 eyes of 28 preterm infants and 38 eyes of 20 term infants. The infants were divided into two groups according to their gestational ages at birth as follows: preterm group, <37 weeks and term group, ≥37 weeks. Pupil dilation was attained with tropicamide 0.5% and phenylephrine 2.5%. Intraocular pressure measurements were performed with Icare PRO (Icare Finland Oy, Helsinki, Finland) before and after pupil dilation. A paired t test was used to compare the measurements before and after pupil dilation. Results: The mean intraocular pressure change was -1.04 ± 3.03 mmHg (6.20/-11.40 mmHg) in the preterm group and -0.39 ± 2.81 mmHg (4.60/-9.70 mmHg) in the term group. A statistically significant difference in intraocular pressure was observed only in the preterm group after pupil dilation (p=0.01). Conclusion: An unexpected alteration in intraocular pressure in newborns may occur after pupil dilation, especially in preterm infants.
RESUMO Objetivo: Avaliar o efeito da dilatação da pupila sobre a pressão intraocular em recém-nascidos pré-termo e a termo. Métodos: Este estudo prospectivo envolveu 55 olhos de 28 bebês pré-termo e 38 olhos de 20 bebês a termo. Os bebês foram divididos em dois grupos, pré-termo e a termo, de acordo com a idade gestacional ao nascimento: grupo pré-termo <37 semanas; grupo a termo ≥37 semanas. A dilatação da pupila foi feita com tropicamida 0,5% e fenilefrina 2,5%. As medições da pressão intraocular foram realizadas com Icare PRO (Icare Finland Oy, Helsinki, Finlândia) antes e depois da dilatação da pupila. O teste t pareado foi usado para comparar as medidas antes e depois da dilatação da pupila. Resultados: A alteração média da pressão intraocular foi de -1,04 ± 3,03 mmHg (+6,20/-11,40 mmHg) no grupo pré-termo e -0,39 ± 2,81 mmHg (+4,60/-9,70 mmHg) no grupo a termo. Uma diferença estatisticamente significativa na pressão intraocular foi observada apenas no grupo pré-termo após a dilatação da pupila (p=0,01). Conclusão: Após a dilatação da pupila, pode ocorrer alteração inesperada da pressão intraocular em recém-nascidos, principalmente em bebês pré-termo.
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Abstract Benign prostatic hyperplasia (BPH) is a multifactorial disease, highly associated with aging and characterized by increased prostate smooth muscle (PSM) contractility. Animal models have been employed to explore the aging-associated PSM hypercontractility; however, studies have focused in old animals, neglecting the initial alterations in early ages. The determination of prostatic dysfunctions onset is crucial to understand the BPH pathophysiology and to propose new BPH treatments. Considering that PSM contractility in 10-month-old rats has already been explored, the aim of the present study was to characterize the PSM contractility in younger rats. Male Wistar control (3.5-month-old), 6- and 8-month-old rats were used. Concentration-response curves to phenylephrine and electrical-field stimulation (EFS) were conducted in prostate from all groups. For the first time, we showed that 6- and 8-month-old rats exhibit PSM hypercontractility. The increased prostate contractility to phenylephrine starts around at 6-month-old, worsening during the aging. The 8-month-old rats exhibited hypercontractility to phenylephrine and EFS compared to the control and 6-month-old groups. Reduced phenylephrine potency was observed in 8-month-old rats, indicating an increased age-dependent prostate sensibility to this agonist. Collectively, our findings support the use of 6- and 8-month-old aged rats as new models to explore prostate hypercontractility in BPH.
