Drugs for the eye

CHAPTER 104


Drugs for the eye


The drugs addressed in this chapter are used to diagnose and treat disorders of the eye. Our primary focus is on glaucoma. Many of the drugs considered here are discussed at length in other chapters. Accordingly, discussion here is limited to their ophthalmologic applications.




Drugs for glaucoma


The term glaucoma refers to a group of diseases characterized by visual field loss secondary to optic nerve damage. The most common forms of glaucoma are primary open-angle glaucoma and acute angle-closure glaucoma. These forms differ with respect to underlying pathology and treatment. With either form, permanent blindness can result.


In the United States, glaucoma is the leading cause of preventable blindness. Of the 120,000 Americans blinded each year by glaucoma, 90% could have saved their sight with timely treatment. Unfortunately, many afflicted persons are unaware of their condition: Of the 4 million Americans with glaucoma, only 50% are diagnosed.


Before discussing glaucoma, we need to review the role of aqueous humor in maintaining intraocular pressure (IOP). As indicated in Figure 104–1, aqueous humor is produced by the ciliary body and secreted into the posterior chamber of the eye. From there it circulates around the iris into the anterior chamber, and then exits the anterior chamber via the trabecular meshwork and canal of Schlemm. If outflow from the anterior chamber is impeded, back-pressure will develop, and IOP will rise. Conversely, if production of aqueous humor falls, IOP will decline.


image
Figure 104–1  Anatomy of the normal eye.


Pathophysiology and treatment overview



Primary open-angle glaucoma





Management.

Treatment of POAG is directed at reducing elevated IOP, the only risk factor we can modify. Although POAG has no cure, reduction of IOP can slow or even stop disease progression.


The principal method for reducing IOP is chronic therapy with drugs. Drugs lower IOP by either (1) facilitating aqueous humor outflow or (2) reducing aqueous humor production. As indicated in Table 104–1, the first-line drugs for glaucoma belong to three classes: beta-adrenergic blocking agents (beta blockers), alpha2-adrenergic agonists, and prostaglandin analogs. Other options—cholinergic drugs and carbonic anhydrase inhibitors—are considered second-line choices. All of the antiglaucoma drugs are available for topical administration, the preferred route. For more than 25 years, the beta blockers (eg, timolol) have been considered drugs of first choice. However, the alpha2 agonists (eg, brimonidine) and prostaglandin analogs (eg, latanoprost) are just as effective as the beta blockers, and have a more desirable side effect profile. Accordingly, these drugs have joined the beta blockers as first-choice agents. Because drugs in different classes lower IOP by different mechanisms, combined therapy can be more effective than monotherapy. Because all of these drugs are applied topically, systemic effects are relatively uncommon. Nonetheless, serious systemic reactions can occur if sufficient absorption takes place.



If drugs are unable to reduce IOP to an acceptable level, surgical intervention to promote outflow of aqueous humor is indicated. Options include laser trabeculoplasty and trabeculectomy (done with conventional surgical techniques).



Angle-closure glaucoma

Angle-closure glaucoma is precipitated by displacement of the iris such that it covers the trabecular meshwork, thereby preventing exit of aqueous humor from the anterior chamber. As a result, IOP increases rapidly and to dangerous levels. This disorder is referred to as angle-closure or narrow-angle glaucoma because the angle between the cornea and the iris is greatly reduced (Fig. 104–2). Angle-closure glaucoma develops suddenly and is extremely painful. In the absence of treatment, irreversible loss of vision occurs in 1 to 2 days. This disorder is much less common than open-angle glaucoma.


image
Figure 104–2  Comparative anatomy of the eye in open-angle and angle-closure glaucoma.
A, Note that the angle between the iris and cornea is open in open-angle glaucoma, permitting unimpeded outflow of aqueous humor through the canal of Schlemm and trabecular meshwork. B, Note that the angle between the iris and cornea is constricted in angle-closure glaucoma, thereby blocking outflow of aqueous humor through the canal of Schlemm and trabecular meshwork.

Treatment consists of drug therapy (to control the acute attack) followed by corrective surgery. A combination of drugs (osmotic agents, short-acting miotics, carbonic anhydrase inhibitors, topical beta-adrenergic blocking agents) is employed to suppress symptoms. Once IOP has been reduced with drugs, definitive treatment can be rendered with surgery. Options include laser iridotomy and iridectomy performed by conventional surgery. Both procedures alter the iris to permit unimpeded outflow of aqueous humor.



Drugs used to treat glaucoma



Beta-adrenergic blocking agents


Actions and use in glaucoma.

Five beta blockers—betaxolol, carteolol, levobunolol, metipranolol, and timolol—are approved for use in glaucoma. Dosing is topical. These agents cause minimal disturbance of vision and are considered first-line drugs for glaucoma, although prostaglandin analogs are becoming favored. Formulations and dosages of the beta blockers are summarized in Table 104–2.



The beta-adrenergic blockers lower IOP by decreasing production of aqueous humor. Reductions in IOP occur with “nonselective” beta blockers (drugs that block beta1 and beta2 receptors) as well as with “cardioselective” beta blockers (drugs that block beta1 receptors only).


Beta blockers are used primarily for open-angle glaucoma. They are suitable for initial therapy as well as maintenance therapy. Beta blockers, in combination with other drugs, are also employed for emergency management of acute angle-closure glaucoma.


The basic pharmacology of the beta blockers is discussed in Chapter 18.



Adverse effects. 



Systemic.


Beta blockers can be absorbed in amounts sufficient to cause systemic effects. For example, instilling 1 drop of 0.5% timolol in each eye can produce the same blood level as taking 10 mg of timolol by mouth (the usual starting dose for hypertension). Effects on the heart and lungs are of greatest concern.


