Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 25 OCULAR CLINICAL PHARMACOLOGY
Table 25.1 Topical ophthalmic preparations and common
trade names
Drug Trade name Manufacturer
Corticosteroids
1% prednisolone Prednefrin Forte Allergan
acetate
0.1% phenylephrine
0.1%
Maxidex
Alcon
dexamethasone
alcohol
1% hydrocortisone Hycor Eye Ointment Sigma
1% hydrocortisone Hycor Eye Drops Sigma
Corticosteroids and antibacterials
0.25% prednisolone Amacin
with neomycin,
polymyxin B and
sulfacetamide
1% prednisolone Optigentin-S
and gentamicin
VR
Laboratories
Jurox
Nonsteroidal anti-inflammatory drugs
Flurbiprofen 0.03% Ocufen Allergan
Diclofenac 0.1% Voltaren Ciba-Vision
Ketorolac 0.5% Acular Alcon
Miscellaneous anti-inflammatory drugs
Ciclosporin Optimmune Schering-Plough
Sodium
Opticrom
Fisons
cromoglycate 4%
Anti-infective drugs
Gentamicin Soligental Virbac
Tobramycin Tobrex Alcon
Ciprofloxacin 0.3% Ciloxan Alcon
Ofloxacin 0.3% Ocuflox Allergan
Fusidic acid Conoptal Boehringer
Ingelheim
Cloxacillin Orbenin Pfizer
Polymyxin B,
Neosporin Ointment Wellcome
bacitracin
Natamycin 5% Natacyn Alcon
Aciclovir Zovirax Glaxo
SmithKline
Mydriatics
Atropine 0.5%, 1%, Atropine Sigma
Tropicamide 1% Mydriacyl Alcon
Miotics
Pilocarpine 1–2% PV Carpine
Sigma
drops
Demecarium Humorsol MSD
Local anesthetics
Proparacaine 0.5% Opthaine Allergan
Alcaine Alcaine Alcon
Glaucoma
Dorzolamide Trusopt MSD
Brinzolamide Azopt Alcon
Dorzolamide/timolol Cosopt MSD
Latanoprost Xalatan Pharmacia &
Upjohn
Travaprost Travatan Alcon
Bimatoprost Lumigan Allergan
Table 25.2 Suggested routes of administration for the eye
Topical Subconjunctival Systemic
Eyelids ++ + +
Conjunctiva + + + Doxycycline
– cats
Cornea + ++ +
Sclera + + +
Iris, ciliary body + + + +
Vitreous + +
Retina ++
Optic nerve ++
Orbit/retrobulba ++
Other mechanisms that help to protect the eye include
continuous turnover of the precorneal tear film, rapid
turnover of intraocular fluids, active transport mechanisms
within the eye that can eliminate substances, and
marked anatomical and physiological compartmentalization
within the eye. If a drug is unable to enter the
eye for any of these reasons, its therapeutic efficacy will
be greatly reduced.
Covered by the tear film, the cornea is the main
barrier to topical drugs entering the eye. If the drug
applied to the cornea is irritant, reflex tearing may wash
it away before it has had a chance to penetrate.
The cornea is composed of lipid epithelium. This
layer can be penetrated easily by fat-soluble compounds
but is relatively impermeable to ionized compounds. In
contrast, the stroma can be readily penetrated by ionized
solutions but the passage of fat-soluble compounds is
severely restricted. The innermost layer is Descemet’s
membrane and the corneal endothelium. This layer is
also lipid and acts similarly to the corneal epithelium in
relation to drug passage.
For drugs to be able to pass readily through the
cornea they need to be able to convert between the
ionized and nonionized forms. Drugs, such as chloramphenicol
and atropine, which exist in equilibrium
between the two forms can readily reach high intraocular
concentrations. In some cases of corneal ulceration,
where the epithelium has been removed, many watersoluble
(ionized) drugs are able to penetrate readily into
the eyeball.
Other factors that may affect the intraocular penetration
of topically applied drugs include:
● the size of the drug molecule – the smaller, the
better the penetration
● the drug concentration – the higher, the better the
penetration. Clinically it is common to fortify
antibacterials, such as gentamicin, that are used to
treat serious corneal infections.
The blood–eye barrier acts to severely impede the transfer
of blood-borne drugs into the eye. Fortunately,
ocular inflammation reduces the blood–eye barrier,
558