viagra

Viagra® and erectile dysfunction therapy

In this article we will try to understand what viagra is, how it acts on erections and its effectiveness against erectile dysfunction.

Let's also find out what are the best therapies and the best remedies to fight the problems related to erection and what are the natural alternatives to viagra.

Viagra® and erectile dysfunction therapy

Medicines and effective remedies against one of the most common urogenital pathologies in humans

Over the centuries there has been a huge market for parts of creatures that have had the misfortune of being associated with male virility, in the belief that consuming these parts could stimulate erection or act as an aphrodisiac.

The elective treatment in cases where the disorder is of psychological origin is psychotherapy, the reference professional is the sexologist and the approach is focused on the solution of the symptom in the short term. However, when there is an organic cause of erectile dysfunction, associated with risk factors such as diabetes, advanced age or endothelial dysfunction, it is possible to intervene with food supplements or drugs to promote vasodilation in the corpora cavernosa of the penis during sexual arousal, favoring the 'erection.

L'apomorphine it was in the past a drug used for erectile dysfunction, in fact, when it is injected under the skin, it causes erection in men. However, apomorphine has fallen into disuse due to its powerful emetic effect (induces vomiting), an unacceptable side effect for the use of the drug. During the 1990s, when homosexuality was still considered a psychiatric disease, apomorphine was used in aversion therapy in the wrong attempt to cure homosexuality by conditioning individuals to associate homoerotic stimuli with nausea and vomiting caused by apomorphine. . Also there papaverine, if injected into the corpus cavernosum of the penis, it induces erection; rather inconvenient route of administration for the therapeutic purpose of the drug, moreover the administration must be performed by a specialist in urology.

In 1997 the first drug with unexpected therapeutic potential against erectile dysfunction was synthesized in the United Kingdom: sildenafil (Viagra®), which has become a precursor to the class of drugs called phosphodiesterase type 5 inhibitors.

These drugs have revolutionized the treatment of erectile dysfunction thanks to the practical route of administration by mouth one hour before sexual intercourse and its effectiveness. There are contraindications for these drugs and can cause even very serious side effects, so their use must be approved by the attending physician, and purchased in pharmacies with a medical prescription.

Remedies and therapies for erectile dysfunction

Let's see which are the most effective nowadays.

Food supplement

It has been shown that adding moderate amounts of the amino acid to the diet arginine it can improve erection by increasing the endogenous production of nitrogen monoxide (NO), a very important biological mediator with a vasodilating effect in the arteries of the corpora cavernosa of the penis, of which the amino acid is a direct precursor. This effect is obtained by taking 2 grams of arginine per day, away from meals.

There are food supplements based on arginine and other its precursors such as citrulline is arginine alpha-ketoglutarate (AKG), available in pre-dosed tablets or powders; the intake of 2-3 grams per day of these substances increases the production of NO in the body.

In addition to having a vasodilating effect, NO prevents damage from atherosclerosis and exerts an anti-inflammatory, anti-hypertensive action in the body and prevents platelet aggregation and the formation of thrombus.

Phosphodiesterase 5 (PDE5) inhibitors

They are the drugs of choice in the drug therapy of erectile dysfunction. The first to go on sale was thesildenafil (Viagra®), also known as the blue pill, accidentally discovered by researchers from the pharmaceutical industry Pfizer in an attempt to synthesize a drug against hypertension andangina pectoris, painful pathology due to a reduced blood supply in the coronary arteries of the heart. The drug was patented and marketed by Pfizer in 1998, and has since become one of the best-selling drugs in the world. Subsequently, from 2007 onwards, three other drugs entered therapy:vardenafil (Levitra®), tadalafil (Cialis®) is avanafil (Spedra®).

