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Can we predict which patients are at risk of having an ungradeable digital image for screening for diabetic retinopathy?

PURPOSE: We aimed to determine the reasons for, and variables which predicted, ungradeable retinal photographs during screening patients for diabetic retinopathy. MATERIALS AND METHODS: Age, duration of diabetes, visual acuity, and HbA1c were recorded. Following dark adaptation, a single 45 degrees nonmydriatic photograph was taken of each fundus. The pupils were then dilated and the photograph repeated. Using slit lamp biomicroscopy, lenticular changes (LOCS III), and fundus appearance were recorded. RESULTS: In ungradeable photographs the fovea could not be visualised in 98% of cases of images from nonmydriatic photography, and in 88% if mydriasis was used. Poor definition in the nonmydriatic image was associated with a subsequent ungradeable mydriatic photograph (P=0.001), however, the positive predictive value was poor (34%). Age, posterior subcapsular cataract, and near vision predicted ungradeable status of nonmydriatic photographs (P<0.001, P=0.004, P=0.006, respectively; regression analysis). Nuclear colour and poor definition of the nonmydriatic photograph predicted ungradeable status of mydriatic photographs (P=0.006 & P=0.001, respectively). CONCLUSION: Inability to visualise the fovea is the commonest cause of an ungradeable image from digital retinal photography. Age and posterior subcapsular cataract were best predictors of ungradeable status of nonmydriatic fundus photographs. Nuclear colour was the strongest predictor for ungradeable mydriatic photography.

Adolescent↗

Randomized clinical trial of the efficacy and safety of tropicamide and phenylephrine in preoperative mydriasis for phacoemulsification.

PURPOSE: To compare the mydriatic effect and safety between different concentrations of tropicamide and phenyle-phrine in preoperative mydriasis for phaco-emulsification. METHODS: Two hundred and seventeen consecutive eyes in the same number of Chinese patients undergoing phaco-emulsification under local or topical anaesthesia in a university-based eye hospital were analyzed. Patients were randomized into two groups by cluster randomization, each group receiving a different preoperative mydriatic regimen. Regimen A consisted of tropicamide 1.0% with phenylephrine 2.5%, and Regimen B consisted of tropicamide 0.5% with phenylephrine 0.5%. The main outcome measures were horizontal pupillary diameter, systolic, diastolic and pulse pressure and pulse rate. RESULTS: The group who received Regimen A attained a mean horizontal pupillary diameter of 7.00 +/- 1.06 mm. Their pupils were significantly larger than those receiving Regimen B (6.61 +/- 1.03 mm, P = 0.007). No untoward cardiovascular effects were noted in either groups. CONCLUSION: Regimen A attained better preoperative mydriasis for phacoemulsification than Regimen B. Both regimens were safe with regard to their cardiovascular effects. The combination of tropicamide 1.0% and phenylephrine 2.5% is recommended as preoperative mydriatic for phacoemulsification in Chinese patients who have darkly pigmented irides.

Aged↗

Latent dysautonomic pupillary lateralization in cluster headache. A pupillometric study.

Forty-five patients with cluster headache in the asymptomatic phase were studied by electronic pupillography, testing autonomic function of both pupils pharmacologically. Topical sympathetically-acting mydriatics, tyramine and cocaine and the cholinoceptor blocker, homatropine, induced defective mydriatic responses on the symptomatic side, indicating latent impairment of sympathetic function. The abnormality was found in interattack intervals of the cluster period or during intercluster phases. The tyramine test can be proposed for objective diagnosis of cluster headache. We postulate that cluster attacks are triggered and lateralized by a permanent latent unilateral sympathetic dysfunction. Lithium reduced the mydriatic response to tyramine of the pupil contralateral to the pain, thus restoring the equilibrium between both pupils; this therapy may correct the asymmetric sympathetic function by attenuating the activity in the asymptomatic side.

Adolescent↗

Topical phenylephrine may result in worsening of visual loss when used to dilate pupils in patients with vaso-occlusive disease of the optic nerve.

