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Metabolism (clearing of the drug from the body) of tadalafil can be slowed by liver disease, kidney disease, and concurrent use of certain medications (such as erythromycin, ketoconazole, and protease inhibitors). Slowed breakdown allows tadalafil to stay in the body longer and potentially increase the risk for side effects. Therefore, the dose and frequency of tadalafil has to be lowered in the following examples: After isolating the toxin, the researchers radioactively labeled and injected a purified form of the toxin, Tx2-6, into rats that suffered from high blood pressure and severe erectile dysfunction. The investigators then measured the presence of the toxin in the animals' penises and used the toxin to contract and relax strips of penile tissue. Results showed improved levels of nitric oxide, which led to penile relaxation and erections. Effectiveness of tadalafil in these studies was assessed using a sexual function questionnaire. Study participants also were asked if they were able to achieve vaginal penetration and to maintain erections long enough for successful intercourse. Surgeons began providing patients with inflatable penile implants in the 1970s. Could ED be a sign of heart disease? Tell your doctor about any heart disease risk factors you may have, such as: Erection begins with sensory or mental stimulation, or both. Impulses from the brain and local nerves cause the muscles of the corpora cavernosa to relax, allowing blood to flow in and fill the spaces. The blood creates pressure in the corpora cavernosa, making the penis expand. The tunica albuginea helps trap the blood in the corpora cavernosa, thereby sustaining erection. When muscles in the penis contract to stop the inflow of blood and open outflow channels, erection is reversed. Therefore, men with these conditions should not use tadalafil without having these conditions evaluated and stabilized first. 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