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ORIGINAL ARTICLE
Year : 1989  |  Volume : 37  |  Issue : 4  |  Page : 176-178

The hypotensive effect of verapamil eye drops on ocular hypertension


J.K. JLN Medical College and Hospital, Ajmer-305 001, India

Correspondence Address:
J K Goyal
J.K. JLN Medical College and Hospital, Ajmer-305 001
India
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Source of Support: None, Conflict of Interest: None


PMID: 2638305

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  Abstract 

Verapamil eye drops (0.125%) were prepared in phosphate buffer (pH7). Ten patients with unilateral (5 cases) or bilateral (5 cases) ocular hypertension received the drug topically three times daily for two weeks. A significant reduction in the mean ocular tension was observed in 6 right eyes at the end of the first (4.5 mm Hg Schiotz) and second week (7 mm Hg Schiotz) and in 9 left eyes at the end of the second week (6.7 mm Hg Schiotz). The reduction in tension was minimal (1 mm Hg Schiotz) in the eyes with normal initial values. The systolic and diastolic blood pressured dropped by 12.8 mm Hg and 4.0 mm Hg in the first week and by 11.2 mm Hg and 5.4 mm Hg in the second week respectively. There was also a reduction in the mean pulse rate by 7 beats and 13 beats in the first and second week of therapy. These observations indicate persistent hypotensive effect of topical Verapamil on ocular hypertension and some amount of systemic absorption of the drug from eye.


How to cite this article:
Goyal J K, Khilnani G, Sharma D P, Singh J. The hypotensive effect of verapamil eye drops on ocular hypertension. Indian J Ophthalmol 1989;37:176-8

How to cite this URL:
Goyal J K, Khilnani G, Sharma D P, Singh J. The hypotensive effect of verapamil eye drops on ocular hypertension. Indian J Ophthalmol [serial online] 1989 [cited 2020 May 25];37:176-8. Available from: http://www.ijo.in/text.asp?1989/37/4/176/26054



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  Introduction Top


Calcium ions play a significant role in the muscular contraction and in the coupling of electric excitation to the cellular secretion [1]. The aqueous humor is a secre­tate and thus its formation is affected by several factors. The hydrostatic pressure in the ciliary arterioles plays an interaction between Calcium and Calmodulin in the vascular smooth muscles. A number of drugs are devel­oped which selectively inhibit the entry of Calcium inside the cell membrane and Verapamil is a prototype [2] The pharmacological profile of this agent is very similer to that of a number of B-adrenergic blocking drugs namely Timolol. The Latter is widely used in the treatment of glaucoma. A reduction in ocular tension for about 10 hours has been recently shown with a single instillation of Verapami1 [3].

The objective of the present work was to evaluate the effect of multiple doses (instillations) of topical Vera­pamil on ocular tension in patients with sustained ocular hypertension.


  Material and methods Top


Verapamil eye drops were prepared by diluting a paren­teral solution (inj. Isoptin 2.5 mgm/ml) with an equal Amount of phosphate buffer (pH7) to give a final strength of 0.125%. This was found to be nonirritating to rabbit and human eyes.

Ten patients enrolled in the present study were fully apprised of the purpose and an informed consent was taken individually. The criteria of exclusion were active ocular infection, unstable cardiovascular disease, pre­vious Betablocker intake, ocular surgery within the past six months and secondary glaucoma. Pregnant and nursing mothers were also excluded. Each patient was carefully evaluated and was included in the study when there was a persistant elevation of ocular tension equal to or greater than 21 mm Hg (Schiotz). Only two con­secutive higher readings were considered.

The baseline testing included measurment of pulse-rate and blood-pressure after 30 minutes rest, complete ocular examination and tonometry. The latter was per­formed by an experienced ophthalmologist with a stan­dard Schiotz .tonometer. The patients were given a supply of sterile Verapamil eye drops and were trained to instill 2 drops into each eye at 6 AM, 2PM and 10 PM regularly for 14 days. They were instructed to report on the 8th and 15th day or earlier if restlessness, headache, giddiness, redness of eye, swelling, blurring of vision or ocular itching occurred. The repeat measurements of pulse, blood-pressure and tonometry were performed at the end of the first and second week during the same time, in order to avoid the influence of diurnal variations in ocular tension on the results.


  Observations Top


All patients tolerated the eye drops very well and in one patient there was slight ocular itching felt on the first day but it disappeared with continued instillations. Of the 10 patients, 5 had unilateral and an equal number had bilateral ocular hypertension. Thus, out of 20 eyes, six right and nine left eyes recorded elevated tension and 5 eyes (4 right and 1 left) were normotensive. The initial levels of ocular tension are shown in [Table - 1]. Verapamil use resulted in a reduction of tension in the first and second week. In the first week there was a reduction (mean.SD) of 4,52. 1.73 (17%) and 2.54.3.81 (9%) mm Hg in six right and nine left eyes. In the second week, a drop of 7.0. 2.87 and 6.66. 2.09 mm Hg was recorded in the 'corresponding eyes. The paired 't' test analysis showed that these reductions were significant over baseline values, in the right eyes in the first and second week and in the left eyes in the first and second week in the left eyes in the second week. In 4 normotensive right eyes the tension dropped by 1.0 mm (6%) only and in one left eye with normal initial tension, a slight and insignifi­cant rise ws recorded which was in the normal range.