Four patients (age range 54-82, 1F 3M) diagnosed with non-arteritic ischemic optic neuropathy experienced acute worsening of visual function after instillation of phenylephrine for dilated funduscopic examination. They experienced decreased visual function immediately or shortly after administration of topical mydriatic drops given in preparation for funduscopy. In all cases one drop each of 2.5% phenylephrine and 0.5-1% tropicamide was used. Three patients had classical risk factors such as hypertension, diabetes, and had a contralateral "disc-at-risk". The female and youngest patient had ischemic optic neuropathy presumed secondary to lupus erythematosus. The time from acute visual loss to presentation to neuro-ophthalmic care ranged from 1-6 days. The time of onset of the decline in visual function varied from 45 minutes (patient with lupus) to 12 hours after instillation of mydriatic drops. Visual acuity at diagnosis ranged from 20/40-20/400. Phenylephrine is a mydriatic with vasoconstrictive properties, which may be absorbed through the cornea, thus yielding non-negligible intraocular concentrations. Vasoconstriction of the watershed posterior ciliary capillary beds may result in further precipitating infarction of already compromised circulatory territories in edematous optic nerves. Because phenylephrine is a known vasoconstrictor in vivo and in vitro, it is more likely to cause deleterious vasoconstriction and an acute decline in visual function in patients with acute ischemic optic neuropathy than tropicamide. The routine practice of using phenylephrine to prepare patients for funduscopic assessment should be re-examined, particularly in patients with ischemic optic neuropathy.

Administration, Topical↗

Effective degree of mydriasis with phenylephrine and tropicamide.

The mydriatic effects of several concentrations of phenylephrine and of tropicamide were studied in 84 young adults for 90 min following topical instillation. Pupillary diameter was estimated (a) under ambient photopic illumination and (b) when illumination was increased to that associated with direct ophthalmoscopy. Evaluation was made of the "degree of mydriasis," i.e., the difference in pupillary diameter between the eye receiving the mydriatic agent and the contralateral control eye when the pupillary light reflex was stimulated. In subjects with light or hazel irides, phenylephrine caused maximal dilatation in 60 to 75 min, mean values being 5.6 mm with 1 drop of 2%, 6.0 mm with 2 drops of 2.5%, and 7.1 mm with 1 drop of 10%. Maxiumum degrees of mydriasis were 3.0 mm with 2 drops of 2.5% and 3.1 mm with 1 drop of 10%. With 0.5% tropicamide, maximum diameter was 8.0 mm in 30 min in subjects with light, hazel, or brown irides, and the maximum degree of mydriasis was 5.0 mm. It is concluded that when a mydriatic agent is used to facilitate intraocular visualization, neither specification in terms of (a) maximum diameter under ambient illumination nor (b) degree of mydriasis provides optimal characterization. It is suggested that the "clinically effective diameter," i.e., pupillary diameter under illumination corresponding to that to be used during examination, would be the most useful specification.

Adaptation, Ocular↗

The effect of mydriasis from phenylephrine on corneal shape.

PURPOSE: A previous study reported that pharmacologically-dilated pupils changed the corneal shape. Researchers used mydriatic agents with significant cycloplegic effect. The current study investigates the effect of mydriasis on corneal shape using phenylephrine alone, where phenylephrine has minimal effect on the accommodative system and whether corneal topography can be done after pupil dilation. METHODS: Forty-four young healthy subjects with one eye randomly selected for mydriasis were used in this study. Twenty-two received one drop of 2.5% phenylephrine (group 1); the other 22 subjects had one drop of 0.4% benoxinate instilled prior to the application of 2.5% phenylephrine (group 2). They were matched for age and refractive error. Anterior chamber depth, pupil size and corneal parameters were compared before and after mydriasis. The corneal parameters included best-fit sphere (BFS), surface asymmetry index (SAI), surface regularity index (SRI) and the axial and tangential powers in the form of flattest and steepest powers, and in the form of M, J(0), and J(45) vector presentation. RESULTS: Group 1 and group 2 subjects had similar pre-mydriatic baseline ocular parameters. The mean (+/- SD) pupil dilation was 1.24 +/- 0.59 mm for group 1 and 1.80 +/- 0.95 mm for group 2. The dilation was significantly larger in group 2 (unpaired t-tests: t = 2.36, p = 0.02). There were no significant changes in corneal parameters from mydriasis in either group. CONCLUSIONS: Previous investigations used mydriatic agents, which affected not only the pupil size but also accommodation. The current study found that mydriasis from phenylephrine, with minimal effect on accommodation, did not result in significant corneal alteration, and corneal topography can be measured after pupil dilation with phenylephrine.

