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PubMed1991

Abuse potential and pharmacological comparison of tramadol and morphine.

The purpose of the study was to assess the abuse potential of the opioid analgesic tramadol. Tramadol (75, 150 and 300 mg), morphine (15 and 30 mg) and placebo were tested intramuscularly in volunteer non-dependent opiate abusers. Subjective, behavioral and miotic changes were assessed prior to dosing and intermittently for 12 h after drug administration. Morphine produced typical subjective effects, opiate identifications and miosis. Tramadol 75 and 150 mg were not different from placebo. Although tramadol 300 mg was identified as an opiate, it produced no other morphine-like effects. These findings suggest that tramadol has a low abuse potential by the parenteral route.

Adult↗
PubMed1979

Jaborandi: an interdisciplinary appraisal.

In spite of many references to Pilocarpus Jaborandi Holmes in ethnological and botanical sources and suggestions of its employment for a variety of diseases, it has not been possible to pin down the use of its leaves to any particular purpose amongst South American Indians. While the medically important jaborandis are species of Pilocarpus, it is true that this vernacular name is commonly applied to other rutaceous and numerous piperaceous plants as well. The introduction of jaborandi leaves to western medicine goes back to 1873, when Symphronio Coutinho went to Europe, taking with him samples of the leaves. The copious sweating and salivation brought about by the leaves attracted the attention of French physicians. Soon jaborandi leaves were being employed in the treatment of many diseases. In 1875, Hardy and Gerrard independently discovered the alkaloid pilocarpine. Most therapeutic applications of jaborandi leaves and pilocarpine fell into disuse and were discontinued. What remained was the use of the latter in ophthalmology, where it had been introduced as a miotic by Weber in 1876. The mixture of pilocarpine and another natural product, physostigmine, remains to this day one of the mainstays in ophthalmology.

Alkaloids↗
PubMed1996

QRI, a retina-specific gene, encodes an extracellular matrix protein exclusively expressed during neural retina differentiation.

Neural retina development results from growth arrest of neuroectodermal precursors and differentiation of postmitotic cells. The QRI gene is specifically expressed in Müller retinal glial cells. Its expression coincides with the stage of withdrawal from the cell cycle and establishment of differentiation and is repressed upon induction of retinal cell proliferation by the v-src gene product. In this report, we show that the QR1 gene encodes several glycosylated proteins that are secreted and can either associate with the extracellular matrix or remain diffusible in the medium. By using pulse-chase experiments, the 100-103 kDa forms seem to appear first and are specifically incorporated into the extracellular matrix, whereas the 108 and 60 kDa polypeptides appear later and are detected as soluble forms in the culture medium. We also report that expression of the QR1 gene is developmentally regulated in the chicken. Its mRNA is first detectable at embryonic day 10, reaches a maximal level at embryonic day 15 and is no longer detected at embryonic day 18. Immunolocalization of the QR1 protein in chicken retina sections during development shows that expression of the protein parallels the differentiation pattern of post-miotic cells (in particular Müller cells and rods), corresponding to the two differentiation gradients in the retina: from the ganglion cell layer to the inner nuclear layer and outer nuclear layer, and from the optic nerve to the iris. At embryonic day 10, expression of the QR1 protein(s) is restricted to the optic nerve region and the inner nuclear layer, colocalizing with Müller cell bodies. As development proceeds, QR1 protein localization spreads towards the iris and towards the outer nuclear layer, following Müller cell elongations towards the photoreceptors. Between embryonic days 16 and 18, the QR1 protein is no longer detectable in the optic nerve region and is concentrated around the basal segment of the photoreceptors in the peripheral retina. Our results suggest a role for the QR1 gene product in the process of growth arrest and establishment of photoreceptor differentiation.

Animals↗
PubMed2006

Modulation of the central nervous effects of levomethadone by genetic polymorphisms potentially affecting its metabolism, distribution, and drug action.

