Products
Phosphodiesterase-5 inhibitors are commercially available in the form of film-coated tablets and meltable tablets. Sildenafil (Viagra) was the first active ingredient from this group to be approved in the United States, the EU, and many countries in 1998. Generics are also available today. Sildenafil was originally to be developed by Pfizer for the treatment of angina pectoris. In 1992, erection-promoting effects were discovered as a side effect in a clinical trial. In 1993, the first trials were conducted for erectile dysfunction (ED). This article refers to ED. Other indications exist (see below).
Structure and properties
PDE-5 inhibitors have structural similarities to the natural substrate cGMP (cyclic guanosine monophosphate). The figure shows the binding of sildenafil to phosphodiesterase 5 (PDB 2H42):
Effects
Phosphodiesterase 5 inhibitors (ATC G04BE) have vasodilatory and antihypertensive properties. During sexual stimulation, nitric oxide (NO) is released from nerve and endothelial cells in the corpus cavernosum, which activates guanylate cyclase in the smooth muscle cell. This forms cyclic guanosine monophosphate (cGMP) from guanosine triphosphate (GTP). cGMP leads to smooth muscle relaxation in the corpus cavernosum, blood influx and erection. cGMP is degraded by phosphodiesterase 5 (PDE 5) to guanosine monophosphate (GMP). Phosphodiesterase 5 inhibitors inhibit the breakdown of cGMP, enhancing its effects.
- GTP: guanosine triphosphate.
- CGMP: cyclic guanosine monophosphate
- GMP: guanosine monophosphate
Indications
For the treatment of erectile dysfunction in men (erectile dysfunction). Other indications:
- Pulmonary arterial hypertension
- Functional symptoms of benign prostatic hyperplasia
Dosage
According to the professional information. The drugs are taken at least 30 minutes to 1 hour before sexual activity, depending on the active ingredient. Earlier administration is sometimes possible. Tadalafil has a long half-life of 17.5 hours and can be administered up to 36 before sexual intercourse. PDE-5 inhibitors, unlike alprostadil, only work when sexual stimulation is present. When taken with food, the onset of action is delayed. Maximum daily doses must be observed.
Abuse
PDE-5 inhibitors are also taken by men without erectile dysfunction, contrary to regulatory statements. The potential adverse effects and insufficient attention to precautions are problematic. In addition, numerous counterfeit drugs are circulating, mainly distributed via the Internet.
Active ingredients
- Avanafil (Spedra)
- Sildenafil (Viagra, Revatio, generic).
- Tadalafil (Cialis, Adcirca) – long half-life.
- Vardenafil (Levitra, Vivanza)
Not on sale in many countries:
- Lodenafil (Helleva, Brazil).
- Mirodenafil (Mvix, Korea)
- Udenafil (Zydena, Korea)
- Zaprinast (precursor of sildenafil).
Contraindications
Contraindications include (selection):
- Hypersensitivity
- Combination with nitrates and nitric oxide donors such as molsidomine and amyl nitrite.
- Combination with guanylate cyclase stimulators such as riociguat.
- Patients who are advised against sexual activity, e.g., patients with severe cardiovascular disease or severe heart failure
Full precautions can be found in the drug label.
Interactions
The agents enhance the antihypertensive properties of nitrates and NO donors, which may result in a severe and dangerous drop in blood pressure. The combination is therefore contraindicated. With other antihypertensive drugs, an increased decrease in blood pressure is also possible. PDE-5 inhibitors are metabolized mainly by CYP3A4. Corresponding drug interactions with CYP inhibitors and CYP inducers are possible.
Adverse effects
The most common adverse effects include headache, visual disturbances (such as blurred vision, changes in color vision), low blood pressure, dizziness, flushing, nasal congestion, and indigestion.PDE-5 inhibitors can rarely cause serious side effects such as hearing loss, heart attack, stroke, severe visual disturbances, and painful permanent erection (priapism).
