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World Journal of Gastroenterology Feb 2014To compare the efficacy and safety of recombinant streptokinase (rSK) and phenylephrine-based suppositories in acute hemorrhoidal disease. (Randomized Controlled Trial)
Randomized Controlled Trial
AIM
To compare the efficacy and safety of recombinant streptokinase (rSK) and phenylephrine-based suppositories in acute hemorrhoidal disease.
METHODS
A multicenter (14 sites), randomized (1:1), open, parallel groups, active controlled trial was done. After inclusion, subjects with acute symptoms of hemorrhoids, who gave their written, informed consent to participate, were centrally randomized to receive, as outpatients, rSK (200000 IU) or 0.25% phenylephrine suppositories, which had different organoleptic characteristics. Treatment was administered by the rectal route, one unit every 6 h during 48 h for rSK, and up to a maximum of 5 d (20 suppositories) for phenylephrine. Evaluations were performed at 3, 5 and 10 d post-inclusion. The main end-point was the 5(th)-day complete clinical response (disappearance of pain and edema, and ≥ 70% reduction of the lesion size). Time to response and need for thrombectomy were secondary efficacy variables. Adverse events were evaluated too.
RESULTS
5(th) day complete response rates were 83/110 (75.5%) and 36/110 (32.7%) with rSK and phenylephrine suppositories, respectively. This 42.7% difference (95%CI: 30.5-54.2) was highly significant (P < 0.001). The advantage was detected since the early 3(rd) day evaluation (37.3% vs 6.4% for the rSK and active control groups, respectively; P < 0.001) and was kept even at the late 10(th) day assessment (83.6% vs 58.2% for rSK and phenylephrine, respectively; P < 0.001). Time for complete response was significantly shorter (P = 0.031; log-rank test) in the rSK group (median: 4.9 d; 95%CI: 4.8-5.0) with respect to the active control (median: 9.8 d; 95%CI: 9.8-10.0). Thrombectomy was necessary in 1/59 and 8/57 patients with baseline thrombosis in the rSK and phenylephrine groups, respectively (P = 0.016). There were no adverse events attributable to the experimental treatment.
CONCLUSION
rSK suppositories showed a significant advantage over a widely used over-the-counter phenylephrine preparation for the treatment of acute hemorrhoidal illness, with an adequate safety profile.
Topics: Adolescent; Adult; Aged; Female; Hemorrhoids; Humans; Male; Middle Aged; Phenylephrine; Streptokinase; Suppositories; Thrombolytic Therapy; Treatment Outcome; Young Adult
PubMed: 24587636
DOI: 10.3748/wjg.v20.i6.1594 -
Journal of Stroke and Cerebrovascular... Oct 2014Prior reports have linked both ischemic and hemorrhagic stroke to use of sympathomimetic drugs including phenylephrine. The purpose of this study is to describe the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Prior reports have linked both ischemic and hemorrhagic stroke to use of sympathomimetic drugs including phenylephrine. The purpose of this study is to describe the first case, to our knowledge of intracerebral hemorrhage (ICH) after oral use of phenylephrine and to systematically review the literature on phenylephrine and acute stroke.
METHODS
A case report and review of the literature.
RESULTS
A 59-year-old female presented with thunderclap headache, right hemiparesis, aphasia, and left gaze deviation. Head computed tomography (CT) showed a left frontal ICH with intraventricular and subarachnoid extension. She had no significant past medical history. For the previous 30 days, the patient was taking multiple common cold remedies containing phenylephrine to treat sinusitis. CT and magnetic resonance angiography showed no causative vascular abnormality. Catheter cerebral angiography supported reversible cerebral vasoconstriction syndrome (RCVS). Phenylephrine was determined to be the most likely etiology for her hemorrhage. A review of the literature, found 7 cases describing phenylephrine use with acute stroke occurrence: female, 5 of 7 (71%); route of administration, nasal (n = 3), ophthalmic (n = 2), intravenous (n = 1), intracorporeal injection (n = 1). Stroke types were subarachnoid hemorrhage (n = 5), ICH (n = 4), and ischemic (n = 1). One case reported RCVS after phenylephrine use.
CONCLUSIONS
It is scientifically plausible that phenylephrine may cause strokes, consistent with the pharmacologic properties and adverse event profiles of similar amphetamine-like sympathomimetics. As RCVS has been well described in association with over-the-counter sympathomimetics, a likely, although not definitive, causal relationship between phenylephrine and ICH is proposed.
