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Sildenafil citrate
Sildenafil citrate, commonly known as Viagra, was originally developed as a treatment for hypertension and angina but was found to cause unwanted side effects of prolonged erections. It works by inhibiting phosphodiesterase type 5, allowing for increased blood flow to cause an erection. It is prescribed for erectile dysfunction and pulmonary hypertension. Common side effects include headache, flushing, and nasal congestion. It should not be taken with nitrates due to the risk of dangerously low blood pressure.
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Sildenafil citrate
- 1. Sildenafil Citrate DR. MANOJKUMAR SINGH 1ST YR PG PHYSICAL MEDICINE AND REHABILITATION PMCH PATNA
- 2. HISTORY- • Pfizer originallysought for a PDE inhibitor that might act as a new antihypertensive and antianginal drug. • Studies were done to see what side effects would come from increased dosages. Volunteers reported back with side effects like head aches, visual problems, and prolongment of penile erections. • According to the British Press, but not Pfizer, Peter Dunn and Albert Wood invented sildenafil.
- 3. Synthesis of Sildenafil •Methylation of 3-propylpyrazole-5-carboylic acid ethyl ester with hot dimethy sulfate. • Hydrolysis with NaOH • Nitration with fuming Nitric Acid • Carboxamide formation with refluxing thionyl chloride/ NH4OH • Reduction of Nitro group to Amino • Acylation with 2-ethoxybenzoyle chloride • Cyclization • Sulfonation to the chlorosulfonyl derivative • Condesation with 1-methylpiperazine
- 4. MEDICAL USES- *ERECTILE DYSFUNCTION *PULMONARYHYPERTENSION * prevention and treatment of high-altitude pulmonary edema associated with altitude sickness. *Antidepressant-associated sexual dysfunction
- 5. NONMEDICAL USE- * Recreationaluse belief that the drug increases libido, improves sexual performance, or permanently increases penis size *Jet lag research * Sports * Analogs Acetildenafil is a structural analog of sildenafil, one of the PDE5 inhibitors found in a number of "herbal" aphrodisiac products sold over-the-counter.
- 6. ERECTILE DYSFUCTION- • Initialdose: 50 mg orally once a day, as needed, 1 hour prior to sexual activity • Maintenance: 25 to 100 mg orally once a day, as needed, 1 hour prior to sexual activity.
- 7. PUL. HYPERTENSION DOSE- •Initial dose: 5 or 20 mg orally three times a day, 4 to 6 hours apart • -Maximum dose: 20 mg orally three times a day • Injection: • -Initial dose: 2.5 or 10 mg IV bolus three times a day.
- 8. MECHANISM OF ACTION- •The mechanism of action of sildenafil involves the protection of 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 (vasodilation) of the intimal cushions of the helicine arteries. This smooth muscle relaxation leads to vasodilation and increased inflow of blood into the spongy tissue of the penis, causing an erection
- 9. CONTRAINDICATION- • When takingnitric oxide donors, organic nitrites and nitrates, such as glyceryl trinitrate (nitroglycerin), sodium nitroprusside, amyl nitrite. • In men for whom sexual intercourse is inadvisable due to cardiovascular risk factors • Severe hepatic impairment (decreased liver function) • Severe impairment in renal function • Hypotension (low blood pressure) • Recent stroke or heart attack • Hereditary degenerative retinal disorders (including genetic disorders of retinal phosphodiesterases)
- 10. • Because sildenafilis a vasodilator (although mainly locally), it needs to be used cautiously because it lowers blood pressure. • Viagra should not be given to patients who are taking nitrates, because nitrates are also a strong vasodilator. The use of both could cause major heart problems. • Also, the use of CYP3A4 or P450 inhibitors (which are the cytochromes responsible for Viagra metabolism), greatly increases the risk of negative side effects. • • Some CYP3A4 inhibitors include Erythromycin, Cimetidine. • One major P450 inhibitor is Ritonavir
- 11. ADVERSE EFFECTS- • HEADACHE •NASAL CONGESTION • DIZZINESS • FLUSHING • FALL IN BP • LOOSE MOTIONS • IMPAIRMENT OF COLOUR DISCRIMINATION
- 12. PHARMACOKINETICS • Sildenafil citrateis rapidly absorbed after oral administration - Total Bioavailability: 40% • Its pharmacokinetics are dose proportional over the recommended range • Sildenafil citrate is metabolized mainly by hepatic metabolism and excreted mainly in the feces.