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Acute effects of topical phenylephrine on aqueous humor dynamics and corneal endothelial permeability in man.

Acute effects of topical phenylephrine, an alpha-1 adrenergic agonist, on the aqueous humor dynamics and corneal endothelial permeability were studied by means of the oral fluorescein method in 11 normal young volunteers. Twenty microliters of phenylephrine HCL (10%) was instilled in one eye and the placebo in the other eye in a double masked manner. The instillations were carried out 0.5 hour before, and 2, 4 and 6 hours after the fluorescein ingestion. Fluorophotometric measurements were carried out in the central cornea, anterior chamber and plasma ultrafiltrate, and the aqueous-cornea transfer coefficient in reference to the corneal volume (kc.ac), the transfer coefficient in the anterior chamber by diffusion (kd.pa) and by flow (kfa) were calculated in each eye. The thickness of the cornea (CT), intraocular pressure (IOP) and anterior chamber volume (Va) were also measured. No significant difference was found in the CT, kc.ac, corneal endothelial permeability (kc.ac x the thickness of the stroma), Va, IOP and kfa between the experimental and control eyes, while the kd.pa was significantly smaller in the experimental eyes (paired t-test, P less than 0.01). The iris permeability factor (kd.pa x Va) decreased significantly to 0.74 +/- 0.26 (Mean +/- SD) of the control (P less than 0.01). The aqueous flow rate (kfa x Va) averaged 0.95 +/- 0.21 of the control, and the difference from unity was not significant (P greater than 0.1).

Adult↗

Spectrophotometric determination of ephedrine hydrochloride and phenylephrine hydrochloride.

A method is described for quantitative determination of the sympathomimetic amines ephedrine HCl and phenylephrine HCl. The method is based on the interaction of N-alkylvinylamine formed from the condensation of the free secondary amine group and acetaldehyde with chloranil to give a vinylamino-substituted quinone. The colored product for ephedrine HCl and phenylephrine HCl exhibits 2 maxima at about 320 and 680 nm. All variables were studied to optimize reaction conditions. The relationship between absorbance and concentration was linear within 1-25 micrograms/mL under the conditions studied for both drugs at both wavelengths. The method has been applied to the analysis of some pharmaceutical formulations including tablets and eye drops with good recoveries (98.75-100.4%).

Ephedrine↗

Effect of combined 1% cyclopentolate-10% phenylephrine eye drops on systemic blood pressure of glaucoma patients.

Sixty-two patients with glaucoma had eye drops containing 1% cyclopentolate hydrochloride and 10% phenylephrine hydrochloride applied two or three times to one or usually both eyes to dilate their pupils as part of routine eye examinations. Systemic (brachial) blood pressure was monitored before and after drug application. Fifty of the patients had either no change in blood pressure or a decrease. Only two patients had a rise of 20 mm Hg or more in either systolic or diastolic blood pressure. In these two cases the increases were 34/4 and 22/20 mm Hg. Ten patients had an increase ranging from 10 to 20 mm Hg in either systolic or diastolic pressure. The results suggest that a clinically dangerous rise in systemic blood pressure from use of these drops is not common. However, to lessen the risk further, it seems advisable to use drops containing 10% phenylephrine only when lower concentrations are ineffective in dilating the pupils.

Aged↗

Systemic reaction to subconjunctival phenylephrine.

After a subconjunctival injection of phenylephrine, cocaine and atropine, a patient's blood pressure rose to 220/180 mmHg. This rise was followed by hypotension, pulmonary edema, and subendocardial ischemia, all of which resolved spontaneously within 12 hours. This report reemphasizes the hazardous effects on blood pressure of phenylephrine applied to the eye.

Atropine↗

Intracorporeal phenylephrine in the treatment of priapism.

PURPOSE: The effectiveness and complications of intracorporeal phenylephrine without aspiration or irrigation as a treatment for priapism were assessed. MATERIALS AND METHODS: Nine consecutive patients who presented with priapism were treated with 0.5 mg. phenylephrine diluted in 2 cc normal saline injected directly into the corpus cavernosum. Blood pressure and pulse were measured before and after injection, and monitored every 15 minutes. If no detumescence was noted after 15 minutes the injection was repeated. Neither penile blood aspiration nor irrigation was performed. RESULTS: Of 9 patients 8 responded with detumescence. The number of injections required ranged from 1 to 6. No changes in blood pressure, heart rate or side effects were observed. CONCLUSIONS: We believe that this is a safe and effective method for treatment of priapism. Routine initial aspiration or irrigation of the corpora before intracorporeal injection of alpha-adrenergic agents does not appear to be necessary.