Topics: Administration, Intranasal; Cerebral Angiography; Cerebrovascular Disorders; Female; Headache Disorders, Primary; Humans; Intracranial Hemorrhages; Middle Aged; Phenylephrine; Stroke; Sympathomimetics; Vasospasm, Intracranial
PubMed: 25156786
DOI: 10.1016/j.jstrokecerebrovasdis.2014.04.018 -
Biomedicine & Pharmacotherapy =... Sep 2023Left ventricular hypertrophy leads to heart failure, a serious medical condition associated with high rates of hospitalization and mortality. Limited success with the...
Left ventricular hypertrophy leads to heart failure, a serious medical condition associated with high rates of hospitalization and mortality. Limited success with the existing pharmacological treatments necessitates the development of mechanisms-based new therapies to better control the progression from left ventricular hypertrophy to heart failure. The current work investigated the pharmacological potentials and mechanisms of naturally occurring cinnamic acid in the treatment of left ventricular hypertrophy and heart failure. The in vitro findings reveal that cinnamic acid attenuates the hypertrophic responses and mitochondrial dysfunction in the phenylephrine (PE)-stimulated cardiomyocytes. Furthermore, cinnamic acid offsets PE-induced increases in N-methyladenosine (mA) RNA modification and reductions in the expression of the key mA demethylase FTO in cardiomyocytes. Most importantly, FTO knockdown abrogates anti-hypertrophic and mitochondrial protective effects of cinnamic acid in the PE-stimulated cardiomyocytes. The in vivo results further demonstrate that cinnamic acid mitigates left ventricular hypertrophy, left ventricular systolic dysfunction and ultrastructural impairment of cardiomyocyte mitochondria and myofibrils in the mice subjected to transverse aortic constriction (TAC)-induced pressure overload. Moreover, FTO knockdown abolishes these beneficial effects of cinnamic acid in the TAC mice. In conclusion, the work here demonstrates for the first time that cinnamic acid is effective at mitigating pressure overload-induced left ventricular hypertrophy and heart failure in part by modulating the expression of FTO and the level of FTO-dependent mA RNA modification in cardiomyocytes. These novel findings warrant further evaluation of cinnamic acid as a pharmacological agent/component to complement the existing treatment of pressure overload-mediated left ventricular hypertrophy and heart failure.
Topics: Mice; Animals; Hypertrophy, Left Ventricular; Myocytes, Cardiac; Heart Failure; Phenylephrine; RNA; Mice, Inbred C57BL; Disease Models, Animal; Alpha-Ketoglutarate-Dependent Dioxygenase FTO
PubMed: 37453198
DOI: 10.1016/j.biopha.2023.115168 -
Medicine May 2023Shivering is described as an involuntary, repetitive activity of the skeletal muscles that can have deleterious effects on anaesthetized patients. This study aimed to... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Shivering is described as an involuntary, repetitive activity of the skeletal muscles that can have deleterious effects on anaesthetized patients. This study aimed to evaluate the effectiveness of phenylephrine infusion in preventing perioperative shivering in patients undergoing lower segment cesarean section under spinal anesthesia and to observe the change in the patient's core temperature between the study and control groups.
METHODS
A total of 118 patients scheduled for elective lower segment cesarean section under spinal anesthesia were recruited for this prospective, double-blind, randomized controlled study. The patients were randomized into 2 groups with 59 patients per group. The phenylephrine Group received phenylephrine infusion at a rate of 0.5 mcg/kg/minutes, while the Control Group received normal saline at an equivalent rate. Systolic and diastolic blood pressure, heart rate, core temperature, and the presence and intensity of shivering were recorded before induction and every 15 minutes intraoperatively and postoperatively.
RESULTS
The incidence of intraoperative shivering was significantly lower in the Phenylephrine Group compared to control group (29.1% vs 47.5% respectively; P = .044). Postoperatively, the Phenylephrine Group also had a lower incidence of shivering (34.5% vs 42.4%), but the difference was not statistically significant (P value = 0.391). There were no significant differences in the intensity of shivering between the 2 groups perioperatively, as well as in the systolic and diastolic blood pressure and core temperature. The phenylephrine Group showed a significantly lower heart rate at 15, 30, and 45 minutes after spinal block (P value = .005, .000, and .008, respectively), and at 0 and 30 minutes (P value = .004 and .020 respectively) in the recovery room. There were no significant differences in perioperative adverse events such as hypotension, hypertension, and bradycardia.
