Modern Drugs against Erectile Dysfunction

A Look Back

Thanks to the rapid development of medicine over the past two centuries, many diseases have ceased to threaten humanity. Some, like the terrible black pox, disappeared from the face of the earth altogether, while others became possible to be successfully treated. Even a hundred years ago, the most common thing was death from pneumonia, while now this condition is treated mainly on an outpatient basis. The achievements of radiosurgery, MRI, ultrasound and other technologies are impressive, especially considering how short a period of time they were developed compared to the entire history of mankind. In the late 1990s, a solution was finally found for such a problem as erectile dysfunction, or impotence, a condition characterized by insufficient strength and duration of an erection in a man.

The solution to the problem, over which the sharpest minds of mankind have been fighting throughout the entire period of the existence of civilization, was PDE-5 inhibitors (stands for phosphodiesterase type 5). This is an enzyme that is produced in certain tissues of the human body, mainly in the cavernous bodies of the penis, as well as in the lungs. The production of PDE-5 in the cavernous bodies of the penis occurs some time after the onset of sexual arousal and is a signal for the body to stop erection. In every person this time is individual, and in cases of erectile dysfunction this period is very short.

What Really Works and How

In order to better understand the mechanism of action of PDE-5 inhibitors on male potency, it is useful to become familiar with the biochemical mechanism of erection. An erection is an increase in the volume (size) of the penis, accompanied by a sharp increase in its elasticity, which is due to the stretching and filling of the cavernous bodies with blood during sexual arousal. The erection phenomenon is caused by a complex combination of neurovascular changes in the cavernous bodies of the penis, the final link of which is the relaxation of the smooth muscle elements of the arteries, arterioles and sinusoids. With sexual stimulation, the parasympathetic nervous system is activated. The release of neurotransmitters, in particular nitric oxide from the vascular endothelium of the cavernous bodies, leads to the accumulation of cGMP in the cavernous tissue and the relaxation of smooth muscle cells in the walls of the afferent arteries and cavernous bodies. Filling the lacunae with arterial blood causes compression of the venules and blocking the outflow of blood from the penis. The mechanism of action of PDE-5 inhibitors on the male genital area is associated with influencing the system of nitric oxide - cyclic guanosine monophosphate (cGMP). Inhibition of cGMP destruction leads to a sharp increase in its concentration in cells in which PDE-5 is the main form of phosphodiesterases. This leads to relaxation of smooth muscle cells and dilation to the arteries, since their walls contain these cells. In the case of cavernous arteries, this allows to increase blood flow to the cavernous bodies and, as a result, contributes to the onset of a strong and prolonged erection.

PDE-5 Inhibitors: Main Advantages

All PDE-5 inhibitors have absolutely no effect on the sexual constitution of a man, his libido, as well as the level of sex hormones. The action is manifested only in the presence of sexual arousal or if a man is subjected or subjects himself to sexual stimulation. In composed emotional state, the maximum that threatens the patient is minor side effects, such as a headache, but not the erection itself.

PDE-5 inhibitors don’t cause any type of addiction. Of course, a man can get used to the fact that he performs feats in bed only by taking medicine for insurance, but this problem is already in the field of self-hypnosis and placebo. In fact, taking drugs to increase potency does not carry any risk for either psychological or physical health. This statement is relevant only if the patient follows the recommendations given in the instructions for use, otherwise it is quite possible to harm the body due to the presence of a number of contraindications for such medicines.

In accordance with the recommendations of the US health system, the ideal therapy for erectile dysfunction implies such parameters as simplicity, high efficiency, non-invasiveness, painlessness, rarity and low severity of side effects. All currently available drugs from the group of PDE-5 inhibitors meet the first four requirements and, to one degree or another, the last. They are intended for oral intake, have long ago proved their high efficacy and don’t cause any unpleasant sensations in the process of sexual intercourse. However, different patients demonstrate different sensitivity to substances from this pharmacological group, and therefore, in some cases, it is necessary to select the optimal drug by trial and error. Traditionally, the smallest number of negative and conditionally negative reactions of the body is observed in response to the actions of Cialis (Tadalafil).