AIM: Our aim was to judge the importance of candidate pharmacogenetic modulators of the central nervous effects of levomethadone by both magnitude of the modulatory effect and frequency of the mutation to assess the utility of genotyping for clinical levomethadone therapy in a random sample of subjects that, by distribution of genotypes, resembled the clinical setting. METHODS: Candidate pharmacogenetic modulators were polymorphisms reported to be of functional consequence and therefore potentially important for metabolism, distribution, or pharmacodynamic action of levomethadone, consisting of genes coding for cytochrome P450 (CYP) 2B6 and 3A, as well as 1A2, 2C8, 2C9, 2C19, and 2D6, for P-glycoprotein (ABCB1), and for mu-opioid receptors (OPRM1). The central nervous effects of levomethadone were investigated by means of measuring pupil size in a random sample of 51 healthy volunteers for 9 hours after oral administration of 0.075 mg/kg levomethadone. Plasma concentrations of levomethadone and its metabolites were assessed concomitantly, and to judge the role of metabolites, the affinities of levomethadone and its metabolites at mu-opioid receptors were estimated by use of displacement of the selective mu-opioid receptor agonist [(3)H]-DAMGO ((3)H-[D-Ala(2),N-MePhe(4),Gly-ol(5)]-enkephalin). RESULTS: Pupil size decreased to -41.8% +/- 9.6% from baseline at 3.5 +/- 1.1 hours after levomethadone administration. Miosis was still manifest to a lower degree (-25.1% +/- 12.3%) at the end of the observation period. In carriers of the variant 118G allele (118A>G single-nucleotide polymorphism) of the mu-opioid receptor gene (OPRM1), levomethadone had a 1.74 times (95% confidence interval, 1.4-2.2 times) lower miotic potency (P < .001) as compared with noncarriers (concentration at half-maximum effects, 52.3 nmol/L; 95% confidence interval, 36.7-66.2 nmol/L). The maximum percent decrease in pupil diameter from baseline was 44.9% +/- 7.6%, 33% +/- 6.5%, and 24% +/- 6.9% for carriers of the OPRM1 118AA, AG, and GG genotypes, respectively (P < .001 for AG and GG versus wild type, without significant differences between AG and GG). Other candidate polymorphisms in the ABCB1 or in CYP genes had no significant influence on the effects of levomethadone, either because of lack of functional consequences or because of their low allelic frequency. The metabolites of levomethadone did not contribute to the effects as indicated by low metabolite plasma concentrations and their 120- to 1300-fold lower affinities at mu-opioid receptors as compared with levomethadone. CONCLUSIONS: Among polymorphisms in OPRM1, ABCB1, and CYP genes previously associated with functional consequences in a different context, the most important pharmacogenetic factor modulating the short-term effects of levomethadone is a polymorphism (OPRM1 118A>G) affecting mu-opioid receptors.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Profiling the subjective, psychomotor, and physiological effects of tramadol in recreational drug users.

Tramadol is a mu opioid agonist that also inhibits the reuptake of norepinephrine and serotonin. Because non-medical use of prescription opioids, including tramadol, has increased in the U.S. over the last several years, we sought to profile its subjective, psychomotor, and physiological effects in recreational drug users. Twenty-two subjects received placebo, 50 or 100 mg tramadol, morphine, or 2 mg lorazepam in a randomized, crossover, double-blind design. The last 12 subjects in the study received 25 mg morphine, a dose that is putatively equianalgesic to 100 mg tramadol. In these subjects, morphine induced miosis and several other mu agonist subjective effects; 100 mg tramadol increased "feel drug effect" and drug liking ratings, and decreased pupil size, but the miotic effect was not statistically significant. Lorazepam, but neither tramadol nor morphine, impaired psychomotor performance. When the placebo, tramadol, and lorazepam data from all 22 subjects were analyzed, 100 mg tramadol induced miosis, and several subjective effects were increased significantly, including ratings of drug liking and "want to take again." The present results indicating that a clinically-prescribed dose of oral tramadol has abuse liability-related effects in recreational drug users suggest the need for further abuse liability testing of the oral formulation in opioid abusers.

Adult↗
PubMed2005

Poly(amidoamine) dendrimers as ophthalmic vehicles for ocular delivery of pilocarpine nitrate and tropicamide.

