Sildenafil citrate is a potential oral therapy for treatment of Erectile Dysfunction(ED).

MOA
This Prescription (Rx) drug is a phosphodiesterase enzyme (PDE5) inhibitor. This enzyme is responsible for the degradation cyclic guanosine monophosphate (cGMP) produced in reaction to sexual stimulation. The more cGMP is available, the more durable the erection. It inhibits the PDE5 enzyme, preserving cGMP levels, therefore aiding erection viability and durability Erection of the penis is caused by the filling of the penis with blood. Filling occurs because the blood vessels that bring blood to the penis increase in size and deliver more blood to the penis and at the same time, the blood vessels that take blood away from the penis decrease in size and remove less blood from the penis.

Sexual stimulation that leads to an erection causes the production and release of nitric oxide in the corpora cavernosa of the penis. The nitric oxide causes an enzyme guanylate cyclase, to produce cyclic guanosine monophosphate (cGMP). It is the cGMP that is primarily responsible for increasing and decreasing the size of the blood vessels carrying blood to and from the penis, respectively, and causing the erection. When the cGMP is destroyed by enzyme phosphodiesterase-5, the blood vessels return to their normal size, blood leaves the penis, and the erection ends. It prevents phosphodiesterase-5 from destroying cGMP so that cGMP stays around longer. The persistence of cGMP leads to a more prolonged engorgement of the penis with blood. It relaxes muscles and increases blood flow to particular areas of the body.

PHARMACOKINETICS
Absorption: It is readily absorbed from the bloodstream and the bioavailability is about 40%.
Distribution: It is widely distributed in protein bound form (96% bound to plasma protein) mostly to tissues.
Metabolism: It is metabolized in the liver by an enzyme known as CYP3A4 and others to produce active N-Desmethyl derivatives.
Excretion: It is primarily excreted in the feces (80%) and small amount in the urine.

ADVERSE EFFECTS
1.Facial flushing
2. Headaches
3. Stomach upset
4. Diarrhea
5. Flu-like symptoms
6. Nausea
7. Back pain
8. Muscle aches
9. Low blood pressure
10. Blurred vision
11. Abnormal ejaculation
12. Prolonged erections
13. Sweating
14. General ill feeling
15. Irregular heartbeat
16. Swelling in hands, ankles, or feet
17. Shortness of breath
18. Lightheadedness
19. Fainting

In pre-existing heart disease:
1. Chest pain
2. Heart attacks
3. Death
4. Strokes
5. Palpitations and increased heart rate
6. Vision changes

CONTRAINDICATIONS
1. Hypersensitivity to this drug
2. Patients on nitrate therapy
3. Patients taking a adrenergic receptor antagonist

SPECIAL PRECAUTION
1. Do not take this drugs more than once a day
2. Contact doctor if erection is painful or lasts longer than 4 hours
3. Heart disease
4. Recent history a heart attack (within the past 90 days)
5. Recent history of stroke or congestive heart failure (within the past 6 months)
6. Angina
7. Hypotension
8. Hypertension
9. Liver disease
10. Kidney disease
11. Sickle cell anemia
12. Multiple myeloma
13. Leukemia
14. Haemophilia
15. Stomach ulcer
16. Retinitis pigmentosa
17. Peyronie`s disease (physical deformity of the penis)
18. Diabetes
19. High cholesterol
20. Pre-existing eye problems
21. One who smoke or are over 50 years old

PREGNENCY
Contraindicated

BREAST FEEDING
Contraindicated

ELDERLY
Use with caution

CHILDREN
Contraindicated
NEONATES: Contraindicated

INTERACTIONS
Non-specific beta-blockers, loop and potassium-sparing diuretics enhance efficacy of this drug. Concomitant administration of sildenafil 100mg and amlodipine 5 or 10mg in hypertensive patients led to a mean additional blood pressure reduction of 8mm Hg systolic and 7mm Hg diastolic. Cytochrome P450 inhibitors like erythromycin, ketoconazole, itraconazole are likely to reduce sildenafil clearance.

INDICATIONS
Erectile dysfunction

DOSAGES
Adult: 50 mg taken, 1 hour before sexual activity or anywhere from 0.5 - 4 hours before sexual activity. Based on effectiveness and toleration, the dose may be increased to a maximum 100 mg or decreased to 25 mg. The maximum recommended dosing frequency is once per day.