Adrenergic alpha-Agonists↗

Treatment of the intraoperative penile erection with intracavernous phenylephrine.

A total of 23 patients who had an intraoperative penile erection during endoscopic or penile surgery underwent intracavernous injection of 200 micrograms phenylephrine. Detumescence occurred rapidly in all patients with a single injection. Hemodynamic changes consisted of a transient increase in systolic and diastolic blood pressures (+9%, p < 0.05) without significant change in pulse rate (-5%, p > 0.05). No marked side effect was reported even in elderly patients. Intraoperative penile erection, which seems to be more frequent in patients younger than 50 years, during general anesthesia with propofol or epidural anesthesia, can be treated safely with intracavernous injection of phenylephrine.

Adult↗

[Dapiprazol antagonizes tropicamide- and phenylephrine-induced mydriasis in the elderly].

Dapiprazole eye drops were applied 1 h after topical tropicamide or phenylephrine instillation in 30 elderly subjects. Pupil diameter normalized much earlier than in controls receiving placebo. Dapiprazole constricted the tropicamide-dilated pupil by 1 mm after 1 h and normalized the pupil diameter of the phenylephrine-dilated pupil within 1 h, whereas the pupils of the patients receiving placebo remained dilated. Intraocular pressure did not change; no major side effects were seen.

Adrenergic alpha-Antagonists↗

Putative, selective inhibitors of sarcoplasmic reticulum Ca+(+)-pump ATPase inhibit relaxation by nitroglycerin and atrial natriuretic factor of the rabbit aorta contracted by phenylephrine.

Using three putative, selective inhibitors of the Ca+(+)-pump ATPase of sarcoplasmic reticulum (SR), cyclopiazonic acid, thapsigargin and 2,5-di-(tert-butyl)-1,4-benzohydroquinone, the mechanisms of relaxation of the arterial smooth muscle by cyclic GMP-generating vasodilators were studied in the ring preparations of the rabbit aorta. Nitroglycerin (NTG) and atrial natriuretic factor (ANF) were used as representative cyclic GMP-generating vasodilators. When the above three inhibitors of SR Ca+(+)-pump ATPase were present during the period of reloading of intracellular store sites with Ca++, the phasic contractions induced by phenylephrine or caffeine in the succeeding period in Ca+(+)-free media containing 2 mM EGTA were inhibited in a concentration-dependent manner. With 3 x 10(-5) M of cyclopiazonic acid the inhibition was almost complete for both agonists. NTG and ANF relaxed the aorta contracted by phenylephrine (10(-6) M) and produced an increase in cyclic GMP content. All the three SR Ca+(+)-pump ATPase inhibitors produced a concentration-dependent inhibition of the relaxation by NTG and ANF without affecting the increment of cyclic GMP content. These results indicate that the proper functioning of SR Ca+(+)-pump ATPase is necessary for elicitation of relaxation by NTG and ANF. Enhanced sequestration of Ca++ by SR may be an important mechanism by which these compounds induce relaxation in this type of smooth muscle.

Adenosine Triphosphatases↗

Blood pressure responses to phenylephrine infusions in subjects with Cushing's syndrome.

The pathogenesis of the hypertension associated with Cushing's syndrome is not completely understood. Sensitivity to pressor agents may play a role. We have investigated this possibility by measuring blood pressure (BP) during incrementally increasing infusions of the alpha-adrenergic agonist phenylephrine. Ten subjects (8 women: 2 men), aged 40 +/- 5 years (mean +/- s.e.m.) with Cushing's syndrome were studied. All had raised BP but none had received any anti-hypertensive treatment for at least 16 days before study. Ten age- (40 +/- 5 years) and sex-matched control subjects were also studied. At 13.30, 30 min after a light meal, subjects had an intravenous cannula inserted, ECG leads and a sphygomanometer cuff attached, and then rested supine in a quiet room for 30 min. Phenylephrine was then infused incrementally at intervals of 5 min. The doses used were 0.3, 0.6, 0.9, 1.35 and 2 micrograms/kg/min. Basal mean blood pressure (MAP) was 108 +/- 2 mm Hg (mean +/- s.e.m.) in patients and 74 +/- 3 mm Hg in controls (P < 0.05) and pulse rate was 75 +/- 5 and 68 +/- 3 beats/min (NS), respectively). MAP increased and pulse rate decreased linearly with time. The rate of rise of MAP was 1.7 +/- 0.4 mm Hg/min in subjects and 1.1 +/- 0.2 mm Hg/min in controls (NS). The rate of decrease of pulse was significantly more rapid in Cushing's subjects than in controls (1.4 +/- 0.2; 0.6 +/- 0.1 beats/min2; P < 0.05). The lack of any increased BP response to alpha-adrenergic stimulation suggests that altered sensitivity is not a major cause of the increased BP seen in patients with Cushing's syndrome.

