| Home Features Departments News & Trends  |
Glaucoma Glaucoma Medications: How to Spot The Side EffectsMany factors can cause you to miss side effects related to glaucoma meds. Here’s how to catch them and how to proceed when you do .Avinash S. Patil and
Peter A. Netland, MD, PhD Beta-blockers Ocular beta-blockers can cause serious systemic side effects, primarily affecting the cardiopulmonary and metabolic systems. Once-daily dosing decreases these effects, and nasolacrimal occlusion and gel-forming solutions lower systemic exposure. Nonselective beta-blockers are associated with chronic obstructive pulmonary disease (COPD) and asthma.1 While avoidance of this class of medications is best for patients with these conditions, sometimes patients with asymptomatic pulmonary disease are given these medications. Asking whether patients notice any changes in their breathing or exercise tolerance is helpful. A pulmonary function test is useful for select patients in whom you suspect pulmonary disease. Selective beta-blockers minimize, but do not eliminate, pulmonary side effects.2 Ocular beta-blockers interfere with normal sympathetic stimulation of the heart, resulting in a lower heart rate and blood pressure (See Figure 2).3,4 Many patients requiring IOP-lowering medications also have other conditions (concomitant medications or illnesses, advanced age, etc.)  that make them especially prone to beta blockade. Some ocular
beta-blockers interact with medications for cardiac disease, such as calcium
channel blockers, resulting in severe bradycardia. Discontinuing the topical
beta-blocker alleviates this symptom. Measuring the pulse on all patients on
beta-blockers can identify those with this side effect. Figure 2. Allergic reaction in a patient treated with brimonidine. The patient developed a follicular conjunctivitis after two years and four months on Alphagan therapy. Allergic reactions to alpha-2 agonists may have insidious onset and may mimic viral conjunctivitis. Ocular beta-blockers also cause central nervous system (CNS) side effects, including anxiety, depression, fatigue, lethargy, confusion, sleep disturbance, memory loss, dizziness and sexual dysfunction (decreased libido or impotence).1 These changes are often overlooked because of their subtle nature; a detailed history is the best way to identify these side effects. The local adverse effects of ocular beta-blockers are generally limited. Benzalkonium chloride (BAK) sensitivity is uncommon but can occur in glaucoma patients; treatment with multiple medications containing BAK exacerbates its occurrence.1 Itching and increased hyperemia suggests an allergy, which is treated by switching to an alternate medication. Dry-eye symptoms have been associated with use of Timolol,5,6 primarily because of decreased tear production. Another common local effect is a transient period of blurred vision. Latanoprost The prostaglandin analog, latanoprost (Xalatan), has no systemic side effects.  The drug does have local side effects: mild conjunctival hyperemia
is seen in 15-31 percent of patients compared to approximately 9-16 percent in
patients treated with beta-blockers.7 The clinician should look for
conjunctival hyperemia, and discontinue the medication when patients are
symptomatic. A change in the pigmentation of the iris and eyelashes is one of
the better known side effects of latanoprost (See Figure 1). Figure 1. A 76-year-old male with heterochromia due to monocular Xalatan therapy. The patient had been treated with latanoprost for two years in the right eye, which became more darkly pigmented on therapy. This patient had obvious changes, but clinicians should monitor for more subtle signs of iris color change (darkening) on latanoprost therapy. Studies indicate increased pigmentation occurs in irides of varying pigmentation, typically with intermediate-colored irides. This change may seem obvious, but it is hard to detect, even by the close relatives of the patients, because of its gradual onset. Baseline and follow-up photography of the patient’s irides and eyelashes is the most reliable way of documenting pigmentation changes. Patients on monocular latanoprost therapy need to be warned about this side effect, and clinicians should monitor carefully for this. Patients may develop blurred vision related to cystoid macular edema (CME) or uveitis. Although there are only anecdotal reports, latanoprost may trigger the development of CME or uveitis in patients with pre-existing susceptibilities.8 In these cases, another class of medication should be prescribed. If a patient develops herpetic keratopathy upon initiation of treatment, look for an alternative to latanoprost. If a patient is stable on latanoprost and then develops the condition, consider another medication. In patients with a history of herpetic keratitis, many clinicians avoid latanoprost, although herpetic keratopathy related to latanoprost is reported infrequently. Brimonidine Brimonidine tartrate (Alphagan) is an alpha-2 agonist approved for long-term therapy of glaucoma. Systemic side effects of brimonidine include fatigue, dry mouth and hypotension.9 Carefully monitor for these side effects in patients with a low body-mass. If these symptoms exist in elderly patients, either the dosage should be changed