The purpose of this study was to determine the influence of a controlled incremental increase in size, molecular weight and number of amine, carboxylate and hydroxyl surface groups in several series of poly(amidoamine) (PAMAM) dendrimers for controlled ocular drug delivery. The duration of residence time was evaluated after solubilization of several series of PAMAM dendrimers (generations 1.5 and 2-3.5 and 4) in buffered phosphate solutions containing 2 per thousand (w/v) of fluorescein. The New Zealand albino rabbit was used as an in vivo model for qualitative and quantitative assessment of ocular tolerance and retention time after a single application of 25 microl of dendrimer solution to the eye. The same model was also used to determine the prolonged miotic or mydriatic activities of dendrimer solutions, some containing pilocarpine nitrate and some tropicamide, respectively. Residence time was longer for the solutions containing dendrimers with carboxylic and hydroxyl surface groups. No prolongation of remanence time was observed when dendrimer concentration (0.25-2%) increased. The remanence time of PAMAM dendrimer solutions on the cornea showed size and molecular weight dependency. This study allowed novel macromolecular carriers to be designed with prolonged drug residence time for the ophthalmic route.

Amines↗
PubMed2004

Eccentric capsulorhexis and postoperative dysphotopsia following phacoemulsification.

We report a case of troublesome visual symptoms or dysphotopsia in a 68-year-old patient after right phacoemulsification and implantation of a 3-piece AcrySof(R) MA60BM acrylic intraocular lens (IOL) (Alcon) in the capsular bag. The patient described multiple horizontal streaks in dim lighting conditions with light sources in the right temporal visual field. The anterior capsulorhexis was eccentric, leaving the nasal optic edge and site of polypropylene haptic insertion uncovered by the semi-opaque anterior capsule and the probable source of the flare images. Miotic therapy was poorly tolerated and IOL exchange declined. The case illustrates the importance of creating a central capsulorhexis smaller than the IOL optic to reduce the risk photic phenomena and edge effect with square-edged IOLs.

Aged↗
PubMed2006

Angle closure in highly myopic eyes.

PURPOSE: Patients with angle-closure glaucoma and high myopia are uncommon. We evaluated the clinical characteristics of all patients with angle closure and high myopia in our database and propose possible mechanisms for angle closure in these atypical patients. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Our database of 17938 patients was searched for patients with myopia of spherical equivalent of more than -6.0 diopters and angle closure. Data recorded included age at time of initial consultation, gender, slit-lamp examination results, gonioscopy results, biometric parameters, ultrasound biomicroscopy results (from 1993 onward), clinical diagnosis, and therapy. RESULTS: Twenty patients (11 females, 9 males) were identified. Mean age at the time of consultation was 52.9+/-19.3 years. Angle-closure diagnoses included primary pupillary block (9 patients), pupillary block in an eye with keratoconus (1 patient), pupillary block secondary to a pupillary membrane associated with retinopathy of prematurity (1 patient), plateau iris configuration and syndrome (3 patients), phacomorphic glaucoma in Weill-Marchesani syndrome (2 patients), malignant glaucoma secondary to a scleral buckle (2 patients), miotic-induced angle closure (1 patient), and Marfan syndrome (1 patient). CONCLUSIONS: Angle closure can occur in eyes with high myopia. Causes of angle closure other than relative pupillary block are more common than in the general angle-closure glaucoma population. Careful gonioscopy accompanied by biometry and ultrasound biomicroscopy can lead to the correct diagnosis and individualized management in these eyes.

Adult↗
PubMedDate not supplied

Optics of wide-angle panoramic viewing system-assisted vitreous surgery.

The purpose of the article is to describe the optics of the contact wide-angle lens system with stereo-reinverter for vitreous surgery. A panoramic viewing system is made up of two components; an indirect ophthalmoscopy lens system for fundus image viewing, which is placed on the patient's cornea as a contact lens, and a separate removable prism system for reinversion of the image mounted on the microscope above the zooming system. The system provides a 104 degrees field of view in a phakic emmetropic eye with minification, which can be magnified by the operating microscope. It permits a binocular stereoptic view even through a small pupil (3 mm) or larger. In an air-filled phakic eye, field of view increases to approximately 130 degrees. The obtained image of the patient's fundus is reinverted to form true, erect, stereoscopic image by the reinversion system. In conclusion, this system permits wide-angle panoramic view of the surgical field. The contact lens neutralizes the optical irregularities of the corneal surface and allows improved visualization in eyes with irregular astigmatism induced by corneal scars. Excellent visualization is achieved in complex clinical situations such as miotic pupils, lenticular opacities, and in air-filled phakic eyes.

