Ординатура / Офтальмология / Английские материалы / The Eye Book A Complete Guide to Eye Disorders and Health_Cassel, Billig, Randall_2001

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In the eye, side effects seen with both of these drugs include irritated eyelids and conjunctiva in 10 to 15 percent of patients, and red eyes. This side effect is seen much less often with Propine because as a synthetic derivative of epinephrine, it is inactive when in contact with the external eye. It becomes active after passing into the eye, when it is then converted to epinephrine. Black deposits in the conjunctiva can also be observed in patients who have used epinephrine for a prolonged period of time. (These deposits are usually harmless; however, they can occasionally cause eye irritation and may need to be surgically removed.) Epinephrine and Propine can also cause cystoid macular edema, a fluid swelling of the macula, which can blur someone’s central vision. (This has been noted in patients who’ve had cataract surgery or other procedures resulting in the loss of the eye’s normal lens.) Fortunately, this side effect is usually reversible when the medication is stopped.

The pressure-lowering effect of epinephrine begins in one hour, peaks at about four hours, and lasts about twelve hours. Propine begins working within thirty minutes and has its maximum effect in one hour. Both are usually used twice daily. Because other antiglaucoma drops are known to be more effective, epinephrine and Propine are rarely first-line drugs for glaucoma. They are often used in combination with these other drugs, or alone in patients who can’t tolerate other antiglaucoma drugs because of sensitivities or the risk of serious systemic side effects.

Note: Because both of these hormones have an effect

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on the cardiovascular system, epinephrine and Propine should be used with caution in patients with a history of rapid heartbeats or arrhythmia. They can induce tachycardia, extra heartbeats, elevated blood pressure, and chest pain due to angina. If you have a history of heart problems, it’s essential that you discuss these risks with your eye doctor and your cardiologist.

Antiglaucoma medications related to epinephrine and Propine are isoproterenol, salbutamol, and norepinephrine.

Timoptic and Other Beta-Blockers

Timolol maleate (Timoptic) is known as a beta adrenergic blocking agent, or beta-blocker. Although its exact mechanism of action is not well understood, generally we know that Timoptic lowers intraocular pressure by blocking beta adrenergic receptors in the eye, which are important in the production of aqueous fluid.

Timoptic is a very effective antiglaucoma drug and today is one of the most popular drugs used in the United States to treat glaucoma—either alone or in combination with other medications. Like pilocarpine, Timoptic is more effective in lightly pigmented eyes. Studies have shown it to have a mean reduction in eye pressure of 30 to 33 percent. Several different medical centers looking at Timoptic use in patients with elevated eye pressures have also found that it reduced eye pressure below 22 millimeters of mercury more effectively than either pilocarpine or epinephrine used alone.

Timoptic has been available in solutions of 0.25 per-

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cent and 0.50 percent. Its pressure-lowering effect peaks after about two hours and lasts up to twenty-four hours. Typically it’s given twice a day. Timoptic-XE 0.50 percent is a form now available as a suspension that has been shown to have a longer duration of action and is recommended as a once-a-day drop. As with other glaucoma drops, Timoptic seems to lose its effectiveness over time. Therefore, it is very important to have regular eye exams, so that your eye doctor can change your medication if this happens.

Timoptic’s side effects in the eye are rare, but they include reduced tear production (which can cause dry eyes or make an existing dry-eye condition worse), red eyes due to hypersensitivity reactions, or corneal irritation.

Timoptic is related to propranolol (Inderal), metoprolol (Lopressor), and nadolol (Corgard), which are beta-blocker drugs often used to treat cardiovascular disease. Therefore, the systemic side effects of Timoptic are potentially life-threatening. Again, it’s a must for heart patients to discuss these implications thoroughly with their doctor. Why? Because a drop placed in the eye can flow into the tear sac and then pass into the nose and eventually down to the back of the throat, where it’s swallowed and absorbed into the body—possibly inducing or aggravating certain cardiovascular and pulmonary problems. In particular, Timoptic can lead to a slowing of the heart rate, congestive heart failure, decreased blood pressure, or lightheadedness and irregular heartbeat. Spasm of the lung’s air passages is another important side effect. Fatigue, confusion, impotence, and depression have also

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been associated with Timoptic. Timoptic can also decrease the levels of “good” cholesterol (HDL) in the body. People with elevated “bad” cholesterol should discuss this with their doctor before using this drug for glaucoma.

