Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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Dr Bhanu K Bhakhri

"The Journal of Clinical and Diagnostic Research (JCDR) has been in operation since almost a decade. It has contributed a huge number of peer reviewed articles, across a spectrum of medical disciplines, to the medical literature.
Its wide based indexing and open access publications attracts many authors as well as readers
For authors, the manuscripts can be uploaded online through an easily navigable portal, on other hand, reviewers appreciate the systematic handling of all manuscripts. The way JCDR has emerged as an effective medium for publishing wide array of observations in Indian context, I wish the editorial team success in their endeavour"



Dr Bhanu K Bhakhri
Faculty, Pediatric Medicine
Super Speciality Paediatric Hospital and Post Graduate Teaching Institute, Noida
On Sep 2018




Dr Mohan Z Mani

"Thank you very much for having published my article in record time.I would like to compliment you and your entire staff for your promptness, courtesy, and willingness to be customer friendly, which is quite unusual.I was given your reference by a colleague in pathology,and was able to directly phone your editorial office for clarifications.I would particularly like to thank the publication managers and the Assistant Editor who were following up my article. I would also like to thank you for adjusting the money I paid initially into payment for my modified article,and refunding the balance.
I wish all success to your journal and look forward to sending you any suitable similar article in future"



Dr Mohan Z Mani,
Professor & Head,
Department of Dematolgy,
Believers Church Medical College,
Thiruvalla, Kerala
On Sep 2018




Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."



Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
Ex-President - National Neonatology Forum Gujarat State Chapter
Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018




Dr. Kalyani R

"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



Dr Kalyani R
Professor and Head
Department of Pathology
Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
On Sep 2018




Dr. Saumya Navit

"As a peer-reviewed journal, the Journal of Clinical and Diagnostic Research provides an opportunity to researchers, scientists and budding professionals to explore the developments in the field of medicine and dentistry and their varied specialities, thus extending our view on biological diversities of living species in relation to medicine.
‘Knowledge is treasure of a wise man.’ The free access of this journal provides an immense scope of learning for the both the old and the young in field of medicine and dentistry as well. The multidisciplinary nature of the journal makes it a better platform to absorb all that is being researched and developed. The publication process is systematic and professional. Online submission, publication and peer reviewing makes it a user-friendly journal.
As an experienced dentist and an academician, I proudly recommend this journal to the dental fraternity as a good quality open access platform for rapid communication of their cutting-edge research progress and discovery.
I wish JCDR a great success and I hope that journal will soar higher with the passing time."



Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
Lucknow
On Sep 2018




Dr. Arunava Biswas

"My sincere attachment with JCDR as an author as well as reviewer is a learning experience . Their systematic approach in publication of article in various categories is really praiseworthy.
Their prompt and timely response to review's query and the manner in which they have set the reviewing process helps in extracting the best possible scientific writings for publication.
It's a honour and pride to be a part of the JCDR team. My very best wishes to JCDR and hope it will sparkle up above the sky as a high indexed journal in near future."



Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
Assistant Professor
Department of Pharmacology
Calcutta National Medical College & Hospital , Kolkata




Dr. C.S. Ramesh Babu
" Journal of Clinical and Diagnostic Research (JCDR) is a multi-specialty medical and dental journal publishing high quality research articles in almost all branches of medicine. The quality of printing of figures and tables is excellent and comparable to any International journal. An added advantage is nominal publication charges and monthly issue of the journal and more chances of an article being accepted for publication. Moreover being a multi-specialty journal an article concerning a particular specialty has a wider reach of readers of other related specialties also. As an author and reviewer for several years I find this Journal most suitable and highly recommend this Journal."
Best regards,
C.S. Ramesh Babu,
Associate Professor of Anatomy,
Muzaffarnagar Medical College,
Muzaffarnagar.
On Aug 2018




Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011

Important Notice

Original article / research
Year : 2009 | Month : August | Volume : 3 | Issue : 4 | Page : 1615 - 1620

The Cardio-Vascular Effects Of Topical Timolol, Levobunolol And Betaxolol In Patients Of Chronic Simple Glaucoma

SHARMA R *, KOHLI K* *, KAPOOR B***, MENGI RK****, SADHOTRA P*****.

