What are topical drugs used to treat glaucoma
Topical glaucoma drugs work by reducing intraocular pressure (IOP) either by decreasing aqueous humor production or increasing its outflow. The main classes are: prostaglandin analogues (first-line, e.g. latanoprost), beta-blockers (e.g. timolol), alpha-2 agonists (e.g. brimonidine), carbonic anhydrase inhibitors (e.g. dorzolamide), and miotics (e.g. pilocarpine).
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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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