Adult↗

Comparative study of the effects of 2% ibopamine, 10% phenylephrine, and 1% tropicamide on the anterior segment.

PURPOSE: To assess in normal and glaucomatous eyes the effect of the dopaminergic drug 2% ibopamine on visual acuity, IOP, pupil size and anterior segment geometry, compared with 10% phenylephrine and 1% tropicamide. METHODS: Fifteen healthy subjects and 15 patients with primary open-angle glaucoma, aged from 40 to 70 years (mean age: 54.8 +/- 9.6), were recruited into this open prospective study. After instillation of 2% ibopamine, refraction, visual acuity, pupil diameter, IOP, five A-scan ultrasonographic parameters, and 15 ultrasound biomicroscopy parameters were evaluated. The study was repeated with assessment of the same parameters 20 to 30 days later in 10 subjects (5 normal and 5 with glaucoma), using first 10% phenylephrine and then 1% tropicamide. A second group of 15 healthy subjects, aged from 45 to 70 years (mean age: 53.5 +/- 8.6) was examined to evaluate the dose-response effect and time course on pupil diameter, of ibopamine, phenylephrine, and tropicamide. RESULTS: After 40 minutes 2% ibopamine induced a marked mydriatic effect (from 5 to 9.1 mm; P < 0.0001) greater than that produced by 10% phenylephrine (from 4.7 to 7.9 mm; P < 0.0001) or 1% tropicamide (from 4.6 to 6.9 mm; P < 0.0001), with no changes in refraction or visual acuity. IOP was significantly increased only in patients with glaucoma after instillation of either 2% ibopamine (from 22.2 to 24.8 mm Hg; P < 0.0001) or 1% tropicamide (from 21.2 to 23.6 mm Hg; P = 0.004), whereas 10% phenylephrine induced no statistically significant changes. Ibopamine (2%) caused a significant increase in iris thickness with a reduction of the sulcus ciliaris and posterior chamber depth. The anterior chamber angle (ACA) showed a mean 5 degrees widening with an increase in scleral-iris angle (SIA) and sclera-ciliary process angle. In 11 (37%) of 30 cases, separation of the pupil border and lens surface occurred, whereas contact was maintained only with the zonule in the other 19 (63%) of 30. The changes after 10% phenylephrine instillation were similar, although only the increase in iris thickness and SIA was statistically significant. Tropicamide (1%) induced a slight but significant increase in SIA. CONCLUSIONS: The results confirm the potent mydriatic effect of 2% ibopamine, which is greater than that of either 10% phenylephrine or 1% tropicamide, as well as its ability to induce an increase in intraocular pressure when used in patients with glaucoma alone. These data support the hypothesis that the widening of the ACA induced by 2% ibopamine is due to posterior rotation of the iris plane and ciliary processes. These changes are quantitatively greater than those induced by 10% phenylephrine and 1% tropicamide and are related to the greater mydriatic effect of the drug.

Adult↗

Patients' attitudes towards mydriasis for diabetic eye disease screening.

AIMS: The purpose of the questionnaire was to explore attitudes of patients towards mydriasis for diabetic retinopathy screening. METHODS: Two groups of patients were invited to take part: group 1 comprised patients attending the diabetic clinic and had previous experience of mydriasis, group 2 patients attending the mobile screening unit for non-mydriatic digital retinal photograph and who were not previously used to receiving mydriatic eye drops. Basic demographic data was recorded and the volunteers invited to complete a questionnaire. RESULTS: 292 patients were recruited into group 1 (median age 63 years range 20-94) and 103 into group 2 (median age 68 years range 29-96). 42% of patients in group 2 indicated that they were unhappy with the use of dilating eye drops and 26% of this group reported that they may be discouraged from attending screening for diabetic retinopathy if drops were introduced. These figures were statistically lower in group 1 at 8% and 1-8% respectively (p < 0.001). Blurring of vision was identified as the most troublesome feature of the use of mydriasis for patients. A large proportion of patients drove themselves to their last screening appointment; 58% in group 2 and 39% in group 1. A third of all patients (33%) indicated that they worked outside the home. CONCLUSIONS: Many patients attending diabetic eye screening return to driving and work immediately after the appointment. Introduction of the use of routine drops may discourage attendance. Education and experience may have an important role in improving acceptability of mydriatic eye drops. Retinal screeners need to have clear guidelines with which to advise patients.

