Advertisement

Drugs & Aging

, Volume 12, Issue 3, pp 225–241 | Cite as

Brimonidine

A Review of its Pharmacological Properties and Clinical Potential in the Management of Open-Angle Glaucoma and Ocular Hypertension
  • Julie C. AdkinsEmail author
  • Julia A. Balfour
Adis Drug Evaluation

Abstract

Synopsis

Brimonidine is a highly selective α2- adrenoceptor agonist which reduces intraocular pressure (IOP) by reducing aqueous humour production and increasing aqueous humour outflow via the uveoscleral pathway. Brimonidine is indicated for the topical management of open- angle glaucoma or ocular hypertension.

In 3 large comparative studies in patients with open- angle glaucoma or ocular hypertension, the ocular hypotensive efficacy of brimonidine was maintained during treatment periods of up to 1 year. Mean reductions in peak (measured 2 hours after the morning dose) and trough (measured 12 hours after the evening dose) IOP were 5.6 to 5.9 and 3.3 to 3.7mm Hg, respectively, after 3 or 12 months of treatment with brimonidine 0.2% twice daily. The efficacy of brimonidine in this setting was similar to that of timolol 0.5% twice daily at peak only (−6.0mm Hg), and superior to that of betaxolol 0.25% twice daily at both peak (−3.5mm Hg) and trough (−2.7mm Hg). When added to topical β-adrenoceptor antagonist therapy, initial results showed brimonidine 0.2% twice daily to have additive ocular hypotensive efficacy similar to that of pilocarpine 2% 3 times daily. Thus, brimonidine 0.2% may be a useful adjunct in this setting.

According to combined data from 2 large comparative studies, the most frequent adverse events associated with brimonidine therapy were oral dryness (30.0% of patients), ocular hyperaemia (26.3%) and ocular burning and/or stinging (24.0%). Ocular allergic reactions including allergic blepharitis, blepharoconjunctivitis and follicular conjunctivitis occurred with an incidence of 9.6% in 1 study. In a third comparative study, the incidence of adverse events associated with brimonidine therapy was lower, with conjunctival hyperaemia (11.4%) the most frequently reported event. Changes in systolic and diastolic blood pressure and, to a lesser extent, heart rate have been reported in patients treated with therapeutic doses of topical brimonidine for up to 12 months, but these changes were not clinically significant. Unlike β-adrenoceptor antagonists, brimonidine is not contraindicated in patients with cardiopulmonary disease, although it should be used with caution in individuals with severe cardiovascular disease.

Thus, further studies are warranted to determine the efficacy of brimonidine when used in combination with other glaucoma medications and its efficacy relative to newer drugs such as dorzolamide and latanoprost. However, available data suggest that brimonidine is a promising alternative option for the lowering of IOP in the management of open- angle glaucoma and ocular hypertension, particularly in patients with cardiopulmonary disease in whom topical β -adrenoceptor antagonist therapy is contraindicated.

Pharmacodynamic Properties

Brimonidine is a highly selective α2-adrenoceptor agonist which has markedly greater affinity for α2-adrenoceptors than apraclonidine (23- to 32-fold) and clonidine (6- to 12-fold).

Brimonidine lowers intraocular pressure (IOP) by a dual mechanism of action, involving a reduction in aqueous humour production and an increase in aqueous humour outflow via the uveoscleral pathway. In patients with ocular hypertension, unilateral treatment with brimonidine 0.2% twice daily for 1 week significantly reduced aqueous humour flow (20%) and increased uveoscleral outflow (approximately 5-fold) in the treated eye. Aqueous humour flow was also reduced by 12% in the contralateral eye.

Brimonidine lowers IOP in animals and humans with normotensive or hypertensive eyes. In humans, single ocular doses of brimonidine 0.08, 0.2 and 0.5% reduced IOP for up to 12 hours, with a peak hypotensive effect occurring at 2 hours. Initial pharmacodynamic studies also suggest that, as with other α2-adrenoceptor agonists, the drug may have a neuroprotective effect; however, further research is required to confirm this.

Although topical brimonidine (50 to 500μg) produced miosis in some animal studies, clinically significant changes in pupil size did not occur in humans. Data from animal and human studies suggest that brimonidine does not significantly alter ocular blood flow.

