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PubMedDate not supplied

Pharmacological response data for comparative bioavailability studies of chlorpromazine oral dosage forms in humans: I. Pupilometry.

Owing to the insensitivity of even the presently best chemical or radiological assay procedures, it is not feasible to perform comparative bioavailability studies of chlorpromazine oral drug products using blood or urine sampling; this is particularly the case for oral doses below 100-150 mg/70 kg. In contrast, the use of temporal miotic response data, which correlates with blood levels of unchanged drug, permits dose-response vs time profiles to be recorded with oral dose levels as low as 5-10 mg/70 kg. The monitoring of pupilometric data in up to 16 human volunteers demonstrated a sensitivity to both extents and rates of chlorpromazine bioavailability and revealed differences to exist between liquid and solid oral dosage forms of chlorpromazine.

Adult↗
PubMedDate not supplied

Pupil size and the steady-state pattern reversal visual evoked cortical potential.

30 eye-healthy subjects were being examined, with their pupils reacting, mydriatic or miotic. Their pattern reversal visual evoked cortical potentials (PRVECP's) were recorded under steady-state conditions. Test conditions allowed establishing a statistically significant influence of pupil size on the PRVECP.

Cerebral Cortex↗
PubMed1977

Thymoxamine and intraocular pressure.

Topical treatment with 1% thymoxamine produces in rabbit and human eyes a small but real miotic and tension-lowering effect. The latter is more evident using two different models of experimental ocular hypertension in rabbits. In human open-angle glaucoma eyes, tonographic measurements indicate that the outflow facility is left unchanged by the drug.

Animals↗
PubMed1975

Pupillometric studies in the beagle dog.

A method of measuring pupillary diameter in the dog using a Kowa RC-2 fundus camera, to which an eyepiece graticule had been fitted, is described. Pupil diameter was measured either directly by reading off from the calibrated graticule or from photographs. The pupillary diameters of 105 (53 male, 52 female) untreated English beagles aged between 8 and 32 months were measured under light intensities of 150-200 lux and 1000-1400 lux. Mydriatic and miotic pupillary diameters were measured in 62 male and 80 female dogs. Time-effect curves were plotted for two groups of 5 beagles receiving 75 mug/kg or 175 mug/kg atropine and 100 mug/kg or 300 mug/kg propantheline intravenously. The dose-effect curve for propantheline was found to be linear. A dose of 109 (97-121) mug/kg propantheline increased pupillary diameter by 3 mm, 20 min after administration. The time- and dose-effect curves, the significant sex differences and age dependency seen in this study indicate both a high degree of accuracy and the suitability of both of these methods for use in pharmacological and toxicological studies.

Age Factors↗
PubMed1997

Effects of acetylcholine, carbachol, and mannitol on rabbit corneal endothelial function as assessed by corneal deturgescence.

BACKGROUND: Anterior chamber miotic solutions are widely used in ophthalmic surgery to induce pupillary contraction. We investigated whether the acetylcholine, carbachol, or mannitol present in perfusing solutions can affect corneal endothelial function. METHODS: Freshly dissected deepithelized rabbit corneas were mounted in a Dikstein-Maurice chamber at 36 degrees C. The endothelial sides were perfused with six solutions: (A) 55 mM (1%) acetylcholine Cl plus modified balanced salts; (B) control for A, with acetylcholine Cl replaced by sucrose; (C) 0.55 mM (0.01%) carbachol Cl plus balanced salts; (D) balanced salts solution (BS; control for C); (E) 3% mannitol plus modified balanced salts; and (F) modified balanced salts (control for E, with mannitol replaced by sucrose). Corneal thickness was followed for 3 h in each experiment. The effect of solution E did not differ from that of solution F. RESULTS: The carbachol-containing solution produced a small increase in corneal thickness compared to the control solution, while the acetylcholine-containing solution resulted in corneal thickness lower than that in control preparations. CONCLUSION: From these data, acetylcholine is harmless to the endothelium, and may actually stimulate its fluid pump mechanism. Carbachol, on the other hand, appears to have a detrimental effect.

Acetylcholine↗
PubMed2004

The effects of pupil size on the multifocal electroretinogram.

