Carbamazepin

Gefahreninformationscode (GHS)

• Bildanzeige (GHS)

  

• Alarmwort

  Achtung

• Gefahrenhinweise

  H302：Gesundheitsschädlich bei Verschlucken.

  H317：Kann allergische Hautreaktionen verursachen.

  H336：Kann Schläfrigkeit und Benommenheit verursachen.

• Sicherheit

  P201：Vor Gebrauch besondere Anweisungen einholen.

  P280：Schutzhandschuhe/Schutzkleidung/Augenschutz tragen.

  P302+P352：BEI BERÜHRUNG MIT DER HAUT: Mit viel Wasser/... (Hersteller kann, falls zweckmäßig, ein Reinigungsmittel angeben oder, wenn Wasser eindeutig ungeeignet ist, ein alternatives Mittel empfehlen) waschen.

  P308+P313：BEI Exposition oder falls betroffen: Ärztlichen Rat einholen/ärztliche Hilfe hinzuziehen.

Carbamazepine Chemische Eigenschaften,Einsatz,Produktion Methoden

• R-Sätze Betriebsanweisung:

  R42/43:Sensibilisierung durch Einatmen und Hautkontakt möglich.
  R22:Gesundheitsschädlich beim Verschlucken.
  R20/21/22:Gesundheitsschädlich beim Einatmen,Verschlucken und Berührung mit der Haut.

• S-Sätze Betriebsanweisung:

  S37:Geeignete Schutzhandschuhe tragen.
  S24:Berührung mit der Haut vermeiden.
  S22:Staub nicht einatmen.
  S36/37/39:Bei der Arbeit geeignete Schutzkleidung,Schutzhandschuhe und Schutzbrille/Gesichtsschutz tragen.
  S36:DE: Bei der Arbeit geeignete Schutzkleidung tragen.

• Beschreibung

  Carbamazepine is a synthetic iminostilbene derivative structurally similar to imipramine, a tricyclic antidepressant. While unrelated structurally, carbamazepine shares a similar therapeutic action with phenytoin. Carbamazepine was first discovered in 1953 by Swiss chemist Walter Schindler. Throughout the 1960s, antimuscarinic was used and marketed for trigeminal neuralgia and as an anticonvulsant. By the 1970s, it was being used as a mood stabilizer for patients with bipolar disorder.

• Chemische Eigenschaften

  White or off-white crystalline powder. Soluble in ethanol, acetone, propylene glycol, insoluble in water. Odorless and tasteless.

• Originator

  Tegretol,Geigy,W. Germany,1964

• Verwenden

  Used in treatment of pain associated with trigeminal neuralgia. Anticonvulsant

• Verwenden

  Carbamazepine (CBZ) is a first generation anticonvulsant and mood stabilizing compound that has been used as a therapeutic in the context of neuropathic pain, epilepsy, and affective disorders. It exerts its effects by blocking voltage-gated sodium channels (IC50 = 640 μM), making fewer of these channels available to subsequently open, which leads to decreased high-frequency repetitive firing of action potentials. The estimated IC50 values for inhibition of Nav1.7-, Nav1.3-, and Nav1.8-type channels by CBZ following prolonged inactivation have been reported as 406, 900, and 138 μM, respectively. CBZ can also inhibit L-type Ca2+ channels (IC50 = 974 μM) and has been shown to potentiate GABAA receptors (IC50 >3 mM).

• Definition

  ChEBI: Carbamazepine is a dibenzoazepine that is 5H-dibenzo[b,f]azepine carrying a carbamoyl substituent at the azepine nitrogen, used as an anticonvulsant. It has a role as an anticonvulsant, an EC 3.5.1.98 (histone deacetylase) inhibitor, a mitogen, a glutamate transporter activator, an antimanic drug, an analgesic, a non-narcotic analgesic, an environmental contaminant, a xenobiotic, a drug allergen and a sodium channel blocker. It is a dibenzoazepine and a member of ureas.

• Manufacturing Process

  19.3 parts of iminostilbene are dispersed in 100 parts by volume of toluene. Phosgene is then introduced whereupon the temperature of the reaction mixture rises to 70°C. While boiling under reflux, further phosgene is introduced until all the iminostilbene has dissolved and the hydrogen chloride development is complete. The reaction mixture is then cooled and the 5- chlorocarbonyl iminostilbene which has crystallized out is filtered off under suction. It melts at 168° to 169°C.
  12.8 parts of 5-chlorocarbonyl iminostilbene are dispersed in 128 parts by volume of absolute ethanol and ammonia gas is introduced for three hours into this mixture while stirring at boiling temperature. The reaction is complete after this time; the reaction mixture is cooled and the crystals which precipitate are filtered off under suction. The ammonium chloride is washed from the crystals with water and the residue is recrystallized first from absolute ethanol and then from benzene. 5-carbamyl iminostilbene is obtained which melts at 204° to 206°C.

• Trademarks

  Carbatrol (Shire); Epitol (Teva); Equetro (Shire); Tegretol (Novartis); Teril (Taro).

