Impotence Remedy – PDE5 Inhibitors

For a long time the treatment for sexual impotence was restricted to injections into the penis, mechanisms that create vacuums or prostheses implanted through surgery.

Since the late 1990s, however, there has been a simple and convenient option for erectile dysfunction: phosphodiesterase type 5 (PDE5) inhibitors, known commercially by the brands Viagra, Cialis, Levitra and Spedra.

In this article we will explain how erectile dysfunction medications work. We will also talk about its indications, contraindications and the most common side effects.

If you are looking for information about the causes of sexual impotence, go to the following link: Sexual impotence – Causes and Treatment.

How does erection occur?

To understand how PDE5 inhibitors work, one must first understand how normal erection of the penis occurs.

There are two widely vascularized cylindrical structures within the penis, called the corpus cavernosum.

When a sexual stimulus occurs, blood flow to these structures rises, which causes filling of the corpus cavernosum, erection and increased increase in the size of the penis.

The filling of the cavernous copro causes compression of the penile veins causing blood to be trapped in the penis, which keeps it erect while there is sexual stimulation.

When the man has an orgasm or when the stimulus for erection ends, the corpus cavernosum empties and the penis becomes flaccid again.

For the corpus cavernosum to fill with blood it takes a signal from the central nervous system, which releases a substance called nitric oxide.

Nitric oxide is a neurotransmitter that relaxes the blood vessels of the corpus cavernosum, facilitating the entry of blood into it. As long as there is nitric oxide in the corpus cavernosum, the penis will remain full of blood and erect; When nitric oxide levels drop, the erection ends.

Erection, however, is a more complex process than the one explained above. Hormonal and psychological factors interfere with this mechanism.

For example, men with low testosterone levels cannot produce sufficient amounts of nitric oxide. The same can occur during times of stress or anxiety.

A patient with diabetes and diseased blood vessels may not be able to supply enough blood for the penis to fill up, even if there is enough nitric oxide.

Therefore, erection depends on vascular, neurological, hormonal and psychological factors.

Before moving on, watch a short video about erectile dysfunction of psychological origin.

How do phosphodiesterase 5 inhibitors work?

Briefly, we can say that the substance responsible for the elimination of nitric oxide action is called phosphodiesterase Type 5 (PDE5).

Thus, when we administer drugs that inhibit the action of PDE5, we can increase the time of action of nitric oxide, thus ensuring a greater ease in the supply of blood to the corpus cavernosum and an easier and longer lasting erection.

There are currently 4 different drugs that act on PDE-5 inhibition:

Sildenafil (Viagra®)

Sildenafil, marketed under the name Viagra® since 1998, was the first drug in the class of PDE5 inhibitors to be launched on the market. It is currently the most tested and studied oral drug for sexual impotence.

Dosage

Viagra is sold in tablets of 25 mg, 50 mg or 100 mg, with dosage ranging from 25 mg to 100 mg per day, depending on medical evaluation.

The tablet should ideally be taken on an empty stomach (at least 2 hours after the last meal) and 1 hour before sexual intercourse. Sildenafil is not a medicine to be used every day; The minimum interval between one dose and another should be at least 24 hours.

The action of Viagra begins with 30 minutes and lasts for up to 4 hours, but this does not mean that the patient will have an erection during all this time.

Sildenafil is only a facilitator of erection, because it increases the time of existence of nitric oxide already produced, not directly influencing its production. If there is no sexual stimulation, there will be no stimulus for the release of nitric oxide and consequently erection, just as occurs normally with all people.

Contraindications

Viagra is a fairly safe drug, with more than 12 years on the market. However, like any medication, there are contraindications and side effects. The most well-known contraindication is in patients with heart disease using nitrates.

Sildenafil is a vasodilator and although it acts preferentially on the vessels of the penis, there is also an increase in systemic nitric oxide causing a reduction in blood pressure.

In healthy people this fall is small and is usually asymptomatic. However, the use of Viagra with medicines for hypertension should be done with care. Nitrates (isordil, monocordil, monoket, etc.), used for heart disease, are vasodilators whose action is excessively potentiated by Sildenafil, which can cause a significant drop in blood pressure, syncope and even angina (chest pain due to cardiac ischemia).

