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The mydriatic effect of tropicamide and its diagnostic use in Alzheimer's disease.

The mydriatic effect of topically administered tropicamide was investigated as a possible diagnostic indicator for Alzheimer's disease. Although an initial series seemed to show a correlation between hypersensitivity to tropicamide and intellectual impairment, subsequent testing showed a greater inter- and intra-individual variation than that between the normal group and the group of patients with intellectual impairment. This procedure seems, therefore, to lack sufficient specificity to be useful for such a diagnostic purpose.

Aged↗

A comparison of mydriatic eyedrops in low-weight infants.

The pupils of neonates often need to be dilated to examine the retina for retinopathy of prematurity and other disorders. It is known that low-weight infants (less than 1600 grams) are susceptible to systemic hypertension when 10% or 2.5% phenylephrine eye drops are used. To find the safest and best commercially available mydriatic agent in neonates, 30 low-weight infants were divided evenly into three groups. The drops tested were cyclopentolate 0.5% alone, cyclopentolate 0.5% plus mydriacyl 0.5%, and a combination drop of phenylephrine 1% and cyclopentolate 0.2%. There was no clinically significant effect of any of the drops on systolic blood pressure or pulse rate. The cyclopentolate and phenylephrine combination dilated the pupils by a mean of 2.8 mm which was statistically greater than the other groups (P less than 0.01) and had a longer duration of maximal dilation than the other drops (P less than 0.05).

Blood Pressure↗

A pre-operative mydriatic regime using a single application of tropicamide Novel Ophthalmic Delivery System and guttae phenylephrine 10%.

Tropicamide Novel Ophthalmic Delivery System (NODS) and guttae (g.) phenylephrine 10% was applied once, 2 hours before cataract surgery, as an alternative to our standard pre-operative regime of g. cyclopentolate 1% and g. phenylephrine 10% used four times before surgery. The two treatment groups were compared using a randomised, prospective, observer-masked study design. The horizontal pupil diameter was significantly smaller using the new regime but the per-operative decrease in diameter was not significantly different, suggesting that surgical miosis was not influenced by reducing the number of mydriatic applications. There was no difference in the subjective grading of the pupil, suggesting that adequate mydriasis suitable for cataract surgery was obtained using the alternative regime. No major complications were documented in relation to the use of NODS. We discuss why less intensive mydriasis is likely to be as efficacious and describe its potential advantages.

Aged↗

Haemodynamic responses to subconjunctival mydriatic agents (Mydricaine) used for maintenance of perioperative mydriasis in patients undergoing vitreoretinal surgery.

PURPOSE: To assess the systemic effects of subconjunctival mydriatic agents (Mydricaine). METHODS: Haemodynamic variables were recorded at baseline and during the first 60 min following subconjunctival injection of Mydricaine and normal saline. RESULTS: Statistical analysis of the change in heart rate showed a highly significant difference between the two groups (p < 0.001). There was no significant difference in the effect on systolic or diastolic blood pressure between the two groups. CONCLUSIONS: We advise extreme caution when using Mydricaine via the subconjunctival route in patients with compromised cardiac function.

Adult↗

Vecuronium bromide, phenylephrine and atropine combinations as mydriatics in juvenile double-crested cormorants (Phalacrocorax auritus).

Topical vecuronium bromide (Norcuron) and combinations with atropine and phenylephrine, were evaluated as mydriatics in juvenile double-crested cormorants (Phalacrocorax auritus). Nine cormorants were treated with each of four protocols: 1% atropine; 4 mg/mL vecuronium bromide (total 0.16 mg/eye); atropine with vecuronium; and atropine, 2.5% phenylephrine, followed by vecuronium. Drugs were applied topically at 15-min intervals (0.01 mL/drop). Pupil diameter was measured manually every 15 min with a pupil gauge calibrated to the nearest 0.5 mm. No effect was observed with atropine alone. Average +/- SD peak pupil diameter for vecuronium, atropine/vecuronium, and atropine/phenylephrine/vecuronium were 5.4 +/- 1.1 mm, 5.7 +/- 0.8 mm and 6.2 +/- 0.4 mm, respectively; and duration of peak diameters were 38 +/- 28 min, 79 +/- 71 min and 103 +/- 58 min, respectively. The combined atropine, phenylephrine and vecuronium provided the most consistent dilation with larger average pupil size and longer average duration. No side-effects from vecuronium were observed in these birds.

Animals↗

Probing anterior segment kinetics with focally applied mydriatics.

