Paracetamol

Gefahreninformationscode (GHS)

• Bildanzeige (GHS)

  

• Alarmwort

  Warnung

• Gefahrenhinweise

  H302：Gesundheitsschädlich bei Verschlucken.

• Sicherheit

  P264：Nach Gebrauch gründlich waschen.

  P264：Nach Gebrauch gründlich waschen.

  P270：Bei Gebrauch nicht essen, trinken oder rauchen.

  P301+P312：BEI VERSCHLUCKEN: Bei Unwohlsein GIFTINFORMATIONSZENTRUM/Arzt/... (geeignete Stelle für medizinische Notfallversorgung vom Hersteller/Lieferanten anzugeben) anrufen.

  P501：Inhalt/Behälter ... (Entsorgungsvorschriften vom Hersteller anzugeben) zuführen.

Acetaminophen Chemische Eigenschaften,Einsatz,Produktion Methoden

• ERSCHEINUNGSBILD

  FARBLOSE KRISTALLE ODER KRISTALLINES PULVER

• ARBEITSPLATZGRENZWERTE

  TLV nicht festgelegt.
  MAK nicht festgelegt.
  

• AUFNAHMEWEGE

  Aufnahme in den Körper durch Verschlucken.

• INHALATIONSGEFAHREN

  Eine belästigende Partikelkonzentration in der Luft kann schnell erreicht werden.

• WIRKUNGEN NACH WIEDERHOLTER ODER LANGZEITEXPOSITION

  Möglich sind Auswirkungen auf die Nieren und die Leber mit nachfolgenden Funktionsstörungen nach Verschlucken.

• LECKAGE

  Persönliche Schutzausrüstung: Atemschutzgerät mit Partikelfilter entsprechend der Arbeitsplatzkonzentration des Stoffes. Verschüttetes Material in Behältern sammeln; falls erforderlich durch Anfeuchten Staubentwicklung verhindern. NICHT in die Umwelt gelangen lassen.

• R-Sätze Betriebsanweisung:

  R22:Gesundheitsschädlich beim Verschlucken.
  R36/37/38:Reizt die Augen, die Atmungsorgane und die Haut.
  R52/53:Schädlich für Wasserorganismen, kann in Gewässern längerfristig schädliche Wirkungen haben.
  R36/38:Reizt die Augen und die Haut.
  R40:Verdacht auf krebserzeugende Wirkung.

• S-Sätze Betriebsanweisung:

  S26:Bei Berührung mit den Augen sofort gründlich mit Wasser abspülen und Arzt konsultieren.
  S36:DE: Bei der Arbeit geeignete Schutzkleidung tragen.
  S61:Freisetzung in die Umwelt vermeiden. Besondere Anweisungen einholen/Sicherheitsdatenblatt zu Rate ziehen.
  S37/39:Bei der Arbeit geeignete Schutzhandschuhe und Schutzbrille/Gesichtsschutz tragen.
  S22:Staub nicht einatmen.

• Beschreibung

  Acetaminophen differs from the nonsteroidal anti-inflammatory agents described in that it is devoid of anti-inflammatory and antirheumatic properties. It was recently shown that acetaminophen, like aspirin, inhibits cyclooxygenase action in the brain and is even stronger than aspirin. On the other hand, the mechanism of analgesic action of acetaminophen is not fully clear, since it acts poorly on peripheral cyclooxygenase.

• Beschreibung

  Acetaminophen is an analgesic and antipyretic compound. Unlike many NSAIDs, which inhibit both COX-1 and COX-2, early studies suggested that acetaminophen is a poor inhibitor of both isoforms. However, it does inhibit COX-2 by 83% and COX-1 by 56% in human blood ex vivo, albeit at a high 1,000 mg dose, with IC₅₀ values of 25.8 and 113.7 μM, respectively. Acetaminophen is enzymatically and non-enzymatically converted to several reactive metabolites that contribute to adverse or indirect effects, including liver injury. At toxic doses, the acetaminophen metabolite N-acetyl-4-benzoquinone imine (NAPQI; ) depletes glutathione reserves in the liver, leading to an accumulation of NAPQI and subsequent hepatocyte necrosis. Acetaminophen decreases glutathione levels and reduces glutathione peroxidase activity in mice when administered at a dose of 250 mg/kg and induces ferroptotic cell death in primary mouse hepatocytes, an effect that can be blocked by the ferroptosis inhibitor ferrostatin-1 . Acetaminophen has analgesic and antipyretic properties in animal models.

• Chemische Eigenschaften

  White Solid

• Originator

  Trigesic ,Squibb ,US ,1950

• Verwenden

  Acetaminophen is widely used as an analgesic and fever-reducing agent. Acetaminophen is designed for moderate analgesia. It is also effective like aspirin and is used in analgesia for headaches (from weak to moderate pain), myalgia, arthralgia, chronic pain, for oncological and post-operational pain, etc.

• Verwenden

  manufacture of azo dyes, photographic chemicals.

