Free COMLEX Level 1 Sample Questions

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Your First Free COMLEX Level 1 Practice Question

A 65-year-old man presents to the office with a slight blue tint to his visual field. Past medical history reveals type 2 diabetes, hypertension, peripheral vascular disease, erectile dysfunction, and cataracts. He is currently taking metformin, glipizide, metoprolol, hydrochlorothiazide, and sildenafil. Fundoscopic examination is normal.

This patient’s change in vision is most likely due to

• A. blocked conversion of 11-cis rhodopsin to all-trans rhodopsin
• B. excessive vasodilation of retinal vessels leading to rupture
• C. failed closure of sodium channels and subsequent hyperpolarization
• D. inhibition of metarhodopsin II formation
• E. inhibition of phosphodiesterase

The Answer and Explanation

Did you get it right? The correct answer is: E

This patient, presenting with cyanopsia (ie, blue tint to the visual field) with a normal fundoscopic examination, is likely experiencing a side effect of sildenafil. Sildenafil is used to treat both erectile dysfunction and pulmonary hypertension through the inhibition of phosphodiesterase 5 (PDE5), an enzyme that normally converts cyclic guanosine monophosphate (cGMP) to 5′-guanosine monophosphate (5’-GMP). An increase in the concentration of cGMP causes increased smooth muscle relaxation in reaction to nitric oxide activation and subsequent pulmonary vasodilation, penile smooth muscle relaxation, and increased blood flow.

A characteristic side effect of sildenafil is cyanopsia due to weak inhibition of phosphodiesterase 6 (PDE6) located in photoreceptor cells of the retina. Normally, PDE6 is responsible for the breakdown of cGMP in photoreceptor cells, causing alteration of ion flow through cGMP-gated ion channels and subsequent changes to visual signals to the brain. Inhibition of PDE6 results in higher levels of cGMP and overstimulation of the photoreceptor cell, causing the perception of blue light.

The images below show the mechanism of action of sildenafil. The first illustrates how inhibition of PDE5 results in increased blood flow to the penis and subsequent erection, and the second shows the pathophysiology of cyanopsia via PDE6 inhibition.

Answer A: Blocked conversion of 11-cis rhodopsin to all-trans rhodopsin would stop photoreception from occurring. This conversion is catalyzed by light, so only a lack of light would cause this effect. This patient is not experiencing a complete lack of vision and sildenafil does not act on this step of photoreception.

Answer B: Excessive vasodilation of retinal vessels leading to rupture describes a retinal hemorrhage. Patients with retinal hemorrhage will present with blurry vision, floaters, and possible partial or complete vision loss. Patients with retinal hemorrhage do not present with cyanopsia, as seen in this patient, and sildenafil works on the smooth muscle in the corpus cavernosum of the penis, not the vessels of the eye.

Answer C: Failed closure of sodium channels and subsequent hyperpolarization would not explain this patient’s cyanopsia. When it is dark, increased cGMP levels produce an inward sodium current and depolarization of the photoreceptor membrane. Sildenafil causes inhibition of phosphodiesterase (which increases cGMP) rather than acting directly on photoreceptor sodium channels.

Answer D: Inhibition of metarhodopsin II formation would occur in the absence of light. After light converts 11-cis rhodopsin to all-trans rhodopsin, a series of conformational changes occur in the opsin that eventually produces metarhodopsin II. This would cause a complete lack of vision rather than cyanopsia, as seen in this patient.

Bottom Line: Sildenafil acts by inhibiting phosphodiesterase 5, which normally converts cyclic guanosine monophosphate to 5′-guanosine monophosphate. An adverse effect of sildenafil is cyanopsia due to weak inhibition of phosphodiesterase 6 in rod photoreceptors.

COMBANK Insight: Indications for PDE inhibitors vary widely. Below is a table summarizing the various PDE inhibitors, their indications, and potential adverse effects.

Phosphodiesterase Inhibitors

cAMP = cyclic adenosine monophosphate; cGMP = cyclic guanosine monophosphate; COPD = chronic obstructive pulmonary disease; PDE = phosphodiesterase; TIA = transient ischemic attack.

For more information, see:

• Sildenafil: StatPearls
• Physiology, vision: StatPearls
• Sildenafil: StatPearls
• Physiology, vision: StatPearls
• First Aid for the USMLE Step 1 2019: 643.
• First Aid for the USMLE Step 1 2020: 246.
• First Aid for the USMLE Step 1 2021: 249.
• First Aid for the USMLE Step 1 2022: 247.
• First Aid for the USMLE Step 1 2023: 245.
• First Aid for the USMLE Step 1 2024: 245

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