The purpose of this study was to examine the effects of convectional flow and anterior segment configuration on drug kinetics. Mydriatics were applied focally at the limbus in order to produce sector dilation of the pupil. Subjects were tested with either tropicamide or phenylephrine, applied at the superior, temporal, inferior, or nasal limbus (or as a conventional drop). Changes in pupil form were analyzed by means of photography, digitization, and circular Fourier series representation. Both tropicamide and phenylephrine were found to produce sector dilation; however, phenylephrine was approximately twice as effective. Applications at the superior limbus were significantly less effective than applications at the inferior limbus. The results are interpreted in terms of anterior segment convectional flow, which is believed to play a substantial role in pharmacokinetics of the anterior segment.

Adult↗

Neuroanatomical aspects of mydriatic action of morphine in rats.

Morphine causes mydriasis in rats. In order to investigate whether this effect is due to direct inhibition of preganglionic pupilloconstrictor neurons in the Edinger-Westphal nucleus (EWN), we injected opiate agonists into the EWN in male albino Charles River rats. Bilateral stereotactic microinjections of morphine (10, 20, 30, 40 micrograms/side) inhibited spinal nociceptive reflexes and caused pronounced catalepsy, but had no effect on pupillary size. The powerful opiate agonist, fentanyl, also elicited analgesia and catalepsy, when given in doses of 5 and 10 micrograms/side, but no dose of fentanyl up to 10 micrograms/side induced mydriasis. Naloxone (10 micrograms/side), given into the EWN, effectively antagonized inhibition of the tail-flick response induced by subcutaneously administered morphine (30 micrograms/kg), but had no effect on the cataleptic and mydriatic actions of systemic morphine. These results indicate that, in the rat, morphine-induced mydriasis is not accounted for by a direct action on the EWN.

Analgesics, Opioid↗

Mydriatic effectiveness of dilute combinations of phenylephrine and tropicamide.

The effects of two solutions, each consisting of a combination of tropicamide and phenylephrine at lower than conventional concentrations, were studied in 79 students at Pacific University College of Optometry. Clinically effective diameters (CED's), measured when the eye was illuminated for direct ophthalmoscopy, were followed for 90 min after mydriatic instillation. Intraocular pressure (IOP), systolic arterial blood pressure (sBP), and the systolic BP/IOP ratio were also monitored for 90 min. Both combination A (0.25% tropicamide + 1.25% phenylephrine) and combination B (0.125% tropicamide + 2.0% phenylephrine) produced CED's as large as produced by 0.5% tropicamide in the opposite eye. By combining a low concentration of a sympathomimetic with a parasympatholytic agent, it is possible to achieve mydriasis superior to that produced by 0.5% tropicamide or 2.5% phenylephrine while reducing the risk of systemic or ocular side effects.

Adult↗

Factors determining the potency of mydriatic drugs in man.

1 The mydriasis resulting from topical application of five atropine-like drugs was measured photographically in man. Drug potency was obtained from log dose-response curves. 2 The in vitro potency of eight cholinoceptor blocking drugs, including those studied in man, was obtained by measuring their affinity constants for binding to the receptors of an isolated preparation of the rabbit sphincter pupillae. Values agreed closely with those obtained for the muscarinic receptors of guinea-pig ileum. 3 In vitro and in vivo potency was compared to obtain a quantitative measure of the relative ease with which drugs gain access to the receptors after topical application. 4 The large differences that occur in the intensity and duration of the mydriatic response to atropine-like drugs is primarily the result of differences in their ability to blcok the receptors. Only with tropicamide does its relatively high accessibility affect its potency in man.

Administration, Topical↗

Pharmacodynamics of a new ophthalmic mydriatic insert in healthy volunteers: potential alternative as drug delivery system prior to cataract surgery.

Cataract surgery requires a satisfactory degree of mydriasis throughout the entire operation. A phase I, open-labelled, randomised, cross-over trial was conducted in 18 healthy volunteers to compare mydriasis obtained with subsequent administration of phenylephrine 10% and tropicamide 0.5% eyedrops or a new insoluble-matrix retropalpebral ophthalmic insert containing 5.38 mg phenylephrine and 0.28 mg tropicamide. Phenylephrine serum concentrations were measured over 6 hr following each treatment administration. Secondary end-points included cardiovascular, general and local tolerance and quantification of bacterial colonisation of the conjunctiva and the cultured insert, respectively. When normalized to the pupil diameter after conventional treatment, the diameter achieved with the insert was 1.13 (95% confidence interval, 0.94-1.48, P=0.38). Moreover, standard eye drops provided faster effective mydriasis than the insert, starting 30 min. as compared to 90 min. upon treatment administration (P<0.01, repeated-measures ANOVA). Phenylephrine concentrations remained almost undetectable for both treatments and no change in heart rate or blood pressure were observed throughout the study. Only three superficial punctuate keratitis were diagnosed with the insert and two with the eye drops. No significant bacterial contamination of conjunctiva swab and cultured insert was observed. The new insoluble-matrix retropalpebral ophthalmic mydriatic insert produced similar but delayed effective and prolonged mydriasis as compared to the standard delivery system. In addition to its potential usefulness in patients undergoing cataract surgery, such new ophthalmic delivery system may be an advantage in children who need to undergo fundus photography due to the single administration and excellent tolerance as well.

