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Evidence summaries

The Side Effects and Interactions of Topical Beta Blockers in Glaucoma Therapy

Topical beta blockers appear to have local and systemic adverse effects, which may be serious. Level of evidence: "B"

Commonly used medical treatment for glaucoma is a topicalnon-selective blocker, such as timolol. However, a sufficient amount of this agent can be absorbed through the nasopharyngealmucosa into the systemic circulation 2, thereby potentially causing bradycardia and respiratory impairment. These changes, in particular the bronchospasm, may be of clinical significance in the elderly 3, 4, who commonly have undiagnosed reversible airway obstruction 5, 6.

Such individuals are also likely to have other medical conditions (e.g. cardiac, respiratory or neurological disease) that may be induced or exacerbated by topical ophthalmic agents. Moreover, polypharmacy is common in elderly people, and this is associated with an increased risk of drug interactions.

A historical cohort study by Kirwan ym. 7 was performed to determine the incidence of airways obstruction in subjects with no previous history of airways obstruction, following treatment with topical beta antagonists for glaucoma for the period 1993-7.

For selective topical beta antagonists 12 of 324 treated subjects developed airways obstruction, compared with 112 of 9 094 controls (adjusted hazard rate 3.0, 95 % confidence interval 1.6 to 5.4). For non-selective topical beta antagonists, the corresponding figures were 69 of 2321 subjects compared with the same control group (adjusted hazard rate 2.2, CI 95 % 1.6 to 3.0). There was no significant difference between groups, p = 0.47, chi(2) test, both being associated with a significantly increased risk of airways obstruction.

Selective topical beta antagonists do appear to have an excess risk of airways obstruction in this population setting and should be subject to the same prescribing caveats as unselective topical beta antagonists.

  • Quality of the study: high-quality
  • Suitability for Finnish population: suitable
  • Comment: There is no difference in pulmonary side effects between selective and non-selective beta blockers. Both are not recommended especially to those asthma patients, whose asthma is labil, i.e. not stable with regular asthma medication.

In another study by Waldock A ym 8 141 newly diagnosed glaucoma patients were recruited and underwent a full ocular, cardiovascular, and respiratory examination, including an electrocardiogram (ECG) and spirometry.

At the initial examination, 17 patients (13 %) had ECG evidence of first degree heart block, seven were prescribed latanoprost,six with brimonidine, and four with betaxolol. . Eight patients were found to have arespiratory wheeze, four were prescribed brimonidine and the otherfoulatanoprost.

They were reviewed 3 months later. One eye of each patient was randomly chosen for analysis, performed using analysis of variance and the chi(2) test.

Timolol was associated with lowered pulse rates and reductions in the spirometry measurements. 41 % of patients using brimonidine complained of systemic side effects and over 55 % of patients using betaxolol complained of ocular irritation including dry eye. 28 % of patients required an alteration in their glaucoma management.

Latanoprost appears to be useful as a primary treatment for glaucoma patients, due from low incidence of local and systemic side effects. Timolol causes a reduction in measurements of respiratory function, a concern in view of the potential subclinical reversible airways disease in the elderly glaucoma population. Brimonidine is associated with substantial, unpredictable systemic side effects and betaxolol causes ocular irritation. Spirometry is advised in all patients receiving topical beta blocker therapy to control their glaucoma 8.

  • Quality of the study: moderate
  • Suitability for Finnish population: suitable
  • Comment: Patients with cardiovascular diseases and respiratory disorders with or without coexisting medication should have an internistic consultation or examination in health care centre, before prescribing them beta blockers.

The long-term use of antiglaucoma medication including beta blockers, induces changes in both tear film and conjunctival surface. Such changes may be related to the medication or the duration of treatment, but may also be due to the preservatives used in the commercial product 9.

  • Quality of the study: moderate
  • Suitability for Finnish population: suitable
  • Comment:Betablockers and adrenergics shoud not be prescribed to dry eye patients

Summary: The beta blockers should not be prescribed to dry eye patients. The ophthalmologists should ask their glaucoma patients the cardiovascular and pulmonary status before prescribing them beta blockers. The possible side effects should be told the patient. On control visits the physician's duty is also to ask possible side effects.

Selective and nonselective beta blockers do not essentially differ in side-effects in asthma patients. In case, that asthma patients must have alone or besides other drugs beta blockers, it is recommended to make lung function tests before and during the beta blocker therapy.

Before starting beta blocker therapy in patients with cardiac and circulatory problems the internal or GP consultation is recommended. Especially old people with many medications are prone to unpredictable synergistic or antagonistic effects.

Comment: The quality of evidence is downgraded by imprecise results (limited study size for each comparison).

The following decision support rules contain links to this evidence summary:

    References

    • Gibson JM, Rosenthal AR, Lavery J. A study of the prevalence of eye disease in the elderly in an English community. Trans Ophthalmol Soc U K 1985;104 ( Pt 2):196-203. [PubMed]
    • Passo MS, Palmer EA, Van Buskirk EM. Plasma timolol in glaucoma patients. Ophthalmology 1984 Nov;91(11):1361-3. [PubMed]
    • Diggory P, Heyworth P, Chau G, McKenzie S, Sharma A, Luke I. Improved lung function tests on changing from topical timolol: non-selective beta-blockade impairs lung function tests in elderly patients. Eye 1993;7 ( Pt 5):661-3. [PubMed]
    • Connolly MJ, Crowley JJ, Charan NB, Nielson CP, Vestal RE. Reduced subjective awareness of bronchoconstriction provoked by methacholine in elderly asthmatic and normal subjects as measured on a simple awareness scale. Thorax 1992 Jun;47(6):410-3. [PubMed]
    • Renwick DS, Connolly MJ. Prevalence and treatment of chronic airways obstruction in adults over the age of 45. Thorax 1996 Feb;51(2):164-8. [PubMed]
    • Bodner C, Ross S, Douglas G, Little J, Legge J, Friend J, Godden D. The prevalence of adult onset wheeze: longitudinal study. BMJ 1997 Mar 15;314(7083):792-3. [PubMed]
    • Kirwan JF, Nightingale JA, Bunce C, Wormald R. Do selective topical beta antagonists for glaucoma have respiratory side effects? Br J Ophthalmol 2004 Feb;88(2):196-8. [PubMed]
    • Waldock A, Snape J, Graham CM. Effects of glaucoma medications on the cardiorespiratory and intraocular pressure status of newly diagnosed glaucoma patients. Br J Ophthalmol 2000 Jul;84(7):710-3. [PubMed]
    • Nuzzi R, Finazzo C, Cerruti A. Adverse effects of topical antiglaucomatous medications on the conjunctiva and the lachrymal (Brit. Engl) response. Int Ophthalmol 1998;22(1):31-5. [PubMed]

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