Adult↗

Iris pigmentation and atropine mydriasis.

The experiments were designed to study the well-known pigment-dependent mydriatic effect of atropine in the eye. In vitro, relative to the accumulation of 3H-atropine by the nonpigmented rabbit iris, the pigmented iris accumulated high amounts of the drug. A nonpigmented tissue, stomch fundus strip, obtained from either albino or nonalbino animals, accumulated relatively low amounts of 3H-atropine. On repeated washings, the accumulated drug from the nonpigmented tissues was rapidly lost, T 1/2 of 14 minutes, while that accumulated by the pigmented iris was retained much longer. Although in vitro aqueous humor from serum-atropinesterase positive rabbits rapidly degraded atropine, extracts from irides of the same type of rabbit gave a single peak radioactivity, with Rf identical to the authentic atropine sulfate. The accumulation of 3H-atropine by pigmented human iris or pigment epithelium was similar to that observed for the pigmented rabbit iris. pA2 values of atropine from nonpigmented iris and from fundus strips varied between 8.58 and 8.88 with slope values close to 1. The pA2 value of atropine in pigmented iris was 8.82; at higher concentrations, atropine was less effective compared to the nonpigmented iris. In the pigmented iris, the lesser effectiveness of the drug at high concentration could be explained on the basis of accumulation of the drug by the pigment cell and its constituents. Thus, the free concentration of the drug in the vicinity of the muscarinic receptor will fall. The lesser concentration will give weaker muscarinic blockade in the pigmented iris. On repeated washing, the atropine blockade of the nonpigmented iris could be easily washed out while that in the pigmented iris was retained. In vivo, the relative T 1/2 for the duration of atropine mydriasis in rabbits were: albino atropinesterase-positive, 3.8 hours; nonalbino atropinesterase-positive, 12.4 hours; albino atropinesterase-negative is greater than or equal to 96 hours. Only the latter T 1/2 for the duration of atropine mydriasis is quite clear. The small magnitude of the mydriatic effect in humans is explained by the loss of free drug to the pigment cells and their constituents. The longer duration of mydriatic effect in the heavily pigmented eye is explained on the basis of slow release of the accumulated drug onto the muscarinic receptor.

Animals↗

Changes in aqueous flare and cells after mydriasis.

The influence of a commonly used short-acting mydriatic agent, tropicamide-phenylephrine, on aqueous flare intensity and cell number was studied both in postsurgical cases and normal subjects. Measurements with a laser flare-cell meter were carried out in 40 patients who had undergone planned extracapsular cataract extraction with posterior chamber intraocular lens implantation. On the second postoperative day, 20 patients received one drop of a combined solution of 0.5% tropicamide and 0.5% phenylephrine, and the remaining patients received no mydriatic agents. Flare-cell meter measurements in the non-mydriasis group were rather difficult, and measurements in 12 out of 20 (60%) cases were discontinued. In the mydriasis group, flare intensity became significantly lower 2 hours after the application (P less than 0.01) and continued to decrease throughout the rest of the measurement period. The cell counts tended to decrease throughout the period after mydriasis and showed significantly lower values compared to the initial value (P less than 0.01). It was considered that measurements with this instrument in postoperative cases are best performed between 30 minutes to 1 hour after the application of the short-acting mydriatic agents. In normal human eyes, the effects of 0.5% phenylephrine-0.5% tropicamide, 0.4% tropicamide, and 5% phenylephrine on aqueous flare and cells were tested separately. Aqueous flare intensity was significantly decreased by tropicamide-phenylephrine at 1, 1.5 and 2 hours (P less than 0.05), by tropicamide at 1 and 1.5 hours (P less than 0.01), and by phenylephrine at 3 hours (P less than 0.01) after the application, respectively. Values returned to normal following these transient decreases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Neurotransmitter control of pupillary motoricity in man].

