Cialis is tadalafil, a second generation phosphatidiesterase 5 inhibitor developed by Eli Lilly and Company for the oral treatment of erectile dysfunction. Research reports show that compared with sildenafil, Cialis is very rapid onset of action, about 15 to 20 minutes, the effect of up to 36 hours. T1/2 to 17.5 h. In a study of 348 men with mild to severe erectile dysfunction, patients randomized to tadalafil 20mg or placebo showed improved sexual success at both 24 and 36 hours compared with placebo, with most men having two successful sexual encounters at 36 hours. There was no difference in the incidence and severity of adverse drug reactions compared with placebo. Headache and indigestion occurred in more than 5% of the men in the Tadalafil group.
[Adverse reactions] No serious adverse reactions were observed, such as facial flushing and visual abnormalities. Occasionally headache, dyspepsia.
[Precautions] Patients who are taking nitrates, angina pectoris, heart disease, uncontrolled hypertension or hypotension, and patients who have had stroke in the past 6 months are prohibited.
Tadalafil (C22H19N3O4, molecular weight 389.4) has been widely used in the treatment of erectile dysfunction in men since 2003 under the trade name Cialis. Eli Lilly and Company sold the commercial expansion rights for PAH treatment to United Therapeutics in 2008. In June 2009 the FDA approved tadanafil for the treatment of patients with pulmonary arterial hypertension (PAH) under the trade name Adcirca in the United States. Tadanafil was introduced in 2003 as a treatment for ED. It is effective 30 minutes after administration, but its optimal efficacy is 2 hours after onset, lasting 36 hours, and its efficacy is not affected by food. Tadanafil is administered in doses of 10 or 20 mg, with an initial recommended dose of 10mg, depending on the patient's response and adverse events. Premarket studies have shown that after 12 weeks of oral administration of 10 or 20mg of tadanafil, the response rate was 67% and 81%, respectively. Many studies have shown that tadanafil is effective in the treatment of ED.
Tadanafil is used to treat erectile dysfunction (ED) and pulmonary hypertension in men.
Mechanism of action
Erectile dysfunction: Tadanafil and sildenafil belong to the same selective type 5 phosphodiesterase (PDE5), but the structure is different from the latter and a high fat diet does not interfere with its absorption. Nitric oxide synthase (NOS) in penile nerve endings and vascular endothelial cells catalyzes the synthesis of nitric oxide (NO) from the substrate l-arginine in response to sexual stimulation. NO activates guanosine cyclase, which converts guanosine triphosphate to cycloguanosine (cGMP), which activates cycloguanosine phosphodependent protein kinase, leading to a decrease in calcium concentration in smooth muscle cells and relaxation of smooth muscle in the cavernosa of the penis and erection. Phosphodiesterase type 5 (PDE5) degrades cGMP into a physiologically inactive product, which shifts the penis into a weakened state. Tadanafil leads to the accumulation of cGMP by inhibiting PDE5 degradation, which relaxes the smooth muscle of the cavernosa, leading to penile erection. Since nitrates are NO donors, their combination with tadanafil can significantly increase cGMP levels and lead to severe hypotension. Therefore, the combination of nitrates and tadanafil is clinically contraindicated.
Tadanafil affects by inhibiting PDES. GMP degrades and may cause an extreme drop in blood pressure and an increased risk of syncope when used in combination with vinegars. CY3PA4 inducer can reduce the abiobioavailability of tadanadana, and the combination with rifampicin, cimetidine, erythromycin, clarithromycin, itraconvax, Ketoconvax, HVI protease inhibitors may increase the plasma concentration of this product, so attention should be paid to the dosage adjustment. So far, there are no reports that the pharmacokinetic parameters of this product are affected by diet and alcohol.