Year : 1995 | Volume
: 43 | Issue : 2 | Page : 73--74
Topical timolol and lipid profile
J Murli Manoher, AK Sharma, R Sahai
From The Department of Ophthalmology, S.P. Medical College, P.O. Bikaner District, Rajasthan, India
J Murli Manoher
From The Department of Ophthalmology, S.P. Medical College, P.O. Bikaner District, Rajasthan
To evaluate the effects of topical timolol on lipid profile, blood samples from 25 patients (16 males and 9 females) were analysed before topical instillation of 0.5% timolol maleate and thereafter at one month and two months. After two months of therapy, the level of high density lipoprotein (HDL) decreased significantly (p < 0.02). The levels of low density lipoprotein (LDL), very low density lipoprotein (VLDL) and triglyceride increased but the changes were not statistically significant. Since low level of HDL is strongly associated with increased risk of myocardial infarction, our study cautions use of topical timolol in patients with low levels of HDL or with previous history of coronary heart disease.
|How to cite this article:|
Manoher J M, Sharma A K, Sahai R. Topical timolol and lipid profile.Indian J Ophthalmol 1995;43:73-74
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Manoher J M, Sharma A K, Sahai R. Topical timolol and lipid profile. Indian J Ophthalmol [serial online] 1995 [cited 2019 Sep 20 ];43:73-74
Available from: http://www.ijo.in/text.asp?1995/43/2/73/25261
Topical beta-adrenergic antagonists such as timolol maleate and betaxolol are frequently used ocular hypotensive agents. Timolol maleate is a nonselective beta-1 and beta-2 antagonist that lacks intrinsic sympathomimetic activity and membrane stabilizing properties. The beta-adrenergic antagonists are prescribed commonly because they are effective in a wide variety of glaucoma conditions and do not produce certain annoying ocular side effects of pilocarpine such as miosis and myopic shift in refraction. However, sufficient amount of these drugs are absorbed through nasal mucosa to cause systemic beta-adrenergic blockade in normal volunteers. The systemic absorption of these drugs change the lipid profile of the body. They reduce the high density lipoprotein (HDL) level of the body and thereby increase the risk of coronary heart disease. However, Longstall found no effect on serum lipoprotein after treatment with topical timolol.
MATERIALS AND METHODS
The patients attending the Department of Ophthalmology, P.B.M. Hospital, Bikaner, were included in this study. The investigations were done in the Department of Biochemistry, S.P. Medical College, Bikaner. A detailed history of present as well as past illness of the patients were taken. The subjects using beta-adrenergic antagonist medication for at least one month prior to recruitment into the study or having a history of diabetes, bronchial asthma, cardiovascular diseases, pregnancy in the past 6 months, were excluded from this study. None of the subjects were using any of the following medications that may alter plasma lipid level: diuretics, antihypertensive, oral contraceptives, steroids, hypercholesterolemic agents and adrenergic antagonist. All volunteers underwent a detailed medical and ocular history, an ophthalmic examination that included measurement of intra-ocular pressure with Schiotz tonometer and fundus examination to assess the optic disc. Body weight was recorded and the subjects were instructed not to change their dietary habits during the study.
Blood Sample Collection and Storage
Venous blood of overnight fasting individuals was obtained and serum was separated. All patients were advised to instil 0.5% timolol maleate eye drops twice a day for two months. Serum samples were collected to study the effect of timolol maleate one month and two months following the recruitment. The total serum cholesterol was estimated by Sackett's method and the serum HDL cholesterol was measured by using precipitants phosphotungstate/mg. Estimation of triglyceride was done by enzymatic GPOPAP method. The total low density lipoprotein (LDL) and very low density lipoprotein (VLDL) were measured by using the formula given by Friedwald.
A total of 30 patients were recruited into the study. Five patients were excluded due to non-compliance or irregular follow-up visits. Of the remaining 25 patients, 16 (64%) were males and 9 (36%) were females. The average age was 50.51 years and 41.00 years in the male and female patients, respectively. No patient suffered from any ocular side effects except for occasional burning sensation after topical instillation of timolol.
