Erectile dysfunction (ED) is defined as the inability to attain or maintain a penile erection sufficient for intercourse, which is observed for three or even more months. In multicenter studies, it has been determined that the incidence of ED, especially in elderly men, is associated with many risk factors, often related: age, diabetes mellitus, atherosclerosis, hypertension, obesity, smoking, alcohol abuse, lifestyle sedentary, depression and relatively low incidence education. Based on 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 can be an early on 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, leading to a rise in the concentration of cyclic guanosine monophosphate (cGMP). cGMP activates a particular protein kinase, under the influence of that your calcium concentration inside the cell decreases and the smooth muscle cells of the arteries relax, which leads to an increase in blood flow to the cavernous bodies and the occurrence of a ‘erection.
In the cavernous tissue, beneath the action of a specific phosphodiesterase type 5 (PDE-5), cGMP is converted 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 results in an increase in its concentration in smooth muscle cells, which promotes erection.
Treatment of erection dysfunction
Most doctors start ED treatment with PDE5. Three PDE type 5 inhibitors have already been approved for medical use in Russia: sildenafil (Viagra), tadalafil (Cialis), vardenafil (Levitra), the pharmacokinetics 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 initial 1.6 times, therefore the drug doesn’t have the opportunity to accumulate, which allows you to use it constantly.
Recently, numerous studies have been carried out 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 system symptoms (LUTS). Generally in most men over 50 with ED, the most typical 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 treatment of LUTS occurring in BPH and discusses in detail 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 results 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 usually do not affect urodynamic parameters: maximum flow rate, detrusor pressure during miction; furthermore, the increase in the amount of prostate antigen when taking tadalafil is related 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 each day, which took into consideration the caliber of the partner’s sex life. The primary 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 divided into groups: patients in a single group received placebo (n = 78), the other received tadalafil 5 mg once each day (n = 264) for 12 weeks. The responses of the men and their partners were collected through the entire study. Compared 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 each day, the caliber of sexual life of men and their partners SQoL was significantly higher than in the placebo group (p < 0.001).
Tadalafil side effects discussion
Regarding the the increase in the amount of studies devoted to the constant usage of tadalafil in the clinic, you will find 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, of which only three men stopped taking the drug – in one case because of headaches and dizziness, and in two cases because of cause of abdominal pain.
A lot of 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 study 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 study 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 study, the structure of concomitant diseases was as follows: arterial hypertension – 31%, diabetes – 21%, hyperlipidemia – 17%, cardiovascular system disease – 5%. Cases of adverse development of cardiovascular events (CVTEAE) were retrospectively analysed: myocardial infarction, sudden cardiovascular and cerebrovascular death. Additionally, patients were split into risk groups, including obesity, smoking, and over 65 years of age.
CVTEAEs per 100 patient-years were calculated by dividing the number of patients with this 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 using 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 data show that the incidence of serious cardiovascular events through the first 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 must be said that the drug tadalafil, which is successfully used for the treatment of ED on demand, can be utilized continuously once each day for several months and even years. Evaluations of continuous usage of tadalafil are high, particularly when taking into consideration the interests of both partners and the side effects are comparable to those of placebo. The inclusion of tadalafil in the therapy of LUTS in BPH looks promising, however, further studies are essential to research the interaction of the drug with ?- generico cialis 40mg -adrenergic blockers and 5?-reductase blockers, confirmed by practical experience.