Obstetrics & Gynaecology/PDE-5 inhibitor

PDE-5 inhibitors

also: sildenafil · Viagra · tadalafil · vardenafil

Overview

Erectile dysfunction (and pulmonary hypertension). The nitrate interaction is one of the most heavily tested drug pairings.

Mechanism

Inhibit phosphodiesterase-5 → prevent breakdown of cGMP in vascular smooth muscle → sustained NO-mediated vasodilation. In the penis this enhances corpus cavernosum engorgement; in the pulmonary vasculature it lowers pulmonary arterial pressure.

Indications

Erectile dysfunction (first-line)
Pulmonary arterial hypertension (sildenafil/tadalafil)
Tadalafil: also BPH

The agents

Sildenafilshort-acting

~4 h, before activity

Also PAH.

Tadalafillong-acting

up to 36 h / daily

"Weekend pill"; also BPH + PAH.

Adverse effects

Headache, flushing, dyspepsia, nasal congestioncommon

Visual disturbance (blue tinge — sildenafil)common

Cross-reactivity with retinal PDE-6.

Priapismserious

Hypotensionserious

Profound with nitrates/nicorandil.

Cautions & contraindications

Concurrent nitrates or nicorandilall

Both raise cGMP → dangerous hypotension. THE classic contraindication.

Recent MI / stroke, unstable angina, hypotensionall

Caution with alpha-blockersall

Additive hypotension — separate dosing.

Interactions

Nitrates / nicorandil → severe hypotension (absolute)
CYP3A4 inhibitors (ritonavir, ketoconazole, erythromycin) raise levels
Alpha-blockers — additive hypotension

Monitoring & kinetics

Cardiovascular fitness for sexual activity; symptom response

Oral before activity (sildenafil) or daily/long-acting (tadalafil).

Choosing it

true

Source: BNF — Drugs for erectile dysfunction