Changes in systolic and diastolic blood pressure and, to a lesser extent, heart rate have been reported in patients and healthy volunteers treated with therapeutic doses of topical brimonidine; however, these changes were not associated with adverse clinical effects. In 3 large comparative studies, brimonidine 0.2% twice daily for up to 12 months had a minimal effect on systolic (mean change −3.52 to +0.64mm Hg) and diastolic blood pressure (−1.7 to +1.04mm Hg) and heart rate (−0.1 to −3.1 beats/min).

Pharmacokinetic Properties

Studies in rabbits suggest that the intraocular absorption of brimonidine occurs primarily via the cornea and, to a lesser extent, via the conjunctival and scierai pathways. In this species, the ocular absorption and retention of brimonidine are increased by drug binding to ocular melanin. Peak drug concentration and terminal elimination half-life values in the iris-ciliary body were, respectively, approximately 4- and 580-fold greater in pigmented than albino rabbits’ eyes after a single dose of brimonidine 0.5% (20.1 vs 5.0 mg/L and 580 vs 1 hours).

In common with other drugs applied topically to the eye, brimonidine can enter the systemic circulation; peak plasma concentrations were <0.3 μg/L after administration of a single ocular dose of brimonidine (0.08 to 0.5%) to both eyes of healthy volunteers. The plasma elimination half-life of brimonidine was approximately 2 to 5 hours.

In vitro and in vivo studies suggest that brimonidine undergoes extensive hepatic metabolism, mainly by liver aldehyde oxidase to produce oxo- and dioxo-brimonidine derivatives. In animal studies, urinary excretion was the major route of elimination, accounting for approximately 60 to 75% of an orally or intravenously administered dose.

Therapeutic Potential

In a dose-ranging study in 186 patients with glaucoma or ocular hypertension, topical administration of brimonidine 0.08, 0.2 and 0.5% twice daily produced significant reductions in mean morning IOP throughout a 1-month treatment period. After 28 days of treatment 16, 31 and 21% of patients, respectively, treated with brimonidine 0.08, 0.2 and 0.5% experienced a ≥20% reduction in IOP. A dose-frequency study showed similar efficacy with twice-daily and 3-times-daily administration of brimonidine 0.2%.

In 3 large double-masked comparative studies, the ocular hypotensive efficacy of brimonidine was maintained during treatment periods of up to 1 year. Brimonidine 0.2% administered twice daily was almost as effective as timolol 0.5% and more effective than betaxolol 0.25% both administered twice daily. After 3 or 12 months of treatment, mean reductions in peak (measured 2 hours after the morning dose) and trough (measured 12 hours after the evening dose) IOP ranged from 5.6 to 5.9 and from 3.3 to 3.7mm Hg, respectively, with brimonidine. Corresponding reductions were 6.0 and 5.9mm Hg with timolol and 3.5 and 2.7mm Hg with betaxolol. Timolol was significantly more effective than brimonidine at reducing trough IOP Clinically significant effects on cup-to-disc ratio and visual field were not demonstrated with any drug in these studies.

Initial results suggest that brimonidine 0.2% twice daily may be a useful adjunct in the management of patients with primary open-angle glaucoma or ocular hypertension inadequately controlled with topical β-adrenoceptor antagonist therapy.

Tolerability

According to combined tolerability data from 2 large comparative studies (n = 513), dry mouth (30.0%), ocular hyperaemia (26.3%), ocular burning and/or stinging (24.0%), headache (18.7%), blurred vision (17.5%), foreign body sensation (17.0%) and fatigue and/or drowsiness (15.8%) were the most frequent adverse events among patients treated with brimonidine 0.2% twice daily for 6 or 12 months. Other ocular adverse events including pruritus, allergy, corneal staining and erosion and conjunctival follicles occurred in <11% of patients. In these studies, brimonidine was associated with a significantly higher incidence of dry mouth (30 vs 15.5%), ocular allergy (9.6 vs 0.2%) and conjunctival follicles (7.8 vs 2.9%) than timolol (0.5% twice daily; n = 413), whereas ocular burning and stinging were significantly more common with timolol (40.7 vs 24.0%). All other reported adverse events occurred with a similar frequency in the 2 treatment groups.

In another comparative study, brimonidine 0.2% twice daily was associated with a significantly lower incidence of blurred vision than betaxolol 0.25% twice daily (0 vs 5.0%) but tended to cause more ocular allergy (4.8 vs 0%). Although ocular allergy may develop during brimonidine treatment, it appears to occur far less frequently than with the α2-adrenoceptor agonist apraclonidine.

