Effects of timolol maleate, levobunolol and apraclonidine on intraocular pressure, pupil size, blood pressure and heart rate in beagles

The aim of this study was to evaluate changes in intraocular pressure (IOP), pupil size (PS), blood pressure (BP), heart rate (HR), and ECG variables (Pms wave PmV, PR interval, QRS complex, RMV wave and QT intervals) over time during the instillation of 0.5% timolol, 0.5% levobunolol and 0.5% aprac...

Full description

Autores:
Padua Martínez, Ivan Ricardo
Ribeiro Pinto, Alexandre
Martínez Padua, Pedro Pablo
Guimaraes, Patricia Jordao
Silva, Miguel Ladino
Piso Trujillo, Dunia Yisela
Martins, Bianca
Aldrovani Rodrigues, Marcela
Semolin, Livia María
Camacho, Aparecido Antonio
Laus, José Luiz
Tipo de recurso:
Article of journal
Fecha de publicación:
2016
Institución:
Universidad Cooperativa de Colombia
Repositorio:
Repositorio UCC
Idioma:
OAI Identifier:
oai:repository.ucc.edu.co:20.500.12494/1519
Acceso en línea:
https://hdl.handle.net/20.500.12494/1519
Palabra clave:
Oftalmología veterinaria
Rights
openAccess
License
Licencia CC
id COOPER2_951839a9c4b2549c8d6e0c936c4551c7
oai_identifier_str oai:repository.ucc.edu.co:20.500.12494/1519
network_acronym_str COOPER2
network_name_str Repositorio UCC
repository_id_str
dc.title.spa.fl_str_mv Effects of timolol maleate, levobunolol and apraclonidine on intraocular pressure, pupil size, blood pressure and heart rate in beagles
title Effects of timolol maleate, levobunolol and apraclonidine on intraocular pressure, pupil size, blood pressure and heart rate in beagles
spellingShingle Effects of timolol maleate, levobunolol and apraclonidine on intraocular pressure, pupil size, blood pressure and heart rate in beagles
Oftalmología veterinaria
title_short Effects of timolol maleate, levobunolol and apraclonidine on intraocular pressure, pupil size, blood pressure and heart rate in beagles
title_full Effects of timolol maleate, levobunolol and apraclonidine on intraocular pressure, pupil size, blood pressure and heart rate in beagles
title_fullStr Effects of timolol maleate, levobunolol and apraclonidine on intraocular pressure, pupil size, blood pressure and heart rate in beagles
title_full_unstemmed Effects of timolol maleate, levobunolol and apraclonidine on intraocular pressure, pupil size, blood pressure and heart rate in beagles
title_sort Effects of timolol maleate, levobunolol and apraclonidine on intraocular pressure, pupil size, blood pressure and heart rate in beagles
dc.creator.fl_str_mv Padua Martínez, Ivan Ricardo
Ribeiro Pinto, Alexandre
Martínez Padua, Pedro Pablo
Guimaraes, Patricia Jordao
Silva, Miguel Ladino
Piso Trujillo, Dunia Yisela
Martins, Bianca
Aldrovani Rodrigues, Marcela
Semolin, Livia María
Camacho, Aparecido Antonio
Laus, José Luiz
dc.contributor.author.none.fl_str_mv Padua Martínez, Ivan Ricardo
Ribeiro Pinto, Alexandre
Martínez Padua, Pedro Pablo
Guimaraes, Patricia Jordao
Silva, Miguel Ladino
Piso Trujillo, Dunia Yisela
Martins, Bianca
Aldrovani Rodrigues, Marcela
Semolin, Livia María
Camacho, Aparecido Antonio
Laus, José Luiz
dc.subject.spa.fl_str_mv Oftalmología veterinaria
topic Oftalmología veterinaria
description The aim of this study was to evaluate changes in intraocular pressure (IOP), pupil size (PS), blood pressure (BP), heart rate (HR), and ECG variables (Pms wave PmV, PR interval, QRS complex, RMV wave and QT intervals) over time during the instillation of 0.5% timolol, 0.5% levobunolol and 0.5% apraclonidine in clinically normal dogs. Ten adult beagles were used. Baseline values were measured at 8a.m., 2p.m. and 8p.m., for three consecutive days. A waiting period of 10 days between the administrations of each drug was established. For 15 consecutive days, the drug being tested was instilled in one eye of each dog twice a day (7a.m. and 7p.m.). The parameters were evaluated at the aforementioned times on days 3, 6, 9, 12 and 15. Data were statistically compared using the Bonferroni test and one-way repeated measures analysis of variance (P<0.05). The Pearson test was used to evaluate any correlation between QT interval, HR and BP. The tested drugs did not find a decrease in IOP. A significant decreased in PS was observed in almost all dogs following levobunolol administration, relative to the control eye. A significant decrease in HR was observed on day 3 following levobunolol treatment, while apraclonidine induced an increase on day 15. Blood pressure was reduced in all measurement time points following apraclonidine treatment. A negative correlation between QT interval and HR was only observed in dogs treated with timolol. In conclusion, levobunolol was the only drug that induced significant alterations in PS. Apraclonidine was the only drug that induced systemic hypotension. Timolol was the only drug to that induced a negative correlation between QT and HR.
