Carbonic Anhydrase Inhibitors for Glaucoma

Carbonic anhydrase inhibitors lower intraocular pressure by reducing aqueous production. Topical agents (dorzolamide, brinzolamide) are used as add-on therapy; oral acetazolamide gives a greater and faster fall and is used for acute pressure rises, before surgery and short-term when drops are not enough.

Mechanism. Inhibition of carbonic anhydrase II in the ciliary processes reduces bicarbonate formation and sodium and fluid movement into the posterior chamber, reducing aqueous secretion by up to 40 to 60 percent with oral drugs.

Pharmacokinetics. Topical drugs reach the aqueous humour and show low systemic levels, but accumulate in red blood cells. Acetazolamide is well absorbed orally, with peak effect at 1 to 4 hours, half-life 6 to 9 hours, and renal excretion unchanged; the modified-release form lasts 8 to 12 hours.

• Dorzolamide 2 percent: more stinging.
• Brinzolamide 1 percent suspension: more comfortable; blurred vision for a short time.
• Acetazolamide: greater effect; systemic side effects; used short-term.
• Methazolamide: oral alternative with fewer renal effects.
• Fixed combinations: dorzolamide with timolol; brinzolamide with brimonidine.

Regimens.

• Dorzolamide 2 percent: one drop three times daily alone, or twice daily as add-on to a beta blocker or prostaglandin analogue. Brinzolamide 1 percent: one drop two or three times daily.
• Acetazolamide: 250 mg orally two to four times daily (125 mg in older adults, and in children 5 to 10 mg/kg every 6 to 8 hours), or modified-release 250 to 500 mg twice daily; acute angle closure 500 mg once, orally or by slow intravenous injection.
• Take oral doses with food, with plenty of fluid, and add potassium supplements if long-term.

Selection. Add-on third-line topical drug; useful when beta blockers are contraindicated. Reserve oral acetazolamide for short courses (acute angle closure, perioperative pressure spikes, cystoid macular oedema, idiopathic intracranial hypertension) and for people who cannot use drops or are awaiting surgery.

Contraindications. Hypersensitivity to sulphonamides (relative), severe renal or hepatic impairment, hyponatraemia, hypokalaemia, hyperchloraemic acidosis, adrenocortical failure; topical drugs in corneal endothelial disease (risk of oedema); oral acetazolamide in pregnancy first trimester and in sickle cell disease (risk of haemolysis and hyphaema complications, use with care).

Effects. Topical: stinging, bitter taste, blepharoconjunctivitis, corneal oedema. Oral: paraesthesia of fingers and mouth, taste disturbance, fatigue, depression, loss of appetite, diuresis, metabolic acidosis, hypokalaemia, renal stones, aplastic anaemia, Stevens-Johnson syndrome, transient myopia.

Interactions. High-dose aspirin (toxicity), lithium, digoxin and diuretics (hypokalaemia), topiramate (acidosis and stones), carbamazepine and phenytoin (raised levels), ciclosporin, oral antidiabetic drugs.

Monitoring. Oral therapy beyond a few weeks: serum electrolytes and bicarbonate, creatinine and full blood count at baseline and then every 3 to 6 months; report fever, rash, sore throat.

Special groups. Pregnancy: avoid, especially in the first trimester. Breastfeeding: low milk levels; use with care. Older adults: lower dose. Region: in resource-limited settings acetazolamide is often the main alternative to surgery and laser; check electrolytes and kidney function before long courses and advise on fluids to reduce stone risk.