Glaucoma beta-blockers

Hyaluronic acid is a linear polysaccharide found in the highest concentrations in soft connective tissues where it fills an important structural role in the organization of the extracellular matrix (23,24). It has been used in ophthalmic preparations to enhance ocular absorption of timolol, a beta blocker used for the treatment of glaucoma (25), and in a viscoelastic tear formulation for conjunctivitis (26). The covalent binding of adriamycin and daunomycin to sodium hy-aluronate to produce water-soluble conjugates was recently reported (27). 

Acetazolamide is a carbonic anhydrase inhibitor that is administered orally for the treatment of glaucoma. Topical carbonic anhydrase inhibitors include dorzolamide and brinzolamide. Carbonic anhydrase inhibitors reduce the production of aqueous humour, thereby reducing intraocular pressure. They can be used alone or in addition to beta-blocker therapy in glaucoma patients. 

Pilocarpine is classified as a tertiary amine that has parasympathomimetic activity. When administered as eye drops, it causes pupillary constriction or miosis and is therefore indicated in the treatment of glaucoma. In glaucoma, multiple-drug therapy may be necessary to achieve the desired intraocular control. Pilocarpine may be used in combination with topical beta-blockers such as timolol. 

Glaucoma Management of open-angle (chronic simple) glaucoma may be used in combination with miotics, beta blockers, hyperosmotic agents, or carbonic anhydrase inhibitors. 

Carteolol (Cartrol/ Ocupress Ophthalmic) [Beta Blocker/ Glaucoma Agent] Uses HTN, T lOP, chronic open-angle glaucoma Action Blocks [3-adrenergic receptors (p, 2)1 ISA Dose Ophth 1 gt in eye(s) bid Caution [C (1st tri) D (2nd 3rd tri), /-] Cardiac failure, asthma Contra Sinus bradycardia heart block >lst-degree bronchospasm Disp Ophth soln SE Drowsiness, sexual dysfxn, bradycardia, edema, CHF, ocular conjunctival... 

Timolol, Ophthalmic (Timoptic) [Antiglaucoma Agent/Beta Blocker] Uses Glaucoma Action BB Dose 0.25% 1 gt bid T to daily when controlled use 0.5% if needed 1 gtt/d gel Caution [C (1st tri D 2nd or 3rd), /+] Disp Sohi, gel SE Local irritation Interactions See Timolol EMS See Timolol OD Unlikely from ophthalmic form... 

Brooks AM and Gillies WE. Ocular beta blockers in glaucoma management Clinical pharmacology aspects. Drugs Aging 1992 2 208-221. 

Topical beta-blockers can precipitate asthma and therefore must not be used to treat this patient s glaucoma. Topical prostaglandin analogues (e.g. latanoprost drops) are used as first-line treatment of glaucoma together with a sympathomimetic agent, brimonidine, as an alternative to beta-blockers in asthmatic and COPD patients. 

Legal claims arising from glaucoma therapy may be divided into three categories adverse effects of beta-blockers, retinal detachments after initiation of miotic therapy, and complications resulting from use of CAIs. 

A beta-blocker may be used in the treatment of primary open-angle glaucoma, but these drugs are contraindicated for use in persons with chronic obstructive pulmonary disease and heart block (see Chapter 10). A careful history should be taken before initiating therapy to avoid potentially fatal ramifications. It is advisable to monitor patients who are taking beta-blockers (e.g., pulse, blood pressure) and to inquire about side effects at periodic follow-up examinations. 

Gross F), Schuman)S. Reduced ocular hypotensive effect of topical beta-blockers in glaucoma patients receiving oral beta-blockers. ) Glaucoma 1992 1 174-177. 

The respiratory and cardiovascular adverse effects of topical therapy with timolol or betaxolol have been studied in a randomized, controlled trial in 40 elderly patients with glaucoma (83). Five of the 20 allocated to timolol discontinued treatment for respiratory reasons, compared with three of the 20 patients allocated to betaxolol There were no significant differences in mean values of spirometry, pulse, or blood pressure between the groups. This study confirms that beta-blockers administered as eye-drops can reach the systemic circulation and that serious adverse respiratory events can occur in elderly people, even if they are screened before treatment for cardiac and respiratory disease. These events can occur using either the selective betaxolol agent or the non-selective timolol. 

A 60-year-old man with open-angle glaucoma developed an allergic contact conjunctivitis and dermatitis from carteolol, a topical non-cardioselective beta-blocker (149). He had extensive cross-reactivity to other topical beta-blockers, such as timolol and levobunolol. Cross-reactivity among different beta-blockers is possibly due to a common lateral aliphatic chain. 

A 70-year-old woman treated with topical timolol for glaucoma developed a papular eruption on the arms and back, consistent with prurigo. All tests were within the reference ranges. There was no improvement after 1 month of topical corticosteroids. The eruption cleared completely within 1 month of timolol withdrawal. Betaxolol eye-drops were introduced and the eruption recurred within 1 week. When beta-blocker therapy was replaced by synthetic cholinergic eye-drops (drug unspecified) the eruption cleared completely without any recurrence a year later. 

Hemodynamic changes after the topical ocular use of beta-blockers sometimes include only small reductions in heart rate and resting pulse rate and an insignificant reduction in blood pressure. However, patients with cardiovascular disorders, especially those with an irregular heart rate and dysrhythmias, are certainly at risk (SEDA-4, 339). Bradycardia, cardiac arrest, heart block, hypotension, palpitations, syncope, and cerebral ischemia and stroke can occur (356). Rebound tachycardia has been reported after withdrawal of ophthalmic timolol (88,357). Continuous 24-hour monitoring of blood pressure has shown that beta-blocker eye-drops for glaucoma can increase the risk of nocturnal arterial hjq>otension (358). 

Eyes with potential angle closure require a miotic drug and should not be treated with beta-blockers alone. To exclude the risk of precipitating glaucoma in a susceptible individual, gonioscopy is recommended before starting topical beta-adrenoceptor antagonist therapy. 

The effects of topical brimonidine and timolol have been compared in two trials in 926 subjects with glaucoma or ocular hypertension already using systemic beta-blockers (5). Concurrent systemic beta-blocker therapy had no deleterious effects on ocular hypotensive efficacy and no impact on safety with topical brimonidine, but the combination of timolol and brimonidine significantly reduced systolic and diastolic blood pressures and heart rate compared with brimonidine alone. This observation suggests that ocular hjrpotensive agents other than beta-blockers, such as brimonidine, may be appropriate as a first-choice therapy for glaucoma in patients concurrently taking systemic beta-blockers. 

Glaucoma is a disorder of vision accompanied by an increase in ocular pressure. Although mostly replaced by other drugs (e.g., beta blockers and pilocarpine), anti-ChE drugs such as ecothiopate are still used in the treatment of these common disorders. 

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