Sildenafil

Gefahreninformationscode (GHS)

• Bildanzeige (GHS)

  

• Alarmwort

  Achtung

• Gefahrenhinweise

  H225：Flüssigkeit und Dampf leicht entzündbar.

  H370：Schädigt die Organe.

• Sicherheit

  P210：Von Hitze, heißen Oberflächen, Funken, offenen Flammen und anderen Zündquellenarten fernhalten. Nicht rauchen.

  P260：Dampf/Aerosol/Nebel nicht einatmen.

  P280：Schutzhandschuhe/Schutzkleidung/Augenschutz tragen.

  P301+P310：BEI VERSCHLUCKEN: Sofort GIFTINFORMATIONSZENTRUM/Arzt/... (geeignete Stelle für medizinische Notfallversorgung vom Hersteller/Lieferanten anzugeben) anrufen.

  P311：GIFTINFORMATIONSZENTRUM/Arzt anrufen.

Sildenafil Chemische Eigenschaften,Einsatz,Produktion Methoden

• R-Sätze Betriebsanweisung:

  R36/37/38:Reizt die Augen, die Atmungsorgane und die Haut.

• S-Sätze Betriebsanweisung:

  S22:Staub nicht einatmen.
  S24/25:Berührung mit den Augen und der Haut vermeiden.
  S36:DE: Bei der Arbeit geeignete Schutzkleidung tragen.
  S26:Bei Berührung mit den Augen sofort gründlich mit Wasser abspülen und Arzt konsultieren.

• Beschreibung

  Sildenafil was launched as Viagra in the US for the treatment of organic orland psychological male erectile dysfunction (ED). It is an orally bioavailable pyrazolopyrimidinone derivative structurally related to zaprinast, with vasodilating and potential anti-inflammatory activities. Upon oral administration, sildenafil selectively targets and inhibits cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5), thereby inhibiting the PDE5-mediated degradation of cGMP found in smooth muscle and increasing cGMP availability. This results in prolonged smooth muscle relaxation in the corpus cavernosum of the penis, thereby causing vasodilation, blood engorgement and a prolonged penile erection.

• Chemische Eigenschaften

  Sildenafil citrate is a white to off-white crystalline powder soluble in DMF, acetic acid and slightly soluble in methanol. Solubility of sildenafil citrate is pH dependent and it decreases with increase of pH. pH ranges between 3.7 and 3.8 and the pKa from 8.2 to 9.6.

• Originator

  Pfizer (UK)

• Verwenden

  Sildenafil is a phosphodiesterase-5 (PDE5) inhibitor. It is indicated for the treatment of erectile dysfunction (ED). Sildenafil is an orally active selective type 5 cGMP phosphodiesterase inhibitor.

• synthetische

  The first synthetic route of sildenafil accomplished the preparation of its pyrazole derivative from ethyl 3-butyrylpyruvate and hydrazine hydrate in acetic acid, followed by the selective N-methylation of the pyrazole ring with dimethyl sulfate. The carboxylic acid was obtained after alkaline hydrolysis was subjected to nitration, followed by treatment with concentrated ammonium hydroxide solution to sequentially deliver the corresponding carboxamide derivative. The nitro group of the mentioned carboxamide derivative was then reduced to an amino group by stannous chloride/hydrochloric acid in ethanol, leading to the formation of the main 4-aminopyrazole structure. Mild amidation of the aminopyrazole derivative by the appropriate benzoyl chloride was performed, followed by cyclization mediated by hydrogen peroxide under basic environment which led to the formation of pyrimidinone heterocycle ring. Chloro-suIphonylation of pyrimidinone derivative imposed selectively on the 50 position of the phenyl ring, led to the aroyl sulfonyl chloride derivative which was then coupled with N-methylpiperazine to afford sildenafil.
  
  synthesis of sildenafil

• Definition

  ChEBI: Sildenafil is a pyrazolo[4,3-d]pyrimidin-7-one having a methyl substituent at the 1-position, a propyl substituent at the 3-position and a 2-ethoxy-5-[(4-methylpiperazin-1-yl)sulfonyl]phenyl group at the 5-position. It has a role as a vasodilator agent and an EC 3.1.4.35 (3',5'-cyclic-GMP phosphodiesterase) inhibitor. It is a pyrazolopyrimidine, a member of piperazines and a sulfonamide.

