What are topical drugs used to treat glaucoma
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I now have excellent data from Katzung's pharmacology textbook. Here is the complete answer:
Topical Drugs Used to Treat Glaucoma
Glaucoma raises intraocular pressure (IOP) either by overproduction of aqueous humor or impaired drainage. Topical medications work by one of two mechanisms: reducing aqueous secretion or enhancing aqueous outflow. There are six drug classes.
1. Prostaglandin Analogues (First-line)
Drugs: Latanoprost, bimatoprost, travoprost, tafluprost, unoprostone
Mechanism: Increase aqueous outflow via the uveoscleral pathway (prostaglandin F2α analogues relax ciliary muscle and widen outflow channels).
Key features:
- Currently the drugs of choice to initiate glaucoma treatment
- Once-daily dosing (usually at night)
- Very few systemic adverse effects
- Local effects include increased iris pigmentation (heterochromia), eyelash lengthening, and periorbital fat atrophy
2. Beta-Adrenoceptor Blockers
Drugs: Timolol, betaxolol, carteolol, levobunolol, metipranolol
Mechanism: Decrease aqueous humor secretion from the ciliary epithelium (beta-1/2 blockade reduces cAMP-driven fluid secretion).
Key features:
- Still commonly used, especially in combination therapy and when cost is a concern
- Betaxolol is beta-1 selective and relatively safer in respiratory disease
- Contraindications/cautions: bradycardia, heart block, heart failure, asthma, obstructive airway disease
- Do not affect pupil size or accommodation (unlike miotics)
3. Alpha-2 Agonists
Drugs: Brimonidine, apraclonidine
Mechanism: Dual action - decrease aqueous secretion AND increase uveoscleral outflow.
Key features:
- Brimonidine is highly selective for alpha-2 receptors; less systemic cardiovascular effect
- Apraclonidine is used short-term (e.g. post-laser procedures) due to high rate of allergic reactions
- Side effects include ocular allergy, dry mouth, drowsiness, and rebound hyperemia
4. Carbonic Anhydrase Inhibitors (CAIs) - Topical
Drugs: Dorzolamide, brinzolamide
Mechanism: Inhibit carbonic anhydrase in the ciliary epithelium, decreasing aqueous humor secretion (bicarbonate formation is blocked).
Key features:
- Less effective than prostaglandins or beta-blockers as monotherapy
- Can be used in combination
- Local stinging/burning common with dorzolamide (less with brinzolamide due to neutral pH)
- Oral CAIs (acetazolamide, methazolamide) are more potent but carry systemic side effects (metabolic acidosis, renal stones)
5. Cholinomimetics (Miotics)
Drugs: Pilocarpine (direct agonist), carbachol (direct agonist); physostigmine (cholinesterase inhibitor, now rarely used)
Mechanism: Ciliary muscle contraction opens the trabecular meshwork, increasing aqueous outflow.
Key features:
- Largely replaced by prostaglandins and beta-blockers for chronic open-angle glaucoma
- Still used for acute angle-closure glaucoma emergencies (constrict the pupil, pulling iris away from trabecular meshwork)
- Higher incidence of local adverse effects: miosis (dim vision), brow ache, myopic shift, possible retinal detachment with long-term use
6. Rho Kinase (ROCK) Inhibitors
Drug: Netarsudil (also combined with latanoprost as Rocklatan)
Mechanism: Inhibits Rho kinase, increasing trabecular outflow by relaxing trabecular meshwork cells and reducing episcleral venous pressure.
Key features:
- Relatively newer class (FDA approved 2017)
- Once-daily dosing
- Common side effect: conjunctival hyperemia, cornea verticillata
Summary Table
| Class | Drugs | Mechanism | Dosing |
|---|---|---|---|
| Prostaglandin analogues | Latanoprost, bimatoprost, travoprost | ↑ uveoscleral outflow | Once daily |
| Beta-blockers | Timolol, betaxolol | ↓ aqueous secretion | Twice daily |
| Alpha-2 agonists | Brimonidine, apraclonidine | ↓ secretion + ↑ outflow | 2-3x daily |
| Topical CAIs | Dorzolamide, brinzolamide | ↓ aqueous secretion | 2-3x daily |
| Cholinomimetics | Pilocarpine, carbachol | ↑ trabecular outflow | 4x daily |
| ROCK inhibitors | Netarsudil | ↑ trabecular outflow | Once daily |
Treatment approach: Start with a prostaglandin analogue monotherapy. If IOP target is not reached, add a beta-blocker or other agent. Fixed-dose combinations (e.g. latanoprost + timolol, dorzolamide + timolol) improve adherence. Surgical options (trabeculectomy, laser) are considered when medical therapy fails.
- Katzung's Basic and Clinical Pharmacology, 16th Edition - "The Treatment of Glaucoma" box, p. 256 and Table 10-3 (Topical drugs used in open-angle glaucoma)
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