A phosphodiesterase 5 inhibitor.
Sildenafil
Tradename Viagra.
A medication used to treat erectile dysfunction and pulmonary arterial hypertension.
If effective for treating sexual dysfunction in women is unclear.
It is taken by mouth or injection into a vein.
Onset is typically within 20 minutes and lasts for about 2 hours.
Pregnancy category US: B (No risk in non-human studies).
Bioavailability 41%
Protein binding about 96%
Metabolism by Liver: CYP3A4 (major) CYP2C9 (minor).
Metabolites- N-desmethylsildenafil with about 50% potency for PDE5.
Elimination half-life 3–4 hours
Excretion via feces about 80%, urine about 13%.
Common side effects include: headaches, heartburn, and flushed skin.
Rarely, side effects include: prolonged erection that can lead to damage to the penis, vision problems, and hearing loss.
It should not be taken by people on nitrates such as nitroglycerin as this may result in a serious drop in blood pressure.
It acts by blocking phosphodiesterase 5 (PDE5), an enzyme that promotes breakdown of cGMP.
cGMP regulates blood flow in the penis.
It also results in dilation of the blood vessels in the lungs.
ITS primary indication is treatment of erectile dysfunction.
It may help men who experience antidepressant-induced erectile dysfunction.
In pulmonary hypertension it
improves some markers of disease, but it does not appear to affect the risk of death or serious side effects.
Sildenafil and other PDE5 inhibitors are used to alleviate vasospasm and treat severe ischemia and ulcers in fingers and toes for people with secondary Raynaud’s phenomenon.
Adverse effects include: headache, flushing, indigestion, nasal congestion, and impaired vision, photophobia and blurred vision.
Some individuals see everything tinted blue.
It is linked sildenafil use with non-arteritic anterior ischemic optic neuropathy.
Rare serious adverse effects include: prolonged erections, severe hypotension, myocardial infarction, ventricular arrhythmias, stroke, increased intraocular pressure, and sudden hearing loss.
Protease inhibitors inhibit the drug’s metabolism increasing plasma levels of sildenafil and increasing the incidence and severity of side effects.
Erythromycin and cimetidine, both of which can also lead to prolonged plasma half-life levels.
The use of sildenafil and an α1 blocker
at the same time may lead to low blood pressure.
Contraindications include:
Concomitant use of nitrates,
such as:
nitroglycerin
isosorbide mononitrate
isosorbide dinitrate
sodium nitroprusside
Concomitant use of soluble guanylyl cyclase stimulators
It should not be used if sexual activity is inadvisable due to underlying cardiovascular risk factors.
It protects cyclic guanosine monophosphate (cGMP) from degradation by cGMP-specific phosphodiesterase type 5 (PDE5) in the corpus cavernosum.
Nitric oxide (NO) in the corpus cavernosum of the penis binds to guanylate cyclase receptors, which results in increased levels of cGMP, leading to smooth muscle relaxation and vasodilation of the arteries.
Act as a potent and selective inhibitor of cGMP-specific phosphodiesterase type 5 (PDE5), which is responsible for degradation of cGMP in the corpus cavernosum.
It acts as a competitive binding agent of PDE5 in the corpus cavernosum, resulting in more cGMP and better erections.
Without sexual stimulation, it should not cause an erection.
Has a hepatic metabolism using cytochrome p450 enzymes, mainly CYP450 3A4 but also by CYP2C9 (minor route) hepatic isoenzymes.
The major product is N-desmethylated sildenafil, which has an affinity for the PDE receptors, of about 40% of that of sildenafil.
The metabolite is responsible for about 20% of sildenafil’s action.
It is excreted as metabolites predominantly in the feces, about 80% of administered oral dose, and to a lesser extent in the urine, around 13%.
Absorption is reduced with a high-fat meal.
When taken orally it results in an average time to onset of erections of 27 minutes, with a range from 12 to 70 minutes.
Sublingual administration results in an average onset of action of 15 minutes and lasting for an average of 40 minutes.
Mouth spray preparations have a faster onset of action.
Can cause reduction in systolic blood pressure by 8 to 10 mm Hg in clinical trials.
Should not be administered to patients taking nitrate medications.
Headaches, flushing, dyspepsia, nasal congestion, abnormal vision and dizziness are the most common adverse events and are dose related.
Can cause a transient phenomenon with difficulty in discriminating blue-green hues.
Viagara in combination with alpha-1 adrenergic blocking agents can cause profound hypotension.
Should not be taken within 4 hours of any alpha-1 adrenergic antagonist.
To be effective must be taken on an empty stomach at least one hour before sexual activity.
Dose ranges from 25-100 milligrams.