• Indications

  Sildenafil (Viagra) is a selective inhibitor of PD-5, an enzyme that inactivates cGMP. Vardenifil (Levitra) is a particularly effective inhibitor of PD-5. It has a shorter onset of action and can be used in smaller doses than sildenafil. Other drugs used in the treatment of ED exert their effects through other biochemical pathways, both central and peripheral.

• Trademarks

  Viagra (Pfizer);Segurex.

• Therapeutic Function

  Vasodilator

• Mechanism of action

  Sildenafil is readily absorbed after oral administration and reaches peak plasma levels after about an hour. It undergoes hepatic metabolism and has a terminal half-life of about 4 hours.An initial dose of 50 mg is taken about an hour prior to sexual activity to induce penile erection.

• Clinical Use

  Sildenafil is a selective inhibitor of cGMP-specific PD-5 and therefore inhibits the degradation of cGMP. PD-5, the predominant type in the corpus cavernosum, also is present in other tissues (e.g., lungs, platelets, and eye). The selective inhibition of this enzyme facilitates the release of nitric oxide and smooth muscle relaxation of the corpus cavernosa. Sildenafil enhances erection by augmenting nitric oxide–mediated relaxation pathways. It has been suggested that sildenafil’s mechanism of action is due to cross-talk between cGMP- and cAMPdependent transduction pathways within the cavernous muscles.

• Nebenwirkungen

  Orally administered sildenafil is an effective and well-tolerated treatment for men with ED, including those with diabetes mellitus. It has also been used for so-called salvage therapy in men who do not respond to intracorporeal injections of other agents. Headache is a common side effect, as are flushing and rhinitis.More serious side effects include definite or suspected myocardial infarctions and cardiac arrest.

• Enzyminhibitor

  Sildenafil is rapidly absorbed and peaks in concentration (127–560 ng/mL) after 0.5 to 2.0 hours, displaying a half-life of 3 to 4 hours for the full therapeutic dose (25–100 mg). It is 96% bound to plasma proteins and is metabolized by the liver CYP3A4. The metabolite N-desmethylsildenafil possesses approximately 50% of the activity of the parent molecule.

• Arzneimittelwechselwirkung

  Potentially hazardous interactions with other drugs
  Alpha-blockers: enhanced hypotensive effect - avoid for 4 hours after sildenafil.
  Antibacterials: concentration increased by clarithromycin and erythromycin - consider reducing sildenafil dose or frequency.
  Antifungals: concentration increased by ketoconazole - reduce initial dose for ED and avoid for PAH; concentration increased by itraconazole - reduce initial dose of sildenafil.
  Antivirals: ritonavir significantly increases sildenafil concentration - avoid; concentration possibly increased by saquinavir, fosamprenavir and indinavir - reduce dose of sildenafil; concentration reduced by etravirine; side effects possibly increased by atazanavir; increased risk of ventricular arrhythmias with saquinavir - avoid; avoid with telaprevir; avoid with tipranavir for PAH.
  Cobicistat: concentration of sildenafil possibly increased - reduce initial dose for ED and avoid for PAH.
  Nicorandil: enhanced hypotensive effect - avoid.
  Nitrates: enhanced hypotensive effect - absolutely contraindicated.
  Riociguat: enhanced hypotensive effect - avoid.

• Stoffwechsel

  In vitro metabolism studies for sildenafil have shown that the primary metabolite, N-desmethylsildenafil, and the minor metabolite, oxidative opening of the piperazine ring, are mediated by CYP3A4, CYP2C9, CYP2C19, and CYP2D6. The estimated relative contributions to clearance were 79% for CYP3A4, 20% for CYP2C9, and less than 2% for CYP2C19 and CYP2D6. These results demonstrate that CYP3A4 is the primary cytochrome mediating N-demethylation and that drugs inhibiting CYP3A4 likely impair sildenafil biotransformation and clearance. The pharmacokinetics of radiolabeled sildenafil were consistent with rapid absorption, first-pass metabolism, and primarily fecal elimination of N-demethylated metabolites. The absorption of sildenafil following oral administration was rapid (~92%), whereas the oral bioavailability was approximately 38% as a result of first-pass metabolism.

Sildenafil Upstream-Materialien And Downstream Produkte

Sildenafil Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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