*(M.D) Senior Demonstrator ,**(M.D) Associate Professor,***(M.D) Professor and Head, Postgraduate Deptt.of Pharmacology and Therapeutics,****(M.S) Associate Professor ,*****(M.S)Professor and head, Postgraduate Deptt.of Ophthalmology ,Govt. Medical College, Jammu.(India).

Correspondence Address :
Dr Rashmi Sharma, 216-A,
Last-Morh Gandhi- Nagar Jammu Tawi.
Pin: 180004. J&K state (INDIA)
E.mail:drrashmi@india.com

Abstract

Background: β–adrenergic antagonists are the most commonly prescribed drugs for glaucoma. However, these drugs can be absorbed into the systemic circulation through the naso-lacrimal duct to produce various systemic side effects.
Aims: The present study was conducted to evaluate the effects of topical timolol, levobunolol and betaxolol on the cardiovascular system in Indian patients of chronic simple glaucoma.
Settings And Design: This prospective randomized single-blind parallel study was conducted in the Department of Pharmacology and Therapeutics in collaboration with the Department of Ophthalmology of a teaching institute.
Methods And Material: Forty newly diagnosed patients of chronic simple glaucoma were included in the study. 16 patients (23 eyes), 12 patients (19 eyes) and 12 patients (20 eyes) were randomized to receive 0.5% timolol maleate, 0.5% levobunolol hydrochloride and 0.5% betaxolol hydrochloride respectively, as one drop twice a day instillation for 12 weeks. Blood pressure, pulse rate and intraocular pressure of each patient were recorded at 0, 6 and 12 weeks.
Statistics: Effects of the individual drug on various study parameters were analysed using the paired t–test. P values <0.05 were taken as significant. A comparative analysis of the effects of the three drugs on the above parameters was done by using the analysis of variance test. Inter-group comparison was done using the Turkey test.
Results: Topical timolol, levobunolol and betaxolol lowered IOP by 13.05 ± 1.53, 14.05 ±1.47 and 7.58 ± 0.90 mm of Hg respectively, at 6 weeks and by 16.12±1.67, 16.28 ±1.85 and 8.53±0.98 respectively, at 12 weeks (P<0.001) .Both topical timolol and levobunolol produced more reduction in IOP than topical betaxolol, with P-values of 0.004 and 0.002 at 6 and 12 weeks respectively. All the three drugs produced a statistically significant reduction in the pulse rate and systolic and diastolic blood pressure, indicating the systemic absorption of β-blockers in a concentration enough to alter the cardiovascular parameters of the patients .On comparative analysis using analysis of variance, a statistically insignificant difference for change in the three parameters was observed among the three groups .
Conclusion: The results of our study necessitate an urgent need for ophthalmological physicians to exclude all the possible cardiovascular problems in the patients before prescribing a topical β-blocker.

Keywords

Timolol, levobunolol, betaxolol, blood pressure, cardiovascular, glaucoma

How to cite this article :

SHARMA R ,KOHLI K, KAPOOR B, MENGI RK, SADHOTRA P. THE CARDIO-VASCULAR EFFECTS OF TOPICAL TIMOLOL, LEVOBUNOLOL AND BETAXOLOL IN PATIENTS OF CHRONIC SIMPLE GLAUCOMA. Journal of Clinical and Diagnostic Research [serial online] 2009 August [cited: 2018 Sep 26 ]; 3:1615-1620. Available from
http://www.jcdr.net/back_issues.asp?issn=0973-709x&year=2009&month=August&volume=3&issue=4&page=1615-1620&id=545

Drugs whch are topically instilled in the eyes can cause potentially serious systemic effects by their systemic absorption through the nasolacrimal duct. The β–adrenergic antagonists are the most commonly prescribed drugs for glaucoma (1). The topical administration of timolol, can cause the plasma levels to rise as high as that obtained after intra-venous administration(1).This is because, 50%-70% of the drug escapes first pass metabolism (degradation of drug while passing through intestinal membrane and liver before its absorption into the systemic circulation) (1),(2). However, betaxolol is a cardio-selective β1–adrenergic antagonist with the theoretical advantage of fewer systemic effects(3),(4) Another drug, levobunolol, a potent non-selective β–adrenergic antagonist, with a longer duration of action (more than 24 hours after single instillation ), has been marketed in India (5). A few studies are available, which demonstrate the effect of topical β–blockers on the cardiovascular system (6),[ 7]. However, we could not come across any such study on Indian patients. As the variation in the drug’s pharmacokinetics and pharmacodynamics with respect to ethnic and genetic variations is a well known fact, we conducted this study to compare the effects of the three topical drugs on the cardiovascular system in Indian patients of chronic simple glaucoma.

