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Chapter 103 Drugs for the Eye Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. Glaucoma Glaucoma – visual field loss secondary to optic nerve damage Leading cause of preventable blindness in the U.S. Of the 4 million Americans with glaucoma, only 50% are diagnosed Forms Primary open-angle glaucoma (POAG) Acute angle-closure glaucoma Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 2 Fig. 103-1. Anatomy of the normal eye. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 3 Fig. 103-2. 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. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 4 Aqueous Humor Produced in ciliary body Secreted into the posterior chamber of the eye Circulates around the iris into the anterior chamber Exits the anterior chamber via the trabecular meshwork and canal of Schlemm Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 5 Primary Open-Angle Glaucoma Characteristics Most common form of glaucoma in U.S. Progressive optic nerve damage with eventual impairment of vision Devoid of symptoms until significant and irreversible optic nerve injury has occurred Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 6 Primary Open-Angle Glaucoma Risk factors Elevation of intraocular pressure (IOP) African-American (3x more than whites) Family history of POAG Advancing age Goals of treatment Directed at reducing elevated IOP (the only modifiable risk factor) Principal method – chronic therapy with drugs Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 7 Drug Therapy for Glaucoma Drugs lower IOP by either: Preferred route – topical Facilitating aqueous humor outflow Reducing aqueous humor production Systemic effects relatively uncommon Combined therapy more effective than monotherapy If drugs ineffective, surgical intervention to promote outflow of aqueous humor Laser trabeculoplasty Trabeculectomy Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 8 Drug Therapy for Glaucoma First line Beta-adrenergic blocking agents • Timolol Alpha2-adrenergic agonists • Brimonidine (Alphagan) Prostaglandin analogs • Latanoprost (Xalatan) Second line Cholinergic agonists Carbonic anhydrase inhibitors Nonselective adrenergic agonists Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 9 Angle-Closure Glaucoma Also known as narrow-angle glaucoma Precipitated by displacement of the iris that prevents the exit of aqueous humor Develops suddenly and is extremely painful No treatment; irreversible loss of vision in 1-2 days Much less common than open-angle glaucoma Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 10 Angle-Closure Glaucoma Treatment Drug therapy Corrective surgery • Laser iridotomy • Iridectomy Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 11 Beta-Adrenergic Blocking Agents Betaxolol, levobetaxolol, carteolol, levobunolol, metipranolol, and timolol – approved for use in glaucoma Lower IOP by decreasing production of aqueous humor Used primarily for open-angle glaucoma Initial therapy and maintenance therapy Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 12 Beta-Adrenergic Blocking Agents Adverse effects Local – usually minimal Systemic – heart and lungs if absorbed in sufficient amounts (bradycardia, bronchospasm) Asthma patients recommended to use cardioselective (betaxolol and levobetaxolol) Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 13 Prostaglandin Analogs Latanoprost Lowers IOP by facilitating aqueous humor outflow As effective as beta-blockers with fewer side effects Can cause harmless brown pigmentation of the iris Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 14 Alpha2-Adrenergic Agonists Two agents approved for use Apraclonidine – only for short-term therapy Brimonidine (Alphagan) – first-line drug for longterm therapy Common side effects – dry mouth, local burning and stinging, headache, blurred vision, foreign body sensation, and ocular itching Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 15 Pilocarpine Direct-acting cholinergic agonist that causes: Miosis Contraction of the ciliary muscle Now considered a second-line drug Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 16 Cholinesterase Inhibitor Echothiophate (Phospholine Iodide) Long duration of action Inhibits the breakdown of ACh, promotes accumulation of ACh at muscarinic receptors No longer a first-line drug Adverse effects • Myopia; absorption into the system can cause parasympathomimetic responses Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 17 Carbonic Anhydrase Inhibitor Dorzolamide (Trusopt) topical Decreases IOP by decreasing production of aqueous humor Generally well tolerated (ocular stinging, bitter taste, 10%-15% allergic reaction) Acetazolamide and methazolamide – two systemic CAIs Adverse effects Nervous system, teratogenic, acid-base disturbances, electrolyte imbalances Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 18 Cycloplegics and Mydriatics Cycloplegics – paralyze ciliary muscles Mydriatics – dilate the pupil Uses Adjunct to measurement of refraction Intraocular examination Intraocular surgery Treatment of anterior uveitis Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 19 Cycloplegics and Mydriatics Adverse effects Blurred vision and photophobia Precipitation of angle-closure glaucoma Anticholinergic effects Phenylephrine, an adrenergic agonist Mydriatic agent (pupil dilation) Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 20 Allergic Conjunctivitis Inflammation of the conjunctiva in response to an allergen Seasonal or perennial Itching, burning, thin watery discharge Results from biphasic immune response Symptoms peak 20 minutes after allergen exposure, abate 20 minutes later, reappear after 6 hours Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 21 Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 22 Allergic Conjunctivitis Mast cell stabilizers H1 receptor antagonists NSAIDs Glucocorticoids (short-term) Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 23 Age-Related Macular Degeneration (ARMD) Painless, progressive disease that blurs central vision and limits perception of fine detail Leading cause of blindness in older Americans: about 15 million have the disease Dry ARMD Wet (neovascular) ARMD Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 24 Age-Related Macular Degeneration (ARMD) Stages Management of dry ARMD Early Intermediate Advanced Antioxidants and zinc, multiple vitamins Management and treatment of wet ARMD Laser therapy Photodynamic therapy Angiogenesis Inhibitors Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 25 Additional Ophthalmic Drugs Demulcents (artificial tears) Ocular decongestants Glucocorticoids Dyes Antiviral agents Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. 26
