Carbonic Anhydrase Inhibitors

Carbonic anhydrase is a zinc-containing enzyme which catalyses the hydration of carbon dioxide. The addition of H₂0 to CO₂ results in the formation of bicarbonate (HCO₃).¹ A class of drugs - carbonic anhydrase inhibitors (CAIs) - block the action of this enzyme. The principle indication is in the treatment of glaucoma. The inhibition of carbonic anhydrase isoenzyme II in the ciliary body decreases bicarbonate secretion into the posterior chamber by ciliary epithelial cells. This results in a decrease in the production of aqueous humour.

There are three drugs licensed for UK use:

• Acetazolamide
• Dorzolamide
• Brinzolamide

Acetazolamide

• Acetazolamide is administered orally or intravenously (intramuscular injections being too painful because of the alkaline nature of the solution). Its principal use is as an adjunct in the short-term treatment of open-angle glaucoma and secondary glaucoma. It is also used peri-operatively in angle-closure glaucoma. On occasion, it is used in the long-term management of chronic glaucoma as a last resort.
• It is licensed for use as a diuretic but its effect is weak and it is not often used for this purpose.
• It has an unlicensed use in the treatment of altitude sickness (acute mountain sickness).²
• Acetazolamide is sometimes used in specific areas in the management of epilepsy. It is useful for the control of seizures occurring during the menstrual period (catamenial epilepsy).³ It may also be used as a second-line drug for both tonic-clonic and partial seizures, and is occasionally helpful in atypical absence, atonic and tonic seizures ⁴

Dorzolamide and Brinzolamide

These are licensed for use in patients with glaucoma as an adjunct for patients who do not respond to beta-blockers alone or those in whom beta-blockers are contra-indicated. They come in the form of topical eye drops only. There appears to be no difference in efficacy.⁵ Dorzolamide only needs to be administered twice a day when used as an adjunct to beta-blockers whereas Brinzolamide needs to be used three times a day.

Acetazolamide

• Acetazolamide is a sulphonamide and as such can cause blood dyscrasias and rashes.⁶ In its rare long-term use, the prescriber will also have to be wary of electrolyte disturbance and metabolic acidosis.⁷
• Cautious use is recommended in pregnancy. There have been no reports of fetal toxicity in humans, although some abnormalities have been found in animal studies and the degree of placental transfer is unknown.
• Acetazolamide has not been detected in significant amounts in breast milk.⁸

Dorzolamide and Brinzolamide^9,10

• Systemic absorption can occur. Caution should be exerted in patients with hepatic impairment, closed angle glaucoma, sulphonamide hypersensitivity, a history of renal calculi, pre-existing chronic corneal defects or history of ocular surgery.
• The drugs should not be used in pregnancy or lactation due to lack of data.

Acetazolamide⁷

Contra-indications include hypokalaemia, hyponatraemia, hyperchloraemic acidosis, severe hepatic impairment; renal impairment and sulphonamide hypersensitivity.

Dorzolamide and Brinzolamide ^9,10

Contra-indications include renal impairment, hyperchloraemic acidosis, pregnancy and breastfeeding.

Acetazolamide⁷

Being a sulphonamide drug, there is a whole host of possible adverse effects. Common ones include flushing, thirst, headache, drowsiness, polyuria, and gastro-intestinal disturbance.

Dorzolamide and Brinzolamide ^9,10

These are relatively safe drugs. The main side effect is local irritation. One study suggested this is less of a problem with Brinzolamide. Rarely, absorption can lead to systemic side effects, such as gastro-intestinal disturbance.

Acetazolamide⁷

Blood count, renal function and bicarbonate level should be monitored with prolonged use.

Dorzolamide and Brinzolamide ^9,10

Regular monitoring is not required unless patients have relevant co-morbidities. Contact lens wearers should be regularly monitored by an ophthalmologist.

Being mild loop diuretics the significant interactions of CAIs are caused by hypokalaemia. This may be relevant with drugs such as cardiac glycosides, flecainide and lithium. Hypotension can be caused in combination with antihypertensives. This is much less likely to happen with the topical preparations than with acetazolamide, but is not unknown. Acetazolamide can increase the serum concentration of carbamazepine.