• Verwenden

  dispersing agent in liquid scintillation counting

• Verwenden

  Analgesic; antipyretic

• Verwenden

  antiinfectant

• Definition

  ChEBI: Paracetamol is a member of the class of phenols that is 4-aminophenol in which one of the hydrogens attached to the amino group has been replaced by an acetyl group. It has a role as a cyclooxygenase 2 inhibitor, a cyclooxygenase 1 inhibitor, a non-narcotic analgesic, an antipyretic, a non-steroidal anti-inflammatory drug, a cyclooxygenase 3 inhibitor, a xenobiotic, an environmental contaminant, a human blood serum metabolite, a hepatotoxic agent, a ferroptosis inducer and a geroprotector. It is a member of phenols and a member of acetamides. It is functionally related to a 4-aminophenol.

• Indications

  Acetaminophen (Tylenol) is an effective antipyretic and analgesic that is well tolerated at therapeutic doses. It has only weak antiinflammatory activity; thus, it is not useful in the treatment of rheumatoid arthritis and other inflammatory conditions.

• Manufacturing Process

  About 250 ml of a reaction mixture obtained by the electrolytic reduction of nitrobenzene in sulfuric acid solution and containing about 23 grams of paminophenol by assay is neutralized while at a temperature of 60°C to 65°C, to a pH of 4.5 with calcium carbonate. The calcium sulfate precipitate which forms is filtered off, the precipitate washed with hot water at about 65°C and the filtrate and wash water then combined. The solution is then extracted twice with 25 ml portions of benzene and the aqueous phase is treated with 0.5 part by weight, for each part of p-aminophenol present, of activated carbon and the latter filtered off. The activated carbon is regenerated by treatment with hot dilute caustic followed by a hot dilute acid wash, and reused a minimum of three times.
  To the filtrate obtained, there are then added about 0.2 gram of sodium hydrosulfite or sodium sulfite and 15.0 grams of anhydrous sodium acetate in about 27 grams of acetic anhydride at 40°C. The reaction mixture formed is cooled to 8°C to 10°C with stirring and held at this temperature for 60 minutes. A crystalline precipitate of about 27 grams of N-acetyl-paminophenol is obtained melting at 169-171°C. This is equivalent to a yield of 85%.
  In lieu of utilizing calcium carbonate as the neutralizing agent, calcium hydroxide, barium hydroxide, barium chloride or other alkaline earth metal salt or hydroxide forming an insoluble sulfate may be employed.

• Trademarks

  Acephen (G & W); Infants’ Feverall (Actavis); Injectapap (Ortho-McNeil); Neopap (Polymedica); Tylenol (McNeil);Anacin;Crocin.

• Therapeutic Function

  Analgesic, Antipyretic

• Weltgesundheitsorganisation (WHO)

  Paracetamol, a widely used analgesic and antipyretic is known, in case of overdose, to cause liver damage, frequently with fatal outcome. In recommended dosages this risk does not occur. Paracetamol is listed in the WHO Model List of Essential Drugs.

• Synthesis Reference(s)

  The Journal of Organic Chemistry, 27, p. 1092, 1962 DOI: 10.1021/jo01050a543
  Tetrahedron Letters, 22, p. 1257, 1981 DOI: 10.1016/S0040-4039(01)90289-8

• Allgemeine Beschreibung

  Odorless white crystalline solid. Bitter taste. pH (saturated aqueous solution) about 6.

• Air & Water Reaktionen

  Slightly soluble in water.

• Reaktivität anzeigen

  Acetaminophen is sensitive to light. Incompatible with strong oxidizers. 

• Brandgefahr

  Flash point data for Acetaminophen are not available; however, Acetaminophen is probably combustible.

• Flammability and Explosibility

  Non flammable

• Biologische Aktivität

  Cyclooxygenase inhibitor; may be selective for COX-3 (IC 50 values are 460, > 1000 and > 1000 μ M for canine COX-3, and murine COX-1 and COX-2 respectively). Widely used analgesic and antipyretic agent.

• Mechanism of action

  The mechanism of action of paracetamol is not well understood, but it may act in a similar fashion to NSAIDs, with inhibition of cyclo-oxygenase enzymes COX-1 and COX-2 to reduce the phenoxyl radical formation required for COX-1 and 2 activity and prostaglandin synthesis. I t has selectivity for inhibition of prostaglandin synthesis with low concentrations of peroxidases and arachidonic acid, but limited effect at higher concentrations and, therefore, has limited anti-inflammatory effects. Unlike opioids, paracetamol has no well-defined endogenous binding sites. I n some circumstances, it may exhibit a preferential effect on COX-2 inhibition. There is growing evidence of a central antinociceptive effect of paracetamol. It has also been found to prevent prostaglandin production at the cellular transcriptional concentration, independent of COX activity.