The pupillary responses to different agonists and antagonists of the sympathetic and parasympathetic systems have been studied in normal volunteers. The eyedrops were instilled unilaterally and the responses were evaluated by measuring the changes in diameter of the pupils (in millimeters). All the eyedrops induced an unilateral response on the instilled side. The mydriatic substances (phenylephrine, thropamide, tyramine) showed an evident and lasting action. Phenylephrine 1% was found to be a threshold dose to acquire the mydriatic effect. The beta blocking agent (timolol) induced a short mydriatic response, while methaproterenol did not change the pupillary diameter. Clonidine caused an unilateral mydriasis. The alpha blocking agent and the parasympathetic system stimulation agent induced miotic effects The results are discussed with particular reference to the possible mechanism of the pupillary response to timolol and clonidine.

Clonidine↗

Action of opioid agonist-antagonist drugs on the pupil and nociceptive responses in mice.

Opioid derivatives with mixed agonist-antagonist activities are becoming increasingly more popular in analgesia. We tested the mydriatic and analgesic activity of morphine in mice in comparison with similar effects of three agonist-antagonist agents: buprenorphine, butorphanol and nalbuphine. We also examined the antagonistic action of these three drugs by evaluating the analgesia and mydriasis in animals pretreated with morphine. The analgesic effect was assayed using the hot plate method while the pupillary responses were measured with a binocular operating microscope. Morphine produced dose-dependent mydriasis and analgesia in mice. The morphine-type agent buprenorphine and two nalorphine-type agonist-antagonists, butorphanol and nalbuphine, caused agonistic mydriatic and analgesic effects, usually less effective then morphine. Buprenorphine proved to have higher agonist activity than butorphanol and nalbuphine. The difference between butorphanol and nalbuphine was not statistically significant. A correlation between the mydriatic and the analgesic activity, known to exist among opioid derivatives with agonist activity only, was also demonstrated in the three investigated agonist-antagonist agents. Morphine-induced mydriasis and analgesia were reversed by all three agonist-antagonist drugs, but buprenorphine is a significantly weak antagonist in comparison with butorphanol and nalbuphine. An antagonistic property (antimydriatic and antianalgesic effects after pretreatment with morphine) of both nalorphine-type investigated drugs was not statistically significant, except for the antianalgesic effect of nalbuphine in doses 1 and 3 mg.kg(-1), which was higher in comparison with butorphanol.

Journal Article↗

Functional characterization of alpha-adrenoceptors mediating pupillary dilation in rats.

Previously, we reported that the alpha(1A)-adrenoceptor, but not the alpha(1D)-adrenoceptor, mediates pupillary dilation elicited by sympathetic nerve stimulation in rats. This study was undertaken to further characterize the alpha-adrenoceptor subtypes mediating pupillary dilation in response to both neural and agonist activation. Pupillary dilator response curves were generated by intravenous injection of norepinephrine in pentobarbital-anesthetized rats. Involvement of alpha(1)-adrenoceptors was established as mydriatic responses were inhibited by systemic administration of nonselective alpha-adrenoceptor antagonists, phentolamine (0.3-3 mg/kg) and phenoxybenzamine (0.03-0.3 mg/kg), as well as by the selective alpha(1)-adrenoceptor antagonist, prazosin (0.3 mg/kg). The alpha(2)-adrenoceptor antagonist, rauwolscine (0.5 mg/kg), was without antagonistic effects. alpha(1A)-Adrenoceptor selective antagonists, 2-([2,6-dimethoxyphenoxyethyl]aminomethyl)-1,4-benzodioxane (WB-4101; 0.1-1 mg/kg) and 5-methylurapidil (0.1-1 mg/kg), the alpha(1B)-adrenoceptor selective antagonist, 4-amino-2-[4-[1-(benzyloxycarbonyl)-2(S)- [[(1,1-dimethylethyl)amino]carbonyl]-piperazinyl]-6,7-dimethoxyquinazoline (L-765314; 0.3-1 mg/kg), as well as the alpha(1D)-adrenoceptor selective antagonist, 8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione (BMY-7378; 1 mg/kg), were used to delineate the adrenoceptor subtypes involved. Mydriatic responses to norepinephrine were significantly antagonized by intravenous administration of both WB-4101 and 5-methylurapidil, but neither by L-765314 nor by BMY-7378. L-765314 (0.3-3 mg/kg, i.v.) was also ineffective in inhibiting the mydriasis evoked by cervical sympathetic nerve stimulation. These results suggest that alpha(1B)-adrenoceptors do not mediate sympathetic mydriasis in rats, and that the alpha(1A)-adrenoceptor is the exclusive subtype mediating mydriatic responses in this species.