Changes in systolic and diastolic blood pressure and heart rate have been reported in patients treated with therapeutic doses of topical brimonidine for up to 12 months, but these changes were not clinically significant.

Dosage and Administration

In the management of open-angle glaucoma and ocular hypertension, the recommended dose of brimonidine is 1 drop of a 0.2% solution instilled into the affected eye(s). The recommended dosage regimen is 3 times daily in the US and twice daily in all other countries where the drug is approved.

Brimonidine may impair the ability to drive or operate machinery. It should be used with caution in patients with severe cardiovascular disease, hepatic or renal impairment, depression, cerebral or coronary insufficiency, Raynaud’s phenomenon, orthostatic hypotension or thromboangiitis obliterans. Brimonidine should not be used in patients receiving monoamine oxidase inhibitors. Caution is also recommended in patients receiving concomitant β-adrenoceptor antagonists, antihypertensives, cardiac glycosides or tricyclic antidepressants.

Wearers of soft contact lenses should allow a period of at least 15 minutes to elapse between instillation of the drug and insertion of their lenses.

Keywords

Glaucoma Adis International Limited Timolol Ocular Hypertension Betaxolol 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Burke J, Schwartz M. Preclinical evaluation of brimonidine. Surv Ophthalmol 1996 Nov; 41Suppl. 1: S9–18PubMedCrossRefGoogle Scholar
  2. 2.
    Chien DS, Homsy JJ, Gluchowski C, et al. Corneal and conjunctival/scleral penetration of p-aminoclonidine, AGN-190342, and clonidine in rabbit eyes. Curr Eye Res 1990 Nov; 9: 1051–9PubMedCrossRefGoogle Scholar
  3. 3.
    Quigley HA. Open-angle glaucoma. N Engl J Med 1993 Apr; 328(15): 1097–106PubMedCrossRefGoogle Scholar
  4. 4.
    Dreyer EB. Preserving eyesight with foresight. Harvard Health Lett 1994 Oct; 19: 4–6Google Scholar
  5. 5.
    Sommer A. Intraocular pressure and glaucoma. Am J Ophthalmol 1989; 107(2): 186–8PubMedGoogle Scholar
  6. 6.
    Klein BEK, Klein R, Sponsel WE, et al. Prevalence of glaucoma: the Beaver Dam Eye Study. Ophthalmology 1992; 99: 1499–504PubMedGoogle Scholar
  7. 7.
    Burke J, Manlapaz C, Kharlamb A, et al. Therapeutic use of α2-adrenoceptor agonists in glaucoma. In: Lanier S, Limbird L, editors. Alpha2-adrenergic receptors: structure, function and therapeutic implications. Reading: Harwood Academic Publishers, 1996: 179–87Google Scholar
  8. 8.
    Cambridge D. UK-14,304, a potent and selective α2-agonist for the characterisation of α-adrenoceptor subtypes. Eur J Pharmacol 1981; 72: 413–5PubMedCrossRefGoogle Scholar
  9. 9.
    Toris CB, Gleason ML, Camras CB, et al. Effects of brimonidine on aqueous humor dynamics in human eyes. Arch Ophthalmol 1995 Dec; 113: 1514–7PubMedCrossRefGoogle Scholar
  10. 10.
    Burke J, Kharlamb A, Shan T, et al. Adrenergic and imidazoline receptor-mediated responses to UK-14,304-18 (brimonidine) in rabbits and monkeys: a species difference. Ann N Y Acad Sci 1995 Jul 12; 763: 78–95PubMedCrossRefGoogle Scholar
  11. 11.
    Matsuo T, Cynader MS. Localization of alpha-2 adrenergic receptors in the human eye. Ophthalmic Res 1992; 24: 213–9PubMedCrossRefGoogle Scholar
  12. 12.
    Serle JB, Steidl S, Wang R-F, et al. Selective α2-adrenergic agonists B-HT 920 and UK14304-18. Effects on aqueous humor dynamics in monkeys. Arch Ophthalmol 1991 Aug; 109:1158–62PubMedCrossRefGoogle Scholar
  13. 13.
