Phosphodiesterase-5 Inhibitors

Phosphodiesterase-5 inhibitors are most widely known and prescribed for their functions in treating erectile dysfunction. Sildenafil and tadalafil are also used in the treatment of pulmonary hypertension due to their abilities to relax pulmonary arterioles.  Both indications rely on the inhibition of phosphodiesterase-5, which results in increased levels of cGMP, which relaxes smooth muscles in arterioles and improved blood flow.  

Of note, combination of phosphodiesterase inhibitors and nitrates can result in a severe loss of blood pressure, so care must be taken in avoiding this combination of medications.  Another unique adverse reaction is the possible loss of blue/green visual discrimination.

Class Drugs

• Avanafil

• Sildenafil

• Tadalafil

• Vardenafil

Class Mechanism of Action

Inhibits phosphodiesterase-5, which results in increased levels of cGMP (decreases conversion to GMP)

Sexual stimulation cascade: Sexual stimulation-> NO production -> Stimulates guanylyl cyclase -> Increases cGMP -> Relaxes smooth muscle -> Increases blood flow -> Erection

No effect in absence of sexual stimulation

Class Applications

Erectile dysfunction

Pulmonary hypertension (sildenafil, tadalafil)

Class Adverse Effects

Headaches, flushing, dyspepsia, nasal congestion

Loss of blue/green discrimination in vision

Priapism

Important drug interaction:

• Administration of PDE-5 inhibitors is contra-indicated in the presence of nitrates.

Results in severe hypotension

• Caution when using PDE-5 inhibitors with alpha blockers as combination may significantly reduce blood pressure

Drug Table

Drug Name	Application	Comments	Image
Avanafil			"Van" "Filling Gas Tank"
Sildenafil		Pharmacokinetics; Taken 1 hour before anticipated sexual activity	"Silicone" "Filling Gas Tank"
Tadalafil	Also approved for treatment of benign prostatic hypertrophy (BPH)	Pharmacokinetics; Slow onset of action, approved for daily dosing	"Tadpole" "Filling Gas Tank"
Vardenafil		Pharmacokinetics; Taken 1 hour before anticipated sexual activity	"Garden" "Filling Gas Tank"