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Animais , Masculino , Ratos , Hiperplasia Prostática/patologia , Envelhecimento/genética , Músculo Liso/anormalidades , Fenilefrina/agonistas , Sintomas do Trato Urinário Inferior/complicaçõesRESUMO
The dorsal raphe (DR) nucleus is involved in a myriad of physiological functions, such as the control of sleep-wake cycle, motivation, pain, energy balance, and food intake. We have previously demonstrated that in ad libitum fed rats the intra-DR administration of phenylephrine, an α-1 receptor agonist, does not affect food intake, whereas clonidine, an α-2 receptor agonist, potently stimulates food intake. These results indicated that in fed rats an increased adrenergic tonus blocked food intake, since the activation of α-2 auto-receptors, which decreases pre-synaptic release of adrenaline/noradrenaline, affected food intake. Thus, in this study we assessed whether the response to adrenergic stimuli would differ after overnight fasting, a situation of low adrenergic activity in the DR. Intra-DR administration of adrenaline and noradrenaline blocked food intake evoked by overnight fasting. Similarly, phenylephrine administration decreased hunger-induced food intake. These changes in food intake were accompanied by changes in other behaviors, such as increased immobility time and feeding duration. On the other hand, intra-DR administration of clonidine did not affect food-intake or associated behaviors. These results further support the hypothesis that in fed animals, increased adrenergic tonus in DR neurons inhibiting feeding, while in fasted rats the adrenergic tonus decreases and favors food intake. These data indicate a possible mechanism through which adrenergic input to the DRN contributes to neurobiology of feeding.
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Environmental hexachlorobenzene (HCB) increases blood pressure (BP) in female rats, causing alterations in arterial structure and function. Here we study the role of Angiotensin II receptor type 1 (AT1) in HCB-induced hypertension through the use of AT1 antagonist losartan. HCB-treated male rats showed a 22.7% increase in BP which was prevented by losartan. Losartan blocked HCB-induced changes in arterial morphology (decreased aorta cell number and increased wall thickness). Losartan also prevented HCB-induced alterations in artery relaxation by acetylcholine and nitroprusside but not the reduction in the maximum contraction by phenylephrine. Losartan rescued arterial molecular alterations caused by HCB (i.e. an increase in TGF-ß1 and AT1 expression and a decrease in eNOS expression and nitrite levels) and reduced hydrogen sulfide plasma concentration. In conclusion: in this work we demonstrate that AT1 activity is involved in HCB effects on the vascular system leading to hypertension.
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The authors previously demonstrated that newborn llama (NBLL) express high levels of α1 adrenergic receptors, which provide a potent vasoconstriction response when compared with newborn sheep (NBSH) gestated at sea level. However, data regarding the impact of chronic gestational hypobaric hypoxia on α-adrenergic vasoconstriction in the neonatal life has not been studied. We evaluated if gestation under chronic hypobaric hypoxia modifies α1-adrenergic vasoconstrictor function in NBLL and NBSH. We compared the vasoconstrictor response induced by potassium and α-adrenergic stimuli in isolated small femoral arteries of NBLL and NBSH gestated at high altitude (HA; 3,600 m) or low altitude (LA; 580 m). The maximal contraction (R MAX) and potency (EC50) to potassium, noradrenaline (NA), and phenylephrine (PHE) were larger in HA-NBLL than LA-NBLL. R MAX to potassium, NA, and PHE were lower in HA-NBSH when compared with LA-NBSH and potency results were similar. Competitive blockade with prazosin showed that RNLL LA/HA have a similar pA2. In contrast, NBSH had increased pA2 values in HA when compared with LA. Finally, small femoral arteries denudated or treated with LNAME in LA and HA lacked NO or endothelium participation in response to PHE stimulation. In contrast, NBSH displayed that denudation or blockade with LNAME support NO or endothelium participation in response to PHE activation. In conclusion, HA chronic hypoxia enhances α1 adrenergic receptor activity in small femoral arteries in NBLL to a higher degree than NBSH, implying a higher vasoconstriction function.
