Question 1

What is the Meaning of Sildenafil Non-Responder?

Accepted Answer

A Sildenafil Non-Responder is a patient, typically a male with erectile dysfunction (ED), who fails to achieve a clinically satisfactory therapeutic response despite receiving an adequate trial of sildenafil citrate, the active ingredient in Viagra, at the maximum tolerated dose. This clinical classification is important because it indicates a need to investigate alternative pharmacological or non-pharmacological treatment strategies for their sexual health concern. Non-response may be due to a variety of underlying physiological factors, including severe endothelial dysfunction, psychogenic causes, or advanced hormonal deficiencies that limit the drug's mechanism of action. Clinicians must conduct a thorough diagnostic workup to determine the specific cause of treatment failure and guide the next therapeutic step.

Question 2

What is the Origin of Sildenafil Non-Responder?

Accepted Answer

The term arose directly from the widespread clinical use of sildenafil following its introduction as the first oral phosphodiesterase type 5 (PDE5) inhibitor for ED in the late 1990s. As the drug became a first-line treatment, clinicians needed a precise term to categorize patients who did not benefit from the therapy. This designation helps guide subsequent treatment decisions, moving the patient toward second-line agents or more invasive interventions. The identification of non-responders drove further research into the pathophysiology of ED.

Question 3

What is the Mechanism of Sildenafil Non-Responder?

Accepted Answer

Sildenafil works by inhibiting the PDE5 enzyme, which normally breaks down cyclic guanosine monophosphate (cGMP), a secondary messenger that causes smooth muscle relaxation and vasodilation. In non-responders, the mechanism is often compromised upstream of PDE5 inhibition. For example, if the body is unable to generate sufficient nitric oxide (NO) due to severe endothelial damage or is severely androgen deficient, there may not be enough cGMP produced in the first place for sildenafil to preserve effectively. This lack of initial substrate renders the drug ineffective despite adequate dosing.

Sildenafil Non-Responder

Meaning

Origin

Mechanism

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