    Gabelt BT, Robinson JC, Hubbard WC, et al. Apraclonidine and brimonidine effects on anterior ocular and cardiovascular physiology in normal and sympathectomized monkeys. Exp Eye Res 1994 Dec; 59: 633–44PubMedCrossRefGoogle Scholar
  14. 14.
    Serle JB, Podos SM, Lee P-Y, et al. Effect of α2-adrenergic agonists on uveoscleral outflow in rabbits [abstract]. Invest Ophthalmol Vis Sci 1991; 32 Suppl.: 867Google Scholar
  15. 15.
    Burke JA, Potter DE. Ocular effects of a relatively selective α2 agonist (UK-14, 304-18) in cats, rabbits and monkeys. Eye Res 1986; 5(9): 665–76CrossRefGoogle Scholar
  16. 16.
    Manlapaz CA, Kharlamb AB, Williams LS, et al. IOP, pulmonary and cardiac effects of anti-glaucoma drugs brimonidine (AlphaganR), timolol and betaxolol [abstract no. 3792-B393]. Invest Ophthalmol Vis Sci 1997; 38 Suppl.: S814Google Scholar
  17. 17.
    Nordlund JR, Pasquale LR, Robin AL, et al. The cardiovascular, pulmonary, and ocular hypotensive effects of 0.2% brimonidine. Arch Ophthalmol 1995 Jan; 113: 77–83PubMedCrossRefGoogle Scholar
  18. 18.
    Derick RJ, Robin AL, Walters TR, et al. Brimonidine tartrate: a one-month dose response study. Ophthalmology 1997 Jan; 104: 131–6PubMedGoogle Scholar
  19. 19.
    Rosenthal AL, Walters T, Berg E, et al. A comparison of the safety and efficacy of brimonidine 0.2%, BID versus TID, in subjects with elevated intraocular pressure [abstract no. 5071-B681]. Invest Ophthalmol Vis Sci 1996 Feb 15; 37(3): S1102Google Scholar
  20. 20.
    Schuman JS. Clinical experience with brimonidine 0.2% and timolol 0.5% in glaucoma and ocular hypertension. Surv Ophthalmol 1996 Nov; 41Suppl. 1: 27–37CrossRefGoogle Scholar
  21. 21.
    Schuman JS, Horwitz B, Choplin NT, et al. A 1-year study of brimonidine twice daily in glaucoma and ocular hypertension. Arch Ophthalmol 1997 Jul; 115: 847–52PubMedCrossRefGoogle Scholar
  22. 22.
    Serle JB. A comparison of the safety and efficacy of twice daily brimonidine 0.2% versus betaxolol 0.25% in subjects with elevated intraocular pressure. Surv Ophthalmol 1996 Nov; 41Suppl. 1: S39–47PubMedCrossRefGoogle Scholar
  23. 23.
    Walters TR. Development and use of brimonidine in treating acute and chronic elevations of intraocular pressure: a review of safety, efficacy, dose response, and dosing studies. Surv Ophthalmol 1996 Nov; 41Suppl. 1: S19–26PubMedCrossRefGoogle Scholar
  24. 24.
    Bhandari A, Orgul S, Bacon D, et al. Effect of brimonidine on optic nerve blood flow in rabbits [abstract no. 3631-B232]. Invest Ophthalmol Vis Sci 1997; 38 Suppl.: S738Google Scholar
  25. 25.
    Lachkar Y, Migdal C, Dhanjil S, et al. The effect of brimonidine on ocular blood flow [abstract no. 3602-B203]. Invest Ophthalmol Vis Sci 1997; 38 Suppl.: S778Google Scholar
  26. 26.
    Maier C, Steinberg GK, Sun GH, et al. Neuroprotection by the α2-adrenoreceptor agonist dexmedetomidine in a focal model of cerebral ischemia. Anesthesiology 1993 Aug; 79(2): 306–12PubMedCrossRefGoogle Scholar
  27. 27.
    Reis DJ, Regunathan S, Meeley MR Imidazole receptors and clonidine-displacing substance in relationship to control of blood pressure, neuroprotection, and adrenomedullary secretion. Am J Hypertens 1992; 5: 51S–7SPubMedGoogle Scholar
  28. 28.
    Lynch DR, Dawson TM. Secondary mechanisms in neuronal trauma. Curr Opin Neurol 1994; 7:510–6PubMedCrossRefGoogle Scholar
  29. 29.
    Yoles E, Muler S, Schwartz M, et al. Injury-induced secondary degeneration of rat optic nerve can be attenuated by α2-adrenoceptor agonists AGN 191103 and brimonidine [abstract no. 540-B452]. Invest Ophthalmol Vis Sci 1996 Feb 15; 37(3): S144Google Scholar