Material and Methods

This study has been described according to the CONSORT guidelines for the presentation of clinical trials. This prospective randomized single-blind parallel study was conducted in the Department of Pharmacology and Therapeutics in collaboration with the Department of Ophthalmology of a teaching institute over a period of six months after taking permission from the institutional ethics committee. It was a time bound study and all the newly registered cases of chronic simple glaucoma (who agreed to enter the study) on two specific OPD (out patient department) days per week, were included in the study.

Inclusion Criteria
A total of fifty newly diagnosed patients with seventy six eyes of chronic simple glaucoma, of both the sexes in the age group of 40 to 80 years, with painless diminution of vision, glaucomatous optic disc damage and glaucomatous field changes, attending the Ophthalmology OPD were initially enrolled for the study. All the patients were subjected to detailed medical and ophthalmic history assessment, complete medical and ocular examination, haematological tests like Hb, BT, CT , TLC , DLC and ESR , biochemical tests like L.F.T., RFT. and blood sugar fasting, urine for routine examination, X-ray chest and E.C.G .

Exclusion Criteria
Patients having one of the following conditions were excluded from the study :- a history of hypersensitivity to timolol ,betaxolol and levobunolol ,ophthalmic surgical procedures within three months of the study, a history of bronchial asthma or chronic obstructive pulmonary disease, cardiac dysfunction including sick sinus syndrome , sinus– bradycardia , 2nd or 3rd degree heart block, congestive heart failure and myocardial infarction within the past six months ,diabetes mellitus, myasthenia gravis , any systemic malignancy ,liver and renal diseases, psychiatric problems and use of more than one intraocular pressure lowering drugs or any other concommitant drug therapy.

Finally, 40 newly diagnosed patients with sixty two eyes were included in the study after complete screening for the exclusion criteria. The male:female ratio was 11:5, 5:7 and 7:5 in the timolol, levobunolol and betaxolol groups respectively. All patients had baseline (intraocular pressure) IOP>26mmHg. Written informed consent was obtained from all the patients. Fifty opaque envelopes containing random numbers (drugs in code forms), generated with the help of table of randomization, were prepared in advance by an investigator who was not related to the study. Whenever, a study participant was found to be eligible, an envelope was opened by another person in the department and the patient was put on the allocation plan as found inside the envelope in coded form. 23 eyes of 16 patients, 19 eyes of 12 patients and 20 eyes of 12 patients were randomized to receive 0.5% topical timolol maleate ( Iotim®-F.D.C. ltd ), 0.5% levobunolol hydrochloride (Betagan ® - Allergan ) and 0.5% betaxolol hydrochloride ( Optipress ® - Cipla ) respectively as 1 drop12 hourly instillation (Table/Fig 1) . 0.5% Timolol maleate, 0.5% levobunolol hydrochloride and 0.5% betaxolol hydrochloride were manufactured by FDC Pharmaceuticals Ltd., Allergan Pharmaceuticals and Cipla Pharmaceuticals respectively. All the study drugs were purchased from the market. Drugs in each group were from the same batch. However, the concentration of the drug reaching the systemic circulation has direct influence on the cardiovascular parameters. The selection of 23 eyes in 16 patients, 19 eyes in 12 patients and 20 eyes in 12 patients in the timolol, levobunolol and betaxolol groups respectively, was done due to ethical constraints and hence, study drugs were only instilled in the glaucomatous eyes and not in the healthy eyes of the patients.

Before providing drugs to the patients, the cover labels on the bottles were removed and replaced by paper slips containing the study code. Hence, the patients were not aware about the nature of the drug. All the patients were advised to instill eye drops at 10 o’clock in the morning and in the evening and to maintain a personal diary mentioning the time and date of instillation. Each patient was kept under treatment for 12 weeks and had to undergo three post–registration visits at 0, 6 and 12 weeks. Baseline intraocular pressure (IOP), systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate (PR) of each patient were recorded at ‘0’ week (Table/Fig 2).