CONCLUSION
Phenylephrine infusion reduces the incidence of perioperative shivering in lower segment cesarean sections under spinal anesthesia.
Topics: Humans; Pregnancy; Female; Phenylephrine; Vasoconstrictor Agents; Cesarean Section; Prospective Studies; Shivering; Hypotension; Anesthesia, Spinal; Double-Blind Method; Anesthesia, Obstetrical
PubMed: 37171298
DOI: 10.1097/MD.0000000000033721 -
Critical Care (London, England) Jan 2012The renal clearance of infused crystalloid fluid is very low during anaesthesia and surgery, but experiments in conscious sheep indicate that the renal fluid clearance... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
The renal clearance of infused crystalloid fluid is very low during anaesthesia and surgery, but experiments in conscious sheep indicate that the renal fluid clearance might approach a normal rate when the adrenergic balance is modified.
METHODS
Sixty females (mean age, 32 years) undergoing laparoscopic gynecological surgery were randomized to control group and received only the conventional anesthetic drugs and 20 ml/kg of lactated Ringer's over 30 mins. The others were also given an infusion of 50 μg/kg/min of esmolol (beta1-receptor blocker) or 0.01 μg/kg/min of phenylephrine (alpha1-adrenergic agonist) over 3 hours. The distribution and elimination of infused fluid were studied by volume kinetic analysis based on urinary excretion and blood hemoglobin level.
RESULTS
Both drugs significantly increased urinary excretion while heart rate and arterial pressure remained largely unaffected. The urine flows during non-surgery were 43, 147, and 176 ml in the control, esmolol, and phenylephrine groups, respectively (medians, P<0.03). When surgery had started the corresponding values were 34, 65 and 61 ml (P<0.04). At 3 hours, averages of 9%, 20%, and 25% of the infused volume had been excreted in the three groups (P<0.01). The kinetic analyses indicated that both treatments slowed down the distribution of fluid from the plasma to the interstitial fluid space, thereby preventing hypovolemia.
CONCLUSIONS
Esmolol doubled and phenylephrine almost tripled urinary excretion during anesthesia-induced depression of renal fluid clearance.
Topics: Adult; Anesthesia, Intravenous; Diuretics; Female; Gynecologic Surgical Procedures; Hemodynamics; Humans; Middle Aged; Phenylephrine; Propanolamines; Urination; Young Adult
PubMed: 22289281
DOI: 10.1186/cc11175 -
Pharmacological Research Apr 2023We reported previously that α-adrenoceptor (α-AR) ligands inhibit chemokine receptor (CR) heteromerization partners of α-AR. The underlying mechanisms are unknown and...
We reported previously that α-adrenoceptor (α-AR) ligands inhibit chemokine receptor (CR) heteromerization partners of α-AR. The underlying mechanisms are unknown and in vivo evidence for such effects is missing. Utilizing CCR2 and α-AR as prototypical partners, we observed in recombinant systems and THP-1 cells that α-AR enhanced whereas its absence inhibited Gαi signaling of CCR2. Phenylephrine and phentolamine reduced the CCR2:α-AR heteromerization propensity and inhibited Gαi signaling of CCR2. Phenylephrine cross-recruited β-arrestin-2 to CCR2, and reduced expression of α-AR, CR partners (CCR1/2, CXCR4) and corresponding heteromers. Phentolamine reduced CR:α-AR heteromers without affecting β-arrestin-2 recruitment or receptor expression. Phenylephrine/phentolamine prevented leukocyte infiltration mediated via CR heteromerization partners in a murine air pouch model. Our findings document that α-AR ligands inhibit leukocyte migration mediated by CR heteromerization partners in vivo and suggest interference with α-AR:CR heteromerization as a mechanism by which CR partners are inhibited. These findings provide new insights into the pharmacology of GPCR heteromers and indicate that an agonist and antagonist at one GPCR can act as antagonists at heteromerization partners of their target receptors.
