Pharmacology of the Eye

The eye is mostly isolated from the body (cornea and lens are avascular), so most eye drugs are given as eyedrops. These are especially good for treating conditions of the anterior segment.

Eyedrops must deliver drugs through the cornea, which has a hydrophobic epithelium but hydrophilic stroma.

Dipivalyl epinephrine (Dipivefrine) is very hydrophobic, so it penetrates the corneal epithelium and is converted to epinephrine within the eye. Clever.

Drugs will drain into the nasolacrimal duct, and from there can reach significant systemic levels.

The iris constrictor and ciliary muscle have muscarinic ACh receptors.

The iris dilator and trabecular meshwork have adrenergic receptors.

Mydriatics (dilators) have red caps

Miotics (constrictors) have green caps

Beta-blockers have yellow caps.

Eye Anaesthetics

These drugs are often abused by patients, and should never be prescribed for home use.

--Proparacaine

--Tetracaine

--Cocaine

Eye Dilators (“Mydriatics”)

--Tropicamide, Atropine, Scopolamine are all muscarinic antagonists.

--Phenylephrine is an adrenergic agonist. One drop of phenylephrine causes systemic side effects.

Adie’s Pupil (persistent pupil dilation)

Disruption of parasympathetic input to the iris sphincter causes a dilated pupil.

**This decreased input causes upregulation of the number of muscarinic receptors!

**Because of the extra receptors, a very dilute drop of pilocarpine (too weak to constrict a normal pupil) will constrict an Adie’s Pupil. This is “denervation supersensitivity.”

Constriction of a large pupil with dilute pilocarpine is diagnostic for Adie’s Pupil.

Horner’s Syndrome (persistent pupil constriction)

Disruption of sympathetic input to the iris dilator causes a constricted pupil on the side of the lesion.

**Cocaine blocks norepinephrine reuptake, enhancing pupil dilation. In Horner’s there is no norepinephrine in the synapse, so in Horner’s cocaine can’t dilate the pupil.

Cycloplegia and Strabismus

Cycloplegia is paralysis of the ciliary muscle, so accommodation can’t occur.

Atropine and Cyclopentolate inhibit parasympathetics, relaxing the ciliary body.

**Atropine is used to treat strabismus. Atropine is put in the good eye, which makes the good eye unable to focus. This is liking putting a patch on the good eye. It forces the cortex to develop better vision in the bad eye.

Dry eyes

--Restasis is the drug of choice for dry eyes.

Glaucoma Treatment

1. Parasympathomimetics stimulate contraction of the ciliary muscle, which pulls open the trabecular meshwork and relieves intraocular pressure.

Pilocarpine is a direct muscarinic agonist.

Phospholine iodide is an anti-cholinesterase that keeps more ACh in the synapse.

2. Beta-blockers are the most common glaucoma treatment. Reduce production of aqueous humor.

Side effects include exacerbation of congestive heart failure and COPD.

3. Alpha-agonists such as Brimonidine reduce the production of aqueous humor and promote its pupillary outflow. Systemic side effects are common.

4. Carbonic Anhydrase Inhibitors reduce the production of aqueous humor.

5. Prostaglandins potently decrease intraocular pressure by increasing drainage of aqueous humor.

Side effects include darkening of the iris, and longer/bushier eyelashes.

6. THC (marijuana) is not used because of its other effects…

Infectious Diseases of the Eye

Herpes Simplex keratitis: Trifluorothymidine, Acyclovir

Herpes Zoster keratitis: Acyclovir+Famciclovir

Cytomegaloviral keratitis: Cidofovir

Onchocerchiasis (river blindness): An annual dose of Ivermectin kills the worms completely.

Use of Vitamin A

Vitamin A deficiency causes xerophthalmia (drying of the eye surface) and night blindness.

Vitamin A supplements cure xerophthalmia and reduce overall childhood mortality by 1/3!

Effects of Systemic Drugs on the Eye

**Oxygen given to premature infants causes retinal neovascularization and “retinopathy of prematurity.”

--Sulfa drugs can cause Stevens-Johnson syndrome, which can lead to scarring and blindness.

--Corticosteroids frequently lead to elevated intraocular pressure and glaucoma. Cataracts too.

--Topiramate (anti-epileptic) can cause bilateral acute angle-closure glaucoma.

This often presents as rapid onset of decreased vision and terrible pain.

Category: Pharmacology Notes