Database of diseases - Sexual health

Drugs for erectile dysfunction -PDE 5 inhibitors   

Erectile dysfunction is one of the most common sexual dysfunctions in men. Many men suffering from this disorder are afraid of complications in the form of impotence. Below we present a description of the currently basic group of medicinestype 5 phosphodiesterase inhibitorstreating erectile dysfunction.
 

FOSFODIESTERES TYPE 5 TYPICAL INHIBITORS (Viagra, Levitra, Cialis, etc.)


Antiretroviral phosphodiesterase type 5 inhibitors (PDE 5 inhibitors) are currently the first line medicines for the treatment of erectile dysfunction.

Phosphodiesterase type 5 inhibitors belong to the group of vasoactive drugs - ie those that control the concentration of physiological vasodilator and vasodilating substances circulating in the blood vessels. There are 3 medicines available in Poland: sildenafil (Viagra), vardenafil (Levitra) and tadalafil (Cialis). These drugs differ slightly in chemical structure, especially tadalafil, and the duration of action, while the mechanism of their action is identical. Patients' tests showed different preferences for the selection of these drugs. It turned out that 17.4% of people with erectile dysfunction valued only sildenafil; 43% - vardenafil; 39% - tadalafil.



What is the mechanism of sexual arousal in which PDE5 inhibitors are involved?

At the moment of sexual arousal, the brain sends signals to the nerve cells in the penile core. These cells control the action (contractility) of the smooth muscle in the arteries that supply blood to the penile corpora of the penis. In the period preceding sexual arousal, these muscles are "constricted" and restrict the flow of blood to the corpus cavernosum. Nerve cells, after receiving a signal from the brain, increase the production of nitric oxide and relax the arteries


Nitric oxide (NO) - acts as a "cock" to increase the blood supply. 

Increased secretion of nitric oxide initiates the widening of the arteries and the abundant blood flow to the so-called cavernous bodies of the penis. The cavernous bodies are constructed in such a way that when filling, they stiffen the penis. From the point of view of the physiology and hydraulics of our body - the erection occurs thanks to the filling of the penile bodies of the penis with blood.


Sometimes, however, nitric oxide is not enough ...

In a healthy human, the endothelium of the arteries produces the necessary amount of nitric oxide (NO). It is also able to increase its production in response to nerve stimuli, or changes in the speed of blood flow caused by increased demand. (A certain physiological amount of nitric oxide is constantly produced, and as a result, systemic arteries are always in a state of "relaxation" - ie relaxation.) However, in many men due to the progression of atherosclerosis, hormone imbalance caused by aging and testosterone deficiency, penile injuries, neurosis, psychological tension, or nervous disorders (especially the sympathetic nervous system) - the production of nitric oxide is too weak or short-lived. This leads to disturbed - weak and too short erections.


Physiological reactions that "involve" the physiological mechanisms of erection are necessary for restoring an erection.

Nitric oxide does not act directly, but indirectly, through mediating biochemical reactions.
1. Activates the chemical "intermediary" which is the enzyme - guanilate cyclase (constantly present in the walls of the arteries).
2. The activation of guanilate cyclase results in an increase in the concentration of a substance that determines the physiological ability of the erection, called cyclic quanosine monophosphate (abbreviated as cGMP).


 

 

The most important substance is the physiological "switch" of the erection.

 

How long can erection last?

As long as sexual stimulation of the brain continues and a sufficiently high concentration of active cyclic quanosine monophosphate (cGMP) is maintained. Unfortunately, this substance readily goes into its inactive form - the usual quanosine monophosphate (GNP). It is physiologically switched off by a constant enzyme type 5 phosphodiesterase


The type 5 phosphodiesterase (PDE 5) enzyme is a physiological "erection" switch.

As we remember - the erection initiates a cascade of psychic and biochemical reactions ending with an increase in the chemical concentration of the "switch" of the cyclic quanosine monophosphate. In a healthy man, there is a dynamic balance between this psycho-physiological process that allows erection and the activity of the "disabling" enzyme. In erectile dysfunction, biochemical erection stimulators (nitric oxide, guanilate cyclase, active cyclic quanosine monophosphate) are usually too small, and their inactivation (exclusion) by the exclusion enzyme works well unless we block the enzyme!


What happens if we block the physiological "erection" switch?