This is an investigation of the effect of changing the pupil diameter on the P1 amplitude and latency of the multifocal electroretinogram (mfERG). MfERGs were recorded using a custom built wide field electrophysiological system. An array of 61 empirically scaled hexagons was used to stimulate the visual field. The duration of overall recording period was 8 min, segmented into 16 intervals each lasting 30 s. A combination of mydriatics and miotics were used to pharmacologically alter the pupil size and diameters between 1 and 10 mm were measured. There was a reduction in mfERG P1 amplitude in some cases greater than 50% (mfERG P1 amplitude 53 nV at 8 mm to 25 nV at 1 mm), with a change in pupil diameter of 7 mm. The mfERG P1 latency increased in some cases by as much as 8 ms in the central 40 degrees (mfERG P1 latency 39 ms at 8 mm to 47 ms at 1 mm). These results suggest that pupil size has significant effects on mfERG P1 amplitude and latency.

Electroretinography↗
PubMed1981

Miosis from echothiophate in patients with total oculomotor nerve paralysis from intracranial abnormalities.

Seven subjects with intracranial pathologic abnormalities received bilateral instillations of echothiophate. Six had unilateral third (oculomotor) nerve paralysis; one had unilateral third nerve paresis. All 14 eyes became miotic. Miosis was greater in the defective eye in three subjects, greater in the normal eye in two subjects, and equal in two subjects. The neurons originating in the ciliary ganglion and terminating on the sphincter pupillae muscle may exhibit spontaneous activity. Echothiophate, by preventing acetylcholine hydrolysis, may have allowed this transmitter to accumulate and to produce miosis. The amount of maximal miosis in the abnormal eye after bilateral instillation of echothiophate drops may vary from that in the normal eye. The causes of this variation include denervation supersensitivity of the sphincter pupillae muscle, partial paresis of the dilator pupillae muscle, and increased drug penetration in the abnormal eye.

Adult↗
PubMedDate not supplied

Quantification on the pinhold effect.

Can the pinhold principle be practically applied to solving the problem of providing useful vision for aphakics without resorting to aphakic spectacles? The authors have experimentally quantified the pinhold effect and concluded that the pinhold, successfully produced by miotics in certain patients or by a thin, dyed contact lens, may have clinical value.

Contact Lenses, Hydrophilic↗
PubMed1995

Pupillary and cardiovascular responses to the cold-pressor test.

Little is known about the structures and mechanisms involved in the autonomic response to sensory and nociceptive stimulation. In this study, we recorded simultaneously pupil diameter, blood pressure, heart rate and pain levels during a cold-pressor test in 10 healthy subjects. The aim was to evaluate the different components of the Autonomic Nervous System involved in the response to a thermal-painful stimulus. A biphasic pupillary response was observed: an initial, short-lasting mydriasis, followed by a miotic phase, this latter characterized by rhythmic fluctuations of pupil diameter. The blood pressure response was monophasic with a moderate increase observed from the second minute of the test. Pain intensities remained stable on medium-high levels throughout the test. The topical application of thymoxamine and homatropine clarified some aspects of the pupillary response. The systemic administration of naloxone suggested a role of opiates in the modulation of pupillary and cardiovascular response to the cold-pressor test.

Administration, Topical↗
PubMed1993

CGRP(8-37) and CGRP(32-37) contract the iris sphincter in the rabbit eye: antagonism by spantide and GR82334.

The effects of intracameral injections of CGRP(8-37) and CGRP(32-37) on pupil diameter and blood-aqueous barrier have been investigated in rabbits. The rabbits, which were pretreated with indomethacin and a muscarinic antagonist (biperiden), responded with miosis to both CGRP fragments. CGRP(8-37) was much more potent than CGRP(32-37) but one order of magnitude less potent than substance P. Nerve blockade with tetrodotoxin did not affect the response, indicating a direct effect on the iris sphincter muscle. Pre-treatment with the unselective tachykinin receptor antagonist spantide or the NK1 receptor selective antagonist GR82334 caused a rightward shift of the dose-response curves for both fragments, while the CCK receptor antagonist loxiglumide had no inhibitory effect. Neither of the fragments induced any marked leakage of Evans blue into the aqueous humor indicating that there was no agonistic interaction with CGRP receptors in the eye. We conclude that CGRP(8-37) and CGRP(32-37) are miotic agents in the rabbit eye, possibly by acting as neurokinin receptor agonists.