Humans↗
PubMed2001

Bilateral neurotrophic keratopathy complicating Vidian neurectomy.

PURPOSE: To present a case of bilateral neurotrophic keratopathy with miosis after bilateral Vidian neurectomy for vasomotor rhinitis. METHODS: Observational case report. RESULTS: A 68 year-old man presented with irritation and blurred vision in both eyes 2 weeks after bilateral Vidian neurectomy. Slit-lamp examination revealed a large epithelial defect, typical of neurotrophic keratopathy, in the inferior two-thirds of cornea in both eyes. Corneal sensitivity test with a Cochet-Bonnet anesthesiometer and electrical study of the blink reflex indicated bilateral trigeminal dysfunction. Both pupils were miotic, and tests with hydroxyamphetamine 1% and epinephrine 0.1% showed postganglionic sympathetic nerve damage. The corneal epithelial defects healed after 2 months of treatment with systemic prednisolone, vitamin B(12) and tarsorrhaphy. CONCLUSION: Neurotrophic keratopathy associated with dry eye syndrome may be a serious complication of Vidian neurectomy.

Aged↗
PubMed2003

Combined phacoemulsification, intraocular lens implantation, and vitrectomy for eyes with coexisting cataract and vitreoretinal pathology.

PURPOSE: To report the preoperative, intraoperative, and postoperative outcomes of combining phacoemulsification and posterior chamber intraocular lens (IOL) implantation with pars plana vitrectomy in eyes with significant cataract and coexisting vitreoretinal pathology. DESIGN: Retrospective, consecutive, interventional case series. METHODS: Charts of patients undergoing combined procedures at the Wilmer Ophthalmologic Institute between March 1995 and May 2000 were reviewed. RESULTS: In all, 122 eyes of 111 patients were identified. Patient ages ranged from 27 to 89 years (mean 65). Forty-three eyes had diabetic retinopathy; 11 had undergone vitrectomy previously. Macular pathology (hole, membrane, choridal neovascularization) was present in 69 eyes. The most common indications for surgery were diabetic vitreous hemorrhage, macular hole, epiretinal membrane, and retinal detachment. In all cases, phacoemulsification and IOL implantation were performed before vitreoretinal surgery. Preoperative vision ranged from 20/30 to light perception and postoperative vision ranged from 20/20 to no light perception. In 105 patients vision improved, in 7 there was no change, and in 10 vision decreased. Postoperative complications included opacification of the posterior capsule, increased intraocular pressure, corneal epithelial defects, vitreous hemorrhage, retinal detachment and iris capture by the IOL. CONCLUSIONS: Combined surgery is a reasonable alternative in selected patients. Techniques that may simplify surgery and reduce complications include: careful, limited, curvilinear capsulorhexis; in-the-bag placement of IOLs; use of IOLs with larger optics; suturing of cataract wounds before vitrectomy; use of miotics and avoidance of long-acting dilating drops in patients with intravitreal gas; and use of wide-field viewing systems.

Adult↗
PubMed1997

Latanoprost for uncontrolled glaucoma in a compassionate case protocol.

