How do PDE-5 inhibitors for erectile dysfunction actually work?

All you need to know about how erectile dysfunction medications work.


Most people will have heard of Viagra – the little blue, diamond-shaped pill that spices up the sex lives of millions of couples. But not many know what PDE-5 inhibitors actually do or how Cialis, Levitra, Viagra, and co. act to keep the penis erect for longer.


What is PDE-5 and how does it work?

PDE-5 stands for phosphodiesterase 5 and it’s the enzyme responsible for shutting down an erection.

When a man becomes aroused, neural signals trigger the production of nitric oxide. This, in turn, stimulates the production of cyclase–cyclic guanosine monophosphate (cGMP). The cGMP plays a key role in relaxing the penis muscles. Once the smooth muscles in the penis relax, blood flows into it and the sex organ becomes erect. The body then recruits PDE-5 to stop an erection by degrading cGMP and promoting blood flow out of the penis. Without it, erections would last forever.

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Normal erections are long enough for men to engage in satisfactory sex, but when the body produces too much or too little PDE-5, an erectile disorder may be the consequence.

Erectile dysfunction – when men aren’t able to get or maintain an erection - is the consequence of too much PDE-5. It is incredibly common with roughly 50% of those over the age of 50 years experiencing the condition.

Priapism is much rarer and is caused by too little PDE-5. It can lead to erections that last more than four hours.


PDE-5 inhibitors for erectile dysfunction

For patients experiencing erectile dysfunction, PDE-5 inhibitors may be the answer. There are three different types of PDE-5 inhibitors – sildenafil (Viagra)l, tadalafil (Cialis) and vardenafil (Levitra). They don’t differ dramatically, although tadalafil causes erections that last the longest (up to 36 hours). It’s best to consult a healthcare provider before making a decision as the medications’ side effects tend to vary.


“The range of treatments is expanding all the time and the more options we have, the better the chances of improvement,” explained Dr. Ivor Cullen, a consultant urologist at the University Hospital Waterford, UK. “There’s a lack of understanding and embarrassment around this topic but men should see their doctors about it. They will be helped.”


All PDE-5 inhibitors are associated with risks and side effects. In some people, they may cause headaches, visual disturbances or flushing. PDE-5 inhibitors also interact with other medicines. People who are taking beta-blockers or nitrates to treat heart and cardiovascular conditions should not be taking PDE-5 inhibitors. Speak to your healthcare provider and read the enclosed information before taking any new medication.    



  1. Corbin, J. (2004). Mechanisms of action of PDE5 inhibition in erectile dysfunction. International Journal of Impotence Research, 16/S1: S4-S7. DOI:
  2. Yafi, F., Jenkins, L., Albersen, M., Corona, G., Isidori, A., Goldfarb, S., & Maggi, M. et al. (2016). Erectile dysfunction. Nature Reviews Disease Primers, 2/1. DOI:
  3. Brant W.O., Bella A.J., Gracia M.M., Lue T.F. (2007) Priapism. In: Hohenfellner M., Santucci R.A. (eds) Emergencies in Urology. Springer, Berlin, Heidelberg
  4. Smith, W., McCaslin, I., Gokce, A., Mandava, S., Trost, L., & Hellstrom, W. (2013). PDE5 inhibitors: considerations for preference and long-term adherence. International Journal of Clinical Practice, 67/8: 768-780. DOI:
  5. Taylor, J., Baldo, O., Storey, A., Cartledge, J., & Eardley, I. (2009). Differences in side-effect duration and related bother levels between phosphodiesterase type 5 inhibitors. BJU International, 103/10: 1392-1395. DOI:
  6. Don’t let erectile dysfunction get you down. (2019). Retrieved September 19, 2019, from <>

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