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European Journal of Pharmacology Mar 2019The aim of the study was to investigate the analgesic effects of adding serotonin to oxybuprocaine or proxymetacaine preparations. We employed a rat model of the...
The aim of the study was to investigate the analgesic effects of adding serotonin to oxybuprocaine or proxymetacaine preparations. We employed a rat model of the cutaneous trunci muscle reflex (CTMR) to conduct the dose-response curves and duration of drugs (oxybuprocaine, proxymetacaine, or serotonin) as an infiltrative anesthetic. The use of isobolographic methods to analyze the drug-drug interactions. We showed that oxybuprocaine and proxymetacaine, as well as serotonin produced dose-dependent skin antinociception. On the basis of 50% effective dose (ED), the rank order of drug potency was serotonin [7.22 (6.45-8.09) μmol/kg] < oxybuprocaine [1.03 (0.93-1.15) μmol/kg] < proxymetacaine [0.59 (0.53-0.66) μmol/kg] (P < 0.01 for each comparison). The sensory block duration of serotonin was longer (P < 0.01) than that of oxybuprocaine or proxymetacaine at the equipotent doses (ED, ED, and ED). The mixture of serotonin with oxybuprocaine or proxymetacaine produced a better analgesic effect than the drug itself. We have concluded that oxybuprocaine, proxymetacaine, or serotonin displays dose-related cutaneous analgesia. Oxybuprocaine or proxymetacaine is more potent and has a shorter duration of cutaneous analgesia than serotonin. Serotonin produces a synergistic antinociceptive interaction with oxybuprocaine or proxymetacaine.
Topics: Administration, Cutaneous; Anesthesia, Local; Anesthetics, Local; Animals; Dose-Response Relationship, Drug; Drug Interactions; Male; Procaine; Propoxycaine; Rats; Rats, Sprague-Dawley; Serotonin; Skin
PubMed: 30639797
DOI: 10.1016/j.ejphar.2019.01.009 -
Clinical & Experimental Optometry Nov 2023Reducing the time between drop instillation and refraction reduces the time paediatric patients and young adults spend in practice, facilitating more eye examinations...
CLINICAL RELEVANCE
Reducing the time between drop instillation and refraction reduces the time paediatric patients and young adults spend in practice, facilitating more eye examinations daily.
BACKGROUND
The current procedure for paediatric cycloplegic refraction is to wait for at least 30-minutes post-instillation of a cycloplegic before measuring spherical equivalent refraction. This study compared cycloplegia at 20- and 30-minutes following 0.5% proxymetacaine and 1.0% cyclopentolate in 12-13-year-olds.
METHODS
Participants were 99 white 12-13-year-olds. One drop of proxymetacaine hydrochloride (Minims, 0.5% w/v, Bausch & Lomb, UK) followed by one drop of cyclopentolate hydrochloride (Minims, 1.0% w/v, Bausch & Lomb, UK) was instilled into both eyes. Spherical equivalent refraction was measured by autorefraction (Dong Yang Rekto ORK-11 Auto Ref-Keratometer) at 20- and 30-minutes post-instillation. Data were analysed through paired t-testing, correlations, and linear regression analysis.
RESULTS
There was no significant difference in level of cycloplegia achieved at 20- (Mean spherical equivalent refraction (standard deviation) 0.438 (1.404) D) and 30-minutes (0.487 (1.420) D) post-eyedrop instillation (t (98) = 1.667, = 0.099). The mean spherical equivalent refraction difference between time points was small (0.049 (0.294) D, 95% confidence interval =-0.108 ̶ 0.009D). Agreement indices: Accuracy = 0.999, Precision = 0.973, Concordance = 0.972. Spherical equivalent refraction at 20- and 30-minutes differed by ≤0.50D in 92% of eyes, and by <1.00D in 95%.
