[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [Phosphodiesterase-5 inhibitors](https://durgical.com/en/pharmacology/classes/phosphodiesterase-5-inhibitors/) › Sildenafil # Sildenafil ## Phosphodiesterase-5 inhibitors? Phosphodiesterase-5 inhibitors A PDE5 inhibitor that relaxes smooth muscle: it treats erectile dysfunction and, in other strengths, pulmonary arterial hypertension. Updated Nov 1, 2026 ## Quick facts **Group** [Phosphodiesterase-5 inhibitors](https://durgical.com/en/pharmacology/classes/phosphodiesterase-5-inhibitors/) **Target** Phosphodiesterase type 5 (cGMP-specific phosphodiesterase) **Used for** Erectile dysfunction · Pulmonary arterial hypertension **Key effects** Headache and flushing · Dyspepsia · Nasal congestion **Monitor** Blood pressure · Vision and hearing complaints **ATC** G04BE03 No doses: the clinician sets them by the current guideline. On this page - The basics Mechanism of action - Indications - Adverse effects - Pharmacokinetics - Memory aid - Safety Contraindications - Key interactions - What is monitored - Administration and safety - Pregnancy and breastfeeding - Nursing care - Study Test yourself - Connections Connections ## Mechanism of action ✂**Phosphodiesterase type 5 (cGMP-specific phosphodiesterase)**Sildenafil ⓘ The figure shows sildenafil in the catalytic site of human PDE5, where cGMP is normally hydrolysed (crystal structure). **Target in 3D:** Phosphodiesterase type 5 (cGMP-specific phosphodiesterase). PDB structure 1UDT (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/1UDT) · Drag to rotate · pinch to zoom Sildenafil is a competitive, selective inhibitor of PDE5, the enzyme that hydrolyses cyclic GMP. During sexual stimulation, nitric oxide released in the corpus cavernosum activates guanylyl cyclase; sildenafil stops cGMP from being broken down, so the smooth muscle relaxes and blood flows in. It has no effect without that nitric oxide signal. In the lungs, the same action relaxes the pulmonary arteries and lowers pulmonary vascular resistance in pulmonary arterial hypertension. It is about ten times less selective against PDE6 of the retina, which explains transient colour vision changes. - Nitric oxide activates guanylyl cyclase and cGMP is made - Sildenafil blocks PDE5, so cGMP is not broken down - cGMP and protein kinase G relax vascular smooth muscle - Erection is easier; pulmonary vascular resistance falls ## Indications - Erectile dysfunction [Erectile dysfunction →](https://durgical.com/en/conditions/erectile-dysfunction/) - Pulmonary arterial hypertension (WHO group 1), to improve exercise ability and delay clinical worsening [Pulmonary hypertension and cor pulmonale →](https://durgical.com/en/conditions/pulmonary-hypertension-and-cor-pulmonale/) ## Adverse effects ### Common - Headache and flushing - Dyspepsia - Nasal congestion - Transient blue-green colour vision changes or blurred vision - Back pain, myalgia and limb pain - Nosebleeds, especially with pulmonary hypertension due to connective tissue disease ### Serious (rare, important) - Severe hypotension with nitrates or riociguat - Priapism (erection lasting more than four hours) - Sudden loss of vision from non-arteritic anterior ischaemic optic neuropathy (NAION) - Sudden decrease or loss of hearing - Pulmonary oedema in pulmonary veno-occlusive disease - Vaso-occlusive crises in pulmonary hypertension due to sickle cell disease ## Contraindications - Use of organic nitrates or nitric oxide donors in any form, regularly or occasionally - Use of riociguat or another guanylate cyclase stimulator - Hypersensitivity to sildenafil - Caution when sexual activity is inadvisable because of heart disease ## Key interactions **Nitrates (glyceryl trinitrate, isosorbide mononitrate or dinitrate, amyl nitrite)** Profound, potentially fatal hypotension; contraindicated **Riociguat** Additive hypotension; contraindicated **Alpha blockers (doxazosin, tamsulosin) and other antihypertensives** Additive fall in blood pressure, with symptomatic hypotension **Strong CYP3A4 inhibitors (ritonavir, ketoconazole, itraconazole, erythromycin)** Much higher sildenafil levels and more side effects **Bosentan and other CYP3A inducers** Lower sildenafil levels **Other PDE5 inhibitors** Combination is avoided ## What is