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Your assignment is to prepare and submit a paper on pharmacology and mechanism of action of sildenafil citrate.
Your assignment is to prepare and submit a paper on pharmacology and mechanism of action of sildenafil citrate. Sildenafil citrate is widely used to treat erectile dysfunction in men and to increase the libido, and the action of the drug in this area is well documented (Carlson, 1997). However, the drug is also known to increase the fertility of women, affecting the embryo growth, and the drug vasodilates the fetoplacental circulation through a cGMP-dependent mechanism that shows increased responsiveness to NO (Maharaj, et al. 2009).
Sildenafil citrate was released commercially in 1998 by Pfizer Inc. to treat male erectile dysfunction. The chemical formula is 5-[2-ethoxy-5-(4-methyl piperazine-1-ylsulfonyl) phenyl] -1-methyl-3-propyl-6, 7-dihydro-1-H-pyrazolyl [4-3-d] pyrimidine-7-one. The molecular formula is C22H30N6045 (Umrani and Goyal, 1999).
The mechanism of action in men is very documented in a number of studies (Boolell, et al. 1996. Goldstein, I. and Feldmen, 1997. Israel, 1998. Steers, 1998. RxList, 2014.).The drug does not directly cause an erection, the action is towards the response to sexual stimulation. It acts by releasing nitric oxide - NO in the penile muscle called corpus cavernosum when sexual stimulation is given. NO activates guanylate cyclase enzyme and protects cyclic guanosine monophosphate - cGMP from undergoing degradation by the cGMP-specific phosphodiesterase type 5 - PDE5, formed in the corpus cavernosum of the penis. NO on the penile muscle, bonds with the receptors of guanylate cyclase, and this increases the concentration of cGMP. The next action is vasodilation of the helicine arteries, and increases the blood flow to the spongy tissue of the corpus cavernosum, thereby causing an erection. This molecular structure is similar to that of cGMP, forming a PDE5 binding agent, and allows for longer and sustained erections. However, the drug cannot act passively and is only activated when there is sufficient sexual stimulation. The liver breaks down Sildenafil through hepatic metabolism by means of the cytochrome p450 enzymes that are formed by the hepatic isoenzymes, CYP4503A4, and CYP2C9 that metabolize the enzymes to create N-demethylated sildenafil.