Adrenergic Fibers↗

Effects of 2% ibopamine on pupil, refraction, anterior segment anatomy and intraocular pressure.

The aim of the study was to determine the effects of a dopaminergic drug, 2% ibopamine, on the pupil, intraocular pressure and other ocular and ultrasound biometric variables. Thirty healthy subjects and 15 patients with primary open-angle glaucoma, aged from 40 to 78 years (mean age: 59.2 +/- 11), were included in two prospective open controlled trials. In the first, the mydriatic effect of 2% ibopamine and its inhibition and reversibility were evaluated in 15 healthy subjects using the alpha1-adrenergic drug, 0.5% dapiprazole. In the second, refraction, visual acuity, pupil diameter, intraocular pressure and 5 A-scan ultrasound biometric variables were evaluated in 15 healthy subjects and in 15 glaucoma patients. As early as forty min after administration of 2% ibopamine, a marked mydriatic effect (7.3 vs 3.9 mm; P < 0.0001), which was completely inhibited or reversed by 0.5% dapiprazole, was detected. The drug induced no changes in refraction, visual acuity or A-scan ultrasound biometric variables in any of the subjects examined. In healthy subjects, the intraocular pressure values were not changed to a statistically significant extent (13.8 vs 14.8 mm Hg; P = 0.668), whereas a slight, though significant, hypertensive effect (24 vs 22.2 mm Hg; P = 0.002) was observed in the glaucoma patients. The study confirms the intense mydriatic effect of 2% ibopamine with no changes in refraction, visual acuity or A-scan ultrasound biometric variables. The drug has no effect on intraocular pressure in healthy subjects, but induces a significant hypertensive effect in patients with initial glaucoma. This characteristic could be used for early diagnosis of primary open-angle glaucoma.

Adrenergic alpha-Antagonists↗

Morphine-induced pupillary fluctuation: physiological evidence against selective action on the Edinger-Westphal nucleus.

In the rat, the predominant pupillary effect of morphine sulfate (30 mg/kg, i.p.) is mydriasis, interrupted periodically by miotic excursions. Using infrared video pupillometry, respirometry and EEG recording, we had previously reported that miotic excursions are always correlated with the onset of EEG bursting, while mydriatic excursions are preceded by respiratory slowing and correlated with EEG burst cessation. In the current study, we found that during morphine-induced EEG bursting and related miosis, delivery of an alerting stimulus to the rat caused an immediate conversion sequence composed of respiratory slowing, burst cessation and mydriatic excursion. We also simulated morphine-induced EEG bursting through non-opioid means by delivering kindling electrical stimuli to the amygdala. When the stimulus was given during morphine-induced mydriasis, the stimulus-induced bursting resulted in a miotic excursion identical to spontaneous morphine-induced miotic excursions. These results indicate 1) that the reticular activating system is involved in morphine-induced mydriatic excursions and 2) that EEG bursting is not simply correlated with morphine-induced miotic excursions, but causes them. Collectively, these results strengthen our hypothesis that the Edinger-Westphal nucleus is not the site in which the selective, receptor-mediated pupillary effects of morphine are initiated.

Amygdala↗

Do junior house officers routinely test visual acuity and perform ophthalmoscopy?

