EPINEPHRINE

 

EPINEPHRINE

 

HISTORY

Erdmann (1900) used subconjunctival epinephrine for glucoma patients. Hamburger (1923) administered topical epinephrine to lower intraocular pressure (IOP).

PHARMACOLOGY

It mediates reduction of IOP through stimulation of alpha and beta adrenergic receptors. The prodrug form of epinephrine is dipivefrin which must be biochemically transformed to it's active state. Endogenous enzymes in the cornea cleave the two pivalic acid side chains on dipivefrin, liberating epinephrine.

CLINICAL PHARMACOLOGY

Epinephrine is an endogenous neurohumor, synthesized by the adrenal medulla and carried by the circulation to local effector sites. It is metabolized primarily by the enzymes, monoamine oxidase, and catechol-O-methyltransferase.

Epinephrine lowers IOP by it's effects on conventional and unconventional outflow channels of the eye. In the conventional outflow channel it acts by beta-2 receptor mediated mechanisms.

Acute administration of epinephrine increases IOP and aqueous humor formation. This phenomenon is mediated by beta-receptors because timolol a beta adrenergic antagonist can block this increase in aqueous production. This effect seems to diminish with chronic administration of epinephrine.

PHARMACEUTICS

Epinephrine is available as bitartrate, borate and hydrochloride salts. All appear to be equally effective in reducing IOP.

PHARMACOKINETICS

Following topical administration, IOP decreases within one hour, reaching a minimum in 1-4 hours. IOP returns to baseline in 12-24 hours. Thus, in some patients IOP maybe controlled by once daily administration. The effectiveness of epinephrine varies with the concentration, the commercial forms range from 0.5-2.0%.

THERAPEUTIC USE

The agent is used for open-angle, secondary and closed angle glaucomas (in patients with patent iridotomies). The drug may enter systemic circulation and cause side effects.

It can also precipitate or aggravate angle-closure glaucoma.

SIDE EFFECTS

Around 50% patients on epinephrine become intolerant to the drug.

Ocular signs:

Lid and conjunctiva- hyperemia, blepharoconjunctivitis, skin blanching, adrenochrome deposits, madarosis, ocular pemphigoid.

Lacrimal system- punctal stenosis, epidermalized puncta, lacrimal stones.

Cornea- epithelial toxicity, edema, erosion from tarsal adrenochrome deposits, "black cornea" from diffuse adrenochrome, soft contact lens and prosthetic staining, ?herpetic reactivation.

Uveal tract- mydriasis, angle closure, iridocyclitis.

Retina- aphakic macular edema, ?Central retinal vein occlusion.

Systemic- tachyarrthymia, premature ventricular contractions, skin pallor, systemic hypertension, bronchospasm, cerebrovascular accidents, myocardial infarction, death.

HIGH RISK GROUPS

Epinephrine can cross the placenta and also enter breast milk. It does not cross the blood-brain barrier.

DRUG INTERACTIONS

Beta blockers= There is only slight (1-3 mmHg) reduction in IOP on combining epinephrine and beta blockers.

Miotics= The two agents have additive effect.

Carbonic anhydrase inhibitors= Effect is also additive.

Others= Drugs which block uptake of epinephrine and nor-epinephrine (e.g. reserpine) or that inhibit monoamine oxidase (e.g. phenylzine, transcypromine) or catechol-O-methyltransferase are at greater risk of developing systemic side effects with epinephrine therapy. Therefore, they should not be combined.