Clinical Pharmacology and Therapeutics

426 DRUGS AND THE EYE
Chronic simple glaucoma is due to a limitation of flow
through the trabecular meshwork. Initial treatment is with a topical
β-blocker. Other drugs (e.g. dipivefrine, a prodrug of adrenaline
(epinephrine) designed to penetrate the cornea readily, or
pilocarpine) are added as necessary. Disappointingly, visual
impairment may progress despite adequate control of intra-ocular
pressure and surgery has a place in this, as well as in the
acute form of glaucoma.
DRUGS USED TO TREAT GLAUCOMA
MANNITOL
Mannitol (Chapter 36) is an osmotic diuretic. It is used in an
emergency or before surgery, and is given as an intravenous
infusion (e.g. 100–200 mL of a 20% solution) over 30–60 minutes.
It shifts water from intracellular and transcellular compartments
(including the eye) into the plasma, and promotes
loss of fluid by its diuretic action on the kidney. Its major
adverse effect is dehydration.
CARBONIC ANHYDRASE INHIBITORS
Acetazolamide is used in acute and chronic glaucoma, and it
also has highly specialized uses in certain seizure disorders in
infants, and in adapting to altitude. It was previously used as
a diuretic (see Chapter 36). It is a sulphonamide. It is a competitive
inhibitor of carbonic anhydrase, the enzyme that converts
CO 2 and H 2 O into H 2 CO 3 . Inhibition of this enzyme in
the eye reduces aqueous humour production by the ciliary
body.
Adverse effects
Adverse effects include the following:
• paraesthesiae and tingling;
• nausea, vomiting and loss of taste;
• metabolic acidosis;
• polyuria due to its mild diuretic properties;
• hypersensitivity reactions – particularly of the skin;
• bone marrow suppression (rare).
Acetazolamide is poorly tolerated orally, although a slowrelease
preparation exists which can be given twice daily and
has reduced incidence of side effects. Dorzolamide is a topically
applied carbonic anhydrase inhibitor, whose use may
reduce the need for systemic acetazolamide therapy (see
below). Acetazolamide should not be used in patients with
renal failure, renal stones or known hypersensitivity to
sulphonamides, or in pregnant women.
TOPICAL AGENTS FOR GLAUCOMA
DORZOLAMIDE
Dorzolamide is a topically applied carbonic anhydrase
inhibitor, which may be used either alone or as an adjunct to a
β-blocker. Systemic absorption does occur and systemic side
effects (e.g. rashes, urolithiasis) may require drug withdrawal.
Typical adverse effects include local irritation of the eye and
eyelid with burning, stinging and visual blurring, and a bitter
taste.
PROSTAGLANDIN ANALOGUES
Latanoprost is a prostaglandin F 2α analogue. It can be used in
patients who are intolerant of β-blockers or as add-on therapy
when the response to the first drug has been inadequate.
Latanoprost is an inactive prodrug which readily penetrates
the cornea and is hydrolysed to the free acid. The free acid diffuses
out of the cornea into the aqueous humour and lowers
the intra-ocular pressure by increasing uveoscleral outflow.
Systemic absorption does occur via conjunctival and mucous
membranes. Latanoprost is cleared by hepatic metabolism.
The main side effects are local irritation with stinging, burning
and blurred vision. Punctate keratopathy has occurred, and it
increases the amount of brown pigment in the iris in patients
with mixed-coloured eyes, which may be a cosmetic problem,
especially if treatment is only needed for one eye. Travoprost
and bimatoprost are related prostaglandin analogues.
α 2 -AGONISTS
Brimonidine is a selective α 2 -agonist, used for chronic openangle
glaucoma when other drugs are unsatisfactory. It is used
alone or as an adjunct to β-blocker therapy in chronic glaucoma.
It decreases aqueous humour production and increases
uveoscleral flow. Trace amounts do get into the circulation
and undergo hepatic metabolism. The major toxicities include
local ocular irritation and occasional corneal staining, and systemic
adverse effects include dry mouth (25% of cases),
headache, fatigue, drowsiness and allergic reactions. It is contraindicated
in patients taking monoamine oxidase inhibitors
(MAOIs) and should be used with caution in those with
severe coronary artery disease (CAD) or taking tricyclic
antidepressants.
Apraclonidine is another selective α 2 -agonist which is formulated
for ophthalmic use.
Key points
Drugs and the pupil
• Miosis (pupillary constriction)
– Parasympathetic stimulation:
muscarinic agonists (e.g. carbachol, pilocarpine);
cholinesterase inhibitors (e.g. neostigmine,
physostigmine).
– Sympathetic blockade:
α 1 -antagonists (e.g. phentolamine).
• Mydriasis (pupillary dilatation)
– Parasympathetic blockade:
muscarinic antagonists (e.g. atropine, tropicamide).
– Sympathetic stimulation:
α 1 -agonists (e.g. phenylephrine).