Animals↗
PubMed2006

Phase transition water-in-oil microemulsions as ocular drug delivery systems: in vitro and in vivo evaluation.

Microemuslion (ME)-based phase transition systems were evaluated for ocular delivery of pilocarpine hydrochloride (model hydrophilic drug). These used two non-ionic surfactants, sorbitan mono laurate and polyoxyethylene sorbitan mono-oleate with ethyl oleate (oil component) and water. These systems undergo phase change from ME to liquid crystalline (LC) and to coarse emulsion (EM) with a change in viscosity depending on water content. This study selected five formulations containing aqueous phase at 5% (w/w) (ME 5%), 10% (w/w) (ME 10%), 26% (w/w) (LC), 85% (w/w) (O/W EM) and 100% (solution) with the model drug at 1% (w/w). Incorporation of pilocarpine hydrochloride did not affect the phase behaviour. The viscosity was increased initially with dilution from ME 5% to ME 10% then LC, indicating structuring of the system, before being reduced in the EM formulation. Drug release depended on the viscosity with lower release rates obtained from formulations with high viscosity. The miotic response and duration of action were greatest in case of ME and LC formulations indicating high ocular bioavailability. Thus, phase transition ME is promising for ocular drug delivery as it provides the fluidity with its viscosity being increased after application increasing ocular retention while retaining the therapeutic efficiency.

Animals↗
PubMed2006

Phenylephrine and pilocarpine eye drop test for dementia with Lewy bodies and Alzheimer's disease.

Pupillary response test using dilute phenylephrine, a sympathetic agonist, and dilute pilocarpine, a cholinergic agonist, were performed in 24 patients with dementia with Lewy bodies (DLB), 40 patients with Alzheimer's disease (AD), and 23 normal elderly subjects. The mydriatic response to 0.5% phenylephrine was significantly greater in the DLB group than in the AD and control groups. The mydriatic change correlated inversely with the reduction in cardiac 123I-metaiodobenzylguanidine uptake. In contrast, miotic response to 0.0625% pilocarpine was significantly greater in the DLB and AD groups than in the control group. The pupil assay using combined phenylephrine and pilocarpine eye drop test may be useful in the detection of patients with DLB and AD and in distinguishing between them.

3-Iodobenzylguanidine↗
PubMed1980

Early-onset accommodative esotropia.

Twenty-one patients had esotropia diagnosed before age 12 months. In all of these patients esotropia was eliminated, at least initially, by antiaccommodative therapy consisting of either full hypermetropic spectacles or miotics, or both. Clinical findings evaluated in these patients were comparable to similar clinical factors studied in a larger series of patients with accommodative esotropia, most with onset after 12 months of age. In approximately 50% of these patients early-onset accommodative esotropia deteriorated to a nonaccommodative esotropia that required surgery despite aggressive antiaccommodative therapy. All but one of the surgically treated patients continued to need hypermetropia spectacles postoperatively to maintain alignment.

Accommodation, Ocular↗
PubMedDate not supplied

Effect of decreased retinal illumination on frequency doubling technology.

PURPOSE: To investigate the effect of changes in retinal illumination on Frequency Doubling Technology (FDT). METHODS: Five eyes, of 5 adults who were free from identifiable ocular pathology, were examined using the Snellen chart and the Pelli-Robson chart, conventional automated perimetry, and the full threshold N-30 program of FDT. Each test was performed with and without a 0.9, 1.5, or 2.4 log unit neutral-density (ND) filter placed before the eye. Furthermore, the influence of pupil diameter on FDT test results was compared after treatment with pilocarpine or cyclopentolate with the influence of ND filters. RESULTS: All tests showed a decrease in sensitivity with decreasing retinal illumination. Frequency Doubling Technology showed an especially pronounced and significant decrease in sensitivity. The maximum mean threshold difference in FDT results with ND filter was 31.2 dB while that with the Humphrey Field Analyzer and the Pelli-Robson chart were 13.3 dB and 0.66 log contrast, respectively. The mydriatic state of the pupil increased the sensitivity of FDT and the miotic state decreased it to about the same extent as the the 0.9 ND filter. CONCLUSION: The change in retinal illumination has more impact on FDT than on spatial contrast tests and conventional automated perimetry. It is important to take this into account in evaluating FDT results.