PURPOSE: To evaluate the ocular hypotensive response of latanoprost 0.005% administered as adjunctive therapy in patients with glaucoma who were receiving maximal tolerated medical therapy. METHODS: Consecutive patients entering a latanoprost compassionate clinical trial were enrolled at two sites. Latanoprost 0.005% was administered as a single drop between 6 and 8 PM, and all other medications were continued. Intraocular pressure was measured between 2 and 4 PM. Responders were defined as having a reduction in intraocular pressure of at least 20% from baseline. RESULTS: In 160 eyes of 160 patients, mean baseline intraocular pressure +/- SD was 23.3 +/- 6.9 mm Hg. Intraocular pressure was significantly reduced compared with baseline measurements (P < .01) with mean intraocular pressure measurement reductions of 4.1 +/- 5.2, 4.0 +/- 6.3, and 3.7 +/- 4.2 mm Hg at the 1-, 3-, and 6-month intervals, respectively. A reduction in intraocular pressure of at least 20% was observed in 64 (44.4%) of 144 patients, 46 (43.0%) of 107 patients, and 10 (32.3%) of 31 patients at the 1-, 3-, and 6-month visits, respectively. A 40% reduction in intraocular pressure was observed in 18 (12.5%) of 144 and nine (8.4%) of 107 patients at 1 and 3 months, respectively. Mean reduction in intraocular pressure was similar in the miotic and nonmiotic groups (P > .4 at all intervals). Eight patients (5.0%) developed ocular allergy or irritation necessitating cessation of latanoprost therapy. CONCLUSION: Latanoprost 0.005% may provide significant further intraocular pressure reduction in patients already receiving maximal tolerated medical therapy.

Adolescent↗
PubMed1992

High-pass resolution perimetry in eyes with ocular hypertension and primary open-angle glaucoma.

We analyzed the results of high-pass resolution perimetry on normal eyes, eyes with ocular hypertension, and eyes with primary open-angle glaucoma. The subjects were matched for age and lens density. We controlled for refraction, visual acuity, pupil size, miotic medications, and learning effects. Under these conditions the glaucomatous eyes showed a significant reduction in overall resolution threshold compared to both normal (P less than or equal to .01) and hypertensive eyes (P less than .01). The hypertensive eyes were not significantly different from normal. Standard increment threshold fields and high-pass resolution visual fields had an agreement of abnormality of 67%. Resolution perimetry showed a 92% agreement with standard perimetry in the location of the defect, when the defect was apparent on both tests. These results indicated that resolution perimetry may be useful for diagnosis and management of primary open-angle glaucoma.

Aged↗
PubMed1993

Glaucoma in the immediate postoperative period after penetrating keratoplasty.

In a prospective study 155 consecutive patients undergoing penetrating keratoplasty were examined for postoperative increase in intraocular pressure to determine the frequency and duration of intraocular pressure spikes, risk factors, and response to treatment. Patients were maintained on preoperative glaucoma medications except miotics. Additional medications to lower intraocular pressure perioperatively were not given. Intraocular pressure was measured two to five hours, one day, and one week postoperatively. An intraocular pressure of 30 mm Hg or greater was considered an increase in pressure and was treated according to a standardized protocol. The results were analyzed by procedure as well as by variables commonly perceived to be associated with intraocular pressure increase (history of glaucoma, use of hyaluronate, lysis of the synechiae, or vitrectomy at the time of the operation). Overall, intraocular pressure increases in the early postoperative period occurred in 18 of 155 patients (12%). Pressure increases occurred in ten of 48 patients (21%) with a history of glaucoma; five of 24 patients (21%) undergoing combined penetrating keratoplasty, extracapsular cataract extraction, and posterior chamber intraocular lens implantation; and ten of 43 patients (23%) undergoing vitrectomy at the time of penetrating keratoplasty.

Cataract Extraction↗
PubMed1978

Cholinergic supersensitivity of the iris sphincter in Adie's tonic pupil.

In patients with unilateral Adie's syndrome, we compared the relative supersensitivity of the tonic pupil to methacholine hydrochloride (Mecholyl 2.5%) and pilocarpine 0.125%. We tested a large series of patients and photographed the pupils before and 30 minutes after the eyedrops. In a group of 36 patients, Mecholyl was positive in 64% of the tests; and in a group of 20 patients, pilocarpine 0.125% was positive in 80% of the tests. Eight patients who failed to show supersensitivity with Mecholyl were tested with pilocarpine and five of the eight were shown to be supersensitive. We concluded that pilocarpine, in this concentration is not only an adequate substitute for Mecholyl 2.5%, but is a more sensitive testing substance in unilateral cases, simply because it has a slightly stronger miotic action.

