A busy general ophthalmologist needs to have important side effects and indications for glaucoma medications handy. Here is a quick and dirty guide:
Due to once day dosing, increased potency, and minimal systemic side effects, the most popular drops for primary therapy are the prostaglandins (PG’s). The drop should be given at the time of day which maximizes compliance. Redness is more common and pronounced with bimatoprost, and should be disclosed up front to increase acceptance. Travoprost has a new formulation (Travatan Z) with an ionic based preservative which may be tolerated in some patients with multiple drop allergies. It’s good to mention change in skin color (reversible) and lash growth, but crucial to disclose the potential for permanent darkening of the iris, especially in multicolored, blue/green eyed, and elderly patients. There has been some association with cystoid macular edema (CME), especially in patients with ruptured posterior capsules, though the incidence is relatively low1. In the weeks following cataract surgery, a PG is likely ineffective in reducing IOP and potentiates inflammation.
The generic beta blocker timolol 0.5% is dosed twice daily or once in the morning as an extended release gel. Timolol solution may be equally effective given once in the morning, as it doesn’t really work at night due to decreased sympathetic activity2. Timolol is the only drop currently available in preservative free vials, though the elderly and arthritic may have difficulties. Careful inquiry about shortness of breath, use of inhalers and supplemental oxygen is mandatory. Depression, heart block, and hypoglycemia may also contraindicate its use. Betaxolol (RELATIVELY cardioselective) may be used with great caution in some lung’ers, but won’t help much with cardiac or other side effects. There is an association with dry eye and pseudopemphigoid. Eyelid closure for 5 minutes after placing the drop with or without punctal occlusion decreases systemic absorption and improves ocular absorption. There is a slight crossover effect on the fellow eye, which may be undesirable postsurgically.
Topical carbonic anhydrase inhibitors (CAI’s) are relatively weak, and rarely will suffice as primary therapy. They are commonly used twice daily due to compliance; the pressure rises 1-2 mmHg from 8-12 hours after a dose compared with TID dosing. Systemic effects are very uncommon, with the exception of a metallic taste. Dorzolamide is acidic and stings on application, though better tolerated with proper warning and refrigeration. Brinzolamide is a suspension, so it must be shaken, and blurs vision temporarily. The combination timolol-dorzolamide may be more effective than either drop alone; however, a monocular trial of either drug alone pinpoints the exact source of intolerance in a patient with local side effects.
The topical alpha-2 agonist brimonidine is also less effective than timolol, and has significant local and systemic effects. Twice daily dosing is acceptable. Patients may complain of fatigue and dizziness due to CNS effects. Brimonidine may lead to apnea in prepubertal children and is contraindicated in this age group. Cardiovascular effects may be pronounced when combined with sildenafil and other pro-erectile medications, as well as nitroglycerin. The incidence and severity of ocular allergy is significant.
Oral CAI’s may be very useful in acute and chronic glaucoma as an addition or substitute for topical therapy. Methazolamide can be taken as 25-50 mg orally 2-3x daily and is better tolerated than diamox with less renal effects. Diamox 500 mg sequels may last up to 12 hours, but the shorter acting pills work faster in an acute setting. Patients must be questioned about sulfa allergy, kidney stones, or renal failure. About half of patients are intolerant of these medications due to tingling in the fingertips, GI upset or fatigue. Systemic hyperosmotics may be given orally or intravenously for acute glaucoma. Their use should be limited; they have potentially serious side effects, including intracranial hemorhage, CHF, and renal failure, and their effect is short lived.
Pilocarpine is still the drug of choice for primary acute angle closure and plateau iris, though it may not work well for very high pressures due to iris ischemia. Side effects include induced myopia, brow ache, and retinal detachment. Pilocarpine may cause forward displacement of the lens, sometimes worsening angle closure with chronic use (especially in phacomorphic glaucoma or aqueous misdirection). Phospholine iodide 0.125% is a long-acting acetylcholinesterase inhibitor that has similar effects to pilocarpine and may be effective in some refractory glaucomas. Patients need to be warned of the risk of general anaesthesia within a month of using the drop (due to poor metabolism of succinylcholine).
References
- Wand M, Gaudio AR, Shields MB. Latanoprost and cystoid macular edema in high-risk aphakic or pseudophakic eyes. J Cataract Refract Surg. 2001 Sep;27(9):1397-401.
- Letchinger SL et al. Can the concentration of timolol or the frequency of its administration be reduced? Ophthalmology 100: 1259, 1993.
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