CONCLUSIONS
There was no clinically significant difference in spherical equivalent refraction or level of cycloplegia at 20- and 30-minutes post-eyedrop instillation. The latent time between drop instillation and measurement of refractive error may be reduced to 20 minutes in White 12-13-year-olds and young adults. Further studies must determine if these results persist in younger children and non-White populations.
Topics: Child; Humans; Cyclopentolate; Mydriatics; Ophthalmic Solutions; Presbyopia; Pupil; Refraction, Ocular; Refractive Errors; White People; Adolescent; Propoxycaine
PubMed: 36750050
DOI: 10.1080/08164622.2023.2166398 -
The Journal of Toxicological Sciences Aug 2015Proparacaine is a widely used topical anesthetic in ophthalmic optometry and surgery, and has been reported to have cytotoxic effects on rabbit corneal endothelial cells...
Proparacaine is a widely used topical anesthetic in ophthalmic optometry and surgery, and has been reported to have cytotoxic effects on rabbit corneal endothelial cells after prolonged and repeated usage. Since rabbit is an exceptive mammal whose corneal endothelial cells still maintaining proliferation abilities even in adulthood, whether proparacaine has cytotoxic effects on human corneal endothelial (HCE) cells need to be further verified. Our objectives in the present study were to investigate the cytotoxicity to HCE cells of proparacaine and its underlying mechanisms in vitro and verify the cytotoxicity using cat corneal endothelial (CCE) cells in an in vivo model of cat corneas. Cytotoxic evaluation results indicated that a dose- and time-dependent toxic response of HCE cells to proparacaine over 0.03125% was rated based on morphology and viability, and a toxic response of CCE cells to 0.5% (clinical applied dosage) proparacaine was also rated based on cell density and histology. Importantly, treatment with proparacaine resulted in significant elevation of plasma membrane permeability, cell cycle arrest at S phase, fragmentation of genomic DNA, formation of apoptotic bodies, and externalization of phosphatidylserine (PS) of HCE cells. Moreover, proparacaine demonstrated disrupting effects on mitochondrial transmembrane potential (MTP) of HCE cells and activating effects on caspase-3, -8 and -9. This study demonstrates that proparacaine has notable cytotoxicity to both HCE cells in vitro and CCE cells in vivo, and its dose- and time-dependent cytotoxicity to HCE cells is achieved by inducing apoptosis via a mitochondrion-mediated caspase-dependent pathway. These findings provide new insights into the cytotoxicity and apoptosis-inducing effect of local anesthetics which should be used with great caution in the eye clinic.
Topics: Anesthetics, Local; Animals; Apoptosis; Caspases; Cats; Cell Cycle; Cell Membrane Permeability; Cells, Cultured; DNA Fragmentation; Dose-Response Relationship, Drug; Endothelial Cells; Endothelium, Corneal; Humans; Membrane Potential, Mitochondrial; Phosphatidylserines; Propoxycaine; Rabbits; S Phase; Time Factors
PubMed: 26165639
DOI: 10.2131/jts.40.427 -
Investigative Ophthalmology & Visual... May 2015Dry eye disease (DED) produces ocular pain and irritation, yet a detailed characterization of ocular sensitivity in a preclinical model of DED is lacking. The aim of the...
PURPOSE
Dry eye disease (DED) produces ocular pain and irritation, yet a detailed characterization of ocular sensitivity in a preclinical model of DED is lacking. The aim of the present study was to assess nociceptive behaviors in an aqueous tear deficiency model of DED in the rat.
METHODS
Spontaneous blinking, corneal mechanical thresholds, and eye wipe behaviors elicited by hypertonic saline (5.0 M) were examined over a period of 8 weeks following the unilateral excision of either the exorbital lacrimal gland or of the exorbital and infraorbital lacrimal glands, and in sham surgery controls. The effect of topical proparacaine on spontaneous blinking and of systemic morphine (0.5-3.0 mg/kg, subcutaneous [SC]) on spontaneous blinking and eye wipe responses were also examined.
