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C CLINICAL RESEARCH

IOP is reduced a moderate amount (15 to 20%); however, one notable benefit of the CAIs is the ability to lower IOP
in the night-time hours. This appears to be unique to the CAIs. This makes CAIs a desirable agent for those pa-
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tients in whom progression is occurring despite what appears to be IOP at target, and in those patients with NTG
in whom 24-hour blood pressure monitoring has demonstrated that significant nocturnal dips in blood pressure are
occurring, increasing the relative risk for optic nerve non-perfusion during the night. 344

The mechanism of action for the CAIs is decreased aqueous production. Systemic adverse effects of the topically
applied CAIs are generally taste perversion and headache, while discomfort on instillation is the most frequently
reported symptom. It is important to relay this expected finding to ensure patients do not stop the medication due
to concern that they are causing harm. Blurred vision, hyperemia, and dryness are also common. 345

Of interest is the evolving understanding about the issue of allergy to sulfa drugs and the CAIs. Dorzolamide and
brinzolamide are sulfonamides, and the components of the sulfonamide antibiotics that cause allergy are present
in these non-antibiotic sulfa drugs. Those who have been found to have an allergy to sulfa antibiotics and also to
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CAIs have been deemed to have a tendency to allergy in general rather than this being caused by cross-reactivity
with the sulfonamide. For this reason, patients with sulfa antibiotic allergies are likely to be able to safely use CAI
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glaucoma drops.
Both dorzolamide and brinzolamide are available as FC with 0.5% timolol. These are usually dosed every 12 hours.
Brinzolamide is also available in FC with brimonidine 0.2%, which is dosed three times per day.

Oral drugs in this class, including acetazolamide (250mg tablets) and methazolamide (50mg), are rarely used for the
treatment of primary open angle glaucoma, but may be considered when acute lowering of a very elevated IOP in an
emergency situation (or less commonly, to lower IOP in anticipation of a surgical intervention) is required. Oral ad-
ministration is very effective, with IOP reduction of 30% noted by 30 minutes, peaking at 2 hours and lasting for 6 to
8 hours. Medical considerations are significantly different for systemic use of the CAIs, which are contraindicated
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in the presence of liver or kidney disease, serum electrolyte imbalance and other less common systemic conditions.
The most common adverse effects include malaise, diarrhea, anorexia, metallic taste and polyuria; however, drowsi-
ness or dizziness and depression are also possible. Further CNS, dermatologic, and hematologic adverse effects, as
well as metabolic acidosis may occur. Consultation with the patient’s family physician prior to administering these
agents is recommended, especially in older patients and those for whom medical history is not known.

Muscarinic agonists
Direct- and indirect-acting muscarinic agonists have been used to treat glaucoma since the prior millennium. Only
one agent remains on the market: various concentrations and mechanisms of delivery of pilocarpine (0.25% to 10%;
drops and sustained-release inserts). The mechanism of action of pilocarpine is to increase conventional (trabecular
meshwork) outflow by increased tension on the scleral spur, physically opening the meshwork. The onset of action
of pilocarpine is prompt with peak lowering within 2 hours, but the duration is short, lasting for only 8 hours. 349

While systemic adverse effects are uncommon and these are inexpensive drugs, the need for dosing four times per
day and the significant local adverse effects have led to these drugs being essentially shelved in the management of
open angle glaucoma. However, when glaucoma is progressive, maximal medical therapy has been reached and
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surgical interventions are not possible, these agents can help to lower eye pressure and reduce risk of progression. 351
Pilocarpine is particularly important in primary angle closure glaucoma due to plateau iris or pupillary block once any
acute IOP elevation has been addressed. It could be used effectively (albeit not comfortably) in pigment dispersion
syndrome. The use of pilocarpine should be avoided in uveitic or neovascular glaucoma, and any secondary angle clo-
sure whereby the lens-iris diaphragm is displaced anteriorly would be a relative contraindication for a miotic agent. 352

Clinical Recommendations for IOP lowering with medications: 317,318
IOP reduction for the various classes of medications is approximately:
• Prostaglandin analogues (31-33%): bimatoprost (33%), latanoprost and travoprost (31%)
• Beta-blockers: timolol (27%); betaxolol (23%)
• Alpha agonist: brimonidine (25%)
• CAIs: dorzolamide (21%), brinzolamide (17%); additional nocturnal IOP lowering is an added benefit

52 CANADIAN JOURNAL of OPTOMETRY | REVUE CANADIENNE D’OPTOMÉTRIE VOL. 79 SUPPLEMENT 1, 2017