  30. 30.
    Lai R, Hasson D, Chun T, et al. Neuroprotective effect of ocular hypotensive agent brimonidine. XIth Congress of the European Society of Ophthalmology; 1997 Jun 1–5; Budapest: 439–44Google Scholar
  31. 31.
    Wallicke PA. Basic and acidic fibroblast growth factors have trophic effect on neurons from multiple CNS regions. J Neurosci 1988 Jul; 8(7): 2618–27Google Scholar
  32. 32.
    Wen R, Cheng T, Li Y, et al. Induction of bFGF gene expression in vivo in rat photoreceptors by the α2-adrenergic agonists xylazine and clonidine [abstract]. Soc Neurosci Abstr 1995; 21 (Pt2) Suppl.: S1045Google Scholar
  33. 33.
    Chien D-S, Luo A, Tang-Liu D. Ocular melanin binding of brimonidine (AGN 190342) in vitro [abstract]. Pharm Res 1991 Oct; 8 Suppl.: S–260CrossRefGoogle Scholar
  34. 34.
    Acheampong AA, Shackleton M, Tang-Liu DD-S. Comparative ocular pharmacokinetics of brimonidine after a single dose application to the eyes of albino and pigmented rabbits. Drug Metab Dispos 1995 Jul; 23: 708–12PubMedGoogle Scholar
  35. 35.
    Chien D-S, Dais M, Tang-Liu D. Ocular metabolism of brimonidine in albino rabbits [abstract]. Pharm Res 1992 Oct; 9 Suppl.: S–287CrossRefGoogle Scholar
  36. 36.
    Acheampong A, Kelley E, Chen K, et al. Effect of ocular dose on the systemic absorption and disposition of brimonidine in humans [abstract]. Pharm Res 1994 Oct; 11 Suppl.: S350Google Scholar
  37. 37.
    Acheampong A, Tang-Liu DD-S. Measurement of brimonidine concentrations in human plasma by a highly sensitive gas chromatography/mass spectrometric assay. J Pharm Biomed Anal 1995 Jul; 13: 995–1002PubMedCrossRefGoogle Scholar
  38. 38.
    Tang-Liu D, Daher M, Shackleton M, et al. Use of a sensitive GCMS assay to determine the pharmacokinetic parameters of brimonidine in the mouse, rat, monkey and human [abstract]. Pharm Res 1992 Oct; 9 Suppl.: S345CrossRefGoogle Scholar
  39. 39.
    Salazar M, Shimada K, Patil PN. Iris pigmentation and atropine mydriasis. J Pharmacol Exp Ther 1976; 197(1): 79–88PubMedGoogle Scholar
  40. 40.
    Salminen L, Imre G, Huupponen R. The effect of ocular pigmentation on intraocular pressure response to timolol. Acta Ophthalmol 1985; 63Suppl. 173: 15–8Google Scholar
  41. 41.
    Acheampong AA, Chien D-S, Lam S, et al. Characterization of brimonidine metabolism with rat, rabbit, dog, monkey and human liver fractions and rabbit liver aldehyde oxidase. Xenobiotica 1996 Oct; 26: 1035–55PubMedGoogle Scholar
  42. 42.
    Acheampong AA, Daher M, Tang-Liu D. Pharmacokinetics and metabolism of 14C-brimonidine after intravenous and oral doses to rats and monkeys [abstract]. Pharm Res 1991 Oct; 8 Suppl.: S251Google Scholar
  43. 43.
    The Brimonidine-ALT Study Group. Effect of brimonidine 0.5% on intraocular pressure spikes following 360° argon laser trabeculoplasty. Ophthalmic Surg Laser 1995 Sep-Oct; 26(5): 404–9Google Scholar
  44. 44.
    Barnebey HS, Robin AL, Zimmerman TJ, et al. The efficacy of brimonidine in decreasing elevations in intraocular pressure after laser trabeculoplasty. Ophthalmology 1993 Jul; 100: 1083–8PubMedGoogle Scholar
  45. 45.
    David R, Spaeth GL, Clevenger CE, et al. Brimonidine in the prevention of intraocular pressure elevation following argon laser trabeculoplasty. Arch Ophthalmol 1993 Oct; 111: 1387–90PubMedCrossRefGoogle Scholar
  46. 46.
