A Textbook of Clinical Pharmacology and Therapeutics

●Introduction: ocular anatomy, physiology and

biochemistry 423

●General pharmacokinetics of intra-ocular drug

administration 423

●Drugs used to dilate the pupil 423

●Drugs used to constrict the pupil and to

treat glaucoma 425

●Drugs used to treat eye infections 427

●Drugs used to treat inflammatory disorders in

the eye 427

●Drugs for age-related macular degeneration 428

●Local anaesthetics and the eye 428

●Adverse effects on the eye of systemic drug therapy 428

●Contact lens wearers 429

CHAPTER 52

DRUGS AND THE EYE

INTRODUCTION: OCULAR ANATOMY,

PHYSIOLOGY AND BIOCHEMISTRY

The eye is protected by a series of barriers, namely the
blood–retinal, blood–aqueous and blood–vitreous barriers, and
so represents both an opportunity for localized drug adminis-
tration and also a challenge to drug delivery. See Figure 52.1 for
a cross-sectional view of the anatomy of the eye.
The structures of the eye itself are divided into the anterior and
posterior segments. The anterior segment includes the cornea,
limbus, anterior and posterior chambers, trabecular meshwork,
Schlemm’s canal, the iris, lens and the ciliary body. The posterior
segment consists of the sclera, choroid, retina, vitreous and optic
nerve. The anterior surface of the eye is covered by the conjunc-
tiva. The ocular secretory system is composed of the main lacrimal
gland located in the upper outer orbit, and accessory glands
located in the conjunctiva. The lacrimal gland has both sympa-
thetic and parasympathetic innervation. Parasympathetic inner-
vation is relevant in that many drugs with anticholinergic side
effects cause the symptom of dry eyes (see Table 52.1). Tear
drainage starts through small puncta located in the medial aspects
of the eyelids. Blinking causes tears to enter the puncta and drain
through the canaliculi, lacrimal sac and nasolacrimal duct into the
nose. The nose is lined with highly vascular epithelium which per-
mits direct access of absorbed drugs to the systemic circulation.
Consequently, even though the dose administered as eye drops is
much smaller than the usual dose of the same drug (e.g. timolol)
administered by mouth, the lack of first-pass metabolism may
nonetheless lead to unwanted systemic effects.

THE IRIS AND CILIARY BODY

In the iris, dilator smooth muscle is orientated radially and inner-
vated by the sympathetic system, which produces dilatation

(mydriasis). At the pupillary margin, the sphincter smooth

muscle is organized in a circular orientation with parasympa-

thetic innervation which, when stimulated, leads to pupillary

constriction (miosis) (see Table 52.1 for a summary of the auto-

nomic pharmacology of the eye).

The ciliary body serves two specialized functions, namely

secretion of the aqueous humour and accommodation.

Parasympathetic stimulation contracts the ciliary muscle and

allows the lens to become more convex, focusing on near objects.

Contraction of this muscle also widens the spaces in the trabecu-

lar meshwork and this also explains, in part, the effect of

parasympathomimetics in lowering intra-ocular pressure.

GENERAL PHARMACOKINETICS OF

INTRA-OCULAR DRUG ADMINISTRATION

The bioavailability of intra-ocularly administered drugs

depends on pH and other pharmaceutical properties of the

vehicle. Most ophthalmic drugs in general use are delivered as

drops, usually in aqueous solution. Formulations which prolong

the time for which a drug remains in contact with the eye surface

include gels, ointments, solid inserts, soft contact lenses and col-

lagen shields. Drug penetration into the eye itself is approxi-

mately linearly related to the concentration of drug applied.

Nasolachrymal drainage plays a key role in the systemic

absorption of drugs administered to the eye, and drugs

absorbed via this route circumvent hepatic first-pass metab-

olism. Thus ocular drugs such as β-adrenergic antagonists can

cause wheezing in asthmatic patients. Figure 52.2 shows

potential pathways for drug absorption in the eye.

DRUGS USED TO DILATE THE PUPIL

Mydriasis (pupillary dilatation) is often required for detailed

examination of the retina. Two major groups of drugs are used