Could tadalafil treatment improve circulation and strength in the lower extremities?

Fråga: Could tadalafil treatment improve circulation and strength in the lower extremities?

Sammanfattning: Tadalafil has a vasodilatory effect on smooth muscles in different parts of the body, including blood vessels. It is therefore mechanistically possible that a patient may get better blood supply in the legs (and thus improved strength) from using tadalafil. Furthermore, patients with impaired peripheral circulation, e.g. Raynaud´s phenomenon, have in studies been found to improve after tadalafil treatment, although the mechanism is not fully understood.

Svar: Tadalafil is a selective, reversible inhibitor of cyclic guanosine monophosphate ( cGMP) -specific phosphodiesterase type 5 (PDE5). PDE5 is an enzyme found in the smooth muscle of the corpus cavernosum , vascular and visceral smooth muscle, skeletal muscle, platelets, kidney, lung and cerebellum. Tadalafil is more potent on PDE5 than on other phosphodiesterases. When sexual stimulation releases nitric oxide locally, tadalafil inhibits PDE5, resulting in increased levels of cGMP in the corpus cavernosum. This produces relaxation of smooth muscle and inflow of blood to the penis, producing an erection (1). Tadalafil also has some effect on PDE1, PDE2 and PDE4 (although the effect is >10 000 times higher on PDE5). These enzymes are found in the heart, brain, blood vessels, liver and other organs. Consequently, tadalafil has vasodilatory properties. Hypotension is also a known, less common, side effect of tadalafil (1).

Tadalafil is also used in the treatment of pulmonary hypertension. In pulmonary arterial hypertension the release of nitric oxide by the vascular endothelium is impaired due to reduction of cGMP concentrations in pulmonary vascular smooth muscle. PDE5 is the phosphodiesterase which occurs mostly in the pulmonary vascular smooth muscle. Inhibition of PDE5 by tadalafil increases the concentrations of cGMP, resulting in relaxation of pulmonary vascular smooth muscle cells and vasodilatation of pulmonary vessels (2).

There is no known interaction between diclofenac, paracetamol and tadalafil (3).

A search of the scientific literature revealed a few studies of tadalafil use for improving blood circulation in different patient groups. Among these we found one study of 24 patients with Complex Regional Pain Syndrome (CRPS), a syndrome that usually occurs as a complication of surgery or trauma. CRPS patients either have no apparent nerve injury (type I) or a known nerve injury (type II). Symptoms include persistent pain, impaired sensation, decreased skin temperature, as well as reduced circulation and movement in the lower extremities (4). These symptoms resemble those of the patient with a lumbar herniated disc. The study randomised patients with CRPS type I to received either tadalafil or placebo. There was a significant increase in temperature and reduction of pain in the affected limb in patients who received tadalafil (4). There was also subjective improvement of muscle strength and walking ability in the tadalafil group, (non-significant with objective measurements) (4). Improvement of symptoms has also been found in studies where tadalafil is given to patients with Raynaud´s phenomenon (5). However, increased blood flow in the affected fingers has not been shown, and the mechanism is therefore unknown (6). Studies of healthy athletes have failed to demonstrate any improvement in performance after intake of single dosages of tadalafil (7.8).

In the Swedish adverse reaction registry there are no reports for tadalafil and the patient´s symptoms (9). We recommend that the case is reported as an adverse event to the Swedish medical products agency. Cialis (tadalafil). Lilly. SPC (cited 2014-02-21) Adcirca (tadalafil). Lilly. SPC (cited 2014-02-21) Diklofenak, tadalafil, paracetamol. SFINX interaktionstjänst (cited 2014-02-11) Groeneweg G, Huygen FJ, Niehof SP, Wesseldijk F, Bussmann JB, Schasfoort FC, Stronks DL, Zijlstra FJ. Effect of tadalafil on blood flow, pain, and function in chronic cold complex regional pain syndrome: a randomized controlled trial. BMC Musculoskelet Disord 2008;9:143 Baumhaekel M, Scheffler P, Boehm M. Use of tadalafil in patient with a secondary Raynaud´s phenomenon not responding to sildenafil. Microvasc Res 2005;69(3):178-9 Friedman EA, Harris PA, Wood AJ, Stein CM, Kurnik D. The effects of tadalafil on cold-induced vasoconstriction in patients with Raynaud´s phenomenon. Clin Pharmacol Ther 2007;81(4):503-9 Guidetti L, Emerenziani GP, Gallotta MC, Pigozzi F, Di Luigi L, Baldari C. Effect of tadalafil on anaerobic performance indices in healthy athletes. Br J Sports Med 2008;42(2):130-3 Di Luigi L, Baldari C, Pigozzi F, Emerenziani GP, Gallotta MC, Iellamo F, Ciminelli E, Sgro P, Romanelli F, Lenzi A, Guidetti L. The long-acting phosphodiesterase inhibitor tadalafil does not influence athletes´ VO2max, aerobic, and anaerobic thresholds in normoxia. Int J Sports Med 2008;29(2):110-5 Swedis