Timoptic is also related to other beta-blocking ocular agents, including betaxolol (Betoptic), timolol hemihydrate (Betimol), carteolol (Ocupress), levobunolol (Betagan), and metipranolol (OptiPranolol). Each has advantages and disadvantages. Deciding which betablocker to use for a specific patient is not easy. Doctors need to take into consideration side effects, pressurelowering effect, and price.

Betoptic is a beta-blocker that is more selective in its mode of action, causing fewer breathing problems. It is therefore often used in people with glaucoma who have a history of chronic obstructive pulmonary disease, or those who have developed breathing difficulties with Timoptic. Betoptic, because it is absorbed less by the body than other beta-blockers, appears to cause less fatigue, drowsiness, and depression. A drawback to its use, however, is that in new glaucoma patients and in those on chronic glaucoma therapy, Betoptic has been found to produce less intraocular pressure lowering when compared with other, less-selective, beta-blockers.

Betimol is a variation of Timoptic. Clinical studies have demonstrated that these two drugs have very similar potency and side effects. Ocupress has been found to have special receptor activity and, for reasons not clearly understood, may be a safer choice in people with coro-

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nary heart disease and with serum lipid imbalances. Betagan is a less selective beta-blocker with a long half-life (longer-lasting effect), in theory making it a better once- a-day product than Timoptic. It requires a larger drop size than Timoptic, and many doctors believe that it is therefore relatively expensive. OptiPranolol in many markets is the least expensive nonselective beta-blocker, with similar efficacy to Timoptic. Although ocular inflammation has been found to be a rare side effect of all topical beta-blockers, it appears to be most common with OptiPranolol.

Beta-blockers are very important drugs for the treatment of glaucoma. They are not all the same, and therefore careful consideration must be given when selecting them for patients.

Patients taking drops for glaucoma, especially Timoptic, should know about a technique called punctal occlusion, a way of administering eye drops that’s been proven to minimize these potentially serious side effects by reducing the amount of medication that finds its way from the eye into the throat and circulation. Briefly, here’s the technique: Place your forefinger at the nasal, or inside, corner of your eye, blocking the tear duct. With your other hand, put a drop of medication in the eye. Wipe away any excess drop with a tissue before releasing your forefinger’s compression of the tear duct.

Iopidine and Alphagan

Apraclonidine (Iopidine) and brimonidine (Alphagan) represent a fairly new class of topical antiglaucoma

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drops called alpha agonists. They appear to lower intraocular pressure primarily by decreasing the production of aqueous humor, but they may also secondarily increase uveoscleral outflow (see the discussion of latanoprost below). Because Iopidine and Alphagan selectively stimulate alpha-adrenergic receptors—receptors that aren’t found in large numbers in the heart and lungs—they have little effect on heart rate, blood pressure, and breathing. This means that they can be used— with caution—in people with cardiac and pulmonary problems, unlike beta-blockers such as Timoptic (see above), which can cause severe side effects in these individuals.

Both drugs begin lowering IOP within an hour, peak in about three hours, and are effective for eight to twelve hours. They are usually administered two or three times a day. Unfortunately, Iopidine’s effectiveness significantly decreases with time—even after just a month. Because of this, it’s mainly recommended for people already on maximal antiglaucoma medication (in combination with these or other medications), for a short period of time to control eye pressure in people awaiting a laser procedure or surgery. Iopidine has also been used to prevent postoperative pressure elevation after YAG laser procedures (see below). Alphagan was developed to be effective for a longer period than Iopidine and therefore is the better choice for long-term glaucoma management. It is also more selective for alpha receptor sites than Iopidine, further decreasing the chance for systemic cardiopulmonary side effects.

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As mentioned above, although Iopidine and Alphagan have minimal effects on the heart and lungs, they should still be used with caution in people with hypertension, abnormal or slow heart rates, recent myocardial infarctions, history of strokes, or chronic renal failure. They may also cause an adverse reaction in people taking certain antidepressants. In the eye, the most common side effects of these drugs includes redness, itching, discomfort, and tearing.

