By Doctor Nicola Sacchi - Author of the book: Drugs and doping in sport -
Introduction
Among the latest discoveries in the pharmaceutical field, a prominent role is played by phosphodiesterase type 5 (5PDE) inhibitors used for the treatment of erectile dysfunction.
Mechanism of action of type 5 phosphodiesterase inhibitors
The phenomenon of erection is due to a relaxation of the smooth muscles of the corpora cavernosa of the penis, followed by arterial vasodilation. The parallel constriction of the venous vessels causes stagnation of blood which follows an erection.
The relaxation of the smooth muscles of the corpora cavernosa is a phenomenon mediated by nitric oxide (NO). It activates the enzyme guanylate cyclase which catalyzes the transformation of guanosine triphosphate (GTP) into cyclic guanosine monophosphate (cGMP) which stimulates muscle relaxation . The cGMP is degraded by a phosphodiesterase of which at least six isoenzymes are known. In the corpora cavernosa, the phosphodiesterase involved is phosphodiesterase type 5 (5PDE).
Side effects
There are obviously several possible side effects caused by the intake of these substances. The main risk is linked to the fact that vasodilation can lead to hypotension, with possible cardiovascular decompensation. Treatment of erectile dysfunction has therefore been associated with severe cardiovascular events such as myocardial infarction, intermediate angina pectoris, sudden cardiac death, ventricular arrhythmias, stroke, transient ischemic attack and blood pressure changes.
Furthermore, sildenafil appears to inhibit beta-adrenergic cardiac stimulation; in fact, while the effects of sildenafil on the cardiac level were minimal in conditions of rest, in conditions of beta stimulation or pressure overload, sildenafil decreased the cardiac responses induced by dobutamine and the systolic effects resulting from beta stimulation. It should be added that these effects are certainly aggravated by a non-optimal cardiovascular condition.
Among the side effects it must also be remembered that there may also be disorders such as vomiting, diarrhea, dyspepsia, hot flashes, in addition to the already mentioned pressure changes.
Active ingredients and trade names
Among the molecules mentioned, the progenitor and the first to be marketed was sildenafil (Viagra); following its release on the market, two other drugs of the same class were born, namely tadalafil (Cialis) and vardenafil (Levitra). Of the three compounds, Viagra is the one with the shortest duration of action (6/8 hours) but strongest, while the others have a much longer activity (Cialis beyond 24 hours) but less intense. Recently, avanafil (Stendra) has also been introduced to the market, which differs from other PDE5 inhibitors for a rapid onset of action, about 15 minutes, but also for a shorter duration of action.
Use in pulmonary hypertension and in sports
Type 5 phosphodiesterase inhibitors have recently been shown to be effective also in the treatment of another vascular disease: pulmonary hypertension. This disease is caused by a strong constriction of the blood vessels of the lungs, which reduces the capacity of the lungs. respiratory system to bring oxygen to the body. Due to the vasodilating action, sildenafil and other substances of this class dilate the artery and other pulmonary vessels, causing a lowering of arterial pressure in the lungs and increasing the availability of oxygen. All this makes the molecule in question also able to bring considerable advantages in terms of energy yield under stress: the possible benefits for the user translate into an improvement in the ability to do aerobic exercise.
Particular studies conducted at high altitudes have also shown how sildenafil leads to a significant increase in oxygen saturation in the blood during physical activity. In addition, an increase in maximum workload and maximum cardiac capacity was highlighted.In practice, sildenafil has been shown to significantly improve physical abilities in conditions of hypoxia due to altitude.
In light of these findings, some sportsmen use sildenafil with the aim of improving aerobic performance in long-lasting sports.
There is still little information on the ability of these substances to positively influence physical performance; however, although not all studies are able to demonstrate real benefits for athletes in endurance abilities, the practice of using 5PDE inhibitors prior to performance in endurance sports is increasingly common. The vasodilatory capacities of these substances, particularly in the lungs, can improve the ability to oxygenate the muscles; for this reason more and more endurance sports athletes are using these products.
To confirm this practice among athletes there is also an Italian study published in 2014 [Loraschi et al.], Which examines this practice among cyclists. This study, through an anonymous questionnaire, revealed the fact that in a sample of cyclists, several of them admitted to using Sildenafil before a competition.
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