• Pharmakokinetik

  Paracetamol is absorbed rapidly from the small intestine after oral administration; peak plasma concentrations are reached after 30–60min. It may also be given rectally and intravenously (either as paracetamol or the prodrug propacetamol). It has good oral bioavailability (70%–90%); rectal absorption is more variable (bioavailability ~50%–80%) with a longer time to reach peak plasma concentration. The plasma half-life is approximately 2–3 h.
  Paracetamol is metabolised by hepatic microsomal enzymes mainly to the glucuronide, sulphate and cysteine conjugates. None of these metabolites is pharmacologically active. Aminimal amount of the metabolite N-acetyl-pamino- benzoquinone imine is normally produced by cytochrome P450– mediated hydroxylation. This reactive toxic metabolite is rendered harmless by conjugation with liver glutathione, then excreted renally as mercapturic derivatives. With larger doses of paracetamol, the rate of formation of the reactive metabolite exceeds that of glutathione conjugation, and the reactive metabolite combines with hepatocellular macromolecules, resulting in cell death and potentially fatal hepatic failure. The formation of this metabolite is increased by drugs inducing cytochrome P450 enzymes, such as barbiturates or carbamazepine.

• Clinical Use

  Acetaminophen is weakly acidic (pKa = 9.51) and synthesized by the acetylation of p-aminophenol. It is weakly bound to plasma proteins (18–25%). Acetaminophen is indicated for use as an antipyretic/analgetic, particularly in those individuals displaying an allergy or sensitivity to aspirin. It does not possess anti-inflammatory activity, but it will produce analgesia in a wide variety of arthritic and musculoskeletal disorders. It is available in various formulations, including suppositories, tablets, capsules, granules, and solutions. The usual adult dose is 325 to 650 mg every 4 to 6 hours. Doses of greater than 2.6 g/day are not recommended for long-term therapy because of potential hepatotoxicity issues. Acetaminophen, unlike aspirin, is stable in aqueous solution, making liquid formulations readily available, a particular advantage in pediatric cases.

• Nebenwirkungen

  Side effects are rare and may include hematological reactions, leucopenia, agranulocytosis and other hypersensitivity reactions. Paracetamol has a narrowtherapeutic dose range and overdosage induces severe liver and renal damage via accumulation of a toxic metabolite, N-acetylbenzoquinoneimine (NABQI). Acetylcysteine or methionine, which increase glutathione conjugation of the metabolite, are used as antidote.

• Synthese

  Acetaminophen, p-acetaminophenol (3.2.80), is synthesized by reacting p-aminophenol with acetic anhydride [76,77].

  

• Environmental Fate

  Although a major part of the ingested dose of acetaminophen is detoxified, a very small proportion is metabolized via the cytochrome P450-mixed function oxidase pathway to a highly reactive n-acetyl-p-benzoquinoneimine (NAPQI). The toxic intermediate NAPQI is normally detoxified by endogenous glutathione to cysteine and mercapturic acid conjugates and excreted in the urine. Recent studies have shown that hepatic P450s, CYP2E1, and to a lesser extent CYP1A2 are responsible for conversion of acetaminophen to NAPQI. In acetaminophen overdose, the amount of NAPQI increases and depletes endogenous glutathione stores. Time course studies have shown that covalent binding of reactive NAPQI and subsequent toxicity occur only after cellular glutathione stores are reduced by 70% or more of normal. Mitochondrial dysfunction and damage can be seen as early as 15 min after a toxic dose in mice, suggesting that this may be a critical to cellular necrosis. The NAPQI is then thought to covalently bind to critical cellular macromolecules in hepatocytes and cause cell death. Recent proteomic studies have identified at least 20 known proteins that are covalently modified by the reactive acetaminophen metabolite. The resulting acetaminophen-cysteine (APAP-CYS) protein adducts can be quantified via a highpressure liquid chromatography coupled with electrochemical detection (HPLC-EC). Hepatic necrosis and inflammation develop as a consequence of hepatocellular death, which results in development of clinical and laboratory findings consistent with liver failure. A similar mechanism is postulated for the renal damage that occurs in some patients following acetaminophen toxicity.

• Stoffwechselwegen

  Acetaminophen (APAP) is metabolized by mice, and nine metabolites are identified in the urine. The main metabolites are APAP-glucuronide and 3-cysteinyl- APAP. Hydroquinone metabolites of S-(2,5- dihydroxyphenyl)cysteine and S-(2,5-dihydroxyphenyl)- N-acetylcysteine result from the benzoquinone metabolite of APAP.

• Stoffwechsel

  acetaminophen is undergoes rapid first-pass metabolism in the GI tract primarily by conjugation reactions, with the O-sulfate conjugate being the primary metabolite in children and the O-glucuronide being the primary metabolite in adults. A minor, but significant, product of both acetaminophen and phenacetin is the N-hydroxyamide produced by a CYP2E1 and CYP3A4.

• Lager

  Store at RT

• läuterung methode

  Recrystallise Paracetamol from water or EtOH. The 3,5-dinitrobenzamide complex gives orange crystals from hot H2O and has m 171.5o. [Beilstein 13 H 460, 13 I 159, 13 II 243, 13 III 1056, 13 IV 1091.]

Acetaminophen Upstream-Materialien And Downstream Produkte

Paracetamol Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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