Peculiarities of PDE5 inhibitors
Preparations that block PDE type 5 use the same mechanism and are assigned to activate the nervous system and release nitrogen compounds with oxygen in smooth muscle vascular cells. As a result of sexual stimulation, there is accumulation of cyclic guanosine monophosphate (cGMP). This secondary intermediary appears as a result of the synthesis of the enzyme guanylate cyclase, which is activated by nitric oxide and is a substance that regulates the start of biochemical reactions in the male body necessary for the appearance and subsequent maintenance of an erection in men.
The use of new generation inhibitors is recommended during the period of cessation of stimulation of sexual desire, a decrease in the concentration of cyclic GMP. Its deficiency, resulting from various pathogenetic factors, becomes the main cause of failure or lack of erection. Blockers of phosphodiesterase type 5, destroying cGMP, lead to a reduction in the smooth muscle of the male sexual organ. In this case, there is no direct relaxing effect on the erectile tissue of the penis. The effect of nitrous oxide leads to an increase in the relaxing effect, the appearance of sexual stimulation and an increase in the concentration of the synthesized secondary cGMP intermediary. The preferential localization of the enzymes of type 5 phosphodiesterase occurs in the cavernous tissue. Along with this, their presence is noted in platelets, kidneys, lungs, stomach, and smooth musculature of blood vessels.
Peculiarities of the dispensation of PDE5 inhibitors
After taking drugs that block the fifth type of phosphodiesterase, their dispensation in the male body is individual. This group of medicines is characterized by general undesirable effects, based on their ability for enzyme blocking. Among the side effects there were noted headache of varying intensity, difficulty while breathing through the nasal sinuses, disruption of normal activity of the digestive tract against a backdrop of painful and difficult digestion, hot flashes. The clinical picture of the blockade of eleven isoforms of PDE, which is distinguished by the absence of serious undesirable effects, is not taken into account due to selectivity and reversibility of PDE5 inhibitors.
Cialis causes a lesser degree of phosphodiesterase type 6 enzymes blocking and provides a minimal risk of color perception disorders. Simultaneously, the drug, in comparison with the action of sildenafil and vardenafil, is less selective for isoform 11, the blockade of which did not cause registration of clinical effects. This type of enzyme is found in the testicle tissues. Daily intake of Cialis from 10 mg to 20 mg for 180 days does not adversely affect the development of mature male cells. There is no threat of spermatogenesis.
Pharmacokinetics of therapeutic drugs (Viagra, Levitra, Cialis) in the potency treatment
Despite the rapid absorption of Viagra, Levitra, Cialis from the gastrointestinal tract, the kinetic features of the chemical and biological processes that occur with them in the male body have significant differences. Bioavailability is displayed as a percentage and shows the amount of active substance, freed in the blood plasma after its intake and arrival to the problem organ. This takes into account its losses in the process of absorption from the digestive tract, as well as the result of the first passage through the hepatic barrier. The bioavailability index of Levitra is within 15%, sildenafil – 40%. For Cialis it is 85%. Its definition was carried out indirectly, due to the lack of the possibility of intravenous injection.
The active substance of tadalafil does not dissolve in water. The pharmacokinetics of inhibitors is strongly influenced by the intake of fatty foods that reduce the speed and completeness of absorption of Viagra. The content of fats in food less than 30% does not change these parameters when taking Levitra. However, an increase in the fat content of food to 57% leads to their significant decrease. The speed and level of absorption of Cialis absolutely does not depend on the amount of fat in the diet.
An important indicator is the time to reach the maximum concentration of the active component of the prescribed drug, determining the rate of its absorption from the gastrointestinal tract, as well as the onset of therapeutic effect. After taking Viagra and Levitra, a peak level of their concentration in the blood plasma is observed within 60 minutes. Therapeutic effect of Cialis intake occurs only after two hours.
The clinical picture of the drug efficiency is also determined by the minimum content of active components in the blood plasma, which makes it possible to obtain the desired results long before reaching their peak level. The results of clinical studies have confirmed these findings. Many patients began to notice the positive dynamics within 30 minutes after taking inhibitors blocking the fifth isoform of phosphodiesterase. Each type of medicine has its minimum and maximum therapeutic concentration, which is taken into account by the doctor when prescribing oral ED treatment. The correct dosage of the drug excludes possible side effects.
The half-life period is the time during which the content of PDE5 blockers in the blood plasma should decrease by half from its maximum value. This important indicator is taken into account when characterizing the drugs. Viagra and Levitra have the same half-life period of 4 hours. The index of Cialis exceeds the half-life of its analogues. The concentration of active substance reduces by half after 17.5 hours. The equilibrium content of the drug is reached on the fifth day after the daily intake. Its excess of the initial concentration by 1.6 times excludes the cumulative feather of the drug. Frequent and regular intake of Cialis does not confirm its accumulation in the male body. Such findings were witnessed by clinical studies. At the same time, good tolerability of drugs was recorded by men who regularly took them for two years. Metabolism of enzymes PDE-5 is carried out with the participation of cytochromes. Metabolites excretion occurs with urine and feces.