The initial and the subsequent values of blood-pressure and pulse-rate are shown in [Table - 2]. A mean drop in the pulse-rate was by 7 and 10 beats in the first and second week respectively. The reductions in systolic blood pres­sure by 13 mm and 11 mm and in diastolic pressure by 4 mm and 5.4 mm in the corresponding period. The fall in the mean diastolic pressure was not significant (p 0.05) and in one case only it fell from 80 mm Hg. to 66 mm Hg. at the end of study. Although reduction in the mean systolic pressure was significant statistically (p 0.01), the individual systolic pressures were equal to or above 110mm Hg except in one case in which it was 90 mm Hg at the end of one week of study. Similarly in no case a pulse rate below 70/min was recorded at any time of study. These findings show that although systemic absorption occurs, symptomatic hypotension or bradycar­dia do not occur clinically.


  Discussion Top


The preliminary results of this trial show a significant ocular hypotensive effect of Verapamil eye drops. The effect is profoundly seen in patients with ocular hyper­tension than is those with tensions within normal range. This drop in ocular tension is comparable to that achieved by 0.25% Timolol eye drops instilled twice daily [4]. Our findings are in accordance with the earlier work of Abelson et all but differ from them in not observing contralateral effects as we have used eye drops in both the eyes. Oral administration of Nitendipine, another. Calcium channel blocker, has been shown to drop ocular tension significantly'. This effect was attributed to its peripheral vasodilating effects. Beatty and associates [6] observed a slight rise (1-2%) making the comparisons difficult.

In the present study there has been some depressant effect of topical Verapamil on heart rate and systolic blood pressure. This can be due to some systemic ab­sorption of Verapamil from the eye. Systemic absorption of drugs through ocular tissues is well known for several drugs [7],[8]. Thus a caution is warranted in the use of Vera­pamil in patients with cardiovascular depression but, it may become a drug of choice if the patient suffers from systemic hypertension.

The machanism of ocular hypotensive effect of the drug remains to be elucidated. It may be attributed to its vasodilatory actions on the arterioles [2] or may be a local effect on the secretory epithelium. The inflow, of the aqueous mayalso be decreased due to alterations in the permeability of the ciliary epithelium by Verapamil in­duced changes in the gap junctions between pigmented and nonpigmented -ciliary epithelial cells [9]. Normally, Calcium concentration in the aqueous fluid is about half that of plasma [10] and this may also be altered by the drug. Verapamil may affect the outflow facility by an unknown mechanism. A major advantage of Verapamil over Timolol is that it can safely be given in patients with pre-existing chronic obstructive pulmonary disease and bronchi) asthma. In these disorders Timolol is not a preferred agent.

 
  References Top

1.
Drieffuse, J.J., Green, J.D. and Nordmann, J.J. international symposium on calcium transport in contraction and secretion. Amsterdam. N. Hollant. PP 271-9,1975.  Back to cited text no. 1
    
2.
Antmann, E.M., Stone, P.H. Muller, J.E. and Braunwald, E. Annal. Int. Med. 93:875,1980.  Back to cited text no. 2
    
3.
Abelson, M.B., Gilbert, C.M. and Smith, L.M: Am J. Ophthal:155 1988.  Back to cited text no. 3
    
4.
Batacher,E.D., O'Day, D.M., Shand, D.G. and Wood, A.J.: Trans Am. Aced. Ophthal. 86:60,1979.  Back to cited text no. 4
    
5.
Monica, M.L., Hesse, R.J. and Messerli, F.H.: Am. J. Ophthal. 96:814,1988.   Back to cited text no. 5
    
6.
Beatty, J.E., Krupin, T.,Nicholas, P.F and Becker.: Arch Ophthal 102:1072,1984.  Back to cited text no. 6
    
7.
Havener, W. H. Pharmacokinetics-Routes of Administration. In Ocular Pharma cology, C.V. Mosby Company, Toronto. 5th Ed. pp. 22,302, 1983.  Back to cited text no. 7
    
8.
Katz, I.M. and Berger E.T.: Glaucoma. 3:147,1981.  Back to cited text no. 8
    
9.
Caprioll, J. The cilliary Epithelia and aqueous Humor. In the Adler's physiology of Eye. Ede. Moses. R and Hart, W. 8th Ed. C.V. Mosby, Company Toronto. pp. 204:222, 1987.  Back to cited text no. 9
    
10.
Green, Kand Girsch, S.J.: Heart Cire. Physiol. 17:H765. Quoted from Ref. No.3,1985.  Back to cited text no. 10
    



 
 
    Tables

  [Table - 1], [Table - 2]


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