OCULARIDE EYE DROPS

Indications

• Ocular hypertension
• Open-angle glaucoma

Dosage

Children: Refer to the BNF for Children for appropriate paediatric dosing.

Adults: Apply 1 drop to the affected eye(s) three times daily.

Mechanism of action

Dorzolamide specifically inhibits carbonic anhydrase II, an enzyme crucial for the production of bicarbonate ions in the ciliary processes of the eye. This inhibition disrupts sodium and fluid transport, resulting in decreased secretion of aqueous humor and lower intraocular pressure. The drug exhibits a 4000-fold higher affinity for CA-II compared to CA-I, making it a potent inhibitor in the ocular context.

Pharmacodynamics

As a carbonic anhydrase inhibitor, dorzolamide effectively reduces elevated intraocular pressure in conditions like open-angle glaucoma and ocular hypertension. When used alongside topical beta-adrenergic antagonists, dorzolamide provides an additive effect in lowering intraocular pressure. The maximum reduction in intraocular pressure typically occurs approximately 2 hours after administration.

Pharmacokinetics

Dorzolamide is administered topically as eye drops, leading to systemic absorption that can cause sulfonamide-like side effects. The pharmacokinetic profile is characterized by rapid absorption and a relatively short half-life, necessitating multiple daily doses for sustained effect. It is advised to avoid use in patients with renal impairment due to the risk of metabolic acidosis.

Contra-indications

• History of sulfonamide hypersensitivity
• Severe renal impairment (creatinine clearance less than 30 mL/min)
• Hyperchloraemic acidosis

Adverse effects

• Decreased appetite
• Arthralgia
• Malaise
• Peripheral oedema
• Tremor
• Increased urinary frequency
• Dizziness
• Vertigo
• Bitter vision
• Disorders of vision
• Dry mouth
• Epistaxis
• Local reactions
• Paresthesia
• Severe cutaneous adverse reactions (SCARs)
• Angioedema
• Bronchospasm

Interactions

• Brimonidine
• Beta-blockers

Precautions

• Caution in patients with chronic corneal defects
• History of intraocular surgery
• History of renal calculi
• Low endothelial cell count
• Monitor blood count and plasma electrolyte concentrations with prolonged use

Pregnancy

Avoid-toxicity in animal studies, especially in the first trimester.

Breast-feeding

Use only if benefit outweighs risk; amount too small to be harmful.

Storage

Store at room temperature, away from light and moisture.

Formulations

• Eye drops 2% (Dorzolamide hydrochloride 20 mg/ml)

Mechanism of action

Elevated intraocular pressure is a characteristic manifestation of ocular hypertension or open-angle glaucoma. The level of intraocular pressure (IOP) is governed by the balance between the production of aqueous humour (by ocular ciliary processes) and its outflow from the anterior segment of the eye via trabecular (conventional) or uveoscleral (unconventional) pathways. When there is an increase in the resistance to the trabecular outflow of aqueous humour, the intraocular pressure is elevated. Subsequently, optic nerve damage can occur from blood flow restrictions and mechanical distortion of ocular structures. Optic nerve damage can further result in optic disc cupping and progressive visual field loss (and blindness in some cases). Carbonic anhydrase (CA) is a ubiquitous enzyme that catalyzes the reversible hydration of carbon dioxide to bicarbonate ions and dehydration of carbonic acid. In the ocular ciliary processes, the local production of bicarbonate by CAs promotes sodium and fluid transport. CA-II is a key isoenzyme found primarily in red blood cells (RBCs) that regulates aqueous humour production. Dorzolamide is a highly specific CA-II inhibitor, where it displays a 4000-fold higher affinity for carbonic anhydrase II than carbonic anhydrase I. The inhibition of CA-II in the ciliary process disrupts the formation of bicarbonate ions and reduces sodium and fluid transport, which leads to decreased aqueous humour secretion and reduced intraocular pressure.

Pharmacodynamics

Dorzolamide is a carbonic anhydrase inhibitor that reduces elevated intraocular pressure in open-angle glaucoma or ocular hypertension. When used in combination with topic beta-adrenergic antagonists, dorzolamide has an additive effect of lowering intraocular pressure. The peak ocular hypotensive effect of dorzolamide is observed at about 2 hours following ophthalmic administration.