The Big Three: Viagra, Levitra, Cialis

The first drug from the PDE-5 group, which made a real revolution first in the American and then in the international pharmaceutical market, was Viagra. This drug was developed by the pharmaceutical giant Pfizer for the treatment of pulmonary arterial hypertension, but during clinical trials, an unexpected side effect was found in men, such as increased erection. It was then that scientists realized in which direction they had to work in order to obtain safe and effective means to increase potency.

The active substance of Viagra, which has been successfully used throughout the world for over twenty years, is Sildenafil citrate. This is an artificially synthesized substance, like other PDE-5 inhibitors.

Besides Viagra, the “big three” of ED medications include Cialis and Levitra. These two drugs were developed later and have their own unique features, thanks to which they were able to gain popularity with a sufficiently large number of customers and compete with Viagra.

So, the main feature of Levitra, thanks to which this medicine has received a certain circle of loyal adherents, is a significant prolongation of sexual intercourse. It is achieved by a certain decrease in the sensitivity of the penis, which entails the need to perform a greater number of frictions to achieve orgasm. It cannot be said that Levitra is a drug suitable for the treatment of premature ejaculation as a clinically diagnosed condition, but it is the best choice for men who would like not only to strengthen their erection, but also to enjoy the process of sex longer than usual. The main active substance of Levitra is Vardenafil, also a PDE-5 inhibitor.

The special feature of Cialis that makes many men opt for this particular drug is the officially approved by the regulatory authorities (FDA) the ability to take this medicine on a daily basis. Cialis's active ingredient, the PDE-5 inhibitor Tadalafil, was also approved in 2012 for the treatment of benign prostatic hyperplasia (BPH). This disease is widespread among middle-aged and elderly men: according to approximate data, one in four Americans aged 45-55 years has signs of the initial stage of development of prostate adenoma. Among men over 60, every third, and after 65 years, every second man suffers from symptoms of BPH, in most cases closely related to erectile dysfunction. However, of all the PDE-5 inhibitors currently used to treat erectile dysfunction, only Cialis is recommended for patients with BPH.

The ability to use Cialis on a daily basis is associated with the record duration of action of Tadalafil: this medicine remains in the system for up to 36 hours. Much depends on the individual sensitivity of the organism to the active substance, as well as on the severity of problems with potency, but in any case, this period is at least 30 hours. Cialis is available in dosages of 20, 10 and 5 mg, while the 20 mg version has the longest duration of action. Exactly due to this property Cialis is sometimes used according to daily intake scheme. The main advantages of using Tadalafil on a daily basis, that is, not on demand (shortly before sex), but as a permanent therapy, can be divided into the following interconnected groups:

• Increasing the effectiveness of treatment.
• Achievement of greater “naturalness”, spontaneity of sexual life.
• The possibility of complete cure of erectile disorders.
• Improved blood supply to the cavernous bodies and the entire genital area.
• Favorable effect on the cardiovascular system in general.

In addition to the Big Three drugs, PDE5 inhibitors include udenafil [1] and avanafil. At the moment, these drugs are distributed mainly in Australia and New Zealand, and also begin their journey in European countries.

Generic PDE-5 Inhibitors

In addition to branded drugs, the market for erectile dysfunction drugs is represented by such a wide category as their generics. At the moment, you can buy generics of all drugs from the Big Three: Viagra, Levitra and Cialis. They are manufactured by a huge number of different companies located in many countries of the world, and they are sold under different trade names, but the feature that unites them all is the same active substance as in the prototype drugs.

In 2022, the most popular generics include Cialis Professional, Viagra Super Active and Kamagra Polo.