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Various pathophysiological mechanisms have been implicated in hypertension, but those resulting in vascular dysfunction and remodeling are critical and may help to identify critical pharmacological targets. This mini-review article focuses on central mechanisms contributing to the vascular dysfunction and remodeling of hypertension, increased oxidative stress and impaired nitric oxide (NO) bioavailability, which enhance vascular matrix metalloproteinase (MMP) activity. The relationship between NO, MMP and oxidative stress culminating in the vascular alterations of hypertension is examined. While the alterations of hypertension are not fully attributable to these pathophysiological mechanisms, there is strong evidence that such mechanisms play critical roles in increasing vascular MMP expression and activity, thus resulting in abnormal degradation of extracellular matrix components, receptors, peptides, and intracellular proteins involved in the regulation of vascular function and structure. Imbalanced vascular MMP activity promotes vasoconstriction and impairs vasodilation, stimulating vascular smooth muscle cells (VSMC) to switch from contractile to synthetic phenotypes, thus facilitating cell growth or migration, which is associated with the deposition of extracellular matrix components. Finally, the protective effects of MMP inhibitors, antioxidants and drugs that enhance vascular NO activity are briefly discussed. Newly emerging therapies that address these essential mechanisms may offer significant advantages to prevent vascular remodeling in hypertensive patients.
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Hipertensão/metabolismo , Metaloproteinases da Matriz/metabolismo , Óxido Nítrico/metabolismo , Animais , Humanos , Hipertensão/patologia , Hipertensão/fisiopatologia , Estresse Oxidativo , Remodelação Vascular , VasoconstriçãoRESUMO
Abstract Introduction: Heart preservation benefits cardiac performance after operations decreasing morbidity but the contribution of the vascular reactivity has been neglected. Objective: We evaluated whether cardioprotective solutions, Krebs-Henseleit (KH), Bretschneider-HTK (BHTK), St. Thomas No. 1 (STH-1), and Celsior (CEL), affect vascular reactivity. Methods: Aortic rings from Wistar rats were used in two protocols. First, the rings were exposed to BHTK, STH-1 or CEL for 1 hour of hypoxia at 37 °C. Second, the rings were exposed to 10 °C or 20 °C for 1 hour under hypoxia. After treatment, the rings were immersed in KH at 37 °C, endothelial integrity was tested and concentration-response curves to phenylephrine were performed. Results: In the first protocol, the solutions did not damage the endothelium; CEL and BHTK reduced KCl-induced contractions but not STH-1; only CEL and BHTK reduced vascular reactivity; there was a positive correlation between Rmax and KCl concentration. At 20 °C, 1 hour under hypoxia, the solutions produced similar KCl-induced contractions without endothelial damage. CEL, BHTK and STH-1 decreased vascular reactivity. At 10 °C, STH-1 increased reactivity but CEL and BHTK decreased. After 1 hour under hypoxia in CEL or BHTK solutions, reactivity was similar at different temperatures. At 20 °C, endothelial damage after exposure to STH-1 produced more vasoconstriction than CEL and BHTK. However, at 10 °C, endothelial damage after CEL and BHTK exposure elicited more vasoconstriction while STH-1 showed a small vasoconstrictor response, suggesting endothelial damage. Conclusion: STH-1 decreased reactivity at 20 °C and increased at 10 °C. CEL promoted greater endothelial modulation at 10 °C than at 20 °C, while STH-1 promoted higher modulation at 20 °C than at 10 °C. Vascular tone was reduced by CEL and BHTK exposure, also depending on the KCl concentration.
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Animais , Ratos , Vasoconstritores/farmacologia , Hipóxia , Fenilefrina , Temperatura , Endotélio Vascular , Ratos WistarRESUMO
BACKGROUND: Postoperative Hyperlactatemia (PO-HL) is a frequent condition associated with poor prognosis. In recent years, there has been growing evidence that adrenergic stimulation may contribute to increased lactate levels. The use of adrenergic agonists for the control of intraoperative hypotension is frequent, and its impact on the development of PO-HL is unknown. OBJECTIVE: To evaluate whether the use of intraoperative adrenergic agents is associated with the occurrence of PO-HL. METHODS: This was a prospective observational study. The inclusion criteria were undergoing elective open colon surgery, being ≥60 years old and signing informed consent. The exclusion criteria were cognitive impairment, unplanned surgery, and anticipated need for postoperative mechanical ventilation. Baseline and intraoperative variables were collected, and arterial lactate data were collected at baseline and every 6â¯hours postoperatively for 24â¯hours. Hyperlactatemia was defined as lactate >2.1 mEq.L-1. RESULTS: We studied 28 patients, 61% of whom developed hyperlactatemia. The variables associated with PO-HL in the univariate analysis were anesthetic time, the total dose of intraoperative ephedrine, and lower intraoperative central venous oxygen saturation (ScvO2). Multivariate analysis confirmed the association between the use of ephedrine (pâ¯=â¯0.004), intraoperative hypotension (pâ¯=â¯0.026), and use of phenylephrine (pâ¯=â¯0.001) with PO-HL. CONCLUSIONS: The use of intraoperative ephedrine, phenylephrine and intraoperative hypotension were independently associated with the development of PO-HL. This finding should lead to new studies in this field, as well as a judicious interpretation of the finding of a postoperative increase in lactate levels.