    Gandolfi SA. The additive effect of brimonidine 0.2%, BID compared with pilocarpine 2.0%, TID, in patients on beta-blocker monotherapy [abstract]. Joint European Research Meeting in Ophthalmology and Vision (JERMOV); 1997 Oct 15–19; MontpellierGoogle Scholar
  47. 47.
    Nagasubramanian S, Hitchings RA, Demailly P, et al. Comparison of apraclonidine and timolol in chronic open-angle glaucoma. A three-month study. Ophthalmology 1993 Sep; 100(9): 1318–23PubMedGoogle Scholar
  48. 48.
    Stewart WC, Laibovitz R, Horwitz B, et al. A 90-day study of the efficacy and side effects of 0.25% and 0.5% apraclonidine vs 0.5% timolol. Arch Ophthalmol 1996 Aug; 114: 938–42PubMedCrossRefGoogle Scholar
  49. 49.
    Butler PJ, Jones B. Incidence of characteristics of allergic reaction to apraclonidine 0.5% [abstract]. Invest Ophthalmol Vis Sci 1996; 37Suppl. 3: S201Google Scholar
  50. 50.
    Butler P, Mannschreck M, Lin S, et al. Clinical experience with the long-term use of 1% apraclonidine. Arch Ophthalmol 1995 Mar; 113: 293–6PubMedCrossRefGoogle Scholar
  51. 51.
    Gordon RN, Ritch R, Liebmann JM, et al. Alpha-agonist allergy: is there cross reactivity between apraclonidine and brimonidine? [abstract no. 2601-B291]. Invest Ophthalmol Vis Sci 1997; 38 Suppl.: S559Google Scholar
  52. 52.
    Allergan Inc. AlphaganR: brimonidine tartrate ophthalmic solution 0.2% prescribing information. Irvine, California, USA, 1997Google Scholar
  53. 53.
    Allergan Limited. AlphaganR (brimonidine tartrate ophthalmic solution) 0.2%. Summary of product characteristics. Buckinghamshire, UK, March 1997Google Scholar
  54. 54.
    Migdal C, Gregory W, Hitchings R. Long-term functional outcome after laser surgery compared with laser and medicine in open-angle glaucoma. Ophthalmology 1994; 101: 1651–7PubMedGoogle Scholar
  55. 55.
    Abel Jr RS, Abel AD. Ocular diseases. In: Speight TM, Holford NHG, editors. Avery’s drug treatment. 4th ed. Auckland: Adis International Limited, 1997: 581–605Google Scholar
  56. 56.
    Brooks AMV, Gillies WE. Ocular β-blockers in glaucoma management: clinical pharmacological aspects. Drugs Aging 1992 May-Jun; 2: 208–21PubMedCrossRefGoogle Scholar
  57. 57.
    Patel SS, Spencer CM. Latanoprost: a review of its pharmacological properties, clinical efficacy and tolerability in the management of primary open-angle glaucoma and ocular hypertension. Drugs Aging 1996 Nov; 9: 363–78PubMedCrossRefGoogle Scholar
  58. 58.
    Serle JB. Pharmacological advances in the treatment of glaucoma. Drugs Aging 1994 Sep; 5: 156–70PubMedCrossRefGoogle Scholar
  59. 59.
    Balfour JA, Wilde MI. Dorzolamide: a review of its pharmacology and therapeutic potential in the management of glaucoma and ocular hypertension. Drugs Aging 1997 May; 10: 384–403PubMedCrossRefGoogle Scholar
  60. 60.
    Everitt DE, Avorn J. Systemic effects of medications used to treat glaucoma. Ann Intern Med 1990 Jan 15; 112: 120–5PubMedGoogle Scholar
  61. 61.
    Morrison JC. Side effects of α-adrenergic agonists. J Glaucoma 1995; 4Suppl. 1: S36–8PubMedCrossRefGoogle Scholar
  62. 62.
    Hurvitz LM, Kaufman PL, Robin AL, et al. New developments in the drug treatment of glaucoma. Drugs 1991 Apr; 41: 514–32PubMedCrossRefGoogle Scholar
  63. 63.
    Hodapp E, Kolker AE, Kass MA, et al. The effect of topical clonidine on intraocular pressure. Arch Ophthalmol 1981 Jul; 99: 1208–11PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 1998

Authors and Affiliations

  1. 1.Adis International LimitedMairangi Bay, Auckland 10New Zealand

Personalised recommendations