Cialis Professional is an Australian generic of Cialis, its active ingredient is Tadalafil in the dosage of 20 mg. It is the sublingual version of this medication, which absorbs into bloodstream quicker than ordinary tablets. This increases efficacy and effect onset speed. Many customers report that Cialis Professional is very well tolerated by the organism, and side effects occur seldom.

Viagra Super Active is a generic of Viagra produced in form of gelatin capsules with a dosage of 100 mg of Sildenafil citrate. This form of drug is easier to swallow than traditional pills, and many patients note a quicker onset of action.

Kamagra Polo is an Indian generic of Viagra produced in a very unusual form of chewable tablets. It is available in 100 mg dosage, has a pleasant taste and starts acting much sooner than branded Viagra. Despite the fact that this generic has recently appeared on the market, its popularity is growing every day. No more pills to be swallowed with a significant amount of water. The new version of the drug will especially appeal to men who want to hide from their partners the fact that they are taking any means to increase potency.

Branded and Generic PDE-5 Inhibitors: What Men of Different Age Prefer

Recent statistical studies have shown that in the United States, men of different ages prefer different types of drugs from the group of PDE-5 inhibitors.

As it can be seen, branded drugs are preferred by older men, while generic drug users are slightly younger. This shows that people with more modern views are open to the use of generics, who understand that, in terms of their characteristics, generics are equivalent to their prototypes, and sometimes even surpass them.
US residents in most cases purchase generic ED medications online from international or overseas online pharmacies. A wide range of medicines is always presented here, and delivery to the local post office is carried out in a short time and at an affordable price.

PDE-5 Inhibitors: Prospects for the Future

In 2022, the trend is expected to increase the use of drugs for ED on a daily regimen. Already in the first comparative studies of the use of PDE-5 inhibitors "on demand" and their long-term use (on a daily basis at about the same time of day), it was proved that the effectiveness of the latter approach is at least as good as the conventional method of treatment. This has been proven in the case of Tadalafil.

Today, there is considerable interest in the possibility of using the continuous use of PDE-5 inhibitors in the treatment of not only patients with BPH, but also in those in whom taking drugs “on demand” was ineffective or insufficiently effective. The relevance of this issue is determined by the fact that the proportion of such patients reaches 30-40%. Data from studies show that this approach can achieve a significant improvement in erectile function in 10-20% of patients who initially didn’t respond to treatment with PDE-5 inhibitors or did not respond well enough to it.

In addition, the use of PDE-5 inhibitors on an ongoing basis can improve the state of erectile function in such difficult-to-treat groups of patients as patients with diabetes mellitus and undergoing radical prostatectomy.

Recently, the possibility of improving postoperative potency disorders as a result of daily intake of not only Tadalafil, but also Sildenafil has begun to be actively studied. During the study, patients who underwent bilateral nerve-sparing retropubic radical prostatectomy and did not suffer from erectile dysfunction before surgery, starting from the second month of the postoperative period, received sildenafil at doses of 100 and 50 mg (group 1) or placebo at bedtime (group 2) for 36 weeks. 8 weeks after discontinuation of treatment, 27% of men treated with sildenafil reported the possibility of maintaining a normal sexual life, and only 4% of those receiving placebo.

The clinical feasibility of continuous use of PDE-5 inhibitors has already been proven in the case of pulmonary and systemic hypertension. It is not for nothing that Sildenafil, the active ingredient in Viagra, was originally intended for the treatment of pulmonary arterial hypertension. If it is confirmed that the restoration of normal endothelial function is accompanied by an improvement in the state of the cardiovascular system and a decrease in the incidence of complications, then new prospects will open for long-term continuous use of PDE-5 inhibitors. Although the clinical benefits of chronic PDE-5 inhibitors such as Sildenafil in relation to cardiovascular disease are still not fully established, data from 2020-2021 studies suggest that the improvement in endothelial function observed against the background of such treatment may accompanied by a decrease in the number of cardiovascular complications.