Erectile dysfunction

Question 1

Common indications

Phosphodiesterase inhibitors

Sildenafil

Answer 1

1. Erectile dysfunction
2. Primary pulmonary HTN

Question 2

MOA

Phosphodiesterase inhibitors

Sildenafil

Answer 2

• Sildenafil is a phosphodiesterase (PDE) inhibitor. It is selective for PDE type-5 that is found predominantly in the smooth muscle of the corpus cavernosum of the penis and arteries of the lung.
• For an erection to occur, sexual stimulation is required.
• This releases nitric oxide, which stimulates cyclic guanosine monophosphate (cGMP) production, causing arterial smooth muscle relaxation, vasodilatation and penile engorgement.
• As PDE5 is responsible for the breakdown ofcGMP, inhibition of this enzyme by sildenafil increases cGMP concentrations, improving penile blood flow and erection quality.
• It is worth noting sildenafil does not cause an erection without sexual stimulation.
• In the pulmonary vasculature, sildenafil causes arterial vasodilatation by similar mechanisms so is used to treat primary pulmonary hypertension.

Question 3

Important adverse effects

PDEI

Sildenafil

Answer 3

• Most of the adverse effects of sildenafil relate to its actions as a vasodilator. These include flushing, headache, dizziness and nasal congestion.
• More seriously, hypotension, tachycardia and palpitations can occur and there is a small associated risk of vascular events (e.g. myocardial infarction, stroke).
• If the erection fails to subside for a prolonged period despite absence of stimulation (priapism), urgent medical assistance is required to prevent penile damage.
• Visual disorders including colour distortion are due to inhibition of PDE6 in the retina and should prompt urgent medical review

Question 4

Warnings

PDEI

Sildenafil

Answer 4

• You should not prescribe sildenafil for patients in whom vasodilatation could be dangerous, including those with recent stroke or acute coronary syndrome or with significant history of cardiovascular disease.
• Sildenafil should be avoided or used at a lower dose in people with severe hepatic or renal impairment in whom sildenafil metabolism and excretion is reduced.

Question 5

Important interactions

PDEI

Sildenafil

Answer 5

• Do not prescribe sildenafil for people taking any drug that increases nitric oxide, particularly nitrates or nicorandil, as their combined effects on cGMP (see Mechanisms of action) can cause marked arterial vasodilatation and cardiovascular collapse.
• Prescribe sildenafil with caution in patients taking other vasodilators including α-blockers (should not be taken within 4 hours of sildenafil) and calcium channel blockers, as there is an increased risk of hypotension.
• Plasma concentrations and adverse effects of sildenafil are increased by cytochrome P450 inhibitors, e.g. amiodarone, diltiazem and fluconazole.

Question 6

Prescription, Communication, Monitoring

PEDI

Sildenafil

Answer 6

• Usual dose for ED is 50mg PO (max 1 dose per day)
• Pulmonary HTN- usual dose is 20mg TDS
• The drug will not produce an erection without sexual stimulation
• This should be taken 1 hour before sex to allow sufficient absorption
• If the erection does subside within 2 hours after sex then seek medical advise
• Monitor: efficacy, Side effects. Pulmonary HTN is measured by specialist