Clinical Pharmacology and Therapeutics

DRUGS USED TO CONSTRICT THE PUPIL AND TO TREAT GLAUCOMA 425
to cause pupillary dilatation, namely muscarinic antagonists
(anticholinergics) and sympathomimetics. Short-acting
relatively weak mydriatics, such as tropicamide, facilitate retinal
examination. Cyclopentolate and atropine are preferred
for producing cycloplegia (paralysis of the ciliary muscle) for
refraction in young children. Atropine is also used for the treatment
of iridocyclitis mainly to prevent posterior synechiae,
when it is often combined with phenylephrine.
Table 52.2 shows some commonly used agents, their receptor
effects, dose schedule and toxicity. Agents that dilate the
pupil may abruptly increase the intra-ocular pressure in
closed-angle glaucoma by causing obstruction to the outflow
tract, and are contraindicated in this condition. Patients
should be asked whether they are driving before having their
pupils dilated and should be warned not to drive afterwards
until their vision has returned to normal.
Cornea
Aqueous humour
Iris
Tears
Systemic circulation
Conjunctiva
Sclera
Ciliary body
Figure 52.2: Potential absorption pathways for drugs applied to
the eye.
DRUGS USED TO CONSTRICT THE PUPIL
AND TO TREAT GLAUCOMA
PHYSIOLOGY OF AQUEOUS HUMOUR DYNAMICS
AND REGULATION OF INTRA-OCULAR PRESSURE
Aqueous humour is produced at a rate of 2–2.5 mL per minute
and flows from the posterior chamber through the pupil into the
anterior chamber. Around 80–95% of it exits via the trabecular
meshwork and into the canal of Schlemm and subsequently into
the episcleral venous plexus and eventually into the systemic
circulation. Fluid can also flow via the ciliary muscles into the
suprachoroidal space. The geometry of the anterior chamber differentiates
the two forms of glaucoma, namely open-angle glaucoma
(the more common form) and angle-closure glaucoma
(closed-angle glaucoma). Open-angle glaucoma is usually
treated medically in the first instance, by reducing aqueous
humour flow and/or production. Closed-angle glaucoma is
treated by iridectomy following urgent medical treatment to
reduce the intra-ocular pressure in preparation for surgery.
PRINCIPLES OF THERAPY FOR GLAUCOMA
Acute glaucoma is a medical emergency. Mannitol can reduce
the intra-ocular pressure acutely by its osmotic effect. In addition,
therapy with a carbonic anhydrase inhibitor (intravenous
acetazolamide or topical dorzolamide) may be
required. This is then supplemented with either a topical
β-adrenergic antagonist (e.g. timolol) or a cholinergic agonist
(e.g. pilocarpine), or both.
Table 52.2: Drugs commonly used to dilate the pupil
Drug Receptor Dose, onset of mydriasis Toxicity and other
and schedule
comments
Anticholinergics
Tropicamide Single drop of 0.5% solution, Photosensitivity, blurred vision and
maximum onset of effect is
systemic absorption can occur
in 20–40 min and lasts 3–6 h
Cyclopentolate All anticholinergics are Single drops of 0.5 or 1.0% As for tropicamide
antagonists at the
solution, maximum onset of
M 3 receptor on the
effect is in 30–60 min and
ciliary muscle
lasts 24 h
Atropine Single drop of 0.5 or 1.0% As for tropicamide
solution, maximum onset of
effect is 30–40 min and
lasts 7–10 days
Sympathomimetics
Phenylephrine One of two drops of 10% Systemic absorption can occur (avoid in
solution, lasts up to 12 h
patients with coronary artery disease
or hypertension)