A-Textbook-of-Clinical-Pharmacology-and-Therapeutics-5th-edition
A-Textbook-of-Clinical-Pharmacology-and-Therapeutics-5th-edition
A-Textbook-of-Clinical-Pharmacology-and-Therapeutics-5th-edition
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426 DRUGS AND THE EYE<br />
Chronic simple glaucoma is due to a limitation <strong>of</strong> flow<br />
through the trabecular meshwork. Initial treatment is with a topical<br />
β-blocker. Other drugs (e.g. dipivefrine, a prodrug <strong>of</strong> adrenaline<br />
(epinephrine) designed to penetrate the cornea readily, or<br />
pilocarpine) are added as necessary. Disappointingly, visual<br />
impairment may progress despite adequate control <strong>of</strong> intra-ocular<br />
pressure <strong>and</strong> surgery has a place in this, as well as in the<br />
acute form <strong>of</strong> glaucoma.<br />
DRUGS USED TO TREAT GLAUCOMA<br />
MANNITOL<br />
Mannitol (Chapter 36) is an osmotic diuretic. It is used in an<br />
emergency or before surgery, <strong>and</strong> is given as an intravenous<br />
infusion (e.g. 100–200 mL <strong>of</strong> a 20% solution) over 30–60 minutes.<br />
It shifts water from intracellular <strong>and</strong> transcellular compartments<br />
(including the eye) into the plasma, <strong>and</strong> promotes<br />
loss <strong>of</strong> fluid by its diuretic action on the kidney. Its major<br />
adverse effect is dehydration.<br />
CARBONIC ANHYDRASE INHIBITORS<br />
Acetazolamide is used in acute <strong>and</strong> chronic glaucoma, <strong>and</strong> it<br />
also has highly specialized uses in certain seizure disorders in<br />
infants, <strong>and</strong> in adapting to altitude. It was previously used as<br />
a diuretic (see Chapter 36). It is a sulphonamide. It is a competitive<br />
inhibitor <strong>of</strong> carbonic anhydrase, the enzyme that converts<br />
CO 2 <strong>and</strong> H 2 O into H 2 CO 3 . Inhibition <strong>of</strong> this enzyme in<br />
the eye reduces aqueous humour production by the ciliary<br />
body.<br />
Adverse effects<br />
Adverse effects include the following:<br />
• paraesthesiae <strong>and</strong> tingling;<br />
• nausea, vomiting <strong>and</strong> loss <strong>of</strong> taste;<br />
• metabolic acidosis;<br />
• polyuria due to its mild diuretic properties;<br />
• hypersensitivity reactions – particularly <strong>of</strong> the skin;<br />
• bone marrow suppression (rare).<br />
Acetazolamide is poorly tolerated orally, although a slowrelease<br />
preparation exists which can be given twice daily <strong>and</strong><br />
has reduced incidence <strong>of</strong> side effects. Dorzolamide is a topically<br />
applied carbonic anhydrase inhibitor, whose use may<br />
reduce the need for systemic acetazolamide therapy (see<br />
below). Acetazolamide should not be used in patients with<br />
renal failure, renal stones or known hypersensitivity to<br />
sulphonamides, or in pregnant women.<br />
TOPICAL AGENTS FOR GLAUCOMA<br />
DORZOLAMIDE<br />
Dorzolamide is a topically applied carbonic anhydrase<br />
inhibitor, which may be used either alone or as an adjunct to a<br />
β-blocker. Systemic absorption does occur <strong>and</strong> systemic side<br />
effects (e.g. rashes, urolithiasis) may require drug withdrawal.<br />
Typical adverse effects include local irritation <strong>of</strong> the eye <strong>and</strong><br />
eyelid with burning, stinging <strong>and</strong> visual blurring, <strong>and</strong> a bitter<br />
taste.<br />
PROSTAGLANDIN ANALOGUES<br />
Latanoprost is a prostagl<strong>and</strong>in F 2α analogue. It can be used in<br />
patients who are intolerant <strong>of</strong> β-blockers or as add-on therapy<br />
when the response to the first drug has been inadequate.<br />
Latanoprost is an inactive prodrug which readily penetrates<br />
the cornea <strong>and</strong> is hydrolysed to the free acid. The free acid diffuses<br />
out <strong>of</strong> the cornea into the aqueous humour <strong>and</strong> lowers<br />
the intra-ocular pressure by increasing uveoscleral outflow.<br />
Systemic absorption does occur via conjunctival <strong>and</strong> mucous<br />
membranes. Latanoprost is cleared by hepatic metabolism.<br />
The main side effects are local irritation with stinging, burning<br />
<strong>and</strong> blurred vision. Punctate keratopathy has occurred, <strong>and</strong> it<br />
increases the amount <strong>of</strong> brown pigment in the iris in patients<br />
with mixed-coloured eyes, which may be a cosmetic problem,<br />
especially if treatment is only needed for one eye. Travoprost<br />
<strong>and</strong> bimatoprost are related prostagl<strong>and</strong>in analogues.<br />
α 2 -AGONISTS<br />
Brimonidine is a selective α 2 -agonist, used for chronic openangle<br />
glaucoma when other drugs are unsatisfactory. It is used<br />
alone or as an adjunct to β-blocker therapy in chronic glaucoma.<br />
It decreases aqueous humour production <strong>and</strong> increases<br />
uveoscleral flow. Trace amounts do get into the circulation<br />
<strong>and</strong> undergo hepatic metabolism. The major toxicities include<br />
local ocular irritation <strong>and</strong> occasional corneal staining, <strong>and</strong> systemic<br />
adverse effects include dry mouth (25% <strong>of</strong> cases),<br />
headache, fatigue, drowsiness <strong>and</strong> allergic reactions. It is contraindicated<br />
in patients taking monoamine oxidase inhibitors<br />
(MAOIs) <strong>and</strong> should be used with caution in those with<br />
severe coronary artery disease (CAD) or taking tricyclic<br />
antidepressants.<br />
Apraclonidine is another selective α 2 -agonist which is formulated<br />
for ophthalmic use.<br />
Key points<br />
Drugs <strong>and</strong> the pupil<br />
• Miosis (pupillary constriction)<br />
– Parasympathetic stimulation:<br />
muscarinic agonists (e.g. carbachol, pilocarpine);<br />
cholinesterase inhibitors (e.g. neostigmine,<br />
physostigmine).<br />
– Sympathetic blockade:<br />
α 1 -antagonists (e.g. phentolamine).<br />
• Mydriasis (pupillary dilatation)<br />
– Parasympathetic blockade:<br />
muscarinic antagonists (e.g. atropine, tropicamide).<br />
– Sympathetic stimulation:<br />
α 1 -agonists (e.g. phenylephrine).