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ORIGINAL ARTICLE
Year : 1988  |  Volume : 36  |  Issue : 2  |  Page : 64-66

"Effect of topical timolol on intraocular pressure in the presence of systemic indomethacin in normal subjects"


Sud, 96-B, Kitchlu Nagar, Ludhiana-141 001. Punjab, India

Correspondence Address:
R N Sud
Sud, 96-B, Kitchlu Nagar, Ludhiana-141 001. Punjab
India
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Source of Support: None, Conflict of Interest: None


PMID: 3235163

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  Abstract 

In the present study on 60 normal subjects, the effect of 0.5% timolol eye drops on intraocular tension was assessed in the presence of oral indomethacin. The subjects were categorized in four groups for comparing the results. Also the side effects of timolol maleate were noted. The following conclusions were made:­
1. In cases in whom indomethacin was given along with timolol drops, average fall in intraocular tension was almost identical with those in whom timolol alone was used.
2. The ocular hypotensive effect of timolol maleate eve drops is not attenuated by indomethacin given orally; but before we can conclude that the simultaneous administration of timolol maleate eye drops and indomethacin is entirely without risk of attenuation. We must study the effect of combined administration in patients with glaucoma.


How to cite this article:
Sud R N, Malhotra A. "Effect of topical timolol on intraocular pressure in the presence of systemic indomethacin in normal subjects". Indian J Ophthalmol 1988;36:64-6

How to cite this URL:
Sud R N, Malhotra A. "Effect of topical timolol on intraocular pressure in the presence of systemic indomethacin in normal subjects". Indian J Ophthalmol [serial online] 1988 [cited 2020 Aug 5];36:64-6. Available from: http://www.ijo.in/text.asp?1988/36/2/64/26147


  Introduction Top


Indomethacin, a prostaglandin synthesis inhibitor, was introduced in 1963 for the treatment of rheumatoid arthritis and related disorders. Waitzman and King [1]; and Beitch and Eakinsz [2] showed that prostaglanding PGE 1 or PGE 2 administered into the anterior chamber of rabbit's eye, caused a large elevation of intraocular pressure and Waitzman [3] found that indomethacin caused inhibition of prostaglandin synthesis. It was hypothesised by Watkins and associates [4] that prostaglandin synthesis inhibitors, like indomethacin may attenuate the effect of beta blockers.

Lichter et al [5] conducted a randomized double masked study on 24 healthy normal subjects to determine whether intraocular pressure lowering effect by the beta blocker, timolol maleate, might be inhibited by a prostaglandin synthesis inhibitor, indomethacin. The results showed that a statistically significant drop in intraocular pressure was obtained in the group receiving timolol maleate eye drops alone (p < .01) and that this effect was attenuated with the addition of indomethacin. But in a later study, Lichter et all found no significant difference in the fall of intraocular pressure after timolol and indomethacin, from that after timolol and placebo.


  Material and Methods Top


The present study was undertaken on sixty persons of Indian origin, mostly Punjabi, with normal eyes. They were divided into four groups, A, B, C and D, of 15 each.

In Group A, each subject received timolol 0.5% drops twice a day for three days and placebo tablets three times a day for three days; in group B, 25 mg indomethacin three times a day for three days and placebo drops twice a day for three days; in group C, timolol0.5% drops twice a day for three days and 25 mg indomethacin tablets three times a day for three days and in group D, placebo drops twice a day for three days and placebo tablets three times a day for three days. Intraocular tension, pulse, blood pressure and respiration rate were noted on zero day & 4th day. Any complication during the procedure, local or systemic, was noted.


  Observations Top


The following observations were made:

It was observed that in Group A, the average intraocular tension at the start of the procedure in the right eye was 17.72 mm Hg, which fell to 13.05 mm Hg thus showing a fall of 4.67 mm Hg. In the left eye the average intraocular pressure at the start of the procedure was 17.68 mm Hg. which fell to 13.61 mm Hg., thus showing a fall of 4.07 mm Hg. (Bar Chart). The fall in intraocular tension in this group was statistically significant up to 0.1 % in both eyes.

In Group B, the average intraocular tension at the start of the procedure in the right eye was 16.36 mm Hg which fell to 15.7 mm Hg ID the left eye, the average intra­ocular pressure at the start of procedure was 16.26 mm Hg; which fell to 15.72 mm Hg The right eye showed a fall of 0.86 mm Hg and the left eye 0.54 mm Hg (Bar Chart). In this group, in both eyes, the fall in intraocular tension was not statistically significant.

In Group C, the average intraocular pressure in the right eye at the start of procedure was 16.34 mm Hg which fell to 11.93 mm Hg. showing a fall of 4.41 mm Hg In the left eye, the intraocular pressure at the start of the procedure was 16.18 mm Hg., which fell to 12.03 mm Hg, thus showing a fall in intraocular pressure of 4.15 mm Hg (Bar Chart). This fall in intraocular tension was statistically significant up to 0.1 % in both eyes.