RESULTS
Lacrimal gland excision resulted in mechanical hypersensitivity and an increase in spontaneous blinking in the ipsilateral eye over an 8-week period that was more pronounced after infra- and exorbital gland excision. The time spent eye wiping was also enhanced in response to hypertonic saline (5.0 M) at both 1- and 8-week time-points, but only in infra- and exorbital gland excised animals. Morphine attenuated spontaneous blinking, and the response to hypertonic saline in dry eye animals and topical proparacaine application reduced spontaneous blinking down to control levels.
CONCLUSIONS
These results indicate that aqueous tear deficiency produces hypersensitivity in the rat cornea. In addition, the increase in spontaneous blinks and their reduction by morphine and topical anesthesia indicate the presence of persistent irritation elicited by the activation of corneal nociceptors.
Topics: Analgesics, Opioid; Analysis of Variance; Anesthetics, Local; Animals; Blinking; Cornea; Disease Models, Animal; Dry Eye Syndromes; Fluorescein Angiography; Lacrimal Apparatus; Male; Morphine; Propoxycaine; Rats; Rats, Sprague-Dawley; Sensory Thresholds; Tears
PubMed: 26024120
DOI: 10.1167/iovs.15-16717 -
Journal of AAPOS : the Official... Aug 2015To determine the psychological effects of eyedrops administration in children.
PURPOSE
To determine the psychological effects of eyedrops administration in children.
METHODS
Children requiring eyedrops for cycloplegic refraction were recruited in this cross-sectional study. Nurses administered eyedrops in 2-3 cycles spaced 5-10 minutes apart, and optometrists performed refraction 30 minutes after the last drop. Ophthalmologists, nurses, and optometrists rated the children's cooperation level at first review, after each eyedrop, at refraction, and at final review. Parents chose a personality type best describing their child, and monitored their child's anxiety using a modified Yale Preoperative Anxiety Scale (m-YPAS). Children were "uncooperative" if nurses noted significant distress during the first drop cycle.
RESULTS
A total of 298 children 2-12 years of age were included. Of these, 77 (26%) experienced pre-drop distress and 39 (13%) were uncooperative with drops. Compared to cooperative children, uncooperative children tended to be younger (2.0-4.9 years vs ≥8 years; OR, 4.11; 95% CI, 1.14-14.83; P = 0.031), male (OR, 2.55; 95% CI, 1.06-6.10; P = 0.036), have had a previous negative eyedrop experience (84.2% vs 25.3%; P < 0.001) and were more anxious (m-YPAS scores, 41.4 ± 22.0 vs 30.6 ± 12.6: P < 0.001). Children described as "demanding and aggressive" were more uncooperative than "timid and anxious" children. It took longer to instill drops (3.1 vs 1.3 minutes), and perform refraction (11.6 vs 7.2 minutes) in uncooperative children.
CONCLUSIONS
A small group of children were uncooperative with eyedrops and 26% experienced significant pre-drop anxiety. Factors such as age, sex, a previous negative eyedrop experience, and pre-drop anxiety, associated with uncooperativeness need to be considered when developing strategies to improve the eyedrops experience in children.
Topics: Administration, Topical; Anxiety Disorders; Asian People; Child; Child Behavior; Child, Preschool; Cross-Sectional Studies; Cyclopentolate; Female; Humans; Male; Mydriatics; Ophthalmic Solutions; Patient Compliance; Personality Inventory; Phenylephrine; Propoxycaine; Refraction, Ocular; Singapore; Stress, Psychological; Tropicamide
PubMed: 26296784
DOI: 10.1016/j.jaapos.2015.05.010 -
Veterinary Ophthalmology Jan 2022To determine whether tropicamide, fluorescein, and proparacaine applied topically before sample collection affect the quantity or species of bacteria isolated via...
OBJECTIVE
To determine whether tropicamide, fluorescein, and proparacaine applied topically before sample collection affect the quantity or species of bacteria isolated via aerobic culture.