Latanoprost

Latanoprost (Xalatan) is an exciting new antiglaucoma medication that recently became available. It is one of a new class of drugs, called prostaglandin analogs, now available to people in the United States. Latanoprost appears to act by increasing uveoscleral outflow or increasing aqueous humor absorption by the uveal tissues of the eye, particularly the ciliary body. Fluid in the eye is thus passed to the outside of the eye by way of the suprachoroidal space and sclera, and intraocular pressure is thereby lowered. This medication does not appear to have any effect on the production of aqueous fluid. Previous antiglaucoma medications have acted primarily by lowering intraocular pressure by decreasing the production of intraocular aqueous fluid or by increasing the outflow of aqueous drainage through the anterior chamber angle.

Latanoprost’s unique primary mode of action makes this medication particularly useful as an adjunct with other glaucoma medications that work to lower eye pres-

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sure through different mechanisms. Furthermore, when latanoprost is used alone it has been shown to be potentially more effective than Timoptic, which is now commonly accepted by many as the initial treatment for glaucoma. This effect was also observed when latanoprost was used only once a day compared with Timoptic used twice a day. The ability to use latanoprost once a day, preferably at night—since intraocular pressure is usually at its highest during the early-morning hours—presents an added advantage, since people may well be more likely to use their glaucoma medication following this schedule. (Patient compliance—getting patients to use their medication—is a very common problem. Doctors and patients need to work together to address whatever it is that’s interfering with compliance, whether it’s schedule of drug applications, costs of medications, side effects of medications, or something else.)

You might wonder why all glaucoma patients aren’t placed on latanoprost when they are first diagnosed. The reason, as you can probably guess, is side effects. Latanoprost does not often cause systemic or ocular side effects. Systemic effects—shortness of breath, a slowing of the heart rate, and so on—were observed less often with latanoprost than with Timoptic. On the other hand, latanoprost caused more eye redness than Timoptic. Of particular note, some people taking latanoprost who had mixed eye color—an iris that was blue-brown, graybrown, green-brown, or yellow-brown—developed increased iris pigment, so that a green, blue, or light-col- ored eye turned brown. The long-term effects of this

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pigmentary change, if any, are still unknown. This has made many eye doctors hesitant to use latanoprost as a first-line drug in people with glaucoma.

Carbonic Anhydrase Inhibitors

Carbonic anhydrase inhibitors, or CAIs, block the production of aqueous fluid by inhibiting an enzyme called carbonic anhydrase, which acts on the eye’s ciliary body. Acetazolamide (Diamox) and methazolamide (Neptazane) are well-known carbonic anhydrase inhibitors. They’re prescription medications available in pill form as well as in intravenous and intramuscular preparations.

The pressure-lowering effect of Diamox usually begins in one to two hours, peaks at three to five hours, and lasts up to eight hours; Diamox also comes as a sustained-re- lease capsule, which can last up to twenty-four hours. Neptazane is available in 25-milligram and 50-milligram pills. It begins working in about two hours, lasts about ten to eighteen hours, and is usually prescribed to be taken two or three times a day.

Recently, carbonic anhydrase inhibitors have become available as eye drops as well. Dorzolamide hydrochloride (Trusopt), available in a 2 percent solution, is recommended for use three times a day. Its side effects in the eye include allergic reactions of the eyelids and conjunctiva. Also, because Trusopt is absorbed by the body, patients may note a bitter taste after administering a drop.

With pills, ocular side effects of carbonic anhydrase inhibitors are rare; however, increased nearsightedness

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has been reported. Systemic side effects are much more common and can include numbness and tingling in the extremities, weight loss, fatigue, kidney stones, and lowered blood levels of potassium, which can cause systemic problems and adverse drug effects. A rare form of anemia can also be caused by CAI use. You should review the full list of side effects with your doctor before beginning this drug. Also, carbonic anhydrase inhibitors are sulfonamides, which means they shouldn’t be given to patients with known sulfa allergies. They’re also not recommended for people with severe liver disease, those with advanced lung disease, and pregnant women. Finally, because carbonic anhydrase inhibitors may have an “additive effect”—which may magnify these side effects —it’s not a good idea to combine the drops with pills.

Other Medications

Mannitol, glycerin, and isosorbide are three other medications. These are mainly used as short-term treatments in special, acute situations to lower eye pressures as quickly as possible. Generally they are administered either orally or intravenously for a rapid onset of action and work by drawing fluid from the eye into the bloodstream. At the time of this writing, there are several other topical medications on the horizon for the treatment of glaucoma.