Makindo Medical Notes.com

Cardiac and stroke events have occurred usually associated with sexual activity after taking sildenafil. Whether this is due to the drug itself is unclear. There is a potential for cardiac risk of sexual activity in patients with preexisting cardiovascular disease. See BNF/Drug datasheet for further advice.

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• A phosphodiesterase type 5 inhibitor increasing cGMP
• Increases the number and quality of erections in men with erectile dysfunction
• Profound hypotension with Nicorandil and Nitrates

Physiology of erection

• Erection of the penis involves the release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. Nitric oxide activates the enzyme guanylate cyclase, which results in increased levels of cyclic guanosine monophosphate (cGMP), producing smooth muscle relaxation in the corpus cavernosum and allowing inflow of blood.

Mode of action

• Inhibits cGMP specific phosphodiesterase type 5 (PDE5) - increases cGMP
• Increased cGMP in cavernosal tissues relaxes smooth muscle and permits swelling of corpora with blood
• 4,000-fold selectivity for PDE5 (erection) versus PDE3 (cardiac contractility).
• Sildenafil at a high dose inhibits the activity of PDE-6, which is essential for the functioning of retinal rods cells.

Indications

• Erectile dysfunction, Primary Pulmonary hypertension

Contraindications

• Recent stroke, unstable angina and MI or arrhythmia in last 6 months
• Baseline hypotension or hypertension
• Cardiac failure or IHD causing angina
• Hereditary disorders of retina e.g. retinitis pigmentosa

Side effects

• Headache, Flushing, Nasal congestion, Dyspepsia, Dizziness
• Colour vision changes (blue tinged vision, particularly in low light conditions)
• Priapism, chest pain (ACS), arrhythmias
• Sudden decrease or loss of hearing, seizure, transient global amnesia

Interactions

• Broken down by P450 CYP3A4 and so effects increased by inhibitors such as Erythromycin, grapefruit juice, Ketoconazole and Ritonavir (protease inhibitors)
• Nitrates and Nicorandil can cause severe hypotension and so the combination is contraindicated
• Avoid amyl nitrate "poppers"
• Caution with alpha-blockers with hypotension

Dose

• Erectile dysfunction: Sildenafil 50 mg (Doses from 25 mg ot 100 mg used) taken as needed, approximately 1 hour before sexual activity. Lasts up to 4 hours. Give the advice to seek help if priapism (erection> 4 hours)

References

• Sildenafil in BNF