ANIMALS STUDIED
12 female adult research beagle cross-breed dogs.
PROCEDURES
A conjunctival swab was taken before and after the sequential application of proparacaine, tropicamide, and fluorescein to the same eye (P/T/F) with a five-minute gap between medications. Paired swabs were submitted for aerobic culture. Bacterial enumeration was performed using the spread plate method. Following a one-week washout period, the procedure was repeated using balanced salt solution (BSS). Following a second one-week washout period, the experiment was repeated using ofloxacin 0.3% solution. Colony counts were compared using one-way ANOVA and Tukey post hoc comparison. Bacterial species reduction was compared using a Friedman rank test and Dunn's method.
RESULTS
The bacterial colony count for P/T/F and BSS was significantly higher than the ofloxacin group (p = 0.0052, p = 0.0022). There was no significant difference for colony counts between P/T/F and BSS (p = 0.9295). The most frequently isolated bacteria included: Psychrobacter spp., Staphylococcus spp., Corynebacterium spp., and Streptococcus spp. The bacterial species reduction for P/T/F and BSS was significantly lower than for ofloxacin (p < 0.0001, p = 0.0160). There was no significant difference for species reduction between P/T/F and BSS (p = 0.3749).
CONCLUSIONS
The application of proparacaine, tropicamide, and fluorescein did not significantly decrease the amount or species of bacteria isolated from the conjunctiva in this canine population. The application of these solutions prior to ocular swab collection in healthy dogs is unlikely to affect subsequent culture results.
Topics: Animals; Conjunctiva; Dogs; Female; Fluorescein; Propoxycaine; Tropicamide
PubMed: 34142756
DOI: 10.1111/vop.12914 -
Psychiatria Danubina Sep 2019
Review
Topics: Behavior, Addictive; Diagnostic Errors; Eye Pain; Humans; Male; Middle Aged; Ophthalmic Solutions; Patient Satisfaction; Prescription Drug Misuse; Propoxycaine; Self Medication
PubMed: 31596831
DOI: 10.24869/psyd.2019.360 -
Journal of Ocular Pharmacology and... May 2024This study aimed to determine the onset and duration of action of 3 commercially available topical anesthetic solutions in Brazil, using the Cochet-Bonnet esthesiometer... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
This study aimed to determine the onset and duration of action of 3 commercially available topical anesthetic solutions in Brazil, using the Cochet-Bonnet esthesiometer (Luneau, Paris, France) and to quantitatively assess patient-reported discomfort during application. A prospective, randomized, masked, and double-blind study was conducted, involving 40 eyes from 21 patients. Patients were administered each one of the topical anesthetics weekly, and corneal sensitivity was measured using the Cochet-Bonnet esthesiometer's corneal touch threshold (CTT). Patients rated the burning sensation using a visual analogue scale (VAS). Among the 21 patients (42.9% male), with a mean age of 31.95 years (±standard deviation = 10.17, range = 22.0-58.0), corneal sensitivity significantly decreased 30 s after application, returning to baseline after 30 min for all groups ( < 0.0001). Significant differences in CTT were observed at 5 min, with proparacaine exhibiting a superior anesthetic effect ( = 0.0003), at 10 min, where tetracaine displayed the most substantial anesthetic effect ( = 0.0135), and at 20 min, where tetracaine demonstrated the highest anesthetic efficacy ( < 0.0001). VAS scores indicated the most intense burning sensation with tetracaine ( < 0.0001). Men reported experiencing more discomfort during instillation compared with women ( = 0.0168). Proparacaine exhibited the fastest onset of action among the 3 topical anesthetics and provided a more comfortable eye sensation during instillation. However, tetracaine demonstrated the longest duration of action despite causing more discomfort.