IOP was recorded with the help of an air–puff applantation tonometer on pulse air-200 and a non–contact tonometer (canon T2). To avoid error in the IOP reading, the mean of three readings was recorded at each visit. Blood pressure was measured on the right arm by the same investigator using a standard mercury sphygmomanometer . Phase 1 and phase V Korotkoff’s sounds were used to determine systolic and diastolic blood pressure respectively. Basal blood pressure was measured in the sitting position. Radial pulse at the wrist was felt with the tips of the fingers, with the patient’s forearm being pronated and the wrist slightly flexed. The pulse rate was measured by counting the number of beats per minute. IOP, PR, SBP and DBP of all the patients were again recorded at 6 and 12 weeks before instillation of the next dose. Compliance of the patients was confirmed by checking the patient’s personal diary. Effects of the drugs on IOP, SBP, DBP and PR were measured as primary variables of the study. However, initially other cardiac complications could not be studied because of the short duration of the study.


Statistics
Effects of the individual drug on IOP, PR, SBP and DBP were analysed using paired t–test. P values <0.05 were taken as significant. 95% Confidence intervals (CI) were calculated according to the standard procedures laid down. Each parameter was expressed as mean ±SD (standard deviation) in tables or as mean ± SEM (standard error of mean) in the results. Comparative analysis of the effects of the three drugs on the above parameters was done by using the analysis of variance test (one way). .Inter-group comparison of the effect on IOP was done by using the Turkey test with a 95% confidence interval. For IOP, each eye was considered as a unit and for PR, DBP and SBP, each patient was considered as a single unit

Results

In the present study, topical timolol, levobunolol and betaxolol lowered IOP by 13.1 ± 1.5(CI= 9.8-16.3) , 14.1 ±1.5 (CI=10.9–17.1) and 7.6 ± 0.9 (CI=5.7-9.5) mm of Hg respectively, at 6 weeks and by 16.1±1.7 (CI=12.6-19.7),16.3 ±1.9(CI =12.4 – 20.2) and 8.5±0.9(CI=6.5-10.6) mm of Hg respectively, at 12 weeks(P<0.001) .Both timolol and levobunolol produced more reduction in IOP than betaxolol [after applying analysis of variance (degree of freedom –drug 2,within groups 59 = total 61) followed by Turkey test], with p-values 0.004 and 0.002 at 6 and 12 weeks respectively .

Topical timolol reduced the mean baseline PR (80.7±1.9 beats/min) by 3.5±0.3 (CI=2.81 – 4.19) and 4.4 ±0.4 (CI=3.60 - 5.14) beats/min at 6 and 12 weeks respectively (P value<0.001). Topical levobunolol reduced the mean baseline PR (77.7 ±2.4 beats/min) by 1.5±0.3 (CI=0.93 – 2.07) (P values<0.001) and 2.3±0.7 (CI= 0.90 - 3.76) beats/min (P values<0.01) at 6 and 12 weeks respectively. Topical betaxolol reduced the mean baseline PR (76.8 ±2.1 beats/min) by 2.2±0.3 (CI=1.59 – 2.73) and 2.5±0.5 (CI=1.5 -3.5) beats/min at 6 and 12 weeks of the study respectively (P value<0.001).

Topical timolol lowered the baseline SBP (136.8±3.9 mm of Hg) by 3.9±0.3(CI=3.62- 5.12) and 3.9±0.4 (CI=3.55 - 5.19) mm of Hg at 6 and 12 weeks respectively (p value<0.001); levobunolol lowered the baseline SBP (136.2 ±3.8 mm of Hg) by 1.2±0.5 (CI=2.50 – 4.16) and 1.7±0.6 (CI=1.90 - 4.42) mm of Hg (p value<0.001) at 6 and 12 weeks respectively ; betaxolol lowered the baseline SBP (134 ± 3.1 mm of Hg ) by 3.5±0.7 (CI=2.02 – 4.98) and 5 ± 0.9(CI=2.87 – 7.13) mm of Hg at 6 and 12 weeks respectively (p value<0.001).

