Sildenafil citrate is a potent, competitive phosphodiesterase type 5 isoenzyme inhibitor, it was the first in a class of effective oral treatment for erectile dysfunction(ED) of varying etiologies including erectile dysfunction associated with drugs, diabetes, other general medical conditions and spinal cord injury (Giulinao et al). Sildenafil citrate was initially studied for use in hypertension and angina pectoris but since it induced penile erection to patients who took the drug in clinical trials (ABM), Pfizer decided to market it for erectile dysfunction rather than Angina, and was approved for use for erectile dysfunction by the FDA on March 27th 1998.  Sildenafil popularity with young adults has increased over the years (Peterson, 2001). The availability of sildenafil has changed the view of ED management, as well as increased patient access to disease management resources.(Boyce 2001). A significant portion of the literature describing the use of sildenafil in recreational settings comes from Great Britain. The authors of one British review in 2000 reported that the PDE5 inhibitor was supplied via the Internet, as well as from street sources.(Downie 2000) Opioid abusers were seeking the drug to improve sexual performance that might be adversely affected by long-term opiate use. Healthy menwere also seeking the drug in the belief that it would improve their sexual performance. The perceived risks of obtaining sildenafil via such online sources were assessed in 1999. Ten virtual pharmacies that sold sildenafil pursuant to an online prescription issued by an affiliated physician were assessed for their extent of dispensing the drug despite evident patient contraindications.(Eysenbach et.al1999)  Investigators posed as a 69-year-old obese woman with coronary artery disease and hypertension who complained of having “no orgasm.” Concomitant medications that were listed on the patient’s request form were captopril, pravastatin, atenolol, and erythromycin. One pharmacy offered to supply cimetidine tablets to be used in conjunction with sildenafil, with the explanation that concomitant use would lead to a “56% increase in plasma sildenafil concentrations…increased effectiveness would be noted with the same dose of Viagra taken with 800 mg of cimetidine.”(Eysenbachet al 1999) Three companies provided the requested drug, one of which sent an e-mail message advising the patient to discontinue the use of her other medications when taking sildenafil. Of those that failed to ship the product, two cited importation restrictions, three unknown benefits of the drug in women, and one cardiovascular concerns. The mean purchase cost per tablet was approximately twice that of prescription sildenafil obtained from a U.S. community pharmacy.

Erectile dysfunction is defined as the inability to achieve and sustain an erection of adequate rigidity for satisfactory sexual intercourse during sexual activity of humans. Penile erection is the hydraulic effect of blood entering and being retained in sponge-like bodies within the penis. The process is most often initiated as a result of sexual arousal,when signals are transmitted from the brain to nerves in the penis. The most important organic causes are cardiovascular disease,diabetes , neurological problems(for example,trauma from prostatectomy surgery), hormonal insufficiency (hypogonadism) and the drug side effects.

Psychological impotence is where erection or penetration fails due to thoughts or feeling (psychological reasons) rather than physical impossibility;this is somewhat less frequent but can often be helped. Notably in psychological impotence there is a strong response to placebo treatment. Erectile dysfunction can have severe psychological consequences as it can be tied to relationship difficulties and masculine self-image.

Besides treating the underlying causes such as potassium deficiency or arsenic contamination of drinking water, the first line treatment of erectile dysfunction consist of a trial of PDE5 inhibitors drugs(the first of which was sildenafil ) .In some cases treatment involves prostaglandin tablets in the urethra ,injections into the penis ,a penile prosthesis ,a penis pump or vascular  reconstructive surgery.

