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Phosphodiesterase Inhibitors: Treatment of Erectile Dysfunction

• PDE5 inhibitors: basic pharmacology, side effects, contraindications
• PDE5 inhibitors: Sildenafil
• PDE5 inhibitors: Tadalafil
• PDE5 inhibitors: Vardenafil

Review Literature: (Hatzimouratidis and Hatzichristou, 2007).

Indications for Phosphodiesterase Inhibitors

Erectile Dysfunction

PDE5 inhibitors are used for the medical treatment of erectile dysfunction.

Phosphodiesterase Inhibitors and Benign Prostatic Hyperplasia

Smooth muscle of the prostate and urinary bladder also express type 4 and type 5 phosphodiesterase. The release of NO relaxes the muscle cells and plays an important role during micturition. Randomized studies have shown that treatment with tadalafil relieves BPH symptoms (Laydner et al., 2011) (Oelke et al., 2012).

PDE5 Inhibitors: Mode of Action

The phosphodiesterase type 5 plays a crucial role in the inactivation of the signal transduction for the penile erection. Inhibition of the phosphodiesterase type 5 causes a preponderance of the erectile signal transduction and thus an improvement in erection. The mode of action requires thus for an erection a sufficient sexual stimulation, some innervation of the penis and an anatomical intact erectile tissue.

All phosphodiesterase inhibitors for the treatment of erectile dysfunction inhibit potent and highly specific the type 5 phosphodiesterase. The strong treatment effect and the favorable side effect profile make PDE5 inhibitors the first choice treatment option of erectile dysfunction.

Side Effects of Phosphodiesterase Inhibitors

Nervous system:

Headaches (very often). Dizziness (often).

Eyes:

Visual impairment like blurring or disturbed color vision (often). Eye pain.

Cardiovascular system:

Palpitations, flushing (often). Rarely clinically significant cardiac arrhythmia, angina pectoris or cardiac death (the causality of phosphodiesterase inhibitors in cardiac death is difficult to assess).

Other side effects of phosphodiesterase inhibitors:

Stuffy nose (often). Heartburn or dyspepsia (occasionally). Rarely prolonged erection (priapism). Very rarely severe allergic skin reactions.

Drug Interactions with Phosphodiesterase Inhibitors

Nitrates:

Phosphodiesterase inhibitors potentiate the blood pressure lowering effects of nitrates. Co-administration of nitrates and phosphodiesterase inhibitors is contraindicated.

Alpha blocker:

Increased orthostatic hypotension with simultaneous administration of alpha blocker and phosphodiesterase inhibitors may occur.

Inhibitors of cytochrome P450:

Ritonavir, saquinavir, erythromycin, ketoconazole and itraconazole: enhance phosphodiesterase activity and increase side effects.

Contraindications of Phosphodiesterase Inhibitors

Drugs:

No concomitant therapy with nitrates or potent inhibitors of cytochrome P450 (ritonavir, ketoconazole ...).

Heart:

• Severe heart failure (from NYHA II) or unstable coronary heart disease
• Uncontrolled hypotension
• Caution in aortic stenosis and hypertrophic obstructive cardiomyopathy

CNS:

Recent history of stroke (within 6 months).

Liver:

Severe hepatic insufficiency.

Eye:

• Non-arteritic anterior ischemic optic neuropathy
• Retinitis pigmentosa

Other contraindications of phosphodiesterase inhibitors:

• Galactose intolerance
• Women or children
• Caution in patients with multiple system atrophy.
• Beware of a predisposition for priapism in sickle cell anemia

PDE5-selective Phosphodiesterase Inhibitors

• Sildenafil
• Tadalafil
• Vardenafil

References

  Deutsche Version: Phosphodiesterase Hemmer