In Group D, the average intraocular pressure in the right eye before treatment was 16.21 mm Hg which fell to 16.03 mm Hg, thus showing a fall of O. 18 mm Hg In the left eye, the average intraocular pressure before the start of the procedure was 16.08 mm Hg which fell to 15.72 trim Hg thus showing a fall of0.36 mm Hg (Bar Chart). This fall in intraocular tension was not statistically significant in both eyes

No side effects were observed in any of the groups, and there was no change in pulse, blood pressure and respir­ation.


  Discussion Top


In our study, in Group A, the maximum fall in intra­ocular tension from the base line was 8.4 mm Hg, the minimum fall recorded was 2.7 mm Hg, while two eyes had no fall in intraocular tension and the overall average fall in intraocular pressure was 4.67 mm Hg, in the right eye and 4.07 mm Hg, in the left eye. This fall in intraocular tension was statistically significant up to 0.1 % in both eyes In a similar study by Lichter et a1 [6], the average fall in intraocular pressure was 3.6 mm Hg in the right eye and 3.4 mm Hg in the left eye, which is less than that in our study. In Group C, the average fall in intraocular tension after treatment was 4.41 mm Hg, in the right eye and 4.15 mm Hg, in the left eye but this fall was more than that obtained by Lichter et a1 [6] which was 3.1 mm Hg, in each eye. In both Group A and Group C, the fall in intraocular tension was almost identical and statistically significant up to 0.1% in both eyes These results show that whether indomethacin tablets or placebo tablets are given, the fall in intraocular tension with timolol maleate is identical. The results in our study are identical to those of Lichter et al [6] in their later study i.e. there was no attenuation of effect of timolol on, intraocular tension in the presence of indomethacin.

In a study on 24 healthy normal subjects, Lichter et a1 [5] showed that a statistically significant drop in intraocular pressure was obtained in the group receiving timolol maleate eye drops alone and that this effect was attenu­ated with the addition of indomethacin. Later on, Lichter et al [l] in a randomized, double masked, crossover study of nine healthy subjects showed an average fall in intraocular pressure of 3.6 mm Hg, in the right eye and 3.4 mm Hg, in the left eye with timolol and placebo; the average fall in intraocular pressure with timolol and indomethacin was 3.1 mm Hg, in both eyes and this concluded that simultaneous administration of timolol maleate eye drops and indomethacin is entirely without risk of attenuation

In Group B of our study, the mean base-line intraocular pressure at the start of the procedure was 16.36 mm Hg, in the right eye and 16.26 mm Hg, in the left eye and after giving indomethacin tablets and placebo drops the average fall of intraocular tension was 0.66 mm Hg, in right eye and 0.54 mm Hg, in the left eye and this fall was statistically insignificant BaikofL Charbonnel and Kremer' suggested that during ocular inflammation prostaglandin, PGF 2 and PGE 2 were increased and this might be accompanied by a decrease in intraocular pressure and a potent cyclo- oxygenase inhibitor such as indomethacin might be expected to cause an increase in intraocular pressure, independent of any effect of timolol. In our study indomethacin showed no change on intraocular pressure. This observation is similar to that of a separate study by Lichter et al [6] who showed that in six volunteers the administration of indomethacin 25 mg. three times a day for three days alone did not result in a significant change in intraocular pressure.

In Group D of our study (where placebo drops and placebo tablets were used) the average fall in intraocular pressure was O.18 mm Hg, and0.36 mm Hg, in the right and left eye respectively, but this fall in intraocular pressure was not statistically significant as this can be due to a variation in the intraocular pressure[7].

 
  References Top

1.
Waitzman M. B., King C. D., prostaglandin influence on intraocular pressure and pupil size. Am J. Physiology. 212(2) : 329-334, 1967.  Back to cited text no. 1
    
2.
Beitch RR, Eakins KE., the effects of prostaglandins on the intraocular pressure of rabbit Brit J. Pharmacology. 37 : 158, 1969.  Back to cited text no. 2
    
3.
Waitzman M. B., topical indomethacin in treatment and prevention of intraocular inflammation with special reference to lens extraction and cystoid macular oedema Ann. Ophthal. 11 (3), 489-91, March, 1979.  Back to cited text no. 3
    
4.
Watkins, J; Abet E.C; Hensby C WebsterJ; Dollery C.T., attenuation of hypotensive effect of propranolol and thiazide diuretics by indomethacin. Brit Med. J. 281 : 702, 1980.  Back to cited text no. 4
    
5.
Lichter M, Feldman F, Cohen M. M., Clark L Effect on intraocular pressure of indomethacin and timolol maleate in normal subjects. Am. J. Ophthal. 96 :380, 1983.  Back to cited text no. 5
    
6.
Uchter M, Feldman F, Cohen M. M., Clark L, effect of indomethacin on the ocular hypotensive action of timolol maleate. Am J. Ophthai 98: 79-81, 1984.  Back to cited text no. 6
    
7.
Baikofl G; Charbonnel, B and Kremmer, M. Dosage des prostag­landins dens I humeur aqueuse humaine apres implant intraocu­laire. J. Fr. Ophthal 4 : 592, 1981.  Back to cited text no. 7
    


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Introduction
Material and Methods
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