The main pharmacological differences between these drugs are the time it takes for them to work and the duration of their effect: sildenafil takes about an hour to be effective, while vardenafil and avanafil have an onset of action of about 10-15 minutes. Tadalafil, on the other hand, is also called the weekend pill due to its long-lasting effect. These drugs have no aphrodisiac action; they enhance the vasodilating effect of nitrogen monoxide (NO) released in the arteries of the penis following the increase in sexual desire, the physiological mechanism underlying the erection.

Currently, tadalafil is the only drug approved for the treatment of benign prostatic hyperplasia, a very common disease in men, often associated with erectile dysfunction.

Hormone therapy, prostaglandins and prosthesis implantation

When the cause of dysfunction is of endocrine origin (male hypogonadism), the approved therapy is of the hormonal type testosterone, an androgen physiologically released by the male gonads.

In the event that the intake of PDE5 and testosterone inhibitors are contraindicated, there is a second level therapy based on prostaglandins (PGE2) in the form of urethral suppositories or direct injection into the corpus cavernosum of the penis, thealprostadil (Caverject®) is the reference drug, to be administered before intercourse.

Finally, if all the cases described are ineffective or there are particular contraindications, it is possible to intervene surgically with the implantation of prostheses.

Pharmacological study: mechanism of action of PDE5 inhibitors

PDEs are enzymes that inactivate the cyclic nucleotides adenosine 3 ′, 5′-monophosphate (cAMP) and guanosine 3 ′, 5′-monophosphate (cGMP), catalyzing the hydrolysis reaction of the diesteric 3′-phosphate bond, transforming the substrates into the relative linear inactive forms 5′-AMP and 5′-GMP. There are several enzymatic forms of PDE: forms 4, 7 and 8 are selective for cAMP; forms 5, 6 and 9 are selective towards cGMP; finally the forms 1, 2, 3, 10 and 11 hydrolyze both cyclic nucleotides. At the level of the smooth muscles of the arterioles that regulate the blood flow to the corpora cavernosa of the penis, type 5 PDEs are more expressed.

The cGMP forms a bond with a glutamine residue (Gln-817) present in the enzymatic pocket of the PDE; sildenafil, and other PDE5 inhibitory drugs, thanks to their particular molecular structure, bind PDE5 in the same binding site as cGMP, occupying it and preventing the enzymatic reaction that transforms cGMP into 5′-GMP.

Sildenafil was obtained starting from the chemical structure of theophylline, a drug of xanthine derivation similar to caffeine, used in the therapy of asthma as a bronchodilator (Fig. 1).

Fig.1 – Formula di struttura della teofillina e del sildenafil - Viagra

Fig. 1 - Structural formula of theophylline and sildenafil

Theophylline is more selective to type 3 phosphodiesterases, but suitable molecular substitutions are sufficient to obtain a more selective chemical compound for type 5 phosphodiesterases.

The great success achieved by the sales of sildenafil has prompted other companies to patent and market drugs with the same therapeutic indication (medications me too); in chronological order, vardenafil, tadalafil and finally avanafil came into therapy (Fig. 2).

Fig.2 – Formule di struttura molecolare di vardenafil, tadalafil e avanafil - Viagra

Fig. 2 - Molecular structure formulas of vardenafil, tadalafil and avanafil

On June 22, 2013 the patent protection period of Viagra® expired in Italy, so from that date the equivalent drug is available at a reduced cost.

Warnings and side effects

The administration of these drugs must be followed by the doctor, therefore it is necessary to perform medical checks on the conditions cardiovascular, because there is a percentage of risk of cardiac events associated with sexual activity.

PDE5 inhibitor drugs have been observed to potentiate the hypotensive effects of nitric oxide donor drugs (e.g. amyl nitrite), therefore co-administration is contraindicated to avoid health-threatening hypotension.

PDE5 inhibitors should not be used in people for whom sexual activity is not recommended: patients with severe cardiovascular disorders, unstable angina or severe heart failure.

Among the most commonly reported adverse reactions in patients using these drugs are: headache, hot flashes, dyspepsia, visual disturbances, nasal congestion, dizziness and altered color perception.

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