Adolescent↗

Effects of mydriatic agents on neutrophil migration.

We have investigated the effects of various mydriatic agents on the locomotion of polymorphonuclear leukocytes in vitro. Human as well as rat neutrophils showed a dose-dependent increase of migration into micropore filters when tested against cyclopentolate hydrochloride at a dose range between 16 and 63 micrograms/ml. At higher doses (250 micrograms/ml), a complete inhibition of neutrophil migration was observed. A commercially available cyclopentolate hydrochloride preparation showed identical effects. Little or no changes in neutrophil locomotion were seen with atropine, homatropine, scopolamine or tropicamide when tested at the same concentration range. Since addition of cyclopentolate to either the lower or upper compartment of the multiwell chemotaxis chamber gave virtually the same results, it is assumed that the drug most likely induces a chemokinetic neutrophil response. However, an additional chemotactic effect cannot be excluded. These in vitro observations may help to explain an accidental observation in a patient with severe anterior uveitis who showed a massive, localized leukocyte accumulation on the corneal endothelium after contact with a cyclopentolate-soaked cotton pledget.

Animals↗

[Prescription of mydriatics in the treatment of dosed-angle glaucoma].

The indication for the use of mydriatics in the treatment of dosed-angle glaucoma are discussed. The value of their use consists in the elimination of pupillary block and in an antiphlogistic action. This claimed that these effects prevent the formation of posterior and peripheral anterior synechiae and thus prevent the condition from becoming chronic.

Aged↗

Retinal damage in pigmented and albino rats exposed to low levels of cyclic light following a single mydriatic treatment.

The present study demonstrated that less than three days of exposure to low levels of normally cycled ambient illumination are sufficient to cause death to photoreceptor cells in adult pigmented and albino rat. Cyclic light levels as low as 133 and 320 lux were found to destroy photoreceptor cells. A single mydriatic treatment with atropine immediately preceding the three-day exposure was sufficient to permit the effect in pigmented rats. No mydriasis was required for albino rats. When pigmented rats were reared in either 3 lux or 100 lux, it was found that these different light histories did not significantly affect the rats' subsequent susceptibility, during mydriasis, to retinal damage by cyclic illumination.

Albinism↗

Effect of mydriatics on blood pressure in premature infants.

Systolic blood pressure (SBP) was measured by doppler methods at 5, 15, 30, 45, and 60 minutes in 52 premature infants after triple instillation of aqueous phenylephrine 2.5% and tropicamide 1.0%. Systolic blood pressures were insignificantly increased 3.9 +/- 2.0 mm Hg (mean +/- S.E.) at 15 minutes when compared with controls matched for initial blood pressure, birth weights and age at examination. Though a 964 gm, 28-week Caucasian male with retinopathy of prematurity had been uneventfully dilated, pupillary dilatation one week later with triple instillations of phenylephrine 2.5% and tropicamide 1.07% was accompanied by an acute increase in systolic blood pressure to 108 mm Hg at 15 minutes, which remained elevated for 150 minutes. A new lower dose, single instillation mydriatic became available whose final concentration was phenylephrine 2.5%, tropicamide 0.5% and cyclogyl 0.5%. A single drop was found to produce mydriasis equal to the triple instillation regime. The single administration produced no significant effect on systolic blood pressure in 30 low birth weight infants (birth weight less than 1750 gm) when compared with balanced salt solution (placebo) in a randomized, double--masked study. Mechanisms of acute hypertension after topical mydriasis are discussed.

Blood Pressure↗

A comparison of the pupillary and cardiovascular effects of various mydriatic agents in preterm infants.

We conducted a randomized, masked study of pupillary dilating capabilities and associated cardiovascular effects of three solutions. Thirty-four babies less than 1500 grams at birth were studied at six to eight weeks. Group A (n = 10) received phenylephrine (PE) 2.5% and tropicamide 1.0%; Group B (n = 10) PE 2.5%, tropicamide 0.5%, and cyclopentolate 0.5%, Group C (n = 10) PE 1.0% and tropicamide 1.0%; Group D (n = 4) saline 0.9%. One drop was placed in each eye and repeated five minutes later. Pupillary dilation was measured with a metric ruler by direct observation at one hour. Blood pressure (BP) and heart rate (HR) were monitored, using an oscillometer, immediately prior to the instillation of the drops and at five-minute intervals, for 60 minutes. BP and HR increased transiently in all groups receiving mydriatics but returned to baseline values in 25 minutes. This increase was significant in Groups A and B (2.5% PE: p less than 0.02). Group D (saline) showed no change in BP or HR. Postdrop pupillary size was largest in Group A but the differences were not significant. On exposure to bright light, the pupillary size in Group C was significantly smaller than Groups A or B (7.35 +/- 0.59 mm, 7.23 +/- 0.38 mm and 6.75 +/- 0.57 mm in Groups A, B and C, p less than .01). Nevertheless, dilation was sufficient to allow appropriate examination in all infants (pupillary diameter greater than 6.0 mm). Solutions containing 2.5% PE are most effective for use in LBW infants, but produce cardiovascular effects. Solutions containing 1% PE provide adequate dilation with minimum cardiovascular effects.