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Hiperlactatemia , Hipotensão , Adrenérgicos , Colo , Efedrina , Humanos , Hiperlactatemia/induzido quimicamente , Hiperlactatemia/epidemiologia , Hipotensão/induzido quimicamente , Hipotensão/epidemiologia , Pessoa de Meia-Idade , FenilefrinaRESUMO
INTRODUCTION: Heart preservation benefits cardiac performance after operations decreasing morbidity but the contribution of the vascular reactivity has been neglected. METHODS: We evaluated whether cardioprotective solutions, Krebs-Henseleit (KH), Bretschneider-HTK (BHTK), St. Thomas No. 1 (STH-1), and Celsior (CEL), affect vascular reactivity. Methods: Aortic rings from Wistar rats were used in two protocols. First, the rings were exposed to BHTK, STH-1 or CEL for 1 hour of hypoxia at 37 °C. Second, the rings were exposed to 10 °C or 20 °C for 1 hour under hypoxia. After treatment, the rings were immersed in KH at 37 °C, endothelial integrity was tested and concentration- response curves to phenylephrine were performed. RESULTS: In the first protocol, the solutions did not damage the endothelium; CEL and BHTK reduced KCl-induced contractions but not STH- 1; only CEL and BHTK reduced vascular reactivity; there was a positive correlation between Rmax and KCl concentration. At 20 °C, 1 hour under hypoxia, the solutions produced similar KCl-induced contractions without endothelial damage. CEL, BHTK and STH-1 decreased vascular reactivity. At 10 °C, STH-1 increased reactivity but CEL and BHTK decreased. After 1 hour under hypoxia in CEL or BHTK solutions, reactivity was similar at different temperatures. At 20 °C, endothelial damage after exposure to STH-1 produced more vasoconstriction than CEL and BHTK. However, at 10 °C, endothelial damage after CEL and BHTK exposure elicited more vasoconstriction while STH-1 showed a small vasoconstrictor response, suggesting endothelial damage. CONCLUSION: STH-1 decreased reactivity at 20 °C and increased at 10 °C. CEL promoted greater endothelial modulation at 10 °C than at 20 °C, while STH-1 promoted higher modulation at 20 °C than at 10 °C. Vascular tone was reduced by CEL and BHTK exposure, also depending on the KCl concentration.
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Hipóxia , Vasoconstritores , Animais , Endotélio Vascular , Fenilefrina , Ratos , Ratos Wistar , Temperatura , Vasoconstritores/farmacologiaRESUMO
Abstract Background and objectives: Limited data are present on safety and efficiency of epinephrine for the prophylaxis and treatment of spinal-hypotension. This study was conducted to compare the effect of epinephrine with norepinephrine and phenylephrine on the treatment of spinal-hypotension and ephedrine requirement during cesarean delivery. Methods: One hundred and sixty parturients with uncomplicated pregnancies undergoing elective cesarean delivery under spinal anesthesia were recruited. They were allocated randomly to receive norepinephrine 5 µg.mL−1 (n = 40), epinephrine 5 µg.mL−1 (n = 40), phenylephrine 100 µg.mL−1 (n = 40) or 0.9% saline infusions (n = 40) immediately after induction of spinal anesthesia. Whenever systolic blood pressure drops to less than 80% of baseline, 5 mg of intravenous ephedrine was administered as rescue vasopressor. The incidence of hypotension, total number of hypotension episodes, the number of patients requiring ephedrine, the mean amount of ephedrine consumption and side effects were recorded. Results: There was no statistically significant difference in incidence of maternal hypotension between groups. The number of patients requiring ephedrine was significantly greater in group saline than in group phenylephrine (p< 0.001). However, it was similar between phenylephrine, norepinephrine, and epinephrine groups. The mean ephedrine consumption was significantly higher in group saline than in norepinephrine, epinephrine, phenylephrine groups (p= 0.001). Conclusion: There is no statistically significant difference in incidence of hypotension and ephedrine consumption during spinal anesthesia for cesarean delivery with the use of epinephrine when compared to norepinephrine or phenylephrine. Epinephrine can be considered an alternative agent for management of spinal hypotension.
