Tadalafil: a new role in Raynaud’s phenomenon?

exposure and protection of exposed skin during cold weather, although helpful, are often inadequate in protection. Pharmacological therapy with vasodilators such as calcium channel blockers or angiotensin II receptor antagonists have variable and moderate efficacy at best. Prostacyclins such as iloprost and its analog epoprostenol have been shown to result in good control of RP episodes, as well as healing of DUs; however, its use is limited by continuous intravenous infusions. Moreover, its half-life is short and hence not suitable for long-term therapy [4]. Oral analogs of prostacyclins lack the efficacy of the intravenous prostacyclins and results have been disappointing [5]. Recent studies with the endothelin-1 antagonist, bosentan, have shown it to prevent new DUs; however, paradoxically healing of the existing DUs was slowed [6]. Thus, there is a need for a drug that is easy to administer, safe and efficacious in the treatment of secondary RP. The phosphodiesterase-5 (PDE5) enzyme degrades cGMP, a molecule responsible for NO-mediated vasodilatation. PDE5 inhibitors, by inhibiting PDE5, increase the levels of cGMP, leading to vasodilatation. In addition, by inhibition of platelet activation it also improves microcirculation [7]. In a double-blind, placebocontrolled crossover trial involving 16 patients, sildenafil was effective in reducing the number of Raynaud’s attacks, as well as their severity. It also increased the capillary blood flow velocity measured by laser Doppler [8]. The short and fast action of sildenafil is ideal for the treatment of erectile dysfunction; however, it may not be suitable for chronic conditions such as RP, where a round-the-clock effect is required. Tadalafil is longer acting (half-life: 17.5 h), more specific for PDE5 and does not have the PDE6 inhibitory property, responsible Raynaud’s phenomenon (RP) is an exaggerated physiological phenomenon defined as episodic cold-triggered ischemic vasospasms of the digital arteries and precapillary arterioles. It can be idiopathic or may be a manifestation of underlying connective tissue diseases (CTDs) such as systemic lupus erythematosus, progressive systemic sclerosis (PSS; scleroderma), mixed connective tissue disease or rheumatoid arthritis. RP associated with CTDs is known as secondary RP [1]. It is more severe and causes tissue ischemia, resulting in digital ulcers (DUs). These DUs are often painful and cause progressive digital shortening with significant impairment of hand function and activities of daily living. DUs are a frequent complication in patients with PSS, with an estimated frequency of 17–30% [2].