monitored - Blood pressure, especially with antihypertensives or alpha blockers - Cardiovascular fitness before treatment for erectile dysfunction - Vision and hearing complaints - In pulmonary hypertension: symptoms, exercise capacity and signs of pulmonary oedema ## Administration and safety - Oral tablet or suspension; an intravenous form exists for pulmonary hypertension in patients who cannot take it by mouth - Products for erectile dysfunction and for pulmonary hypertension contain the same drug: patients must not take both - A history of nitrate use, including occasional sublingual tablets or recreational amyl nitrite, is asked about before every start - For erectile dysfunction it is taken before sexual activity, at most once a day ## Pregnancy and breastfeeding Published data have not shown a clear link between sildenafil and birth defects; untreated pulmonary arterial hypertension itself carries serious risks for mother and fetus. ## Nursing care - Ask about chest pain treatment with nitrates and record it clearly; a patient on sildenafil with angina must tell the emergency team - Check blood pressure and for dizziness, especially when starting alpha blockers or antihypertensives - Teach that an erection lasting more than four hours is an emergency - Teach that sudden loss of vision or hearing requires urgent medical care - In pulmonary hypertension, watch for nosebleeds and breathlessness that worsens ## Pharmacokinetics **Absorption** Rapidly absorbed by mouth; a high-fat meal delays the peak **Distribution** Distributes into tissues; highly bound to plasma proteins **Metabolism** Liver, mainly CYP3A4 (CYP2C9 minor), to an active N-desmethyl metabolite **Elimination** Mostly as metabolites in faeces, less in urine **Half-life** About 4 hours (parent drug and active metabolite) **Onset and duration** Peak levels within about an hour of an oral dose ## Memory aid «Nitrates + sildenafil = NO way»: both push the nitric oxide–cGMP pathway, and together they can crash blood pressure. ## Test yourself Think of the answer, then tap the question to see it. ## A patient who took sildenafil arrives with chest pain. Which drug is contraindicated? Nitrates such as glyceryl trinitrate: together with sildenafil they can cause severe hypotension. ## Why can sildenafil cause blue-tinged or blurred vision? It also weakly inhibits PDE6, the phosphodiesterase of retinal photoreceptors. ## Which enzyme metabolises sildenafil, and what happens with ritonavir? Mainly CYP3A4; ritonavir strongly inhibits it and greatly raises sildenafil levels. ## Besides erectile dysfunction, which lung disease is treated with sildenafil? Pulmonary arterial hypertension (WHO group 1). [Add to my cards (4)](https://durgical.app/estudiar/?add=/en/pharmacology/sildenafil/) [More Pharmacology questions →](https://durgical.com/en/practice/?f=pharmacology) ## Connections ## Related drugs 4 - [Tadalafil](https://durgical.com/en/pharmacology/tadalafil/) - [Bosentan](https://durgical.com/en/pharmacology/bosentan/) - [Ritonavir](https://durgical.com/en/pharmacology/ritonavir/) - [Doxazosin](https://durgical.com/en/pharmacology/doxazosin/) ## Related conditions 2 - [Erectile dysfunction](https://durgical.com/en/conditions/erectile-dysfunction/) - [Pulmonary hypertension and cor pulmonale](https://durgical.com/en/conditions/pulmonary-hypertension-and-cor-pulmonale/) [← Back to the class: Phosphodiesterase-5 inhibitors](https://durgical.com/en/pharmacology/classes/phosphodiesterase-5-inhibitors/) Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given. Sources: [DailyMed - SILDENAFIL CITRATE tablet](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8127ff38-2761-49ec-8ce7-7f971f521cfb) (DailyMed (U.S. National Library of Medicine), 2026); [DailyMed - SILDENAFIL tablet, film coated](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1bc081f2-399d-43fa-9e0f-9f8df0118e99) (DailyMed (U.S. National Library of Medicine), 2026); [Sildenafil: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a699015.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=G04BE03) (WHO Collaborating Centre for Drug Statistics Methodology, 2026). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/pharmacology/sildenafil/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/sildenafil/