Pharmacotherapy of male erectile dysfunction with sildenafil
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abstract
Male erectile dysfunction (MED) is a common sexual disorder influenced by psychological, organic, physical, endocrine and neurovascular factors. Parasympathetic stimulation activates cholinergic receptors resulting in increased production of nitric oxide and vasoactive peptides which increase the cyclic guanosine monophosphate (cGMP) and thereby increasing vascular smooth muscle relaxation and vasodilation of corpus cavernosum. This causes rigid penile erection sufficient for sexual intercourse. However, in erectile dysfunction, there is an inability to achieve or maintain a penile erection. One of the current approaches in therapies for MED includes elevating levels of cGMP using phosphodiesterase (PDE) inhibitors. Sildenafil is the first orally active, potent and competitive inhibitor of type-5 cGMP-specific PDE enzyme that has been recently approved for the treatment of MED. Sildenafil is a synthetic methylpiperazine derivative that selectively inhibits PDE in human corpus cavernosum. Sildenafil has demonstrated its effectiveness in erectile dysfunction in several preclinical and clinical studies. It is well- tolerated (50-100 mg/day, p.o.) and safe agent for erectile dysfunction in patients with diabetes, traumatic spinal cord injury, psychological causes and physiological disorders. Adverse events reported include transient headache, dyspepsia, flushing, diarrhea and visual disturbance. The discovery of sildenafil has not only resulted in a huge market for drugs, but also unfolded the pathophysiology of erectile dysfunction. However, more controlled clinical studies are needed to establish the safety of sildenafil in patients with different age groups.