Clinical efficacy of PDE5 blockers
There were studies that compared the efficacy and safety of preparations for blocking phosphodiesterase type 5. Determination of the drugs activity in vitro was carried out in different laboratory conditions, and have differences in the results. The clinical effect depends directly on the bioavailability, elimination rate, interaction with blood proteins, and other factors. The optimal dosage of drugs intake in the impotency treatment is selected experimentally. It should ensure high efficiency of treatment and exclude danger to the life of the patient. The principal difference between PDE5 blockers is the duration of the clinical effect. For Levitra and Viagra, it is within 5 hours, and for Cialis this indicator is 36 hours. However, according to the results of individual studies, the duration of the clinical effect under certain conditions for the first two drugs may exceed the five-hour barrier.
The action of Cialis is stable in duration. Medications with a short effect of the active substance are recommended for use before the sexual intercourse. They often cause mental disorders, due to the dependence of sexual intercourse on the duration of the clinical effect. The use of Cialis provides an opportunity to determine the time of intimacy within 1.5 days. Such a decision is considered economically advantageous in the ratio of cost and effect of the drug. Positive results in the treatment of impotence is determined by a properly selected preparations and an effectively calculated dose. This can only be done by a doctor and should take into account the age and all the characteristics of the man’s body.
Indications for Viagra, Levitra and Cialis (tablets for an erection)
The use of drugs that improve potency is advisable in the following cases:
- impotence or erectile dysfunction;
- physical impossibility to commit sexual intercourse;
- psychological unwillingness of sex;
- premature ejaculation;
- uncertainty in one’s abilities.
What are the side effects of Viagra, Levitra and Cialis?
Blocking of PDE5 can be the cause of undesirable side effects. The intake of Levitra and Viagra, compared with the use of tadalafil, often causes problems with the organs of vision, color perception of the surrounding world, as well as heat or blood tides. Less often is pathology with the food digestion, digestive system functioning, myalgia, which are more common for tadalafil. The long half-life of Cialis causes a higher frequency of pain in muscular tissue, which arise in the evening and at night at rest. Similar phenomena are observed in the clinical studies of other types of PDE5 inhibitors in cases of increased doses or with an increased frequency of intake. Side effects of these drugs are short. Their action time is much less than the therapeutic duration because of the low concentration of the enzyme in the non-cavernous tissue against the background of the high rate of organism adaptation to such situations.
The influence of PDE5 blockers on the cardiovascular system could result in a hypotensive effect and a significant decrease in heart rate. As a result of this feature, simultaneous reception of organic nitrates with inhibitors of the fifth isoform of phosphodiesterase is contraindicated. If it is necessary to regularly consume nitric oxide releasing drugs, it is recommended to take angina attacks into account that can occur at any time after taking Viagra, Levitra, and Cialis or during sexual intercourse. To insure against them is not possible. After cessation of the nitrates intake or their replacement with other drugs with a similar mechanism of work, as well as in the absence of clinical complications, patients are allowed to proceed to the potency treatment with PDE5 inhibitors. At the same time, there is no danger to the patients’ life and health. Nitrates are allowed to be taken one day after using short-acting Viagra, Levitra and 48 hours after taking Cialis. Men’s desire to improve the erection should not be the cause of their well-being deterioration.
In addition, when prescribing ED medication, it is necessary to take into account the loss of sexual activity as a result of complications after a heart attack, stroke, unstable angina or angina pectoris that occurs during intimacy, heart failure, uncontrolled arterial hypertension or hypotension, and heart rhythm disturbance, not subject to control by the patient. Men who are predisposed to prolonged painful erections that are not related to sexual arousal, but caused by myeloma, leukemia or other serious disorders in the body, or who have been diagnosed with an anatomical deformation of the penis, should think twice and take inhibitors with great care.
The combination of alcohol intake with Viagra, Levitra, Cialis
A Viagra pill can be taken 1 hour before having alcoholic beverages. Cialis should be used 15 minutes before having alcohol, and Levitra tablets can be taken together with alcohol.
What is better: Viagra, Levitra or Cialis?
According to the study results in Europe, after having used PDE5 blockers, most men had successful sexual intercourses. Their ratio was the following: Viagra in a dose of 50 to 100 mg was 66%, Levitra at a dose of the drug 20 mg was 65%, Cialis at a dose of 20 mg was 75%. Treatment with Viagra has improved the erection ability of 84% of patients. The intake of Levitra provided an opportunity to eliminate impotence for 80% of men. Tadalafil effectively solved the problem of ED in 80% of patients, returning them the joy of life and confidence in their abilities.
Conclusion
It can be concluded that Viagra, Levitra and Cialis are equally effective for the treatment of erectile dysfunction. The drugs have general indications and contraindications. Cialis has a longer duration and is the drug of choice for uncertain periods of coition. Viagra and Levitra are taken immediately before the intercourse. Side effects from their reception may also differ. Therefore, the optimal choice of the drug depends on the individual preferences and should be done after consulting a physician, who must select the required dose.
The advent of PDE5 inhibitors allowed us to open a new milestone in the solution of this male problem, providing an opportunity to receive positive results. Vardenafil (Levitra) and tadalafil (Cialis) have recently been added to this list along with the first medical preparation sildenafil citrate (Viagra). New drugs have proven themselves in the treatment of erectile dysfunction of organic and psychogenic nature.