Erectile dysfunction affects approximately 10% of men and higher percentages of men of advanced age.(Krenzelok et al 2000). In 1998, the Food and Drug Administration (FDA) approved sildenafil (Viagra®—Pfizer), the first drug in the  phosphodiesterase (PDE) 5 inhibitor class, for the treatment of male erectile dysfunction (ED). As of 2002, the drug was marketed in more than 110 countries, and more than 100 million prescriptions had been issued for the agent.( Padma-Nathan  et al,2002) The availability of sildenafil has changed the view of ED management, as well as increased patient access to disease management resources.( Boyce  et al 2001) Along with the more recently marketed tadalafil (Cialis®—Lilly ICOS) and vardenafil Levitra®—Bayer HealthCare/ GlaxoSmithKline), sildenafil is now considered a first-line agent for treatment of ED, surpassing the use of intracavernosal or intraurethral prostaglandins, oral androgens, and vacuum devices. When used so widely, safety of medications is a particular concern, as even rare adverse effects affect substantial numbers of patients.

Erectile dysfunction is estimated to affect up to 30million men in the United States (Aytac 1999). The disorder is age associated (Goldstein 1998) with estimated prevalence rates of 39 percent among men 40 years old and 67 percent among those 70 years old (Data on file  2005) .


Sildenafil citrate is widely used as an effective and safe oral treatment for erectile dysfunction of various etiologies (Goldstein et al., 1998; Cheitlin et al., 1999; Benchekroun et al., 2003). It is a potent and selective inhibitor of phosphodiesterase type 5 enzymes that acts to break down cyclic guanosine monophosphate (cGMP) (Boolell et al., 1996). The medication amplifies the effect of sexual stimulation by retarding the degradation of this enzyme. Sildenafil has been found effective in several subpopulations of men with erectile dysfunction, including sufferers from diabetes (Basu and Ryder, 2004), hypertension (Feldman et al., 1999), spinal cord injuries (Hultling et al., 2000; Deforge et al., 2006), multiple sclerosis (Fowler et al., 2005), depression (Seidman et al., 2001; Rosen et al., 2004; Tignol et al., 2004; Fava et al., 2006), PTSD (Orr et al., 2006), and schizophrenia (Aviv et al., 2004; Gopalakrishnan et al., 2006), men after resection of the prostate or radical prostatectomy (Nandipati et al., 2006), after renal transplant (Sharma et al., 2006), men on dialysis (Dachille et al., 2006), and men aged 65 years and older (Wagner et al., 2001; Carson, 2004). 

 Psychogenic erectile dysfunction (ED) patients are excellent candidates for sildenafil citrate therapy due to the intact neurovascular pathway. Nevertheless, the drug has been reported to be effective only in about 78% of patients with psychogenic ED (McMahon et al., 2000). It is likely that performance anxiety and sympathetic overtone are the cause of this unresponsiveness to sildenafil citrate during awakening, though data supporting this assumption are lacking (Rosen, 2001). The drug has been found to be effective and well tolerated in men with mild to moderate erectile dysfunction of no clinically identifiable organic cause (Eardley, 2001). 

With the presence of PDE5 in choroidal and retinal vessels sildenafil citrate increase choroidal blood flow and cause vasodilation of the retinal vasculature. The most common symptoms are a blue tinge to vision and an increased sensitivity to light (Kerr and Danesh Meyer, 2009). Adverse effects include headache, visual and retinal disturbances, dizziness and pupil-sparing third nerve palsy (Monastero et al., 2001). There have been reports of non-arteritic anterior ischaemic optic neuropathy and serous macular detachment in users of PDE5 inhibitors; although a causal relationship has not been conclusively shown. Despite the role of cGMP in the production and drainage of aqueous humor these medications do not appear to alter intraocular pressure and are safe in patients with glaucoma. All PDE5 inhibitors weakly inhibit PDE6 located in rod and cone photoreceptors resulting in mild and transient visual symptoms that correlate with plasma concentrations. Psychophysical tests reveal no effect on visual acuity, visual fields or contrast sensitivity; however, some studies show a mild and reversible impairment of blue-green colour discrimination. PDE5 inhibitors transiently alter retinal function on electroretinogram testing but do not appear to be retinotoxic. Despite the role of cyclic nucleotides in tear production there is no detrimental effect on tear film quality. Based on the available evidence PDE5 inhibitors have a good ocular safety profile (Kerr and Danesh-Meyer, 2009).