Tadalafil, trade name Cialis, belongs to a class of chemicals known as PDE5 inhibitors. Tadalafil is used in treatment of erectile dysfunction and pulmonary hypertension. PDE5 inhibitors act through the nitric oxide pathway; when sexual stimulation occurs to the penis, nitric oxide is released. Nitric oxide stimulates release of the guanylate cyclase enzyme. Guanylate cyclase interacts with cyclic-GMP (c-GMP) which relaxes the smooth muscle lining blood vessels of the corpus cavernosum thereby inducing penile erection. In subjects with erectile dysfunction, inhibition of c-GMP specific phosphodiesterase-5 (PDE5) helps treat the inability to achieve erections. Tadalafil is not entirely specific to PDE5; it mildly inhibits other phosphodiesterase enzymes, which is responsible for most side-effects with higher doses of PDE5 inhibitors sometimes experienced by individuals such as vision distortions (caused by phosphodiesterase inhibition in the retina). Tadalafil’s action in treatment of pulmonary hypertension works similarly to its mechanism for treating erectile dysfunction. Super-selective PDE5 inhibitors are currently in development but are unlikely to be introduced soon due to the success in the current market of first-generation PDE5 inhibitors.
Tadalafil is approximately equally effective (adjusted for dosage) to vardenafil and sildenafil citrate, but offers an advantage in its long half-life which allows for nonspecific dosing (making timing of sexual activity less of a concern) and even daily dosing at a low dose which provides for a lower incidence of side-effects:
Selective phosphodiesterase type 5 inhibitors (PDE5Is) have revolutionized the treatment of erectile dysfunction (ED) in men. As an on-demand treatment, PDE5Is have excellent efficacy and safety in the treatment of ED due to a broad spectrum of etiologies. Nevertheless, these drugs do have side-effect profiles that are troublesome to some patients, eg, headache, dyspepsia, myalgia, etc. Furthermore, many patients and their partners dislike the necessity of on-demand treatment for ED, citing a desire for greater spontaneity with sexual interactions. In 2008, approximately 10 years after the release of the first commercially available PDE5I, a paradigm shift in the management of ED occurred with the approval of once-daily dose of tadalafil by the US Food and Drug Administration for the management of ED. The prolonged half-life of tadalafil lends itself well to this dosing regimen and conveys the advantage of separating medication from sexual interactions; lower dose therapy also carries the theoretical benefit of lower incidence of side effects. In this study, we review the current state of the art with respect to this new management strategy for ED, highlighting published reports of the efficacy and tolerability of the daily dose tadalafil regimen.
According to Haider et al, “PDE5A inhibition using long-acting tadalafil is an innovative approach to promote stem cell survival and proliferation in the infarcted heart.”
Yuang finds that tadalafil has an improved outcome on relationship issues caused by ED as measured by PAIRS assessment compared to vardenafil and sildenafil:
Sociopsychological factors play a critical role in the pathogenesis of erectile dysfunction (ED). An optimal therapeutic regimen is supposed to bring sociopsychological benefits to both the patients and their partners. Psychological and Interpersonal Relationship Scales (PAIRS) is an effective measure for evaluating the impact of ED on the psychological aspects and interpersonal relationship of the patients and their partners, as well as for predicting the satisfaction of ED patients with the treatment. PAIRS scores on the effects of phosphodiesterase type 5 inhibitors on ED show a significant decrease in sexual activity-related time concerns of the patients treated with tadalafil, as compared with those medicated with sildenafil or vardenafil. This also underlies the preference of the patients and their partners for tadalafil in clinical practice. The drug attribute associated with the decreased time concerns is the long and outstanding efficacy of tadalafil for up to 36 hours.
Tadalafil is successful in treating pulmonary hypertension alone or in concert with other drugs when necessary:
The pathology of pulmonary arterial hypertension (PAH) is characterized by vascular vasoconstriction, smooth muscle cell proliferation, and thrombosis. Experimental studies have shown the beneficial effect of phosphodiesterase type 5 (PDE-5) inhibitors on pulmonary vascular remodeling and vasodilatation. Randomized clinical trials in monotherapy or combination therapy have been conducted in PAH with sildenafil and tadalafil which significantly improve clinical status, exercise capacity and hemodynamics of PAH patients. Combination therapy of PDE-5 inhibitors with prostacyclin analogs and endothelin receptor antagonists may be helpful in management of PAH. The third PDE-5 inhibitor, vardenafil, is currently being investigated in PAH. Side effects are usually mild and transient and include headache, flushing, nasal congestion, digestive disorders, and myalgia.
 Washington SL, Shindel AW. A once-daily dose of tadalafil for erectile dysfunction: compliance and efficacy. Drug Des Devel Ther. 2010 Sep 7;4:159-71.
 Haider HK, Lee YJ, Jiang S, Ahmad RP, Ryon M Dr, Ashraf M. Phosphodiestrase inhibition with tadalafil provides longer and sustained protection of stem cells. Am J Physiol Heart Circ Physiol. 2010 Sep 10.
 Yuang RQ. [Translated from Chinese: Benefits of tadalafil in sexual activity-related time concerns]. Zhonghua Nan Ke Xue. 2010 Jun;16(6):572-5.
 Kiliçkesmez K, Küçükoğlu MS. [Translated from Turkish: Phosphodiesterase type 5 inhibitors in the treatment of pulmonary arterial hypertension]. Anadolu Kardiyol Derg. 2010 Sep;10 Suppl 2:16-8.
The latter article is intended for educational / informational purposes only. THIS PRODUCT IS INTENDED AS A RESEARCH CHEMICAL ONLY. This designation allows the use of research chemicals strictly for in vitro testing and laboratory experimentation only. Bodily introduction of any kind into humans or animals is strictly forbidden by law.