Adie Syndrome↗
PubMed1998

The effects of cataract extraction on the visual field of eyes with chronic open-angle glaucoma.

PURPOSE: To investigate effects of cataract extraction and intraocular lens placement on the visual field of eyes with chronic open-angle glaucoma. METHODS: A retrospective review was conducted of 41 eyes of 41 patients with visually significant cataract and chronic open-angle glaucoma who had undergone automated static perimetry within 6 months before and 6 months after phacoemulsification with intraocular lens placement. RESULTS: Comparison of preoperative and postoperative testing showed that the mean visual acuity, foveal threshold, and mean deviation improved significantly (P < .0001), while the mean pattern standard deviation and corrected pattern standard deviation worsened significantly (P < or = .03). Eyes not receiving miotics preoperatively did not have a significant postoperative change in the mean pattern and corrected pattern standard deviations. Increasing severity of glaucoma-related visual field loss was significantly associated with less improvement in the postoperative mean deviation (P = .0001). Only two (5%) of 41 eyes had worsening of the mean deviation of 1.0 dB or greater. The foveal threshold improved more than the mean deviation did but not significantly more, except in eyes with severe visual field loss. CONCLUSIONS: Cataract extraction resulted in statistically significant improvement in visual acuity and foveal threshold in most eyes with glaucoma. In eyes with mild or moderate glaucoma-related damage, the mean deviation often improved significantly after cataract extraction, but improvement was less predictable in eyes with severe or end-stage damage. The pattern and corrected pattern standard deviations may be reliable indicators of glaucoma-related damage in eyes with cataract but without constricted pupils.

Aged↗
PubMed1995

Influence of diltiazem on the ocular irritative response to nitrogen mustard.

Application of nitrogen mustard to the eye of rabbits causes an anterior segment irritation and a biphasic elevation of intraocular pressure. This intraocular pressure response is composed of an initial peak, produced by neuropeptides released by excited sensory nerves, and a second, slower rise due to prostaglandins. We studied the effect of diltiazem, a calcium antagonist that selectively blocks chemical excitation of sensory nerves, on the inflammatory response to nitrogen mustard. In adult rabbits, intraocular pressure was determined by pneumatonometry; pupil diameter and palpebral opening were measured with a ruler while conjunctival vasodilation, edema and secretion were scored in subjective units (0-8). Aqueous humor protein content was analysed at the end of the experiment. Bilateral application of 1% nitrogen mustard evoked within the first 6 hr an intraocular pressure elevation followed by ocular hypotony, miosis, palpebral closure, conjunctival vasodilation, edema and an elevation of aqueous proteins. Topical application of 10 mM diltiazem, prior to administration of nitrogen mustard elicited by itself a transient, small intraocular pressure increase and reduced significantly the acute intraocular pressure elevation and conjunctival vasodilation evoked by the irritant; delayed conjunctival edema and palpebral closure were also attenuated by 10 mM diltiazem. The decrease of miotic response and of aqueous humor protein content was not significant. Diltiazem at 2.8 mM was effective only in reducing significantly conjunctival edema and vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗
PubMed1986

A study of the mechanism of ocular irritation following YAG laser capsulotomy in rabbits.

The irritative response to Nd:YAG laser capsulotomy was studied in unanaesthetized rabbits. Posterior lens capsulotomy with a total energy of 100 mJ had no effect on the pupil size but increased the intraocular pressure by 5-10 mmHg and caused a breakdown of the blood-aqueous barrier. Anterior lens capsulotomy with a total energy of 20, 60 or 100 mJ caused constriction of the pupil, and an increase in intraocular pressure in a dose-dependent manner, and a breakdown of the blood-aqueous barrier. Indomethacin attenuated all the component parts of the irritative response and (D-arg1, D-pro2, D-trp7,9, leu11)-SP attenuated the miotic response. A combination of indomethacin and the substance P antagonist almost completely abolished the irritative response. This indicates that the acute YAG-laser-induced irritation in the rabbit eye is dependent both on a release of prostaglandins and on substance P, the former probably releasing the latter from sensory nerves.

Animals↗