Resumo Justificativa e objetivos: Existem dados limitados sobre segurança e eficiência da epinefrina na profilaxia e tratamento da hipotensão arterial associada à raquianestesia. O presente estudo foi realizado para comparar o efeito da epinefrina com norepinefrina e fenilefrina no tratamento da hipotensão após raquianestesia e necessidade de efedrina durante o parto cesáreo. Método: Foram recrutadas 160 parturientes com gestações não complicadas, submetidas a cesariana eletiva sob raquianestesia. Elas foram alocadas aleatoriamente para receber norepinefrina 5 µg.mL-1 (n = 40), epinefrina 5 µg.mL-1 (n = 40), fenilefrina 100 µg.mL-1 (n = 40) ou infusão de solução fisiológica NaCl a 0,9% (n = 40) imediatamente após a indução da raquianestesia. Sempre que houvesse redução da pressão arterial sistólica para valor inferior a 80% da linha de base, 5 mg de efedrina iv eram administrados como vasopressor de resgate. A incidência de hipotensão, o número total de episódios de hipotensão, o número de pacientes que necessitaram de efedrina, o consumo médio de efedrina e os efeitos colaterais foram registrados. Resultados: Não houve diferença estatisticamente significante na incidência de hipotensão materna entre os grupos. O número de pacientes que necessitaram de efedrina foi significantemente maior no grupo solução fisiológica do que no grupo fenilefrina (p< 0,001). No entanto, foi semelhante entre os grupos fenilefrina, norepinefrina e epinefrina. O consumo médio de efedrina foi significantemente maior no grupo solução fisiológica do que nos grupos norepinefrina, epinefrina e fenilefrina (p = 0,001). Conclusão: Não houve diferença estatisticamente significante na incidência de hipotensão e consumo de efedrina durante raquianestesia para parto cesáreo com uso de epinefrina quando comparada à norepinefrina ou fenilefrina. A epinefrina pode ser considerada como agente alternativo para o tratamento da hipotensão após raquianestesia.
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Humanos , Feminino , Adulto , Fenilefrina/administração & dosagem , Norepinefrina/administração & dosagem , Efedrina/administração & dosagem , Hipotensão/prevenção & controle , Vasoconstritores/administração & dosagem , Cesárea/efeitos adversos , Cesárea/métodos , Método Duplo-Cego , Estudos Prospectivos , Hipotensão/etiologia , Hipotensão/epidemiologia , Raquianestesia/efeitos adversos , Raquianestesia/métodosRESUMO
BACKGROUND AND OBJECTIVES: Limited data are present on safety and efficiency of epinephrine for the prophylaxis and treatment of spinal-hypotension. This study was conducted to compare the effect of epinephrine with norepinephrine and phenylephrine on the treatment of spinal-hypotension and ephedrine requirement during cesarean delivery. METHODS: One hundred and sixty parturients with uncomplicated pregnancies undergoing elective cesarean delivery under spinal anesthesia were recruited. They were allocated randomly to receive norepinephrine 5 µg.mL-1 (n=40), epinephrine 5 µg.mL-1 (n=40), phenylephrine 100 µg.mL-1 (n=40) or 0.9% saline infusions (n=40) immediately after induction of spinal anesthesia. Whenever systolic blood pressure drops to less than 80% of baseline, 5 mg of iv ephedrine was administered as rescue vasopressor. The incidence of hypotension, total number of hypotension episodes, the number of patients requiring ephedrine, the mean amount of ephedrine consumption and side effects were recorded. RESULTS: There was no statistically significant difference in incidence of maternal hypotension between groups. The number of patients requiring ephedrine was significantly greater in group saline than in group phenylephrine (p <0.001). However, it was similar between phenylephrine, norepinephrine, and epinephrine groups. The mean ephedrine consumption was significantly higher in group saline than in norepinephrine, epinephrine, phenylephrine groups (p=0.001). CONCLUSION: There is no statistically significant difference in incidence of hypotension and ephedrine consumption during spinal anesthesia for cesarean delivery with the use of epinephrine when compared to norepinephrine or phenylephrine. Epinephrine can be considered as an alternative agent for management of spinal hypotension.
