Alpha 2 Agonists for Glaucoma

Topical alpha 2 agonists (brimonidine, apraclonidine) lower intraocular pressure and are used as add-on therapy in open-angle glaucoma and to prevent pressure spikes around laser and surgery.

Mechanism. Stimulation of presynaptic alpha 2 adrenoceptors in the ciliary body reduces norepinephrine release and aqueous production; brimonidine also increases uveoscleral outflow. Apraclonidine has alpha 1 activity and causes vasoconstriction.

Pharmacokinetics. Onset about 1 hour, peak 2 hours; effect lasts 12 hours. Brimonidine crosses the blood-brain barrier more than apraclonidine; systemic half-life about 3 hours; hepatic metabolism.

• Brimonidine 0.1 to 0.2 percent: two or three times daily; preferred long-term agent; lower allergy rate with the 0.1 percent solution. Fixed combinations with timolol and with brinzolamide are available.
• Apraclonidine 0.5 percent: short-term use only because of high allergy rates and tachyphylaxis; apraclonidine 1 percent is given before and after laser procedures.

Regimen. Brimonidine 0.2 percent (or 0.1 percent) one drop two or three times daily, with a 3 to 5 minute interval from other drops. Apraclonidine 1 percent: one drop 1 hour before and immediately after anterior segment laser; apraclonidine 0.5 percent two or three times daily short term for a pressure fall before surgery.

Selection. Second or third drug when prostaglandin analogues and beta blockers are inadequate or contraindicated; useful in patients with asthma or heart block who cannot take beta blockers. Not for use under 2 years of age.

Contraindications. Infants and children under 2 years (apnoea, bradycardia, hypotension, hypothermia, hypotonia); monoamine oxidase inhibitor treatment; hypersensitivity.

Effects. Allergic follicular conjunctivitis and lid reactions (up to 20 percent over time), dry mouth, fatigue and drowsiness, headache, low blood pressure, mild mydriasis, lid retraction; rebound redness after stopping.

Interactions. Central nervous system depressants, tricyclic antidepressants (reduced effect), monoamine oxidase inhibitors (hypertensive risk), antihypertensive drugs and cardiac glycosides (additive effect).

Monitoring. Pressure at 4 to 6 weeks; look for allergic conjunctivitis and stop at first signs.

Special groups. Pregnancy: use with care. Breastfeeding: avoid if possible. Children: avoid under 2 years and use with caution up to 12 years. Older adults: watch for drowsiness and hypotension. Region: long-term follicular reactions are often misdiagnosed as infection; ask about brimonidine before treating a chronic red eye in a glaucoma patient.