cialis 40 generico (ED) means the inability to achieve or maintain a penile erection sufficient for intercourse, that is observed for three or even more months. In multicenter studies, it’s been determined that the incidence of ED, especially in elderly men, is connected with many risk factors, often related: age, diabetes mellitus, atherosclerosis, hypertension, obesity, smoking, alcohol abuse, lifestyle sedentary, depression and relatively low incidence education. In line with the results of the long-term Massachusetts Male Aging Study (MMAS), diabetes mellitus is a major risk factor for ED: 35-75% of men with diabetes are diagnosed with ED. ED may also be an early sign of atherosclerosis and cardiovascular system disease.
Microangiopathies lead to dysregulation of the nitric oxide (NO) system. Formed in nerve endings and endothelial cells during sexual arousal, NO activates the guanylate cyclase system, resulting in a rise in the concentration of cyclic guanosine monophosphate (cGMP). cGMP activates a specific protein kinase, under the influence of which the calcium concentration in the cell decreases and the smooth muscle cells of the arteries relax, which leads to a rise in blood circulation to the cavernous bodies and the occurrence of a ‘erection.
In the cavernous tissue, beneath the action of a particular phosphodiesterase type 5 (PDE-5), cGMP is changed into the inactive 5′-guanosine monophosphate. With insufficient production of NO by ischemic or damaged endothelium, the concentration of cGMP in vascular smooth muscle cells decreases, due to which there is no increase in blood flow to the corpora cavernosa and effective erection will not occur. However, the tissue concentration of cGMP is regulated by both the rate of synthesis and the rate of its destruction by PDE-5. Inhibition of cGMP degradation by phosphodiesterase type 5 inhibitors leads to an increase in its concentration in smooth muscle cells, which promotes erection.
Treatment of erectile dysfunction
Most doctors start ED treatment with PDE5. Three PDE type 5 inhibitors have already been approved for medical used in Russia: sildenafil (Viagra), tadalafil (Cialis), vardenafil (Levitra), the pharmacokinetics of which differ significantly. The half-life for sildenafil and vardenafil is 4 hours, for tadalafil – 17.5 hours. The equilibrium concentration of tadalafil is reached on the 5th day with daily intake and exceeds the original 1.6 times, so the drug doesn’t have the opportunity to accumulate, which allows you to use it constantly.
Recently, a number of studies have been completed showing that the constant usage of tadalafil not only contributes to the maintenance of erectile function, but can also be used to treat lower urinary tract symptoms (LUTS). In most men over 50 with ED, the most frequent disease is benign prostatic hyperplasia (BPH), coupled with LUTS (frequent urination, dependence on abdominal tenderness when urinating, inability to delay voiding, nocturia , incomplete bladder emptying and low urine flow).
KE Andersson, in a review article, discusses the chance of using tadalafil for the treating LUTS occurring in BPH and discusses at length the pathophysiological mechanisms of the development of LUTS. The relationship between the development of LUTS in BPH and ED has been identified in other studies. The outcomes of six completed studies on the usage of tadalafil for the treating ED and LUTS indicate: tadalafil when taken continuously at doses of 2.5; five; 10 and 20 mg do not affect urodynamic parameters: maximum flow rate, detrusor pressure during miction; furthermore, the increase in the level of prostate antigen when taking tadalafil is comparable to taking placebo and is approximately 0.2 mg / ml / year. However, the question of
A fascinating multicenter, double-blind, randomized, placebo-controlled study of taking tadalafil 5mg once a day, which took into account the caliber of the partner’s sex life. The principal assessment criterion for this study was the change between baseline and endpoint erectile function scores, including International Index of Erectile Function (ICEF), Quality of Sex Life (SQoL), and Intercourse Profile. (SQoL), Sexual Life Quality Questionnaire (SLQQ) ). The partners were split into groups: patients in one group received placebo (n = 78), the other received tadalafil 5 mg once a day (n = 264) for 12 weeks. The responses of the men and their partners were collected through the entire study. In comparison to placebo, the tadalafil group showed significant improvement in erection efficiency (p < 0.001), including changes in IIEF, two- and three-question ratio profiles. Furthermore, when taking tadalafil 5 mg once a day, the caliber of sexual life of men and their partners SQoL was significantly greater than in the placebo group (p < 0.001).