Blockade of cardiac beta1 receptors can produce bradycardia and atrioventricular (AV) heart block. Pulse rate should be monitored. Because of their ability to depress cardiac function, beta blockers are contraindicated for patients with AV heart block, sinus bradycardia, and cardiogenic shock. In addition, they should be used with caution in patients with heart failure.


Blockade of beta2 receptors in the lung can cause bronchospasm. Constriction of the bronchi can occur with “beta1-selective” antagonists as well as with “nonselective” beta-adrenergic blockers—although the risk is greatest with the nonselective agents. Only one ophthalmic beta blocker—betaxolol—is beta1 selective. This drug is preferred to other beta blockers for patients with asthma or chronic obstructive pulmonary disease.



Prostaglandin analogs

Three prostaglandin analogs are approved for topical therapy of glaucoma. These drugs are as effective as the beta blockers and cause fewer side effects. Accordingly, they are considered first-line medications for glaucoma. Formulations and dosages are summarized in Table 104–3.




Latanoprost.

Latanoprost [Xalatan], an analog of prostaglandin F2 alpha, was the first prostaglandin approved for glaucoma and will serve as our prototype for the group. The drug is applied topically to lower IOP in patients with open-angle glaucoma and ocular hypertension. Latanoprost lowers IOP by facilitating aqueous humor outflow, in part by relaxing the ciliary muscle. The recommended dosage is 1 drop (0.005% solution) applied once daily in the evening. At this dosage, latanoprost produces the same reduction in IOP as does timolol twice daily.


Latanoprost is generally well tolerated, and systemic reactions are rare. The most significant side effect is a harmless heightened brown pigmentation of the iris, which is most noticeable in patients whose irides are green-brown, yellow-brown, or blue/gray-brown. The effect is rare in patients whose irides are blue, green, or blue-green. Heightened pigmentation stops progressing when latanoprost is discontinued, but does not usually regress. Topical latanoprost may also increase pigmentation of the eyelid, and may increase the length, thickness, and pigmentation of the eyelashes. Other side effects include blurred vision, burning, stinging, conjunctival hyperemia, and punctate keratopathy. Rarely, latanoprost may cause migraine.








Other prostaglandin analogs.


In addition to latanoprost, two other topical prostaglandins are approved for topical therapy of glaucoma. Like latanoprost, these drugs—travoprost [Travatan] and bimatoprost [Lumigan]—reduce IOP by increasing aqueous humor outflow. In clinical trials, these agents were at least as effective as timolol, a representative beta blocker. Interestingly, one drug—travoprost—was more effective in African Americans than in non–African Americans. Like latanoprost, these prostaglandins can cause a gradual increase in brown pigmentation of the iris, which may be irreversible. In addition, these drugs can increase pigmentation of the eyelid and growth of the eyelashes. In fact, bimatoprost, marketed as Latisse, is used for the specific purpose of increasing eyelash length, darkness, and thickness. With both prostaglandins, the most common adverse effect is ocular hyperemia (engorgement of ocular blood vessels). Less commonly, these drugs cause blurred vision, eye discomfort, ocular pruritus, conjunctivitis, dry eye, light intolerance, and tearing. Dosages for glaucoma are summarized in Table 104–3.




Alpha2-adrenergic agonists

Two alpha2 agonists are approved for glaucoma. One agent—apraclonidine—is used only for short-term therapy. The other agent—brimonidine—has emerged as a first-line drug for long-term therapy.



Brimonidine.

Brimonidine [Alphagan] is the first and only topical alpha2-adrenergic agonist approved for long-term reduction of elevated IOP in patients with open-angle glaucoma or ocular hypertension. The recommended dosage is 1 drop 3 times a day. Effects on IOP are similar to those achieved with timolol. The drug lowers IOP by reducing aqueous humor production, and perhaps by increasing outflow. In addition to lowering IOP, brimonidine may delay optic nerve degeneration and may protect retinal neurons from death. This possibility arises from the ability of alpha2 agonists to protect neurons from injury caused by ischemia. The most common adverse effects are dry mouth, ocular hyperemia, local burning and stinging, headache, blurred vision, foreign body sensation, and ocular itching. In contrast to apraclonidine (see below), brimonidine can cross the blood-brain barrier, and hence can cause drowsiness, fatigue, and hypotension. (Recall from Chapter 19 that activation of alpha2 receptors in the brain decreases sympathetic outflow to blood vessels, and thereby lowers blood pressure.) Brimonidine can be absorbed onto soft contact lenses. Accordingly, at least 15 minutes should elapse between drug administration and lens installation.









Pilocarpine, a direct-acting muscarinic agonist


Pilocarpine is a direct-acting muscarinic agonist (parasympathomimetic agent). Administration is topical. The basic pharmacology of the muscarinic agonists is discussed in Chapter 14. Consideration here is limited to the use of pilocarpine in glaucoma.





Adverse effects.


The major side effects of pilocarpine concern the eye. Contraction of the ciliary muscle focuses the lens for near vision; corrective lenses can provide partial compensation for this problem. Occasionally, sustained contraction of the ciliary muscle causes retinal detachment. Constriction of the pupil, caused by contraction of the iris sphincter, may decrease visual acuity. Pilocarpine may also produce local irritation, eye pain, and brow ache.


Rarely, pilocarpine is absorbed in amounts sufficient to cause systemic effects. Stimulation of muscarinic receptors throughout the body can produce a variety of responses, including bradycardia, bronchospasm, hypotension, urinary urgency, diarrhea, hypersalivation, and sweating. Caution should be exercised in patients with asthma or bradycardia. Systemic toxicity can be reversed with a muscarinic antagonist (eg, atropine).

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Jul 24, 2016 | Posted by in NURSING | Comments Off on Drugs for the eye

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