publishDate 2016
dc.date.issued.none.fl_str_mv 2016-11
dc.date.accessioned.none.fl_str_mv 2017-09-15T19:46:25Z
dc.date.available.none.fl_str_mv 2017-09-15T19:46:25Z
dc.type.none.fl_str_mv Artículo
dc.type.coar.fl_str_mv http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.coar.none.fl_str_mv http://purl.org/coar/resource_type/c_6501
dc.type.coarversion.none.fl_str_mv http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.driver.none.fl_str_mv info:eu-repo/semantics/article
dc.type.version.none.fl_str_mv info:eu-repo/semantics/publishedVersion
format http://purl.org/coar/resource_type/c_6501
status_str publishedVersion
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/20.500.12494/1519
dc.identifier.bibliographicCitation.spa.fl_str_mv Padua, I. R.M., Ribeiro, A. P., Padua, P. P. M., Guimarães, P. J., Silva, M. L., Piso, D. Y. T., Martins, B., Aldrovani, M., Semolin, L. M. S., Camacho, A.A., & Laus, J.L.. (2016). Effects of timolol maleate, levobunolol and apraclonidine on intraocular pressure, pupil size, blood pressure and heart rate in beagles. Arquivo Brasileiro de Medicina Veterinária e Zootecnia, 68(3), 641-650. https://dx.doi.org/10.1590/1678-4162-8093
url https://hdl.handle.net/20.500.12494/1519
identifier_str_mv Padua, I. R.M., Ribeiro, A. P., Padua, P. P. M., Guimarães, P. J., Silva, M. L., Piso, D. Y. T., Martins, B., Aldrovani, M., Semolin, L. M. S., Camacho, A.A., & Laus, J.L.. (2016). Effects of timolol maleate, levobunolol and apraclonidine on intraocular pressure, pupil size, blood pressure and heart rate in beagles. Arquivo Brasileiro de Medicina Veterinária e Zootecnia, 68(3), 641-650. https://dx.doi.org/10.1590/1678-4162-8093
dc.rights.cc.none.fl_str_mv Licencia CC
dc.rights.accessrights.none.fl_str_mv info:eu-repo/semantics/openAccess
dc.rights.coar.none.fl_str_mv http://purl.org/coar/access_right/c_abf2
rights_invalid_str_mv Licencia CC
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.publisher.spa.fl_str_mv Universidad Cooperativa de Colombia, Facultad de Ciencias de la Salud, Programa de Medicina Veterinaria y Zootecnia, Ibagué, Colombia, 00000
dc.publisher.program.spa.fl_str_mv Medicina veterinaria y zootecnia
dc.publisher.place.spa.fl_str_mv Ibagué
institution Universidad Cooperativa de Colombia
bitstream.url.fl_str_mv https://repository.ucc.edu.co/bitstreams/40f1a800-4587-464f-b41b-5e1b6b2b336e/download
https://repository.ucc.edu.co/bitstreams/05f99f84-6903-48da-a247-9d2585ae93f4/download
https://repository.ucc.edu.co/bitstreams/5aa338ef-be7d-4909-a013-253c5e4fa930/download
https://repository.ucc.edu.co/bitstreams/fcc0a6fc-0f98-484d-8100-add928f5b161/download
bitstream.checksum.fl_str_mv cb8f4d9b72d863ad6737f22af442cc82
1e9a5818c5068b1b2b0c2b530fad027e
c412fbdef61a59ebda38cdb6347631f4
260217dbb77c5fc618e5364782a30472
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
MD5
repository.name.fl_str_mv Repositorio Institucional Universidad Cooperativa de Colombia
repository.mail.fl_str_mv bdigital@metabiblioteca.com
_version_ 1814246862163542016
