A Textbook of Clinical Pharmacology and Therapeutics

Chronic simple glaucoma is due to a limitation of flow
through the trabecular meshwork. Initial treatment is with a top-
icalβ-blocker. Other drugs (e.g. dipivefrine, a prodrug of adren-
aline(epinephrine) designed to penetrate the cornea readily, or
pilocarpine) are added as necessary. Disappointingly, visual
impairment may progress despite adequate control of intra-ocu-
lar 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 min-
utes. It shifts water from intracellular and transcellular com-
partments (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

Acetazolamideis 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 com-
petitive inhibitor of carbonic anhydrase, the enzyme that con-
verts 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).

Acetazolamideis poorly tolerated orally, although a slow-
release preparation exists which can be given twice daily and
has reduced incidence of side effects. Dorzolamideis a topic-
ally applied carbonic anhydrase inhibitor, whose use may
reduce the need for systemic acetazolamide therapy (see
below).Acetazolamideshould 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

Latanoprostis a prostaglandin F 2 αanalogue. 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.

Latanoprostis an inactive prodrug which readily penetrates

the cornea and is hydrolysed to the free acid. The free acid dif-

fuses 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.Latanoprostis 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

andbimatoprostare related prostaglandin analogues.

α 2 -AGONISTS

Brimonidineis a selective α 2 -agonist, used for chronic open-

angle glaucoma when other drugs are unsatisfactory. It is used

alone or as an adjunct to β-blocker therapy in chronic glau-

coma. 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 sys-

temic adverse effects include dry mouth (25% of cases),

headache, fatigue, drowsiness and allergic reactions. It is con-

traindicated 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.

Apraclonidineis another selective α 2 -agonist which is for-

mulated for ophthalmic use.

426 DRUGS AND THE EYE

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).