Sildenafil (Erectile Dysfunction)
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Sildenafil (Viagra) belongs to a group of medicines called phosphodiesterase type 5 (PDE 5) inhibitors. It works by helping to relax the blood vessels in the penis.
Sildenafil is a treatment for men with erectile dysfunction, sometimes known as impotence. This is when a man cannot get, or keep a hard, erect penis suitable for sexual activity.
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 MECHANISM OF ACTION
The physiological mechanism responsible for erection of the penis involves the release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. Nitric oxide then activates the enzyme guanylate cyclase, which results in increased levels of cyclic guanosine monophosphate (cGMP), producing smooth muscle relaxation in the corpus cavernosum and allowing inflow of blood.
Phosphodiesterase type 5 (PDE5) is the enzyme responsible for degradation of cGMP
Sildenafil, is an inhibitor of phosphodiesterase type 5 (PDE5). When sexual stimulation causes local release of NO, inhibition of PDE5 by sildenafil causes increased levels of cGMP in the corpus cavernosum, resulting in smooth muscle relaxation and inflow of blood to the corpus cavernosum. Sildenafil at recommended doses has no effect in the absence of sexual stimulation.
Sildenafil is rapidly absorbed and acts within 30 min to 1 hour and the effects last for about 4 hours; it has a short plasma half-life of approximately 4 hours.
- Sildenafil is indicated in adult men with erectile dysfunction, which is the inability to achieve or maintain a penile erection sufficient for satisfactory sexual performance. (Viagra)
- Treatment of pulmonary arterial hypertension (See Revatio)
Off-label uses of Viagra:
- To enhance sexual performance in people not diagnosed with erectile dysfunction
- Raynaud's phenomenon, a vasospastic disorder causing discoloration of the fingers, toes, and occasionally other areas.
- Vaginal sildenafil is useful in increasing endometrial thickness and achieving pregnancy in women receiving ovulation induction therapy.
- Altitude sickness: Sildenafil has been shown to be useful for the prevention of High-Altitude Pulmonary Edema (HAPE). HAPE may occur when climbing mountains, fluid accumulates in the lungs and makes breathing difficult. Researchers found that the drug not only prevented this type of edema but also increased the ability to exercise at altitude.
The recommended dose of Sildenafil is 50 mg taken as needed about one hour before sexual activity. the onset of activity may be delayed if taken with food. The dose may be increased to a maximum of 100 mg or decreased to 25 mg depending on the effectiveness and side effects.
Patients with liver problems or severe kidney problems should start treatment with the 25 mg dose.
The maximum recommended dosing frequency is one tablet per day.
Sildenafil metabolism is principally mediated by CYP3A4 (major route) and CYP2C9 (minor route)
- Sildenafil potentiate the hypotensive effects of nitrates and its administration in patients who use nitric oxide donors or nitrates in any form is therefore contraindicated.
- In men for whom sexual activity is inadvisable (e.g.Patients with severe cardiovascular disorders such as unstable angina or severe cardiac failure)
- Severe hepatic impairment
- Hypotension (blood pressure <90/50 mmHg),
- Recent history of stroke or myocardial infarction
- Known hereditary degenerative retinal disorders such as retinitis pigmentosa
- Sildenafil has systemic vasodilatory properties and may augment the blood pressure lowering effect of anti-hypertensive medications.
- Prolonged erections greater than 4 hours and priapism (painful erections greater than 6 hours in duration) have been reported infrequently
- CYP3A4 inhibitors: With the exception of ritonavir for which co-administration with sildenafil is not advised, a starting dose of 25 mg should be considered in patients receiving concomitant treatment with CYP3A4 inhibitors (e.g. atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin)
- Alpha-blockers: Caution is advised when Phosphodiesterase Type 5 (PDE5) inhibitors are co-administered with alpha-blockers (e.g. Alfuzosin, Doxazosin, Tamsulosin...). In some patients, concomitant use of these two drug classes can lower blood pressure significantly leading to symptomatic hypotension. Patients should be stable on alpha-blocker therapy prior to initiating and should initiate Sildenafil at the lowest dose (25 mg)
 PREGNANCY AND LACTATION
Pregnancy Category B (US). Sildenafil (Viagra) is not indicated for use in women.
 SIDE EFFECTS
The most commonly adverse reactions are:
- Visual disorders
- Nasal congestion
- Visual colour distortion (Sildenafil is only about 10-fold as potent for PDE5 compared to PDE6, an enzyme found in the retina which is involved in the phototransduction pathway of the retina. This lower selectivity is thought to be the basis for abnormalities related to color vision)
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