Pyrazinamid

Gefahreninformationscode (GHS)

• Bildanzeige (GHS)

  

• Alarmwort

  Warnung

• Gefahrenhinweise

  H315：Verursacht Hautreizungen.

  H319：Verursacht schwere Augenreizung.

  H335：Kann die Atemwege reizen.

• Sicherheit

  P261：Einatmen von Staub vermeiden.

  P271：Nur im Freien oder in gut belüfteten Räumen verwenden.

  P280：Schutzhandschuhe/Schutzkleidung/Augenschutz tragen.

Pyrazinamide Chemische Eigenschaften,Einsatz,Produktion Methoden

• R-Sätze Betriebsanweisung:

  R11:Leichtentzündlich.
  R34:Verursacht Verätzungen.

• S-Sätze Betriebsanweisung:

  S22:Staub nicht einatmen.
  S24/25:Berührung mit den Augen und der Haut vermeiden.
  S45:Bei Unfall oder Unwohlsein sofort Arzt zuziehen (wenn möglich, dieses Etikett vorzeigen).
  S36/37/39:Bei der Arbeit geeignete Schutzkleidung,Schutzhandschuhe und Schutzbrille/Gesichtsschutz tragen.
  S26:Bei Berührung mit den Augen sofort gründlich mit Wasser abspülen und Arzt konsultieren.
  S16:Von Zündquellen fernhalten - Nicht rauchen.

• Beschreibung

  Pyrazinamide was synthesized in 1952, and it is the nitrogen-analog of nicotinamide. It exhibits hepatotoxicity. Synonyms of this drug are dexambutol, miambutol, esnbutol, ebutol, and others.

• Chemische Eigenschaften

  Crystalline Solid

• Verwenden

  Pyrazinamide is used therapeutically as an antitubercular agent. Pyrazinamide is used to form polymeric copper complexes, create pyrazine carboxamide scaffolds useful as FXs inhibitors, and as a component of mycobacteria identification kits. It is used to study liver toxicity prevention and mechanisms of resistance .

• Verwenden

  Antibacterial (tuberculostatic)

• Verwenden

  An antibacterial agent used to study liver toxicity prevention

• Indications

  Pyrazinamide is a synthetic analogue of nicotinamide. Its exact mechanism of action is not known, although its target appears to be the mycobacterial fatty acid synthetase involved in mycolic acid biosynthesis. Pyrazinamide requires an acidic environment, such as that found in the phagolysosomes, to express its tuberculocidal activity. Thus, pyrazinamide is highly effective on intracellular mycobacteria. The mycobacterial enzyme pyrazinamidase converts pyrazinamide to pyrazinoic acid, the active form of the drug.A mutation in the gene (pncA) that encodes pyrazinamidase is responsible for drug resistance; resistance can be delayed through the use of drug combination therapy.

• Definition

  ChEBI: Pyrazinecarboxamide is a monocarboxylic acid amide resulting from the formal condensation of the carboxy group of pyrazinoic acid (pyrazine-2-carboxylic acid) with ammonia. A prodrug for pyrazinoic acid, pyrazinecarboxamide is used as part of multidrug regimens for the treatment of tuberculosis. It has a role as an antitubercular agent and a prodrug. It is a member of pyrazines, a N-acylammonia and a monocarboxylic acid amide.

• Antimicrobial activity

  It is principally active against actively metabolizing intracellular bacilli and those in acidic, anoxic inflammatory lesions. Activity against M. tuberculosis is highly pH dependent: at pH 5.6 the MIC is 8–16 mg/L, but it is almost inactive at neutral pH. Other mycobacterial species, including M. bovis, are resistant. Activity requires conversion to pyrazinoic acid by the mycobacterial enzyme pyrazinamidase, encoded for by the pncA gene, which is present in M. tuberculosis but not M. bovis. A few resistant strains lack mutations in pncA, indicating alternative mechanisms for resistance, including defects in transportation of the agent into the bacterial cell.

• Acquired resistance

  Drug resistance is uncommon and cross-resistance to other antituberculosis agents does not occur. Susceptibility testing is technically demanding as it requires very careful control of the pH of the medium, but molecular methods for detection of resistance-conferring mutations are available.

• Allgemeine Beschreibung

  White powder. Sublimes from 318°F.

• Allgemeine Beschreibung

  Pyrazinecarboxamide (PZA) occurs as a white crystalline powder that is sparingly soluble in water and slightly soluble in polar organic solvents. Its antitubercular properties were discovered as a result of an investigation of heterocyclic analogs of nicotinic acid, with which it is isosteric. Pyrazinamide has recently been elevated to first-line status in short-term tuberculosis treatment regimens because of its tuberculocidal activity and comparatively low short-term toxicity. Since pyrazinamide is not active against metabolically inactive tubercle bacilli, it is not considered suitable for long-term therapy. Potential hepatotoxicity also obviates long-term use of the drug. Pyrazinamide is maximally effective in the low pH environment that exists in macrophages (monocytes). Evidence suggests bioactivation of pyrazinamide to pyrazinoic acid by an amidase present in mycobacteria.