UNLABELLED: Our objective was to assess junior house officer (JHO) practice of visual acuity testing and ophthalmoscopy in clerking patients. DESIGN: Cross-sectional questionnaire-based study using a standardised structured interview technique. SETTING: A Scottish university teaching hospital employing 65 JHOs. PARTICIPANTS: All medical and surgical JHOs from this hospital were interviewed over a three month period. MAIN OUTCOME MEASURES: Questionnaire-based data on the subjective responses studying current practice of visual acuity testing, and direct ophthalmoscopy with and without topical mydriatics. RESULTS: 18.5% and 4.6% of participants perform daily ophthalmoscopy and visual acuity testing respectively. Most do not routinely use the Snellen chart (80.0%) or topical mydriatics during ophthalmoscopy (75.4%). JHOs claimed these were not easily available in the wards. CONCLUSIONS: The majority of JHOs fail to test visual acuity or perform ophthalmoscopy in clerking patients. This study highlights the poor availability of Snellen charts, functioning ophthalmoscopes, and topical mydriatics in the wards. This warrants further investigation.

Hospitals, Teaching↗

Agents for the treatment of overactive detrusor. VI. Synthesis and pharmacological properties of acetamide derivatives bearing cyclic amines in N-substituents.

With the aim of improving of the efficacy and decreasing the side effects of oxybutynin (1), N-[(tetrahydro-3- or 4-pyridyl)methyl]-, N-(4-piperidyl)-, and N-(3- or 4-piperidylalkyl)-2-hydroxyacetamides (3a-n, 4a-g) and the related carboxamides (3o-r, 4h-k, 13', 17) were synthesized and evaluated for inhibitory activity against urinary bladder rhythmic contraction in rats and for mydriatic activity in rats. Some of these compounds were superior to oxybutynin in both inhibitory activity against bladder contraction and selectivity between inhibitory activity against bladder contraction and mydriatic activity. Among them, N-[(1,2,3,6-tetrahydro-4-pyridyl)methyl]- and N-[(1,2,3,6-tetrahydro-1-methyl-4-pyridyl)methyl]-2-hydroxy-2,2- diphenylacetamide (3e, 3f) exhibited the most potent inhibitory activity against bladder contraction (ED30 = 0.005 and 0.003 mg/kg i.v., respectively). Judging from the effect of 3e on detrusor contraction in vitro in guinea-pigs, it appeared that the inhibitory activity of 3e against bladder contraction in vivo was related mainly to its inhibitory activity against detrusor contraction in vitro induced with carbachol (antimuscarine-like activity). The selectivity (20-fold) of 3e between inhibitory activity against bladder contraction and mydriatic activity was greatly superior to that (0.48-fold) of oxybutynin. Compound 3e was synthesized by debenzylation (method E or F) of the corresponding N-[[1-(4-methoxybenzyl)-tetrahydro-4-pyridyl]methyl] derivative (3k), which was prepared by acylation (method B) of the corresponding (tetrahydro-4-pyridyl)methylamine (7k) or by reduction (method D) of the corresponding pyridinium chloride (14k) with NaBH4.

Acetamides↗

Separate neural mechanisms mediate sufentanil-induced pupillary responses in the cat.

The pharmacologic characteristics of a highly selective mu receptor agonist, sufentanil, were studied on the cat's pupillary responses (size, light reflex and fluctuations) measured with an infrared video pupillometer. The pupillary effects of sufentanil were also compared with those of morphine and clonidine, known mydriatics in the cat. Sufentanil (0.3-10 micrograms/kg i.v.) dose-dependently increased pupillary size and decreased light reflex and fluctuations. Naltrexone (10 micrograms/kg i.v.) pretreatment shifted the dose-response curve to the right by a factor of 26 for pupillary size, 9.5 for light reflex and 7.2 for fluctuations (nonvalid bioassay). Equivalent mydriatic doses of sufentanil (1 micrograms/kg), morphine (0.5 mg/kg) and clonidine (10 micrograms/kg) produced divergent effects on the light reflex and fluctuations. At these doses, morphine was more effective than sufentanil in inhibiting fluctuations. Clonidine was a more potent inhibitor of fluctuations but significantly enhanced the light reflex. Sufentanil (compared with morphine in a previous study) was 298 times more potent than morphine as a mydriatic, 100 times more potent in inhibiting the light reflex, and only slightly more potent in inhibiting fluctuations. These results indicate that separate neural mechanisms control the three pupillary components and that mu opioid receptors are more involved in mediating opiate-induced mydriasis than in inhibiting the light reflex and fluctuations in the cat.

Analgesics, Opioid↗