Assuntos
Efedrina/administração & dosagem , Hipotensão/prevenção & controle , Norepinefrina/administração & dosagem , Fenilefrina/administração & dosagem , Adulto , Raquianestesia/efeitos adversos , Raquianestesia/métodos , Cesárea/efeitos adversos , Cesárea/métodos , Método Duplo-Cego , Feminino , Humanos , Hipotensão/epidemiologia , Hipotensão/etiologia , Estudos Prospectivos , Vasoconstritores/administração & dosagemRESUMO
PURPOSE: Self-administration of topical ophthalmic therapies remains challenging for many patients as errors due to improper technique are common. The aim of the current studies was to evaluate a novel electromechanical topical ocular drug delivery device designed to facilitate precise dosing and accurate delivery with substantially lower drug exposure than conventional eye drops. PATIENTS AND METHODS: Two randomized Phase 1 studies were performed to evaluate the efficacy and safety of a single dose of a topical ophthalmic solution administered as a ~9 µL microfluid stream via the test device compared with a ~30-40 µL drop delivered via conventional dropper in healthy subjects (Trial 1) and glaucoma patients (Trial 2). In Trial 1, a 1% tropicamide/2.5% phenylephrine solution was administered via the test device in one eye and by conventional dropper in the contralateral eye. Pupil dilation was measured at 30 min intervals post-instillation and subject comfort was assessed using a visual analogue scale (range, 0-100). In Trial 2, patients were randomized to receive latanoprost 0.005% via the test device or conventional dropper. Intraocular pressure was measured at baseline and 4-8 hrs post-instillation. RESULTS: In Trial 1 (N=20), mean (SD) pupil diameter 30 mins post-instillation increased by 3.4 (0.9) and 3.5 (1.0) mm in the test and control eyes, respectively. The mean comfort score was 81.7 for the test device versus 57.3 for conventional dropper delivery. In Trial 2 (N=18), the mean change in intraocular pressure following administration of latanoprost was -5.0 (1.8) and -4.3 (3.3) mm Hg in the test and control groups, respectively. No serious adverse events were observed in either study. CONCLUSION: Administration of a single dose of topical ophthalmic therapy via an electromechanical drug delivery device resulted in comparable effects on pupil dilation and intraocular pressure with lower drug exposure and increased patient comfort compared with conventional dropper delivery.
