Clinical evidence
PDE5 inhibitors (sildenafil, tadalafil)
Erectile treatment·Sexual-dysfunction treatments
⚠ Critical
Absolute contraindication with nitrates and 'poppers' — combined cGMP accumulation causes severe, potentially fatal hypotension. Withhold nitrates ≥24 h after sildenafil/vardenafil and ≥48 h after tadalafil. Also potentiates alpha-blockers.
Effect across the cycle
DesireNeutral: No direct effect on desire.
ArousalFacilitatory: Enables genital arousal when sexual stimulation is present.
PerformanceFacilitatory: Restores and sustains erection — the core indication.
ClimaxNeutral: No direct orgasmic effect.
ExperienceFacilitatory: Restored function improves the overall experience.
MemoryNeutral: Not a memory factor.
Mechanism
Inhibit phosphodiesterase-5, preventing cGMP breakdown for sustained cavernosal smooth-muscle relaxation and erection. Require intact nitric-oxide signaling and sexual stimulation; act peripherally and do not directly increase desire. First-line for erectile dysfunction.
Sex differences & notes
Off-label use in women (genital arousal) has modest, mixed evidence; reduced efficacy in nitric-oxide-deficient states such as diabetes.
Key sources
- Kloner et al.; ACC/AHA nitrate guidance
- Urology Textbook (PDE5 pharmacology)