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J Toxicol Clin Toxicol. 2000;38(6):645-51.
Sildenafil: clinical toxicology profile.
Krenzelok EP.
Children's Hospital of Pittsburgh, Department of Pharmacy, University of Pittsburgh, Pennsylvania, USA. krenzehplink.chp.edu
BACKGROUND: Sildenafil is indicated for the treatment of male erectile dysfunction. It has been used successfully in males to remediate problems associated with impaired neural and/or hemodynamic response to sexual stimulation. Sildenafil is a cyclic guanosine-specific phosphodiesterase type 5 inhibitor that prevents the metabolism of cyclic guanosine which produces arterial smooth muscle relaxation within the corpora cavernosa of the penis and ultimately enhances penile tumescence. Inherent to its pharmacology, sildenafil produces mild decreases in systolic and diastolic blood pressure and an array of minimal side effects due to the inhibition of other types of phosphodiesterase. Drug interactions involving the concurrent use of sildenafil with nitrates and nitrites are well-documented and can produce profound hypotension leading to decreased coronary perfusion and myocardial infarction. Sildenafil is metabolized primarily by cytochrome P450 3A4, and inhibitors of this enzyme (e.g., macrolide antibiotics, antifungals, cimetidine) may increase sildenafil serum concentrations and lead to enhanced pharmacological and toxicological effects. The antiviral protease inhibitors have been demonstrated to inhibit first-pass metabolism and increase serum concentrations and half-life of sildenafil. DISCUSSION: Previously unpublished data from the American Association of Poison Control Centers Toxic Exposure Surveillance System indicate that unintentional pediatric exposures to sildenafil are unlikely to be associated with adverse effects. Adults may experience effects similar to those identified in the preclinical trials. This may be due to larger doses in this population, preexisting cardiovascular pathology, or the concomitant use of contraindicated medications.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11185972&dopt=Abstract
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