Topics: Mice; Animals; Ligands; Phentolamine; Phenylephrine; beta-Arrestin 2; Receptors, Adrenergic; Receptors, Adrenergic, alpha-1
PubMed: 36925091
DOI: 10.1016/j.phrs.2023.106730 -
Topics in Cognitive Science Jan 2017We use a spiking neural network model of working memory (WM) capable of performing the spatial delayed response task (DRT) to investigate two drugs that affect WM:... (Comparative Study)
Comparative Study
We use a spiking neural network model of working memory (WM) capable of performing the spatial delayed response task (DRT) to investigate two drugs that affect WM: guanfacine (GFC) and phenylephrine (PHE). In this model, the loss of information over time results from changes in the spiking neural activity through recurrent connections. We reproduce the standard forgetting curve and then show that this curve changes in the presence of GFC and PHE, whose application is simulated by manipulating functional, neural, and biophysical properties of the model. In particular, applying GFC causes increased activity in neurons that are sensitive to the information currently being remembered, while applying PHE leads to decreased activity in these same neurons. Interestingly, these differential effects emerge from network-level interactions because GFC and PHE affect all neurons equally. We compare our model to both electrophysiological data from neurons in monkey dorsolateral prefrontal cortex and to behavioral evidence from monkeys performing the DRT.
Topics: Animals; Guanfacine; Haplorhini; Humans; Memory, Short-Term; Models, Neurological; Neurons; Phenylephrine; Prefrontal Cortex
PubMed: 28001002
DOI: 10.1111/tops.12247 -
Journal of Clinical Monitoring and... Dec 2018Induction of general anesthesia frequently induces arterial hypotension, which is often treated with a vasopressor, such as phenylephrine. As a pure α-agonist,... (Clinical Trial)
Clinical Trial
Induction of general anesthesia frequently induces arterial hypotension, which is often treated with a vasopressor, such as phenylephrine. As a pure α-agonist, phenylephrine is conventionally considered to solely induce arterial vasoconstriction and thus increase cardiac afterload but not cardiac preload. In specific circumstances, however, phenylephrine may also contribute to an increase in venous return and thus cardiac output (CO). The aim of this study is to describe the initial time course of the effects of phenylephrine on various hemodynamic variables and to evaluate the ability of advanced hemodynamic monitoring to quantify these changes through different hemodynamic variables. In 24 patients, after induction of anesthesia, during the period before surgical stimulus, phenylephrine 2 µg kg was administered when the MAP dropped below 80% of the awake state baseline value for > 3 min. The mean arterial blood pressure (MAP), heart rate (HR), end-tidal CO (EtCO), central venous pressure (CVP), stroke volume (SV), CO, pulse pressure variation (PPV), stroke volume variation (SVV) and systemic vascular resistance (SVR) were recorded continuously. The values at the moment before administration of phenylephrine and 5(T) and 10(T) min thereafter were compared. After phenylephrine, the mean(SD) MAP, SV, CO, CVP and EtCO increased by 34(13) mmHg, 11(9) mL, 1.02(0.74) L min, 3(2.6) mmHg and 4.0(1.6) mmHg at T respectively, while both dynamic preload variables decreased: PPV dropped from 20% at baseline to 9% at T and to 13% at T and SVV from 19 to 11 and 14%, respectively. Initially, the increase in MAP was perfectly aligned with the increase in SVR, until 150 s after the initial increase in MAP, when both curves started to dissociate. The dissociation of the evolution of MAP and SVR, together with the changes in PPV, CVP, EtCO and CO indicate that in patients with anesthesia-induced hypotension, phenylephrine increases the CO by virtue of an increase in cardiac preload.
Topics: Aged; Anesthesia, General; Cardiac Output; Female; Hemodynamic Monitoring; Humans; Hypotension; Male; Middle Aged; Phenylephrine; Prospective Studies; Time Factors; Vasoconstrictor Agents
PubMed: 29569112
DOI: 10.1007/s10877-018-0126-3 -
American Journal of Physiology.... Apr 2022Muscle sympathetic nerve activity (MSNA) increases during hyperinsulinemia, primarily attributed to central nervous system effects. Whether peripheral vasodilation...