or the medication itself replaced. Local side effects include hyperemia and allergic reaction. Hyperemia tends to vary during the day, and is usually not a clinical problem. An allergic reaction may be present as follicular conjunctivitis and hyperemia (See Figure 3). This condition is more common with apraclonidine (Iopidine). Switching medications gradually resolves the problem. Dorzolamide and Brinzolamide Two commonly used topical agents, dorzolamide and brinzolamide, are topical carbonic anhydrase inhibitors (CAI). Along with the convenience of a topical medication, these drugs also offer a reduced side-effect profile when compared with oral CAIs. One of the main local side effects of dorzolamide is a 10-12 percent incidence of punctate keratitis, observable at the slit lamp. Less than 5 percent of patients need to change medications for this reason. Other side effects of dorzolamide include stinging, blurred vision, tearing, dryness and photophobia.1 Some of these conditions are thought to be due to the vehicle used to keep the dorzolamide in solution. Patients who have undergone ocular surgery or have dry eye, and continue on dorzolamide, should be carefully watched. Approximately a quarter of the patients taking dorzolamide notice a bitter taste after administration, which can be reduced by the use of punctal occlusion.11 The topical and systemic side effects associated with brinzolamide are fewer than those of dorzolamide, especially the incidence of punctate keratitis (2.7 percent).11 This may be due to the pH of the solution, which is closer to neutral when compared with dorzolamide. Foreign body sensation and blurred vision has been reported by patients. Fixed Combination Therapy Cosopt is a fixed combination of 2% dorzolamide hydrochloride and 0.5% timolol maleate, which provides IOP-reduction greater than that of either dorzolamide or timolol alone. Cosopt has side effects common to beta-blockers and Trusopt.1,11 The most common side effects noted by patients in clinical trials were ocular burning and stinging. Osmotic Drugs Osmotic drugs are available for use by oral or intravenous administration. Oral forms are slower in action, though safer, while intravenous administration has a more rapid and reliable effect.12 In general, osmotic drugs may cause severe dehydration and increase the blood volume, leading to increased pressure on the cardiovascular and renal systems. Take care in identifying elderly patients with borderline cardiac or renal function. Glycerol, an oral osmotic medication, is readily metabolized to glucose and may cause hyperglycemia and ketosis in diabetic patients.13 Additionally, patients frequently experience nausea and vomiting following ingestion of this medication. An alternative oral osmotic medication, isosorbide, is similar to glycerol in its action. Isosorbide provides a distinct advantage for diabetic patients, since it is not metabolized. While it is less likely than glycerol to produce nausea and vomiting, it is more likely to lead to diarrhea. The production of Ismotic (isosorbide) was recently discontinued. Mannitol is an intravenous osmotic drug that is not metabolized, making it suitable for use in diabetic patients. Unfortunately, it also possesses several serious side effects that require careful monitoring. Mannitol’s mechanism of action expands the volume of intravenous fluid in a short time, which can lead to complications in the elderly population.12 Renal failure and cardiovascular complications have been noted in normal and elderly patients after treatment. Serious allergic reactions have also been seen in patients after administration of mannitol. High-risk patients are identified by a positive reaction skin test, although this is usually not practical.14 Pilocarpine, Other Cholinergic Drugs Pilocarpine is a cholinergic drug—one of the oldest classes of medications used to treat glaucoma. Some glaucoma patients on this medication become refractory to treatment during long-term therapy.15 The reason for this is not completely understood, and the situation cannot be resolved by giving successively higher doses of pilocarpine. Systemic side effects are rare, but patients with severe asthma may experience an exacerbation of their pulmonary disease on cholinergic drugs. The most common side effects are local, ocular adverse effects, such as blurred vision, brow ache and decreased night vision. Because of these side effects, cholinergic drugs are not commonly used in glaucoma patients. While the type and frequency of various side effects can be used as a general guide in the decision to utilize a treatment, clinicians should be aware that each patient may have a different side-effect profile for any given medication. The best approach to avoid side effects is to tailor a treatment plan to the patient’s medical history: any known allergies or intolerances, status of the cardiovascular/renal/pulmonary systems, and presence of diabetes or other systemic disorders. With a vigilant eye and ability to elicit complaints from patients, you can steer clear of the perilous side effects associated with the management of glaucoma. Mr. Patil is a research associate at the University of Tennessee, Memphis. Dr. Netland is the director of the Glaucoma Service at the same location.
|