Review Question - QID 217266

This patient has open-angle glaucoma (worsening vision, enlarged cup-to-disc ratio, and elevated intraocular pressure). However, the patient develops bronchospasm (dyspnea, coughing, and fatigue) due to exacerbation of likely undiagnosed COPD (40 pack-year smoking history) because of timolol use, which leads to aqueous humor production decreased by beta-blockade.

Glaucoma is an eye disease caused by damage to the optic nerve and is a leading cause of blindness. In open-angle glaucoma, there is dysfunction to normal drainage by the trabecular meshwork. In acute-angle glaucoma, drainage is directly impeded by the iris. For both cases, an increase of intraocular pressure correlates with nerve damage. Open-angle glaucoma is normally asymptomatic, but there is an insidious peripheral vision loss; classic findings include elevated intraocular pressure and enlarged cup-to-disc ratio. For angle-closure glaucoma, there is rapid, painful vision loss with associated headache and nausea; exam findings include conjunctival injection and fixed-dilated pupil. Elevated intraocular pressures on tonometry, as well as enlarged cup-to-disc ratio, are consistent with glaucoma. Pharmacologic treatment revolves around decreasing intraocular pressure and utilizes 2 therapeutic mechanisms: increase aqueous outflow and decrease aqueous production. The former is accomplished through prostaglandins and cholinergic stimulation. The latter is accomplished through carbonic anhydrase inhibition, alpha-2-agonists, and beta-blockers.

Weinreb et al. review the pathophysiology and management of glaucoma. Currently, prostaglandin analogs are first-line medical treatments. An advantage of prostaglandin analogs and carbonic anhydrase inhibitors is the ability to work during the day and night. Beta-blockers and alpha-agonists are only effective during the day. Prescription of beta-blockers requires careful consideration given their potential significant adverse effects.

Incorrect Answers:
Answer 1: Decreased aqueous humor production by alpha-agonist is the mechanism of brimonidine. It achieves this effect through ciliary body vasoconstriction and decreasing intracellular cAMP. Side effects include contact dermatitis, conjunctivitis, and blurry vision. The patient’s bronchospasm was triggered by beta-adrenergic activation, not alpha-adrenergic.

Answer 3: Increased aqueous humor outflow by rho kinase inhibition is the mechanism of ripasudil and netarsudil. These medications work directly on the trabecular meshwork and Schlemm's canal to increase permeability. They also minimize trabecular meshwork damage from reactive oxidative species. Side effects include conjunctival hyperemia and conjunctival hemorrhages.

Answer 4: Increased ciliary muscle contraction by direct cholinergic stimulation is the mechanism of pilocarpine and carbachol. Through ciliary muscle contraction, the trabecular meshwork is opened up, facilitating increased aqueous humor outflow. Side effects include miosis and cyclospasm.

Answer 5: Increased ciliary muscle contraction by indirect cholinergic stimulation is the mechanism of physostigmine and echothiopate. With ciliary muscle contraction, the trabecular meshwork is opened up, increasing aqueous humor outflow. Side effects include miosis and cyclospasm.


Bullet Summary:
Timolol is used to treat glaucoma and decreases aqueous humor production.