Topical timolol lowered the baseline DBP (79±2.2 mm of Hg ) by 3.9±0.3(CI=3.18 – 4.56) and 3.9±0.4(CI=3.10 - 4.64) mm of Hg at 6 and 12 weeks respectively (p value<0.001), levobunolol lowered the baseline DBP (78.8±1.6mm of Hg) by 1.2±0.5 (CI=0.06 – 2.26) (p value<0.05) and 1.66±0.6 (CI=0.41–2.91) mm of Hg (p value<0.02) at 6 and 12 weeks respectively and betaxolol lowered the baseline DBP (77.7±2.2 mm of Hg) by 3.5±0.7 (CI=2.98 – 4.68) and 5 ± 0.9(CI=2.02 – 4.30) mm of Hg at 6 and 12 weeks respectively (p value<0.001). On comparative analysis using analysis of variance, it was found that there was no statistically significant difference in the effects produced by the three groups on PR, SBP and DBP, both at 6 and 12 weeks (Table/Fig 3),(Table/Fig 4) . No serious side-effect was reported in any of the groups.

Discussion

The β–blocker eye drops after topical administration in the eye, may reach the systemic circulation to produce bradycardia and an arterial hypotensive effect (8). Most of the effects of β–blockers are related to the two known receptor sites β1- receptors, associated with myocardial contraction and β2-receptors, related to vascular smooth muscles (9).Although bradycardia is a normal response to β-adrenergic blockade, in patients with partial or complete atrio-ventricular conduction defects, β-adrenergic antagonists may cause life threatening bradyarrhythmias (3). In our study, timolol, levobunolol and betaxolol produced significant reduction in PR, SBP and DBP in agreement with the previous reports (6),(7),(10). However, a few studies demonstrated a statistically insignificant change in PR, SBP and DBP with timolol ,levobunolol and betaxolol (9),(11),(12). The insignificant effect on PR, SBP and DBP in these studies may be because of the unsatisfactory wash out period and failure to abolish the preexisting effect of the β–blocker in the patients; as they were already receiving timolol therapy before their inclusion in the study .In 1985, Feghli G J et al also reported that there was no effect of betaxolol on blood pressure(BP) (13).The contradictory results of this study, as compared to the present study, may be because of the use of smaller concentrations (0.25%) of betaxolol; which might have failed to produce enough systemic concentrations to cause any notable change in BP. Moreover, in our study, there was no statistically significant difference in the effects produced by timolol, betaxolol and levobunolol on PR, SBP and DBP, in accordance with the previous reports (7),(9),(12),(14). Another study by Atkins JM et al demonstrated an insignificant effect on heart rate produced by 1% topical betaxolol single instillation as compared to the placebo during a ten minute treadmill exercise (2). Whereas, insignificant differences in effects produced by topical timolol and betaxolol on heart rate was reported in the above study, in accordance to our study (2).

However, small sample size and the short duration of the study could be considered as limitations of our study. Moreover, no serious cardiovascular complications were encountered in the three groups by us, as we excluded the patients having the potential for serious adverse reactions due to β–adrenergic blockade from the study. Thus, if there is no evidence of cardiac dysfunction, including sick sinus syndrome, sinus– bradycardia, 2nd or 3rd degree heart block and congestive heart failure, then any of the topical β–adrenergic blockers could be used (1). Still, while the patient is under treatment with topical drugs, he should be monitored for a change in BP and PR. However, β-blockers should be used with caution in patients having advanced glaucomatous optic atrophy, as they can further deteriorate the optical disc changes due to ischaemia (8)due to the hypotension brought about by them. Moreover, topical levobunolol, being a longer acting drug, could prove to be a safer alternative as once daily instillation (11). The gel form of timolol, having the advantages of an efficacy equal to timolol drops, prolonged duration of action, requirement of less frequent administration and poor systemic absorption, could also prove to be a better alternative to topical β-blocker drops (16). However, further studies are required to rationally establish the quantitative superiority of timolol gel over topical β-blocker drops with respect to systemic absorption and changes in cardiovascular parameters after a long duration of therapy. But one should always take caution while prescribing β-blocking drugs in a glaucoma patient with underlying cardiac abnormality .Moreover, absorption of the drug can be reduced by simple closure of the eye or by applying pressure at the base of the nasolacrimal mucosa (1),(15). It is vital that the doctor should give proper indications regarding the instillation of the eye drops and screen the patient for all possible contraindications before prescribing β-blocking drugs in a glaucoma patient.

References

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