Ophthalmic Pharmacology Flashcards

A patient on topical timolol 0.5% for glaucoma develops bradycardia and bronchospasm. Which mechanism best explains the systemic absorption responsible for these side effects?

Answer: Drainage through the nasolacrimal duct with absorption via nasal mucosa into systemic circulation

Topical ophthalmic drops drain through the nasolacrimal duct into the nasal cavity, where the highly vascular nasal mucosa absorbs the drug directly into systemic circulation — bypassing first-pass hepatic metabolism. This is why nasolacrimal occlusion (punctal occlusion) for 1–2 minutes after instillation significantly reduces systemic side effects of beta-blockers like timolol.

Brimonidine 0.2% is prescribed for a 6-week-old infant with elevated IOP secondary to primary congenital glaucoma. What is the primary concern with this choice?

Answer: CNS depression including apnea and hypotension due to immature blood-brain barrier

Brimonidine, an alpha-2 adrenergic agonist, is contraindicated in infants and young children because the immature blood-brain barrier allows CNS penetration, causing potentially life-threatening CNS depression including somnolence, apnea, hypotonia, and cardiovascular depression. Timolol also carries risks in infants, and management typically favors surgical intervention in congenital glaucoma.

A patient undergoes cataract surgery and receives intracameral moxifloxacin for endophthalmitis prophylaxis. Compared to topical fourth-generation fluoroquinolones, what is the primary pharmacokinetic advantage of intracameral administration?

Answer: Achievement of minimum inhibitory concentrations in aqueous humor that topical drops cannot reliably attain

Even with intensive topical fourth-generation fluoroquinolone dosing, aqueous humor drug concentrations often fall below the MIC (minimum inhibitory concentration) required to eradicate common endophthalmitis pathogens such as Staphylococcus epidermidis. Intracameral injection of moxifloxacin delivers the drug directly into the anterior chamber, achieving therapeutic aqueous concentrations reliably and immediately — a key reason studies show it reduces post-cataract endophthalmitis rates more effectively than topical prophylaxis alone.

Which of the following correctly describes the mechanism by which acetazolamide lowers intraocular pressure?

Answer: Inhibition of carbonic anhydrase isoenzyme II in the non-pigmented ciliary epithelium, reducing bicarbonate-driven aqueous humor formation

Acetazolamide is a systemic carbonic anhydrase inhibitor (CAI) that specifically targets carbonic anhydrase isoenzyme II (CA-II) in the non-pigmented ciliary epithelium. CA-II catalyzes the hydration of CO₂ to form bicarbonate and H⁺, which drives the active transport of sodium and water into the posterior chamber. By inhibiting this enzyme, acetazolamide reduces aqueous humor production by approximately 40–60%. Topical CAIs (dorzolamide, brinzolamide) target the same enzyme but also inhibit CA-IV.

A patient with open-angle glaucoma controlled on latanoprost 0.005% develops iris heterochromia after 18 months of unilateral use. Which cellular mechanism is responsible for this finding?

Answer: Proliferation of melanocytes in the iris stroma driven by FP receptor-mediated upregulation of tyrosinase activity

Latanoprost is a prostaglandin F2α (FP receptor) agonist. Sustained FP receptor activation in iris melanocytes stimulates tyrosinase, the rate-limiting enzyme in melanin biosynthesis, leading to increased melanin production within existing melanocytes — not melanocyte proliferation. The result is irreversible increased pigmentation of the iris stroma, most notable in hazel or mixed-color irides. This is a cosmetic change, not inflammatory or malignant, but patients should be counseled before initiating therapy.

Patients receiving long-term topical corticosteroids for chronic uveitis are at risk for steroid-induced ocular hypertension. Which corticosteroid formulation carries the LOWEST risk of this complication while still providing meaningful anti-inflammatory efficacy?

Answer: Loteprednol etabonate 0.5% dosed four times daily

Loteprednol etabonate is a 'retrometabolic' corticosteroid designed to undergo predictable intraocular metabolism to inactive metabolites (Δ1-cortienic acid etabonate) after exerting its anti-inflammatory effect. This reduces receptor-mediated induction of the trabecular meshwork's extracellular matrix — the primary mechanism of steroid-induced IOP elevation. While it has somewhat less potency than prednisolone acetate or difluprednate for severe inflammation, it demonstrates significantly lower rates of IOP spikes, making it the preferred choice for chronic low-to-moderate uveitis management in glaucoma-risk patients.