• Air & Water Reaktionen

  Water soluble.

• Reaktivität anzeigen

  Pyrazinamide is a carbamate ester. Incompatible with strong acids and bases, and especially incompatible with strong reducing agents such as hydrides. May react with active metals or nitrides to produce flammable gaseous hydrogen. Incompatible with strongly oxidizing acids, peroxides, and hydroperoxides.

• Pharmazeutische Anwendungen

  Like isoniazid, pyrazinamide is a synthetic nicotinamide analog, although its mode of action is quite distinct.

• Biochem/physiol Actions

  The active moiety of pyrazinamide is pyrazinoic acid (POA). POA is thought to disrupt membrane energetics and inhibit membrane transport function at acid pH in Mycobacterium tuberculosis. Iron enhances the antituberculous activity of pyrazinamide . Pyrazinamide and its analogs have been shown to inhibit the activity of purified FAS I.

• Pharmakokinetik

  Oral absorption: >90%
  C_max 20–22 mg/kg oral: 10–50 mg/L after 2 h
  Plasma half-life: c. 9 h
  Plasma protein binding: c. 50%
  It readily crosses the blood–brain barrier, achieving CSF concentrations similar to plasma levels. It is metabolized to pyrazinoic acid in the liver and oxidized to inactive metabolites, which are excreted in the urine, although about 70% of an oral dose is excreted unchanged.

• Pharmakologie

  Pyrazinamide is well absorbed from the GI tract and is widely distributed throughout the body. It penetrates tissues, macrophages, and tuberculous cavities and has excellent activity on the intracellular organisms; its plasma half-life is 9 to 10 hours in patients with normal renal function. The drug and its metabolites are excreted primarily by renal glomerular filtration.

• Clinical Use

  Tuberculosis (a component of the early, intensive phase of short-course therapy)

• Clinical Use

  Pyrazinamide is an essential component of the multidrug short-term therapy of tuberculosis. In combination with isoniazid and rifampin, it is active against the intracellular organisms that may cause relapse.

• Nebenwirkungen

  It is usually well tolerated. Moderate elevations of serum transaminases occur early in treatment. Severe hepatotoxicity is uncommon with standard dosage, except in patients with pre-existing liver disease.
  Its principal metabolite, pyrazinoic acid, inhibits renal excretion of uric acid, but gout is extremely rare. An unrelated arthralgia, notably of the shoulders and responsive to analgesics, also occurs.
  Other side effects include anorexia, nausea, mild flushing of the skin and photosensitization.

• Nebenwirkungen

  Hepatotoxicity is the major concern in 15% of pyrazinamide recipients. It also can inhibit excretion of urates, resulting in hyperuricemia. Nearly all patients taking pyrazinamide develop hyperuricemia and possibly acute gouty arthritis. Other adverse effects include nausea, vomiting, anorexia, drug fever, and malaise. Pyrazinamide is not recommended for use during pregnancy.

• Synthese

  Pyrazinamide, pyrazincarboxamide (34.1.11), is synthesized from quinoxaline (34.1.7) by reacting o-phenylendiamine with glyoxal. Oxidation of this compound with sodium permanganate gives pyrazin-2,3-dicarboxylic acid (34.1.8). Decarboxylation of the resulting product by heating gives pyrazin-2-carboxylic acid (34.1.9). Esterifying the resulting acid with methanol in the presence of hydrogen chloride and further reaction of this ester (34.1.10) with ammonia gives pyrazinamide.

  

  
  Pyrazinamide was synthesized in 1952, and it is the nitrogen-analog of nicotinamide. It exhibits hepatotoxicity. Synonyms of this drug are dexambutol, miambutol, esnbutol, ebutol, and others.

• Arzneimittelwechselwirkung

  Potentially hazardous interactions with other drugs
  Ciclosporin: on limited evidence, pyrazinamide appears to reduce ciclosporin levels.

• Stoffwechsel

  Pyrazinamide is metabolised mainly in the liver by hydrolysis to the major active metabolite pyrazinoic acid, which is subsequently hydroxylated to the major excretory product 5-hydroxypyrazinoic acid.
  It is excreted via the kidneys mainly by glomerular filtration. About 70% of a dose appears in the urine within 24 hours mainly as metabolites.

• läuterung methode

  The amide crystallises from water, EtOH or 1:1 hexane/EtOH in four modifications viz -form, -form, -form and 
  form. [R. & S.rum Acta Cryst 28B 1677 1972, Beilstein 25 III/IV 772.]

Pyrazinamide Upstream-Materialien And Downstream Produkte

Pyrazinamid Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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