The mean HDL level before topical timolol therapy was 58.6 ± 9.93 mg%. After one month of therapy, the HDL level decreased by 3.5% (56.5 ± 9.77 mg%) and it further decreased to 51.5 ± 9.35 mg% two months following therapy. The change in the HDL level after one month of therapy was not significant (p < 0.8); however, the change in the level after two months of therapy was significant (p < 0.02). The VLDL and serum triglyceride levels increased after one and two months, but this change was statistically not significant. The LDL level increased after one and two months but was also not significant (p < 0.5). The total change in serum cholesterol was also not significant after topical timolol (Table).
Topical administration of, beta-adrenergic antagonists generally yield a sufficient concentration in the systemic circulation, and thereby produce systemic side effects. However, Longstallfound no significant effects on serum lipoproteins after 15 weeks of topical timolol therapy. In another study, 28 subjects used topical timolol for an average of 76 days. The HDL level decreased by 9%, which was statistically significant. The mean total cholesterol and LDL levels did not change significantly. Another randomised crossover study designed to compare the effects of two topical nonselective beta-adrenergic antagonists, carteolol and timolol, on plasma high density lipoprotein cholesterol level showed carteolol treatment decreased HDL level by 3.3%, while timolol decreased HDL level by 8.0%. These changes, e.g., decreased level of HDL, increased levels of triglyceride and LDL are consistent with the findings of Coleman et al and Freedman et al.
Topical timolol twice a day adversely affected the plasma HDL, cholesterol and triglyceride levels in 25 subjects. However, the total cholesterol and LDL cholesterol levels were not affected significantly. The mean HDL level decreased by 12% after two months of topical timolol application in both the eyes. The decrease in the level of HDL is associated with increased risk of coronary heart disease. A 8.7% elevation of triglyceride is less strongly associated with coronary heart disease.
Therefore, our study indicates that topical timolol should be given cautiously in patients who have either low levels of HDL, higher levels of triglyceride, or previous history of coronary heart disease as well as glaucoma. A lower drug concentration, smaller drop size, once-a-day dosage, the practice of nasolacrimal occlusion and eye lid closure may markedly reduce systemic absorption of topical beta adrenergic antagonists and thus reduce any effects on plasma lipid level.
|1||Coleman AL, Chris Diehl BL, Henry D, et al. Topical timolol decreases plasma high density lipoprotein level. Arch Ophthalmol 108:1260-1263, 1990.|
|2||Longstalll WJ. Topical timolol and serum lipoprotein. Br J Ophthalmol 74:663-664, 1990.|
|3||Sackett. Practical Clinical Biochemistry. Varlay H, Gowen lock AH, Bekl M. William Heinmann. Medical Books Ltd, 4th Ed., pp. 309.|
|4||Burstein, et al. Practical Clinical Biochemistry. Varley H, Gowen lock AH, Bekl M. William Henimann. Medical Books Ltd., 5th Ed., pp. 665, 1970.|
|5||Friedwald WT, Levy RI, Fredrickson DS. Estimation of concentration of LDL Cholesterol in plasma without use of preparative ultracentrifuge. Clin Chem 18:499, 1972.|
|6||Freedman SF, Freedman NJ, Shields MB, et al. Effects of ocular carteolol and timolol on plasma high-density lipoprotein cholesterol level. Am J Ophthalmol 116:600-611, 1993.|
|7||Gordon T, Castelli WP, Hjotland MC, et al. High density lipoprotein as a protective factor against CHD: The Framingham Study. Am J Med 62:704-714, 1977.|
|8||Kannel WB, Castelli WP, Gordon T. Cholesterol in the prediction of atherosclerotic disease: New perspectives based on the Framingham Study. Ann Intern Med 90:85-91, 1979.|
|9||Wilson PW, Gaurison RJ, Castelli WP, et al. Prevalence of coronary heart disease in the Framingham Offspring Study: Role of lipoprotein cholesterols. Am J Cardiol 46:649-654, 1980.|