Adolescent↗

A noninvasive evaluation of baroreceptor sensitivity with the Valsalva maneuver and phenylephrine methods.

In a double-blind crossover study, we compared baroreceptor sensitivity (BS) and latency, derived from the phenylephrine method with BS and latency derived from phase IV of the Valsalva maneuver (VM), using the Finapres, a noninvasive blood pressure monitor. Ten healthy volunteers were enrolled in the study and BS was determined with placebo, atropine (0.03 mg/kg) and atenolol (10 mg) and was expressed as the linear relation between the change in RR interval following the blood pressure rise induced by either phenylephrine or phase IV of the VM (i.e., after cessation of straining). Baseline baroreceptor sensitivity (p<0.001) and baroreceptor sensitivity in the presence of atropine (p<0.02) was smaller with the VM but no differences in baroreceptor sensitivity between the two methods were evident after atenolol. Although no linearity existed between the two methods under any of the experimental conditions, baroreceptor sensitivity in the presence of atropine was significantly smaller (p<0.01)(and latency delayed (p<0.08)) compared to atenolol-induced changes with both methods. We found excellent correlation between baroreceptor sensitivity derived from the ECG tracing and Finapres recorded beat-to-beat pulse intervals (p<0.001; r>0.8, under all conditions) although the correlation after atropine was not as close (p<0.01; r=0.7). The smaller baroreceptor sensitivity induced by the Valsalva maneuver with placebo and atropine, but not with atenolol, suggests a parasympathetically influenced vasodilation, and sympathetically medicated tachycardia during phase IV of the VM.

Adult↗

Comparison of efficacy and tolerance between 1% hydroxyamphetamine plus 0.25% tropicamide (Paremyd) and 0.5% tropicamide combined with 2.5% phenylephrine.

BACKGROUND: Paremyd, consisting of a combination of 1.0 percent hydroxyamphetamine and 0.25 percent tropicamide, is a commercially available eyedrop used clinically for diagnostic mydriasis. This study sought to determine if one drop of Paremyd is equally effective and tolerable as the traditional combination of one drop each of 2.5 percent phenylephrine and 0.5 percent tropicamide. METHODS: A prospective, double-masked, randomized, cross-over study was conducted in 60 normal volunteers ranging from age 20 to 35 years (mean 24.3 years). Twenty-two subjects (36.7 percent) were male, and 32 subjects (53.3 percent) had brown irides. Pupil diameter, amplitude of accommodation, distance and near visual acuity, and subjective comfort of eyedrop instillation were assessed for 8 hours following drug instillation. RESULTS: Significantly more subjects (p < 0.05) experienced adverse ocular symptoms with the tropicamide plus phenylephrine (TP) combination than with Paremyd (P). There was no statistically significant (p > 0.05) difference in mydriatic response between TP and P. During the first hour, however, TP and P demonstrated significant (p = 0.001) differences in cycloplegic effect. CONCLUSIONS: Paremyd appears to be as effective a mydriatic as TP, but with greater comfort on instillation. Paremyd has less effect on accommodation.

Accommodation, Ocular↗

Treatment of neonatal rats with monosodium glutamate attenuates the cardiovascular reactivity to phenylephrine and angiotensin II.