Adaptation, Ocular↗
PubMed1981

Adhesions to manufacturer's trademark on the surface of a posterior chamber lens.

A case is reported in which posterior synechiae to the manufacturer's trademark on the surface of a Shearing intraocular lens were noted ten days after the implantation of the lens. After a short course of low-concentration miotic therapy, the adhesions were broken. We concluded that irregularities on the surface of the lens, such as a manufacturer's trademark, provide a focus for synechiae. We suggest that intraocular lens manufacturers refrain from providing such identification on their products.

Aged↗
PubMed1986

The effect of pilocarpine on the visual field in normals.

Despite generalized consensus that pilocarpine-induced miosis results in some degree of visual field constriction, studies describing the predictability of this occurrence, as well as the nature of the field defects that may be seen, have not been undertaken. We studied 20 normal subjects, ranging in age from 24 to 57 years. Baseline refraction, pupillary measurements, and visual fields were performed in both eyes on a standardized Goldmann perimeter with the I-2e, I-3e, and I-4e test objects. Pilocarpine 2% was then instilled into the study eye and the field repeated at 30 and 120 minutes. An IBM PC computer program, designed by the authors, was used to calculate the area contained within each isopter. The probability of visual field constriction at 30 and 120 minutes after instillation of pilocarpine was found to be significant, especially with pupillary diameters of 2 mm or less. The I-2e isopter was most sensitive to miosis. Visual field constriction persisted with correction of ciliary spasm induced myopia, suggesting that miosis, especially when marked, can independently alter the visual field. The clinician, then, should make every effort to control visual field testing conditions in glaucoma patients on miotics to allow reliable serial comparisons.

Adult↗
PubMed1992

Foreshortening of the inferior conjunctival fornix associated with chronic glaucoma medications.

The authors designed a device to measure the depth of the inferior conjunctival fornix at the slit lamp using topical anesthesia. The fornices of 179 glaucoma patients receiving topical medications for glaucoma and 420 control subjects who had no history of ocular disease were measured. These measurements were age-stratified by decade. A significant foreshortening of the inferior conjunctival fornix was found with aging (P less than 0.01). Patients in their sixth through ninth decades using miotics for 3 years or longer and patients using nonmiotic agents for 3 years or longer exhibited significant foreshortening of the inferior fornix when compared with age-stratified (by decade) control subjects (P less than 0.01). These observations suggest that increasing age and topical medications for glaucoma, or the preservatives, used for 3 years or longer, are independently associated with conjunctival shrinkage.

Adolescent↗
PubMed1997

Expanding forces in aqueous outflow pathways of a nonaccommodating mammal: an approach via comparative dynamic morphology.

Six dog eyes were fixed by intracameral perfusion of fixative at pressures of 0, 5, 10, 15, 20, and 25 cm of water. Eight dog eyes were fixed after the injection in both ocular chambers of a number of cholinergic agents, either singly or in combination. Under the effect of miotics and under increased ocular pressure, the aqueous pathways expand. An analysis of the forces involved in expansion of the exit pathways reveals the primary role of the detached ciliary body in nonaccommodating mammals. Two mechanisms appear to have been conserved in dogs and humans throughout evolution. The first is an active mechanism: the opening of the trabecular meshwork as a consequence of the combined action of the ciliary muscle and the iris and its insertion ligaments-the uveoscleral trabeculate-in dogs, and the longitudinal portion of the ciliary muscle and scleral spur in humans. The second is a passive mechanism: the infundibular arrangement of the drainage structures assisted by the traction on the zonular ligament of the lens, which responds to an increase in pressure in the anterior chamber by widening the pathways, thus favoring outflow.

Accommodation, Ocular↗