Medications used for prostate hypertrophy, such as doxazosin and terazosin, also have vasodilator effects potentiated by Viagra and can cause hypotension. Of this class, tamsulosin appears to be the safest drug to be taken in conjunction with Viagra.

In patients with heart failure, Viagra should also not be used without explicit medical authorization, as it can cause decompensation of the picture.

Patients with a history of stroke, especially in the last 6 months, should also exercise caution with the use of Sildenafil.

Drug interactions

Some medicines alter the effect of Viagra and their combination should be avoided. The most common are:

• Erythromycin.
• Ketoconazole.
• Cimetidine.
• Itraconazole.
• Rifampin.
• Phenytoin.
• Indinavir.
• Ritonavir.

Viagra should not be used in conjunction with other PDE5 inhibitors. There is no potentiation of erection with this combination and there is still a high risk of toxicity.

PDE5 inhibitors at very high doses (above those indicated) can cause stroke and severe hypotension.

Side effects

The most common side effect of Sildenafil is headache and dizziness, caused by the systemic effects of vasodilation. Heartburn is also a common symptom.

Other rarer effects include visual changes such as bluish, blurred or increased sensitivity to light. Hearing changes such as hearing loss (in some cases definitive) may also occur.

Priapism, which is the prolonged and painful erection, is a very rare event, but it can occur after the use of Viagra. Every patient with continuous erection for more than 4 hours should seek an emergency service as there is a risk of ischemia and thrombosis of the penis.

Priapism is a more common side effect when Viagra is used recreationally by young people and associated with other drugs such as ecstasy, cocaine and amphetamines.

Vardenafil (Levitra®)

Levitra is a drug launched in 2003, marketed in tablets of 2.5 mg, 5 mg, 10 mg and 20 mg.

Just like Viagra, it should be taken 1 hour before sexual intercourse, and preferably away from the last meal. The action also lasts approximately 4 hours.

The side effect and contraindication profiles of Levitra are similar to that of Viagra.

Tadalafil (Cialis®)

Cialis was also launched in 2003. It is marketed in tablets of 5 mg, 10 mg and 20 mg.

Although the effectiveness is similar to that of other PDE5 inhibitors, Cialis has a more prolonged effect, which lasts for up to 36 hours.

Regarding adverse effects, Tadalafil does not appear to cause the rare visual changes of Viagra and Levitra.

Avanafil (Spedra® or Stendra®)

Avanafil is the newest PDE-5 inhibitor on the market. Its great difference in relation to the other drugs of the class is the rapid onset of action, usually with 15 minutes, mainly in doses from 100 mg.

Which PDE5 inhibitor to choose?

All PDE5 inhibitors have similar efficacy and side effect profile.

Therefore, the choice of the best drug should be based on the patient’s preferences, including cost, ease of use, and desired duration of action.

To facilitate the choice, some points need to be highlighted:

• Sildenafil is the most studied and the one with the longest safety record among the four drugs.
• Nitrates are contraindicated with all PDE5 inhibitors.
• Sildenafil, Vardenafil and Tadalafil should be taken 60 minutes before sexual activity. Avanafil can be taken 15 to 30 minutes before.
• The duration of action of Sildenafil, Vardenafil and Avanafil is four to five hours. In contrast, Tadalafil is effective for up to 36 hours.
• In individuals with a very active sex life, Tadalafil can be given daily in low doses (2.5 to 5 mg daily).
• Sildenafil and Vardenafil should be taken on an empty stomach. Food does not interfere with the absorption of Tadalafil or Avanafil.

If you have erectile dysfunction, talk about treatment options with a urologist.

References

• Treatment of male sexual dysfunction – UpToDate.
• Erectile Dysfunction: AUA Guideline (2018) – American Urological Association.
• Erectile Dysfunction, Premature Ejaculation, Penile Curvature and Priapism – European Association of Urology.
• Male Sexual Dysfunction – JAMA.
• Recent advances in the treatment of erectile dysfunction – British Medical Journal.