Pharmacology of Glaucoma

Glaucoma affects up to 60 million people worldwide. Left untreated, it leads to permanent loss of vision. Medications are available though, which serve to decrease intraocular pressure and progression of the disease.

There are three main categories of glaucoma:

  • Open-angle glaucoma
  • Closed-angle glaucoma
  • Normal tension glaucoma

Open-angle glaucoma is the most common type. It develops slowly, over time, and is not associated with pain. Open-angle glaucoma is caused by the slowed exit of aqueous humor from the trabecular meshwork – the trabecular meshwork being responsible for draining aqueous humor from the eye.

Closed-angle glaucoma is less common and may develop gradually or suddenly. Sudden onset symptoms include severe eye pain, nausea, mid-dilated pupil and blurred vision. It is caused when the iris blocks the trabecular meshwork.

Normal tension glaucoma occurs when the patient has normal intraocular pressure yet continues to develop damage to the optic nerve.

The purpose of glaucoma medication is to prevent loss of vision.

Medications include:

  • Prostaglandin analogs – latanoprost, bimatoprost
  • Beta blockers – timolol, betaxolol
  • Adrenergic agents – brimonidine
  • Miotic agents – pilocarpine
  • Carbonic anhydrase inhibitors – dorzolamide, brinzolamide, acetazolamide

Let’s review each of these drug classes – how they work, as well as examining their side effect profiles.

Prostaglandin analogs

Examples of prostaglandin analogs include:

  • Bimatoprost
  • Latanoprost

The purpose of prostaglandin analogs is to lower intraocular pressure in open-angle glaucoma and ocular hypertension. Given that prostaglandin analogs cause fewer side effects than many other classes, such as beta blockers, they are generally preferred.

Generally, they are administered once daily.

Prostaglandin analogs are analogs of prostaglandin F2α – which work to reduce intraocular pressure by increasing elimination of aqueous humor through the uveoscleral pathway.

Side effects with prostaglandin analogs include:

  • Blurred vision
  • Conjunctival reddening
  • Ocular irritation
  • Ocular pain
  • Change in eye color

This latter effect may, in some cases, be permanent.

There are no clinically significant drug interactions with ocular prostaglandin analogs.

Beta-blockers

Examples of beta-blockers used in glaucoma include:

  • Timolol
  • Betaxolol

Beta-blockers work by reducing production of aqueous humor from the ciliary body, thereby lowering intraocular pressure.

Generally, they are administered once every 12 hours.

Timolol is associated with an increased risk of bronchospasm but betaxolol, due to its selective beta-1 inhibition, is not.

For this reason, timolol should be avoided in patients with asthma. More local side effects include burning sensation, ocular redness and corneal numbness.

Adrenergic agents

Examples of adrenergic agents used in glaucoma include:

  • Brimonidine

Brimonidine works by two different, but complementary means. It decreases aqueous humor production and it also increases aqueous humor uveoscleral outflow. It achieves this via alpha-2 adrenergic agonism.

Brimonidine is typically administered every 8-12 hours.

Side effects with brimonidine include:

  • Blurring
  • Foreign body sensation
  • Eyelid edema
  • Dryness
  • Headache
  • Fatigue
  • Hypotension
  • Insomnia

Brimonidine decreases intraocular pressure (by 20-30%) to a greater extent than betaxolol (15-20%), to the same extent as timolol, and to a lesser extent than latanoprost (25-32%).

Miotic agents

Examples of miotic agents include:

  • Pilocarpine

Pilocarpine works by acting on the ciliary muscle; contracting that muscle. Contraction of the muscle facilitates the passage of aqueous humor through the trabecular meshwork, reducing intraocular pressure.

Side effects with pilocarpine include:

  • Brow ache
  • Myopia
  • Blurred or dim vision
  • Stinging, burning, eye discomfort
  • Itchiness / redness
  • Headache

Pilocarpine decreases intraocular pressure by 15-25%, on average.

Carbonic anhydrase inhibitors

Examples of carbonic anhydrase inhibitors used in glaucoma include:

  • Dorzolamide
  • Acetazolamide
  • Brinzolamide

Carbonic anhydrase inhibitors work by decreasing aqueous humor production via their inhibition of the enzyme, carbonic anhydrase, in the ciliary body.

Side effects include:

  • Ocular stinging
  • Burning
  • Itch
  • Bitter taste
  • Myopia

Carbonic anhydrase inhibitors are typically administered every 8-12 hours.

Conclusion

Of course, medication is just one part of the answer.

Many other, alternate clinical means are sought to reduce long-term ocular damage that glaucoma can bring. The five medicine classes studied here must be adjusted and tweaked depending on how each patient reacts.

Some experience mild side effects, whereas other patients experience more intolerable side effects and require dose adjusting or complete medication changes.

That, together with other clinical strategies, are used to reduce vision loss over the medium-to-long-term. One of the great problems with glaucoma therapy has, though, been compliance on part of the patient.

Lack of compliance leads to an increased risk of permanent blindness.

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