Ophthalmic Pharmacology Flashcards

A patient on long-term topical timolol 0.5% for glaucoma is scheduled for elective surgery. The anesthesiologist is concerned about drug interactions. Which systemic effect of topical timolol poses the greatest risk during general anesthesia?

Answer: Potentiation of succinylcholine-induced bradycardia and impaired cardiac recovery

Topical timolol, a non-selective beta-blocker, is systemically absorbed through the nasolacrimal duct and conjunctiva. It can potentiate bradycardia from succinylcholine and impair the heart's response to stress during anesthesia. This is a well-documented perioperative risk requiring anesthesiologist awareness and sometimes pre-operative discontinuation.

Apraclonidine (0.5%) is used acutely post-laser procedures to blunt IOP spikes. Which mechanism explains why it is NOT preferred for long-term glaucoma management despite its efficacy?

Answer: High incidence of tachyphylaxis and ocular allergic reactions with chronic use

Apraclonidine is an alpha-2 adrenergic agonist that loses efficacy over time due to tachyphylaxis (up to 48% of patients lose response within months). It also has a high rate of ocular and periocular allergic reactions (follicular conjunctivitis, lid retraction, hyperemia). These factors make brimonidine — a more selective alpha-2 agonist with a better side-effect profile — the preferred long-term alternative.

A patient taking oral carbonic anhydrase inhibitor acetazolamide for refractory glaucoma develops paresthesias and fatigue. Lab work reveals a serum bicarbonate of 18 mEq/L. What is the most accurate explanation for these findings?

Answer: Acetazolamide induces a non-anion gap metabolic acidosis by inhibiting renal tubular carbonic anhydrase

Acetazolamide inhibits carbonic anhydrase in the renal proximal tubule, reducing bicarbonate reabsorption. This causes a hyperchloremic, non-anion gap metabolic acidosis. The resulting low bicarbonate explains the fatigue, and paresthesias are a classic side effect of systemic carbonic anhydrase inhibition. This distinguishes oral CAIs from topical dorzolamide, which avoids these systemic effects.

Latanoprost 0.005% is instilled once daily (evening dosing). A patient asks why evening dosing is specifically recommended rather than morning. What is the pharmacologic rationale?

Answer: Evening dosing aligns peak drug effect with nocturnal IOP elevation, which is the highest-risk period for glaucomatous damage

IOP exhibits a diurnal pattern and is often highest during sleep and early morning hours. Evening dosing of latanoprost ensures peak drug effect (maximum IOP reduction occurring roughly 8–12 hours after instillation) aligns with the nocturnal IOP peak, providing optimal neuroprotection. This pharmacokinetic-circadian timing rationale is the primary clinical reason for the recommended dosing schedule.

A patient with myasthenia gravis is prescribed echothiophate iodide for accommodative esotropia. The surgeon schedules the child for strabismus surgery under general anesthesia 6 weeks later. What is the critical pharmacologic concern?

Answer: Echothiophate irreversibly inhibits plasma cholinesterase, prolonging the action of succinylcholine and risking prolonged apnea

Echothiophate is an irreversible organophosphate cholinesterase inhibitor. It not only inhibits acetylcholinesterase in the eye but also irreversibly inhibits plasma pseudocholinesterase systemically. Succinylcholine (a depolarizing neuromuscular blocker commonly used for intubation) is normally metabolized rapidly by pseudocholinesterase. With echothiophate on board, succinylcholine metabolism is severely impaired, potentially causing prolonged apnea lasting hours. This requires stopping echothiophate 4–6 weeks before any surgery involving succinylcholine.

Intravitreal bevacizumab (Avastin) is used off-label for wet AMD. Compared to ranibizumab (Lucentis), which statement most accurately reflects a pharmacokinetic difference relevant to systemic safety?

Answer: Bevacizumab has a larger molecular weight and its full-length IgG structure allows it to transcytose through the retinal pigment epithelium into systemic circulation more readily than the Fab fragment ranibizumab

Bevacizumab is a full-length IgG1 antibody (~149 kDa) and contains an Fc region, allowing it to undergo Fc-receptor-mediated transcytosis across the retinal pigment epithelium and into systemic circulation. Ranibizumab is a smaller Fab fragment (~48 kDa) lacking the Fc region, which limits its systemic absorption after intravitreal administration. This pharmacokinetic difference underlies the theoretical (and debated) higher systemic VEGF suppression with bevacizumab, which has implications for cardiovascular and wound-healing safety monitoring.