Ophthalmic Beta Blockers

Ophthalmic beta blockers lower intraocular pressure by reducing aqueous production. They have been used for decades, are cheap and widely available, and remain a common first or second drug, although systemic effects limit their use in many older adults.

Mechanism. Blockade of beta-2 (and beta-1) adrenoceptors in the ciliary epithelium reduces cyclic adenosine monophosphate and aqueous humour secretion by about 30 to 50 percent. They have no effect on aqueous production during sleep, so nocturnal efficacy is low.

Pharmacokinetics. Absorbed through the cornea and through nasal and conjunctival mucosa, avoiding first-pass hepatic metabolism, so blood levels can reach those of a low oral dose. Timolol is metabolised by CYP2D6. Effect lasts 12 to 24 hours.

• Timolol 0.25 or 0.5 percent (solution twice daily; gel-forming solution once daily in the morning): non-selective; the reference agent; most potent.
• Levobunolol 0.25 or 0.5 percent: non-selective; once or twice daily.
• Carteolol 1 or 2 percent: non-selective with intrinsic sympathomimetic activity; less effect on heart rate and lipids.
• Betaxolol 0.25 or 0.5 percent twice daily: beta-1 selective; lower pulmonary risk, smaller pressure reduction; may help ocular blood flow.
• Fixed combinations: timolol with dorzolamide, brimonidine, latanoprost, bimatoprost or travoprost.

Regimen. Timolol 0.5 percent one drop twice daily, or 0.25 percent for smaller or older patients, or gel-forming solution once daily in the morning. Check pulse and breathing before starting. Use nasolacrimal occlusion for 2 minutes after each drop.

Selection. Add to a prostaglandin analogue or use first when prostaglandin analogues are unsuitable or not available. Use betaxolol when a beta blocker is wanted in mild chronic lung disease (with caution). Avoid in patients taking systemic beta blockers unless monitored.

Contraindications. Asthma and severe chronic obstructive pulmonary disease; sinus bradycardia, second- or third-degree heart block; uncontrolled heart failure; cardiogenic shock; severe allergic rhinitis (relative).

Systemic effects. Bradycardia, hypotension, bronchospasm, heart failure, fatigue, depression, sleep disturbance and nightmares, impotence, masking of hypoglycaemia symptoms, and aggravation of myasthenia and peripheral vascular disease. Local: dry eye, corneal anaesthesia, blepharitis, allergic conjunctivitis. Neonates exposed through the mother develop bradycardia and apnoea.

Interactions. Oral beta blockers (additive effect), verapamil and diltiazem (heart block), digoxin, amiodarone, and CYP2D6 inhibitors (fluoxetine, paroxetine, quinidine) raise timolol levels.

Monitoring. Pulse, blood pressure and respiratory symptoms at baseline and each visit; pressure at 4 to 6 weeks; drift in effect over time is common (loss of response in some patients).

Special groups. Pregnancy: use with care; stop in the weeks before delivery if possible and check the newborn for bradycardia. Breastfeeding: low milk levels; occlude the tear duct. Children: infants under supervision only. Older adults: lower strength and monitoring for slow heart rate. Region: undiagnosed asthma and hypertension are common; check chest and pulse before prescribing, and teach lid closure on instillation.