Riociguat is approved for pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). Its mechanism — direct stimulation of soluble guanylate cyclase (sGC) — differs from sildenafil in what way?

• A Riociguat activates sGC independent of NO, while sildenafil inhibits cGMP phosphodiesterase downstream ✓
• B Riociguat inhibits endothelin-1 receptors while sildenafil blocks PDE-5
• C Riociguat blocks prostacyclin synthesis while sildenafil enhances prostacyclin receptor signaling
• D Riociguat is an endothelin receptor antagonist while sildenafil targets cGMP

Explanation

Riociguat is a soluble guanylate cyclase (sGC) stimulator that works by two mechanisms: sensitizing sGC to low levels of endogenous NO, and directly stimulating sGC independent of NO — increasing cGMP regardless of endothelial NO availability. Sildenafil (and tadalafil) inhibit PDE-5, preventing cGMP breakdown, thereby increasing cGMP levels only when cGMP is being produced (requiring endogenous NO). The combination of riociguat and PDE-5 inhibitors is contraindicated due to risk of severe hypotension from additive cGMP increase. Endothelin receptor antagonists (bosentan, ambrisentan, macitentan) are a separate PAH drug class.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.