Drugs acting on the eye

Drugs acting on the eye

The eye is a complex sensory organ responsible for sight. Injury or disease to the ocular system can result in vision loss. A variety of ophthalmic preparations (topical, parenteral, and oral) are available for both therapeutic and diagnostic use.  Medications play a key role in the management of chronic dry-eye, diabetic retinopathy, glaucoma, infection, inflammation, and macular degeneration.

The structural anatomy of the eye makes pharmacological treatment a unique challenge. The cornea consists of multiple layers comprised of hydrophobic and hydrophilic properties which can alter topical drug absorption. Although systemic absorption of ophthalmic agents can occur (mentioned in topics below), it is generally minimal as the eye is isolated from systemic vascular access due to the blood-retinal, blood-aqueous, and blood-vitreous barriers.

Figure from: http://slideplayer.com/slide/3862142/  Figure 15.4a Internal Structure of the Eye (sagittal section). Marieb & Hoehn 9th ed. Chapter 15 The Special Senses. Pearson Education, Inc. 2013

Opthalmic Prostaglandin Analogs

For the treatment of glaucoma

Prostaglandin Analogs attenuate intraocular pressure (IOP) by improving the outflow of aqueous humor. Prostaglandin analogs exhibit agonistic activity on FP prostanoid receptors, which promotes uveoscleral outflow. Medications within this class include latanoprost, travoprost, bimatoprost, tafluprost, and unoprostone isopropyl. These topical medications offer the greatest reduction in IOP. Prostaglandin analogs can cause undesirable cosmetic changes such as brown pigmentation of the iris, discoloration of the eyelids, and increased growth/thickness of eyelashes. Other adverse effects include blurred vision, eye irritation, itching, and headache.

Kelly Karpa, Anthony Possanza

Opthalmic α-Adrenoreceptor Agonists

For the treatment of glaucoma

α-Adrenoreceptor Agonists can be applied topically to decrease production of aqueous humor. Ophthalmic α2 agonists include brimonidine and apraclonidine. By activating α2 receptors in the ciliary epithelium, adenylyl cyclase becomes inhibited and cyclic adenosine monophosphate (cAMP) is no longer formed. This hinders ion transport and, thus, fluid production. Over time, these medications appear to improve fluid outflow as well. Adverse effects can include contact dermatitis, dry mouth, headache, hypotension, and somnolence. Use of α2 agonists is contraindicated with concurrent monoamine oxidase inhibitor (MAOI) therapy due to pronounced hypotension.

Kelly Karpa, Anthony Possanza

Opthalmic β-Adrenoreceptor Antagonists

For the treament of glaucoma

β-Adrenoreceptor Antagonists administered topically can reduce IOP by decreasing aqueous humor production. Beta-blockers antagonize the effects of sympathetic neurotransmitters by inhibiting β1 and β2 receptors; however their mechanistic action in glaucoma is unclear. Examples include timolol, betaxolol, carteolol, and levobunolol. Adverse effects, when systemically absorbed can include bradycardia, hypotension, headache, decreased exercise tolerance, and bronchospasm but these systemic effects are rare.

Kelly Karpa, Anthony Possanza

Opthalmic Carbonic Anhydrase Inhibitors

For the treatment of glaucoma

Carbonic Anhydrase Inhibitors (CAIs) work by decreasing production of aqueous humor. Carbonic anhydrase is an enzyme that catalyzes the formation of bicarbonate from carbon dioxide and water (and vice-versa), with the most active isoform being carbonic anhydrase II. Inhibition of this isoenzyme within the ciliary epithelium slows the formation of bicarbonate ions; decreasing the extracellular transport of water necessary for aqueous humor production.

Dorzolamide and brinzolamide are topical medications within this class. Adverse effects include blurred vision and altered taste. Acetazolamide is administered orally and has a higher rate of IOP reduction when compared to topical CAIs. Notable adverse effects of oral therapy include electrolyte imbalance, metabolic acidosis, blood dyscrasias, serious allergic skin reactions, and formation of kidney stones. CAIs are contraindicated in those with sulfonamide allergies and the oral CAI should not be used by individuals with poor kidney/liver function.

Kelly Karpa, Anthony Possanza

Opthalmic Parasympathomimetic Agents

For the treatment of glaucoma

Parasympathomimetic Agents are topical cholinergic agonists that reduce IOP by improving fluid outflow through the trabecular meshwork. Activation of muscarinic (M3) receptors allows for contraction of ciliary muscle fibers, which expands the pores of the trabecular meshwork to enhance outflow. Ophthalmic agents within this class include carbachol and pilocarpine. Adverse effects include sweating, salivation, eye pain, blurred vision, abdominal pain, and headache. Parasympathomimetics are contraindicated in those with uncontrolled asthma

Kelly Karpa, Anthony Possanza