Tadalafil unwanted effects discussion
In connection with the increase in the number of studies devoted to the constant usage of tadalafil in the clinic, there exists a discussion about the side effects and complications associated with taking the drug. In his review article, D. Pushkar et al. provides types of multicenter, randomized, placebo-controlled studies of safe daily tadalafil therapy in men with ED. In a single such study, 184 patients took tadalafil in doses of 5 and 10 mg per day, which only three men stopped taking the drug – in a single case because of headaches and dizziness, and in two cases because of cause of abdominal pain.
Many men with ED have concomitant pathology of the cardiovascular system; the safety of therapy in these patients is specially relevant. A multicenter study conducted in 36 clinics evaluated the dynamics of cardiovascular diseases when taking tadalafil at a dose of 2 to 50 mg each day or up to three times a week. The analysis included 12,487 men (mean age 55 years) with ED treated with tadalafil followed up by 5771 patient-years and 2047 men (mean age 56 years) in the placebo group followed up by 460 patient-years. The analysis excluded patients with premature ejaculation, penile anatomical deformities and prostheses, secondary ED (eg, hypogonadism), unstable angina, myocardial infarction (before 3 months), with systolic blood pressure > 170 or <90 mm Hg. Art. and diastolic blood pressure> 100 or <50 mm Hg. Art. Nitrates have already been used in exceptional cases. The duration of the study ranged from 6 to 27.2 months.
At the beginning of the analysis, the structure of concomitant diseases was the following: arterial hypertension – 31%, diabetes – 21%, hyperlipidemia – 17%, coronary heart disease – 5%. Cases of adverse development of cardiovascular events (CVTEAE) were retrospectively analysed: myocardial infarction, sudden cardiovascular and cerebrovascular death. Additionally, patients were divided into risk groups, including obesity, smoking, and over 65 years of age.
CVTEAEs per 100 patient-years were calculated by dividing the quantity of patients with this particular disease by patient-year (PY) exposure and multiplying by 100. The incidence of myocardial infarction (MI) per 100 patient-years was calculated by dividing the quantity of patients with MI by the PY exposure and multiplying by 100. Patient exposure-years were determined for each patient and calculated from the date of randomization to the date of completion. The exact 95% confidence intervals for CVTEAE were calculated in line with the Poisson distribution. Across all studies, CVTEAEs in tadalafil-treated patients were 0.40/100 patient-years (5771 patient-years of exposure) and 0.43/100 patient-years in the placebo-controlled groups (460 patient-years of exposure ).
The info show that the incidence of serious cardiovascular events during the early stages of tadalafil therapy (i.e., 0 to 3 months) is comparable to the incidence of CVTEAE during 27.2 months of therapy. In patients taking tadalafil, the incidence of serious cardiovascular events (CVTEAE) ranged from 0.17/100 to 0.54/100 patient-years in placebo-controlled and open-label studies. Incidence rates of CVTEAE were comparable in men with erectile dysfunction taking tadalafil to those in patients receiving placebo.
Medical research results
In conclusion, it should be said that the drug tadalafil, which is successfully used for the treating ED on demand, can be used continuously once each day for several months and even years. Evaluations of continuous usage of tadalafil are high, particularly when considering the interests of both partners and the side effects are much like those of placebo. The inclusion of tadalafil in the treatment of LUTS in BPH looks promising, however, further studies are essential to investigate the interaction of the drug with ?-1-adrenergic blockers and 5?-reductase blockers, confirmed by practical experience.