The blockage of the enzyme that disables the erection causes that even the temporary "production" of nitric oxide by erotic nerve stimulated by excitement is sufficient to achieve the proper concentration of the penicillary muscle relaxant - the active cyclic quanosine monophosphate (cGMP). Importantly, the high concentration of this substance - cGMP - can last quite long even without further supply of nitric oxide. In this situation, men with the above-mentioned organic erectile dysfunctions have an erection opportunity, i.e. close to 80% of patients visiting the doctor.


Erythromycin blockers - phosphodiesterase type 5 inhibitors (PDE 5 inhibitors)

That's how it happened - help for men with erectile dysfunction comes with drugs that block the enzyme that blocks the erection. These are the phosphodiesterase type 5 inhibitors already mentioned (PDE5 inhibitors)

The condition for the occurrence of an erection is the right concentration of the substance mentioned above - cyclic quanosine monophosphate (cGMP), which can be called the chemical "switch" of the erection. This substance is able to modulate the concentration of calcium in the smooth muscle of the arteries that supply blood to the penile corpora of the penis. Thanks to this - on the signal from the brain - it "relaxes" (relaxes) the smooth muscles of the penile arteries, which allows a profuse inflow of blood to the corpus cavernosum of the penis, and consequently enables erection.

How they work phosphodiesterase type 5 inhibitors?

They are characterized by an unusual chemical similarity to the activator ("switch") of the erection - the active cyclic quanosine monophosphate (cGMP). Therefore, by their similarity they "cheat" the enzyme that disables the erection. The enzyme chemically binds to the drug, which deprives it of the ability to "turn off" the erection for some time.




Does it affect the erection under the influence of PDE5 inhibitors?

It should not, because these types of drugs do not increase spontaneous blood supply to the penile corpora of the penis. All operate at the "final" stage of the entire process. Therefore, the initial sexual arousal of the brain is still necessary, which then only sends signals initiating erection to the nerve cells in the penis.


Application rulesPDE 5 inhibitors

It's best for about 30-60 min. before the planned relationship. Drugs are administered orally, quickly absorbed from the digestive tract. The maximum concentration reaches, on average, approx. 60 minutes. The beginning of action of sildenafil occurs after approx. 30-60 min; vardenafil after administration on an empty stomach - in 90% of men 30-120 min; tadalafil works after 16-30 minutes. But be careful! Administration during a meal extends the absorption of the drug almost twice.




How long do erection stimulators work - type 5 phosphodiesterase inhibitors?

Sildenafil and vardenafil block the enzyme type 5 phosphodiesterase for several hours. (The half-life of sildenafil and vardenafil is 4-5 hours). This guarantees the secretion of nitric oxide at this time and maintaining the erection of the penis long enough. Tadalafil works the longest and its therapeutic effectiveness lasts for 12-36 hours.


How effective are the PDE5 inhibitors?

Vardenafil is therapeutically effective in 85% of patients at a dose of 20 mg (moderate erectile dysfunction) and in 39% of patients with profound erectile dysfunction. It is also a drug that can be successfully used in the absence of response to sildenafil. Tadalafil is effective at a dose of 20 mg in 87% of patients, sildenafil - in 83%. All medicines are effective in patients with diabetes.


What are the side effects of PDE5 inhibitors?

Side effects do not affect your health, they are transient, usually low to moderate. Usually these are headaches, nausea, vomiting, full nose or hot flashes in the facial area, sometimes blurred vision.


The undesirable interactions with other drugs are noteworthy.

An important contraindication to the use of the drug is the administration of nitrites in the treatment of coronary heart disease. In addition, PDE5 inhibitors should not be used in combination with α-adrenergic antagonists, potent inhibitors of CYP3A4 (eg ritonavir, indinavir, itraconazole, orally administered ketoconazole), as well as antibiotic erythromycin and ... grapefruit juice. Therefore, it is not recommended to drink grapefruit juice, because it increases the effect of the drug, and in the case of erythromycin it may be necessary to reduce the dose.


Finally, a common sense note

Some people who may be disappointed with the ineffectiveness of PDE5 inhibitors should also take into account that the condition of these drugs is the natural sexual arousal caused by the object desirable.


ed. Edward Ozga Michalski, MA;

consultation of prof. dr hab. med. Zbigniew Lew Starowicz