Cardiovascular System↗

Topical mydriatic and cycloplegic spray for Chinese children.

PURPOSE: To assess the efficacy and tolerance of mydriatic and cycloplegic spray versus drops for Chinese children. METHODS: The effects of the spray (cyclopentolate 0.25%, phenylephrine 0.625%, and tropicamide 0.5%) and the drops (cyclopentolate 1%, phenylephrine 0.5%, and tropicamide 0.5%) were evaluated in 29 children (58 eyes) in two separate sessions. There was a 1-week period between the applications of the spray and the drops. Dilated pupil size and refraction after cycloplegia were the primary outcome variables used to assess the efficacy. A subjective discomfort score was used to assess acceptance of the spray and the drops. RESULTS: The mean age of the study population was 4.33 +/- 1.39 years (range, 3 to 8 years). The mean pupil size was 6.9 mm for the spray and 6.6 mm for the drops. The spray appeared to be slightly more effective than the drops, with a mean difference of 0.3 mm that was statistically significant (P = .001, two-tailed t test). No statistically significant difference in cycloplegic response was found between the spray and the drops (P = .535, two-tailed t test). Administration of the spray caused less discomfort than did administration of the drops (P < .001, Wilcoxon signed-rank test). CONCLUSIONS: The spray system appears to be clinically equivalent to the drops for achieving effective pupil dilation and cycloplegia, even in a population with dark irides such as ours. Tolerability and acceptance improved because the spray was applied to the closed eyelids.

Administration, Inhalation↗

Effects of mydriatics and a miotic on ocular discomfort and pupil responses.

Mydriatics produced two different effects on the discomfort threshold following administration of the drugs depending upon whether the mydriasis was produced by paralysis of the sphincter muscle or by activation of the dilator. When the sphincter was paralyzed by tropicamide, the discomfort threshold was elevated during the period of time that the pupillary light reflex was significantly reduced to the flashing stimulus. Initially, phenylephrine-induced mydriasis had no effect on the discomfort threshold, but as the pupil responses returned to normal the threshold rapidly increased and then gradually returned to a pre-drug level. The return of the threshold back to normal seemed to parallel the decline of action of phenylphrine on the dilator muscle. Significant impairment of the light reflex by pilocarpine-produced miosis was also related to an increase of the discomfort threshold.

Humans↗

Effects of alpha-adrenoceptor antagonists on the mydriatic and bradycardic effects of detomidine.

Pupillary and cardiac responses to i.v. injection of detomidine (1-30 micrograms/kg), a novel veterinary sedative analgesic, were observed in rats anesthetized with pentobarbital. Detomidine caused a dose-dependent mydriasis and bradycardia. The alpha 2-adrenoceptor antagonist, yohimbine (0.1-1.0 mg/kg, i.v.), prevented the detomidine-induced mydriasis in a dose-dependent manner. The nonselective alpha-adrenoceptor antagonist, tolazoline at 6 mg/kg, i.v., also prevented the detomidine-induced mydriasis. However, tolazoline at 3 mg/kg, i.v., was not effective in preventing this effect of detomidine. The alpha 1-adrenoceptor antagonist, prazosin at 1.5 mg/kg, i.v., did not reduce the detomidine-induced mydriasis. In contrast to what was found with mydriasis, none of the antagonists at the doses studied prevented detomidine-induced bradycardia. When yohimbine was given i.v., 5 min after the last dose of detomidine (30 micrograms/kg), it promptly and completely reversed mydriasis in all groups. However, yohimbine reversed detomidine-induced bradycardia only in the control group and in the animals pretreated with 1.5 mg prazosin/kg or 3 mg tolazoline/kg. The results suggested that the mydriatic effect of detomidine was mediated by the alpha 2-adrenoceptors, and that mydriasis was a good model for studying alpha 2-adrenoceptor agonists and antagonists. Although the results suggested that the bradycardia effect of detomidine was partially mediated by alpha 2-adrenoceptors, other unknown mechanisms might also be involved.

Adrenergic alpha-Antagonists↗