RESUMO
This study was carried out in order to compare the relative bioavailability of two different formulations containing 400 mg of acetaminophen + 4 mg of phenylephrine hydrochloride + 4 mg of chlorpheniramine maleate, Test formulation (Cimegripe®) and Reference formulation (Resfenol®) in 84 healthy volunteers of both sexes under fasting conditions. The study was conducted in a single dose, randomized, open-label, crossover 3-way and partially replicated. The tolerability was evaluated by the monitoring of adverse events and vital signs, results of clinical and laboratory tests. Plasma concentrations were quantified by validated bioanalytical methods using the ultra-performance liquid chromatography coupled to tandem mass spectrometry. The Cmax, Tmax, AUC0-t, AUC0-inf, T1/2 and Kel pharmacokinetic parameters were calculated from these obtained concentrations. The 90% confidence intervals were constructed for the ratio reference/test from the geometric average of the Cmax and AUC parameters which were comprised between 80% and 125%. Only the Cmax parameter of the phenylephrine was applied the scaled average bioequivalence due to the intraindividual coefficient of variation > 30% obtained, thus extending the acceptance limits of the interval. It can be concluded that the two formulations were bioequivalent in terms of rate and absorption extent and thus interchangeable
Assuntos
Humanos , Masculino , Feminino , Fenilefrina/análise , Cápsulas/classificação , Disponibilidade Biológica , Clorfeniramina/análise , Acetaminofen/análise , Espectrometria de Massas/métodos , Dose Única , Jejum/efeitos adversos , Estudos Cross-Over , Absorção/efeitos dos fármacos , Espectrometria de Massas em Tandem/métodos , Voluntários Saudáveis/classificaçãoRESUMO
Metformin is a widely used drug for the treatment of type 2 Diabetes Mellitus. Several studies have also suggested that metformin decreases blood pressure; although an interaction with α-adrenoceptors has been proposed, this mechanism needs to be further investigated. Since α1-adrenoceptors play a significant role to regulate vascular tone, this study has analysed the potential ability of metformin to block α1-adrenoceptors in rat aorta and tail artery. For this purpose, the contractile responses induced by noradrenaline, methoxamine, and phenylephrine were determined in the absence or presence of metformin in rat aorta and tail artery rings. In both arteries, noradrenaline, methoxamine, and phenylephrine produced concentration-dependent contractile responses. Interestingly, the contractile responses to noradrenaline, methoxamine, and phenylephrine were significantly and differentially blocked by metformin (1, 3.1 and/or 10â¯mM) but not by vehicle. These results suggest that metformin is capable to block α1-adrenoceptors and may explain, at least in part, the anti-hypertensive effect observed in several clinical trials.
Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/farmacologia , Aorta/efeitos dos fármacos , Aorta/fisiologia , Metformina/farmacologia , Receptores Adrenérgicos alfa 1/metabolismo , Cauda/irrigação sanguínea , Animais , Masculino , Metoxamina/farmacologia , Fenilefrina/farmacologia , Ratos , Ratos Wistar , Vasoconstrição/efeitos dos fármacosRESUMO
NEW FINDINGS: What is the central question of this study? The traditional surgical approach for sino-aortic denervation in rats leads to simultaneous carotid baroreceptor and chemoreceptor deactivation, which does not permit their individual study in different situations. What is the main finding and its importance? We have described a new surgical approach capable of selective denervation of the arterial (aortic and carotid) baroreceptors, keeping the carotid bodies (chemoreceptors) intact. It is understood that this technique might be a useful tool for investigating the relative role of the baro- and chemoreceptors in several physiological and pathophysiological conditions. ABSTRACT: Studies have demonstrated that the traditional surgical approach for sino-aortic denervation in rats leads to simultaneous carotid baroreceptor and chemoreceptor deactivation. The present study reports a new surgical approach to denervate the aortic and the carotid baroreceptors selectively, keeping the carotid bodies (peripheral chemoreceptors) intact. Wistar rats were subjected to specific aortic and carotid baroreceptor denervation (BAROS-X) or sham surgery (SHAM). Baroreflex activation was achieved by i.v. administration of phenylephrine, whereas peripheral chemoreflex activation was produced by i.v. administration of potassium cyanide. The SHAM and BAROS-X rats displayed significant hypertensive responses to phenylephrine administration. However, the reflex bradycardia following the hypertensive response caused by phenylephrine was remarkable in SHAM, but not significant in the BAROS-X animals, confirming the efficacy of the surgical procedure to abolish the baroreflex. In addition, the baroreflex activation elicited by phenylephrine increased carotid sinus nerve activity only in SHAM, but not in the BAROS-X animals, providing support to the notion that the baroreceptor afferents were absent. Instead, the classical peripheral chemoreflex hypertensive and bradycardic responses to potassium cyanide were similar in both groups, suggesting that the carotid body chemoreceptors were preserved after BAROS-X. In summary, we describe a new surgical approach in which only the baroreceptors are eliminated, while the carotid chemoreceptors are preserved. Therefore, it is understood that this procedure is potentially a useful tool for examining the relative roles of the arterial baroreceptors versus the chemoreceptors in several pathophysiological conditions, for instance, arterial hypertension and heart failure.