Ophthalmic Pharmacology Flashcards

A patient on long-term topical timolol develops symptomatic bradycardia and fatigue. Which mechanism best explains why this systemic effect occurs despite topical administration?

Answer: Nasolacrimal drainage delivers drug directly to nasal mucosa where it is absorbed without first-pass hepatic metabolism

Nasolacrimal drainage routes topical ophthalmic drugs into the nasal mucosa, which has a rich vascular supply that absorbs drug directly into systemic circulation, bypassing hepatic first-pass metabolism. This can produce full systemic drug effects — particularly dangerous with beta-blockers in patients with asthma, COPD, or cardiac conduction abnormalities. Punctal occlusion or eyelid closure after instillation reduces this risk.

Apraclonidine (0.5%) is used to prevent IOP spikes after laser procedures, but is not suitable for long-term glaucoma management. What is the primary pharmacodynamic reason for this limitation?

Answer: Tachyphylaxis develops due to receptor downregulation, causing loss of IOP-lowering efficacy over weeks to months

Apraclonidine develops significant tachyphylaxis — a rapid decrease in response to repeated administration — due to alpha-2 adrenergic receptor downregulation. Studies show efficacy can diminish substantially within 1–3 months of continuous use, making it unsuitable as first-line chronic glaucoma therapy. Brimonidine, a more selective alpha-2 agonist, has a better tachyphylaxis profile and is preferred for long-term use.

A COT is assisting with a patient who requires dilation but has a documented allergy to tropicamide causing a severe contact dermatitis reaction. Which alternative cycloplegic/mydriatic combination would achieve adequate dilation with the lowest risk of cross-reactivity?

Answer: Cyclopentolate 1% and phenylephrine 2.5%, as these agents belong to entirely different pharmacological classes

Tropicamide is a synthetic antimuscarinic with a benzilate ester structure. Cyclopentolate is also antimuscarinic but has a different cyclopentane-based structure, and phenylephrine is an adrenergic agonist (sympathomimetic) — a completely different pharmacological class. This combination avoids the anticholinergic class altogether for mydriasis while using a structurally distinct cycloplegic. Homatropine, scopolamine, and atropine all share tropane-related ester backbones that may carry cross-reactivity risk. Using phenylephrine for mydriasis plus cyclopentolate reduces overall risk of cross-reactive contact allergy.

Prostaglandin analogs such as latanoprost lower IOP primarily by increasing uveoscleral outflow. Which of the following adverse effects is most directly related to their mechanism of action on ciliary muscle extracellular matrix?

Answer: Periorbital fat atrophy (prostaglandin-associated periorbitopathy) caused by matrix metalloproteinase activation degrading orbital adipose tissue

Prostaglandin analogs upregulate matrix metalloproteinases (MMPs) in the ciliary muscle, remodeling the extracellular matrix to increase uveoscleral outflow. This same MMP activation in periorbital tissues breaks down collagen and adipose stroma, leading to prostaglandin-associated periorbitopathy (PAP): enophthalmos, upper lid ptosis, deepened superior sulcus, and periorbital fat atrophy. This is the adverse effect most directly mechanistically tied to MMP activation — distinct from the FP-receptor mediated iris pigmentation changes (which involve melanogenesis, not matrix degradation).

A patient using brimonidine 0.1% for open-angle glaucoma is started on a monoamine oxidase inhibitor (MAO-I) by their psychiatrist. What is the most significant drug interaction concern?

Answer: MAO-I potentiates brimonidine's systemic alpha-2 agonist effects, risking profound hypotension and CNS depression

Brimonidine is an alpha-2 adrenergic agonist. MAO inhibitors prevent the catecholamine-degrading enzyme monoamine oxidase from breaking down norepinephrine and related amines, potentiating the systemic sympatholytic effects of alpha-2 agonists like brimonidine. The result can be significant systemic hypotension, bradycardia, and CNS depression (drowsiness, sedation, even respiratory depression). This is a contraindicated combination. The prescribing information for brimonidine explicitly warns against concurrent MAO-I use.

When performing a Schirmer's test with anesthesia to measure basal tear secretion, which topical anesthetic is most appropriate and why?

Answer: Proparacaine 0.5%, because it minimally disrupts goblet cell function compared to aminoester anesthetics

Proparacaine (proxymetacaine) 0.5% is the standard anesthetic used for Schirmer's test with anesthesia (Schirmer's II or basic secretion test). It is preferred because it causes less epithelial toxicity and less disruption to goblet cells and the mucin layer than aminoester anesthetics like tetracaine, which at repeated doses can damage the corneal epithelium and alter tear film composition. The goal is to eliminate reflex tearing while preserving basal secretion measurements without introducing confounding chemical irritation. Cocaine causes vasoconstriction that would itself alter lacrimal gland output, making it unsuitable.