spelling Padua Martínez, Ivan RicardoRibeiro Pinto, AlexandreMartínez Padua, Pedro PabloGuimaraes, Patricia JordaoSilva, Miguel LadinoPiso Trujillo, Dunia YiselaMartins, BiancaAldrovani Rodrigues, MarcelaSemolin, Livia MaríaCamacho, Aparecido AntonioLaus, José Luiz2017-09-15T19:46:25Z2017-09-15T19:46:25Z2016-11https://hdl.handle.net/20.500.12494/1519Padua, I. R.M., Ribeiro, A. P., Padua, P. P. M., Guimarães, P. J., Silva, M. L., Piso, D. Y. T., Martins, B., Aldrovani, M., Semolin, L. M. S., Camacho, A.A., & Laus, J.L.. (2016). Effects of timolol maleate, levobunolol and apraclonidine on intraocular pressure, pupil size, blood pressure and heart rate in beagles. Arquivo Brasileiro de Medicina Veterinária e Zootecnia, 68(3), 641-650. https://dx.doi.org/10.1590/1678-4162-8093The aim of this study was to evaluate changes in intraocular pressure (IOP), pupil size (PS), blood pressure (BP), heart rate (HR), and ECG variables (Pms wave PmV, PR interval, QRS complex, RMV wave and QT intervals) over time during the instillation of 0.5% timolol, 0.5% levobunolol and 0.5% apraclonidine in clinically normal dogs. Ten adult beagles were used. Baseline values were measured at 8a.m., 2p.m. and 8p.m., for three consecutive days. A waiting period of 10 days between the administrations of each drug was established. For 15 consecutive days, the drug being tested was instilled in one eye of each dog twice a day (7a.m. and 7p.m.). The parameters were evaluated at the aforementioned times on days 3, 6, 9, 12 and 15. Data were statistically compared using the Bonferroni test and one-way repeated measures analysis of variance (P<0.05). The Pearson test was used to evaluate any correlation between QT interval, HR and BP. The tested drugs did not find a decrease in IOP. A significant decreased in PS was observed in almost all dogs following levobunolol administration, relative to the control eye. A significant decrease in HR was observed on day 3 following levobunolol treatment, while apraclonidine induced an increase on day 15. Blood pressure was reduced in all measurement time points following apraclonidine treatment. A negative correlation between QT interval and HR was only observed in dogs treated with timolol. In conclusion, levobunolol was the only drug that induced significant alterations in PS. Apraclonidine was the only drug that induced systemic hypotension. Timolol was the only drug to that induced a negative correlation between QT and HR.dunia.trujillop@campusucc.edu.coUniversidad Cooperativa de Colombia, Facultad de Ciencias de la Salud, Programa de Medicina Veterinaria y Zootecnia, Ibagué, Colombia, 00000Medicina veterinaria y zootecniaIbaguéOftalmología veterinariaEffects of timolol maleate, levobunolol and apraclonidine on intraocular pressure, pupil size, blood pressure and heart rate in beaglesArtículohttp://purl.org/coar/resource_type/c_6501http://purl.org/coar/resource_type/c_2df8fbb1http://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionLicencia CCinfo:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2PublicationLICENSElicense.txtlicense.txttext/plain; charset=utf-84553https://repository.ucc.edu.co/bitstreams/40f1a800-4587-464f-b41b-5e1b6b2b336e/downloadcb8f4d9b72d863ad6737f22af442cc82MD52TEXTArticulo Ivan.pdf.txtArticulo Ivan.pdf.txtExtracted texttext/plain29521https://repository.ucc.edu.co/bitstreams/05f99f84-6903-48da-a247-9d2585ae93f4/download1e9a5818c5068b1b2b0c2b530fad027eMD53ORIGINALArticulo Ivan.pdfArticulo Ivan.pdfapplication/pdf797547https://repository.ucc.edu.co/bitstreams/5aa338ef-be7d-4909-a013-253c5e4fa930/downloadc412fbdef61a59ebda38cdb6347631f4MD51THUMBNAILArticulo Ivan.pdf.jpgArticulo Ivan.pdf.jpgGenerated Thumbnailimage/jpeg5166https://repository.ucc.edu.co/bitstreams/fcc0a6fc-0f98-484d-8100-add928f5b161/download260217dbb77c5fc618e5364782a30472MD5520.500.12494/1519oai:repository.ucc.edu.co:20.500.12494/15192024-08-09 12:24:08.479open.accesshttps://repository.ucc.edu.coRepositorio Institucional Universidad Cooperativa de Colombiabdigital@metabiblioteca.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