In rats, neonatal administration of monosodium glutamate (MSG) causes serious damage in some hypothalamic and circumventricular areas. The resulting loss of appropriate neurons important for the regulation of blood pressure (BP) may modulate cardiovascular system receptivity in these animals. In the present study, the reactivity of the cardiovascular system to intravenous injection of alpha1-adrenergic receptor agonist phenylephrine (200 microg/kg/ml) and angiotensin II (500 ng/kg in 0.6 ml for 2 min) was investigated in adult rats which had been neonatally treated with MSG or vehicle. BP parameters measured directly in conscious cannulated rats were continuously registered using a computerized system. Under basal conditions, MSG-treated rats had slightly lower systolic, diastolic and mean BP with significant differences in pulse pressure (systolic - diastolic BP). In MSG-treated animals, the maximal increase of mean arterial BP after phenylephrine and the duration of BP elevation after both agents were significantly reduced. Slopes of the linear portion of baroreceptor function curves in control and MSG-treated rats did not differ significantly, indicating that baroreflex efficacy was unchanged. The results obtained by perfusion of the hindlimb vascular bed in situ showed that the pressure responses to increasing doses of noradrenaline in MSG-treated rats were reduced. These findings demonstrate that neonatal treatment of rats with MSG lowers the responsiveness of the cardiovascular system, particularly in response to alpha-adrenergic stimulation. It is suggested that the attenuation of cardiovascular reactivity in MSG-treated rats is, at least partly, caused by diminished vascular responsiveness.

Adrenergic alpha-Agonists↗

Effects of dopamine, dobutamine, dopexamine, phenylephrine, and saline solution on intramuscular blood flow and other cardiopulmonary variables in halothane-anesthetized ponies.

OBJECTIVE: To evaluate the effect on intramuscular blood flow (IMBF) and hemodynamic variables of 4 antihypotensive agents given during anesthesia. ANIMALS: 8 ponies. PROCEDURE: Halothane-anesthetized ponies (n = 6) positioned in lateral recumbency received, on separate occasions, infusions of each of the following 4 agents in serially increasing dosages or saline solution: phenylephrine hydrochloride (0.25, 0.5, 1, and 2 microg/kg of body weight), dopamine (2.5, 5, 10, and 20 microg/kg), dobutamine (1, 2.5, 5, and 10 microg/kg), and dopexamine (0.5, 1, 5, and 10 microg/kg). Changes in IMBF (by laser-Doppler flowmetry) in nondependent and dependent triceps brachii muscles and cardiopulmonary variables were measured. RESULTS: Phenylephrine at all dosages failed to improve IMBF or cardiac index (CI), but increased mean arterial pressure (MAP) and systemic vascular resistance (SVR); 2 ponies had forelimb lameness on recovery. Dopamine (10 microg/kg/min) increased CI, MAP, and IMBF in the dependent muscle. A higher dose (20 microg/kg/min) caused cardiac arrhythmias and muscular tremor. Dobutamine increased Cl, MAP, and IMBF of both forelimbs, effects being significant for 2.5 microg/kg/min, with further improvement as the dosage increased. In 2 ponies, 10 microg of dobutamine/kg/min caused cardiac arrhythmias. Dopexamine (1 and 5 microg/kg/min) increased CI, MAP, and IMBF in the nondependent muscle, and 10 microg/kg/min caused muscular tremor, sweating, and arrhythmias. SVR was reduced after infusion of dopamine, dobutamine, or dopexamine. CONCLUSION: During anesthesia of equids, an increase in Cl and MAP is necessary to improve IMBF in the dependent forelimb. CLINICAL RELEVANCE: Of the agents investigated, dobutamine proved the most consistent in improving IMBF.

Anesthetics, Inhalation↗

Analysis of tablets containing acetylsalicylic acid and phenylephrine by high-performance liquid chromatography.

A high-performance liquid chromatographic method permitted the quantitation of acetylsalicylic acid, phenylephrine, caffeine and phenacetin in tablets, and of the main impurities, salicylic acid and mono- and diacetyl derivatives of phenylephrine. A C8 reversed-phase column was used with a mobile phase containing methanol-1 M phosphoric acid-water 34:5:61 v/v/v.

Journal Article↗

Ephedrine and phenylephrine for avoiding maternal hypotension due to spinal anaesthesia for caesarean section. Effects on uteroplacental and fetal haemodynamics.

