Erectile dysfunction (ED) is defined as the inability to achieve or maintain a penile erection sufficient for intercourse, that is observed for three or more months. In cialis 40 mg , it’s 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. In line with the outcomes 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 identified as having ED. ED can even be an early sign of atherosclerosis and coronary heart 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 an increase 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, that leads to a rise 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, because of which there is no increase in blood flow to the corpora cavernosa and effective erection does not occur. However, the tissue concentration of cGMP is regulated by both rate of synthesis and the rate of its destruction by PDE-5. Inhibition of cGMP degradation by phosphodiesterase type 5 inhibitors results in a rise 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 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 ability to accumulate, which allows one to use it constantly.

Recently, many studies have been carried out showing that the constant use of tadalafil not only plays a part in 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 common 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 an assessment 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 partnership between the development of LUTS in BPH and ED has been identified in other studies. The outcomes of six completed studies on the use of tadalafil for the treatment of 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; in addition, 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 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 divided into groups: patients in one group received placebo (n = 78), another 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. 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 side effects discussion

Regarding the the increase in the amount of studies devoted to the constant usage of tadalafil in the clinic, there is a discussion about the unwanted effects and complications associated with taking the drug. In his review article, D. Pushkar et al. provides examples of multicenter, randomized, placebo-controlled studies of safe daily tadalafil therapy in men with ED. In one 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 due to reason behind abdominal pain.

A lot of men with ED have concomitant pathology of the heart; 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 per day or up to 3 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 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 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 the following: 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 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 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 amount of patients with MI by the PY exposure and multiplying by 100. Patient exposure-years were determined for every 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 data show that the incidence of serious cardiovascular events through the early stages of tadalafil therapy (i.e., 0 to a few 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 ought to be said that the drug tadalafil, which is successfully used for the treatment of ED on demand, may be used continuously once a day for several months and even years. Evaluations of continuous usage of tadalafil are high, especially when taking into consideration 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 needed to research the interaction of the drug with ?-1-adrenergic blockers and 5?-reductase blockers, confirmed by working experience.