Topics: Humans; Male; Female; Tetracaine; Adult; Double-Blind Method; Propoxycaine; Anesthetics, Local; Middle Aged; Prospective Studies; Cornea; Procaine; Young Adult; Ophthalmic Solutions; Pain Measurement
PubMed: 38597912
DOI: 10.1089/jop.2023.0148 -
New application of an old drug proparacaine in treating epilepsy via liposomal hydrogel formulation.Pharmacological Research Jul 2021Proparacaine (PPC) is a previously discovered topical anesthetic for ophthalmic optometry and surgery by blocking the central Nav1.3. In this study, we found that...
Proparacaine (PPC) is a previously discovered topical anesthetic for ophthalmic optometry and surgery by blocking the central Nav1.3. In this study, we found that proparacaine hydrochloride (PPC-HCl) exerted an acute robust antiepileptic effect in pilocarpine-induced epilepsy mice. More importantly, chronic treatment with PPC-HCl totally terminated spontaneous recurrent seizure occurrence without significant toxicity. Chronic treatment with PPC-HCl did not cause obvious cytotoxicity, neuropsychiatric adverse effects, hepatotoxicity, cardiotoxicity, and even genotoxicity that evaluated by whole genome-scale transcriptomic analyses. Only when in a high dose (50 mg/kg), the QRS interval measured by electrocardiography was slightly prolonged, which was similar to the impact of levetiracetam. Nevertheless, to overcome this potential issue, we adopt a liposome encapsulation strategy that could alleviate cardiotoxicity and prepared a type of hydrogel containing PPC-HCl for sustained release. Implantation of thermosensitive chitosan-based hydrogel containing liposomal PPC-HCl into the subcutaneous tissue exerted immediate and long-lasting remission from spontaneous recurrent seizure in epileptic mice without affecting QRS interval. Therefore, this new liposomal hydrogel formulation of proparacaine could be developed as a transdermal patch for treating epilepsy, avoiding the severe toxicity after chronic treatment with current antiepileptic drugs in clinic.
Topics: Animals; Anticonvulsants; Drug Delivery Systems; Electroencephalography; Epilepsy; Hindlimb Suspension; Hydrogels; Liposomes; Male; Maze Learning; Mice, Inbred C57BL; Open Field Test; Propoxycaine; Mice
PubMed: 33932606
DOI: 10.1016/j.phrs.2021.105636 -
Ophthalmologica. Journal International... 2022The study aimed to investigate the effectiveness of topical anesthetic drops in reducing the pain associated with mydriatic eye drops prior to the retinopathy of... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
The study aimed to investigate the effectiveness of topical anesthetic drops in reducing the pain associated with mydriatic eye drops prior to the retinopathy of prematurity (ROP) examination.
METHODS
Premature infants who underwent first-time ROP examinations in an outpatient setting were included in this randomized controlled trial. The study group included the infants who were administered topical anesthesia prior to the first mydriatic drops, and the control group included the infants who were given preservative-free artificial tear drops. Pain assessment was performed using the premature infant pain profile (PIPP).
RESULTS
A total of 66 infants, 35 in the control group and 31 in the study group, were included in the study. The PIPP scores of the infants during the first, second, and third mydriatic drops were 5.3 ± 2.0; 4.9 ± 1.7; and 4.0 ± 1.8, respectively, in the study group and 5.3 ± 1.7; 5.6 ± 1.8; and 4.6 ± 1.8, respectively, in the control group. No significant difference was found in the scores between the two groups. The PIPP score after the third drop was significantly lower than that after the second drop in the control group, and the PIPP score after the third drop was significantly lower than that obtained after the first and second drops in the study group.
DISCUSSION/CONCLUSION
This study showed no significant benefit of the topical anesthetic drop in the prevention of pain associated with mydriatic eye drops. The decrease in the pain response observed in repeated administrations is a novel finding.
Topics: Infant, Newborn; Humans; Propoxycaine; Retinopathy of Prematurity; Mydriatics; Anesthetics, Local; Ophthalmic Solutions; Double-Blind Method; Pain; Anesthesia
PubMed: 36108603
DOI: 10.1159/000526987