The effects of i.v. vasopressors on Doppler velocimetry of the maternal uterine and placental arcuate arteries and the fetal umbilical, renal and middle cerebral arteries were studied during spinal anaesthesia in 19 healthy parturients undergoing elective caesarean section. Fetal myocardial function was investigated at the same time by M-mode echocardiography. The patients were randomized into two groups, to be given either ephedrine or phenylephrine as a prophylactic infusion supplemented with minor boluses if systolic arterial pressure decreased by more than 10 mmHg from the control value. Both the vasopressors restored maternal arterial pressure effectively. The ephedrine group showed no significant differences in any of the Doppler velocimetry recordings relative to the baseline values, but during the phenylephrine infusion the blood flow velocity waveform indices for the uterine and placental arcuate arteries increased significantly and vascular resistance decreased significantly in the fetal renal arteries. Healthy fetuses seem to tolerate these changes in uteroplacental circulation well, however, since the Apgar scores for the newborns and the acid-base values in the umbilical cord were within the normal range in both groups. The results suggest that some caution is required when selecting the specific vasopressor agent, the dosage and the mode of administration for the treatment of maternal hypotension secondary to spinal anaesthesia for caesarean section.

Journal Article↗

Topical phenylephrine for the treatment of middle ear effusion.

One hundred fifty-two children were enrolled in a randomized, controlled clinical trial of the efficacy of phenylephrine hydrochloride nose drops or nasal spray in hastening the resolution of middle ear effusion. Children with persistent effusion were recruited for the study during a return visit two weeks after an episode of acute otitis media. Forty-six patients (30%) dropped out of the study, many because they failed to tolerate the medication, especially the nose drops. Another 27 (18%) had to be excluded because of intercurrent illness or systemic drug therapy. Among those children completing the study, rates of clinical and tympanometric cure during the following four weeks were similar in the drug and placebo groups. In view of the absence of documented clinical efficacy and the practical difficulties inherent in their administration, topical decongestants appear to have a limited role, if any, in treating children with persistent effusion.

Acute Disease↗

High-performance liquid chromatographic determination of phenylephrine and tropicamide in human aqueous humor.

A high-performance liquid chromatographic method for the simultaneous determination of phenylephrine and tropicamide in human aqueous humor was developed. After centrifugation, an aliquot of the supernatant was injected onto the column and the eluent was monitored at 280 nm then 254 nm after 5 min. Separation was performed on a CN column with 0.01 M Pic B8 (octane sulfonic acid)-acetonitrile (65:35, v/v) as mobile phase. The standard curves were linear in the detection range. The precision of the method (expressed by relative standard deviation) and the accuracy (mean error in per cent) were <5% for both intra- and interassays.

Aqueous Humor↗

Fos expression by glutamatergic neurons of the solitary tract nucleus after phenylephrine-induced hypertension in rats.

The baroreflex pathway might include a glutamatergic connection between the nucleus of the solitary tract (NTS) and a segment of the ventrolateral medulla (VLM) called the caudal ventrolateral medulla. The main goal of this study was to seek direct evidence for such a connection. Awake rats were subjected to phenylephrine- (PE-) induced hypertension (N=5) or received saline (N=5). Neuronal activation was gauged by the presence of Fos-immunoreactive (Fos-ir) nuclei. Fos-ir neurons that contained vesicular glutamate transporter 2 mRNA (glutamatergic neurons) or glutamic acid decarboxylase mRNA (GABAergic neurons) were mapped throughout the medulla oblongata. Saline-treated rats had very few Fos-ir neurons. In PE-treated rats, Fos-ir neurons were detected in both NTS and VLM. In NTS, 72% of Fos-ir neurons were glutamatergic and 26% were GABAergic. In the VLM, 41% of Fos-ir neurons were glutamatergic and 56% were GABAergic. In VLM, Fos-ir glutamatergic neurons were evenly distributed and were often catecholaminergic, whereas Fos-ir GABAergic cells were clustered around Bregma -13.0 mm. This region of the VLM was injected with Fluoro-Gold (FG) in eight rats, four of which received PE and the rest saline. Fos-ir NTS neurons retrogradely labeled with FG were detected only in PE-treated rats. These cells were exclusively glutamatergic and were concentrated within the NTS subnuclei that receive the densest inputs from arterial baroreceptors. In conclusion, PE, presumably via baroreceptor stimulation, induces Fos in glutamatergic and GABAergic neurons in both NTS and VLM. At least 29% of the Fos-ir glutamatergic neurons of NTS project to the vicinity of the VLM GABAergic interneurons that are presumed to mediate the sympathetic baroreflex.

Animals↗