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Current advances in ocular pharmacology (Proceedings)

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Apr 01, 2008

A. Routes of Administration

1. Topical—most common route of administration

Degree of penetration of topically applied medications depends on integrity of normal defense mechanisms of the eye. Drug absorption is greatly enhanced by ocular inflammation. Medications put in the conjunctival sac can penetrate the cornea, conjunctiva, or be absorbed systemically via the nasolacrimal system. Topical administration is also affected by the vehicle, molecular size of the drug, drug concentration, pH, electrolyte composition, and preservatives.

Corneal epithelium is the main site of resistance to drug penetration. The cornea may be thought of as a fat-water-fat sandwich. As a result, the epithelium and endothelium are relatively impermeable to electrolytes but are readily penetrated by fat-soluble substances. The stroma is readily penetrated by electrolytes but not by fat-soluble substances. Drugs that have the ability to exist in equilibrium in solution as ionized (water soluble; polar) and unionized (lipid soluble; nonpolar) forms are ideal for topical use, i.e., chloramphenicol, fluoroquinolones, alkaloids. Topical administration is used for treatment of eyelids, conjunctiva, corneal, iris, and anterior uvea.

2. Subconjunctival (bulbar conjunctiva)

This technique requires only topical anesthesia and a tuberculin syringe with a 25- or 27-gauge needle. Volumes should not exceed 0.25 ml in cats and dogs and 1.0 ml in horses and cows. Subconjunctival medication reaches the cornea by slowly leaking out of the injection site. Intraocular drug levels are attained by diffusion through the cornea and sclera. Subconjunctival administration is used for diseases of the cornea, anterior, uvea, anterior vitreous, and sclera.

3. Intravitreal—used infrequently

Antibiotics and antifungal drugs have been effectively used in microgram dosages. Generally injected at the pars plana for infectious endophthalmitis.

4. Systemic—P.O., I.V., I.M.

Generally do not penetrate the anterior segment of the eye as well as topical or subconjunctival medications. Small molecular weight lipid-soluble drugs may penetrate the blood aqueous barrier. Drug penetration is also markedly increased with ocular inflammation. Systemic administration is required for treatment of diseases of the retina, optic nerve, and vitreous.

B. Mydriatics

Mydriatics cause dilation of the pupil by sympathomimetic or parasympatholytic action.

1. Atropine

Direct acting—parasympatholytic, blocks the response of postganglionic cholinergic receptors to acetylcholine. Cycloplegic (paralyzes ciliary musculature).

Strength—0.5%-4%.

Duration—2-4 x day until mydriasis—then as needed.

Lasts 1-2 weeks—dog.

Lasts 4-6 weeks—horse.

Use. Cycloplegic—uveitis/pain. May cause gut stasis in sensitized horses.

2. Tropicamide (Tropicacyl®)

Synthetic parasympatholytic. Cycloplegic (weak).

Duration—Works in ~ 15-20 minutes. Lasts ~ 2-4 hours.

Use—Diagnostic evaluation.

C. Miotics

Topical administration results in pupillary constriction, ciliary muscle contraction, and increased aqueous outflow.

1. Pilocarpine

Direct acting--cholinergic, mimics acetylcholine.

Strength—0.05% - 4%.

Duration—4 – 6 hours

Use. Glaucoma, KCS limited. Often is topically irritating.

2. Carbachol - Carbostat® 0.01%

Used most commonly as an intracameral injection after cataract surgery to decrease potential intraocular pressure spikes.

3. Latanoprost - Xalatan®

Prostoglandin F 2a analog

Strength—0.005%

Currently drug of choice for treatment (miosis) of glaucoma (increases aqueous outflow).