Muscle sympathetic nerve activity (MSNA) increases during hyperinsulinemia, primarily attributed to central nervous system effects. Whether peripheral vasodilation induced by insulin further contributes to increased MSNA via arterial baroreflex-mediated mechanisms requires further investigation. Accordingly, we examined baroreflex modulation of the MSNA response to hyperinsulinemia. We hypothesized that rescuing peripheral resistance with coinfusion of the vasoconstrictor phenylephrine would attenuate the MSNA response to hyperinsulinemia. We further hypothesized that the insulin-mediated increase in MSNA would be recapitulated with another vasodilator (sodium nitroprusside, SNP). In 33 young healthy adults (28 M/5F), MSNA (microneurography) and arterial blood pressure (BP, Finometer/brachial catheter) were measured, and total peripheral resistance (TPR, ModelFlow) and baroreflex sensitivity were calculated at rest and during intravenous infusion of insulin ( = 20) or SNP ( = 13). A subset of participants receiving insulin ( = 7) was coinfused with phenylephrine. Insulin infusion decreased TPR ( = 0.01) and increased MSNA ( < 0.01), with no effect on arterial baroreflex sensitivity or BP ( > 0.05). Coinfusion with phenylephrine returned TPR and MSNA to baseline, with no effect on arterial baroreflex sensitivity ( > 0.05). Similar to insulin, SNP decreased TPR ( < 0.02) and increased MSNA ( < 0.01), with no effect on arterial baroreflex sensitivity ( > 0.12). Acute hyperinsulinemia shifts the baroreflex stimulus-response curve to higher MSNA without changing sensitivity, likely due to insulin's peripheral vasodilatory effects. Results show that peripheral vasodilation induced by insulin contributes to increased MSNA during hyperinsulinemia. We hypothesized that elevation in muscle sympathetic nervous system activity (MSNA) during hyperinsulinemia is mediated by its peripheral vasodilator effect on the arterial baroreflex. Using three separate protocols in humans, we observed increases in both MSNA and cardiac output during hyperinsulinemia, which we attributed to the baroreflex response to peripheral vasodilation induced by insulin. Results show that peripheral vasodilation induced by insulin contributes to increased MSNA during hyperinsulinemia.
Topics: Adult; Baroreflex; Blood Pressure; Heart Rate; Humans; Hyperinsulinism; Insulin; Muscle, Skeletal; Phenylephrine; Sympathetic Nervous System; Vasodilator Agents
PubMed: 35187960
DOI: 10.1152/ajpendo.00391.2021 -
International Journal of Surgery... Dec 2018In the past 20 years, many studies compared phenylephrine with ephedrine to prevent or treat hypotension in elective or emergency cesarean delivery and parturients with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In the past 20 years, many studies compared phenylephrine with ephedrine to prevent or treat hypotension in elective or emergency cesarean delivery and parturients with pre-eclampsia. A meta-analysis of the abovementioned trials is needed.
METHODS
Several databases (PubMed, Embase, Web of Science and Cochrane Library) were searched from inception to April 2018 for trials comparing phenylephrine with ephedrine in cesarean delivery. The primary outcome is the incidence of maternal hypotension.
RESULTS
Thirty-six trials (2439 patients) with elective cesarean delivery, three trials (400 patients) with emergency cesarean delivery and three trials (192 patients) with parturients with pre-eclampsia were included and analyzed. The incidence of hypotension did not differ in the elective surgery group (relative risk 0.83, 95% CI 0.66 to 1.05), emergency surgery group (relative risk 1.02, 95% CI 0.87 to 1.19) and pre-eclamptic parturients group (relative risk 0.93, 95% CI 0.63 to 1.37). The phenylephrine group had a higher incidence of bradycardia and lower incidences of tachycardia and nausea or vomiting in all three patient groups. The phenylephrine group also had lower fetal acidosis rate, higher umbilical artery and vein pH values and less base excess in the elective surgery. The abovementioned outcomes were similar in the emergency surgery group and the pre-eclampsia group. Publication bias for hypotension was detected. However, the trim and fill method demonstrated that the publication bias had little impact on hypotension. Trial sequential analysis of hypotension in elective surgery showed that this meta-analysis lacked a sufficient cumulative sample size and that further studies should be included.
CONCLUSION
Phenylephrine and ephedrine were both effective in maintaining hemodynamic balance. Newborns benefited more from phenylephrine in elective cesarean delivery, but not in emergency cesarean delivery or in parturients with pre-eclampsia. More trials should be included to achieve more conclusive results.
Topics: Adult; Anesthesia, Spinal; Cesarean Section; Ephedrine; Female; Humans; Hypotension; Incidence; Infant, Newborn; Phenylephrine; Pregnancy; Vasoconstrictor Agents
PubMed: 30389535
DOI: 10.1016/j.ijsu.2018.10.039