What Is Sildneafil?
Silagra, one of the most popular generic drugs used in erectile dysfunction, has sildenafil as its active substance. Sildenafil was discovered in 1990s and became the first oral therapy for medicating the problem of insufficient erectile hardness.
The substance belongs to the class of phosphodiesterase type 5 inhibitors (PDE5i). PDE5i act with a predominantly peripheral mechanism, inhibiting PDE5, the main PDE present at the penile level, involved in the degradation of cyclic guanosine monophosphate (cGMP). As a result, an increase in cGMP, the main intra-cellular messenger, is involved in the relaxation of the penile smooth muscle and therefore in the erection process.
Sildenafil is rapidly absorbed after oral administration and becomes active already 20-30 minutes after intake, which should be timed accordingly, on demand, before sexual intercourse. A meal rich in fat does adversely affects the absorption of sildenafil, causing a delay in efficacy.
Sildenafil requires a dose adjustment for milder forms of liver failure (Child A-B, 1). Finally, no dosage adjustment is required for sildenafil in elderly patients (> 65 years).
Sildenafil is indicated for the use in men with erectile difficulty to restore the ability to achieve and maintain erection sufficient for completing a sexual intercource. Sildenafil is approved as an on-demand therapy of ED.
Under the brand name of Revatio, sildenafil is used to treat PAH (pulmonary arterial hypertension). The substance has multiple other off-label uses that reach beyond the scope of this article.
Pharmacological interactions and contraindications
Due to the specific mechanism of action, PDE5i enhance the hypotensive effects of nitrates, therefore the simultaneous use of both drugs is contraindicated. Usually sildenafil is well tolerated when prescribed to patients using antihypertensive drugs. However, greater caution should be reserved for patients treated with α-blockers (especially doxasosine) and β-blockers that interact with α-adrenergic receptors (labetalol and carvedilol). In particular, in patients who already take an optimal dose of sildenafil, the introduction of an α-lytic must include the prescription of the minor dosage. Similarly in patients on α-blocker therapy, sildenafil should be started at the minimum recommended dose. Minor precautions are, however, to be reserved for patients in chronic α-lithic stabilized treatment.
Potent CYP3A4 inhibitors, such as anti-retroviral, anti-fungal (fluconazole, ketoconazole, itraconazole) and antibiotics (rifampicin and azithromycin) can potentially increase the maximum sildenafil concentration. Therefore in the presence of these drugs it is recommended to use a lower dosage.
Finally, sildenafil is contraindicated in subjects with retinitis pigmentosa, due to the possible interaction with PDE type 6, the main retinal phosphodiesterase involved in the disease.
Sildenafil side effects
PDE5 is only one of the members of a larger family of PDEs, which includes at least eleven members. The side effects of sildenafil depend on interaction with other PDE isoforms and include headache, hot flushes, back pain, visual disturbances, nasal congestion and tachycardia, while the most serious events are extremely rare. Transient visual disturbances are linked to PDE6 inhibition, which is expressed almost exclusively in the retina. Hot flushes, headache, tachycardia and nasal congestion are the consequence of the interaction with PDE1 and PDE4, widely distributed on the vascular and bronchial smooth muscles. Finally, PDE11 appears to be involved in the genesis of low back pain.
Where to buy sildenafil?
Sildenafil is available under a variety of trade mark names, Silagra being one of the most popular drugs with efficacy and safety that have been proven with years of patient use. One can order Silagra online from a certified e-tailer; the cost of Silagra in Web drugstores is much lower than that of sildenafil drugs sold in large pharmacy chains. One of the reasons for this phenomenon of price scissors is that virtual shops skip paying the rent and do not have to have so much workforce on their payroll.