• Therapeutic Function

  Analgesic, Anticonvulsant

• Biologische Funktion

  Carbamazepine has become a major drug in the treatment of seizure disorders. It has high efficacy, is well tolerated by most patients, and exhibits fewer long-term side effects than other drugs.
  Oral absorption of carbamazepine is quite slow and often erratic. Its half-life is reported to vary from 12 to 60 hours in humans.The development of blood level assays has markedly improved the success of therapy with this drug, since serum concentration is only partially dose related. Carbamazepine is metabolized in the liver, and there is evidence that its continued administration leads to hepatic enzyme induction. Carbamazepine- 10,11-epoxide is a pharmacologically active metabolite with significant anticonvulsant effects of its own.

• Allgemeine Beschreibung

  Certified pharmaceutical secondary standards for application in quality control provide pharma laboratories and manufacturers with a convenient and cost-effective alternative to pharmacopeia primary standards.
  Carbamazepine is a tricyclic lipophilic compound, with mild anticholinergic activity. It is widely used as an antiepileptic drug for the treatment of simple and complex partial tonic-clonic seizures.

• Biochem/physiol Actions

  Anticonvulsant; ligand for the GABAA receptor benzodiazepine modulatory site. Sodium channel inhibitor.

• Mechanism of action

  In animals, the profile of antiseizure properties for CBZ is similar to that of phenytoin. CBZ is effective in the maximal electroshock (MES) test (electrically induced seizure test) but is ineffective against pentylenetetrazole-induced seizures. It is not effective for absence or myoclonic seizures and, indeed, may exacerbate their onset. Like phenytoin, CBZ acts on voltage-dependent sodium channels to prevent the spread of seizures. CBZ depresses synaptic transmission in the reticular activating system, thalamus, and limbic structures. In a double-blind, crossover study in patients whose seizures were not controlled completely by combinations of AED, CBZ was equal in efficacy to phenobarbital and phenytoin in controlling seizure frequency, and side effects were minimal.

• Pharmakokinetik

  Following the administration of an oral dose, CBZ is slowly absorbed, with the attainment of peak concentration from immediate-release tablets in 4 to 5 hours and from extended-release tablets in 3 to 12 hours. The normal half-life averages between 12 and 17 hours; however, because of autoinduction, the half-life may range from 8 to 29 hours. The half-life for CBZ-10,11-epoxide is 5 to 8 hours. Therapeutic plasma concentrations range from 4 to 12 μg/mL (in adults) and may require a month to achieve a stable therapeutic concentration for the desired antiseizure effect because of induction of hepatic metabolizing enzymes.
  CBZ is principally metabolized by CYP3A4 its 10,11-epoxide, with CYP2C8 and CYP1A2 having minor roles. CBZ epoxide is hydrolyzed to inactive 10,11-dihydroxy CBZ by epoxide hydrolase. CBZ epoxide is active and appears to be more toxic than CBZ. However, CBZ not only induces CYP3A4 activity but also its own metabolism (an autoinducer) as well as UGT and the increased formation of glucuronide metabolites. Like phenytoin, CBZ has been associated with a number of toxic effects, including a drug-induced hypersensitivity syndrome. Although phenytoin-induced hypersensitivity reactions are relatively rare events, they can be potentially life-threatening. Although the mechanism by which CBZ induces hypersensitivity reactions has not been well characterized, recent studies have suggested that the immune reaction may be caused, at least in part, by its metabolism into chemically reactive metabolites, which may be the critical step in the formation of protein adducts and subsequent immune responses.

• Clinical Use

  Carbamazepine is an effective agent for the treatment of partial seizures and generalized tonic–clonic seizures; its use is contraindicated in absence epilepsy. Carbamazepine is also useful in the treatment of trigeminal neuralgia and is an effective agent for the treatment of bipolar disorders.

• Nebenwirkungen

  Like most of the agents that block sodium channels, side effects associated with carbamazepine administration involve the central nervous system (CNS). Drowsiness is the most common side effect, followed by nausea, headache, dizziness, incoordination, vertigo, and diplopia.These effects occur particularly when the drug is first taken, but tolerance often develops over a few weeks. There appears to be little risk of cognitive impairment with carbamazepine.
  Carbamazepine causes a variety of rashes and other allergic reactions including fever, hepatosplenomegaly, and lymphadenopathy, but the incidence of serious hypersensitivity reactions is rare. Systemic lupus erythematosus can occur, but discontinuation of the drug leads to eventual disappearance of the symptoms. Idiosyncratic hematological reactions to carbamazepine may occur, but serious blood dyscrasias are rare. Carbamazepine has been shown to exacerbate or precipitate seizures in some patients, particularly those exhibiting generalized atypical absences.
  While the number of side effects may be fairly large, most are not serious and can be managed. Severe adverse reactions occur less commonly than with phenytoin and similar drugs. The overall incidence of toxicity seems to be fairly low at usual therapeutic doses. Most of the drug interactions with carbamazepine are related to its effects on microsomal drug metabolism. Carbamazepine can induce its own metabolism (autoinduction) after prolonged administration, decreasing its clearance rate, half-life, and serum concentrations. The possibility of autoinduction requires the clinician to reevaluate the patient’s blood levels after a month of carbamazepine therapy. The autoinduction phenomenon is over in about a month.
  Carbamazepine also can induce the enzymes that metabolize other anticonvulsant drugs, including phenytoin, primidone, phenobarbital, valproic acid, clonazepam, and ethosuximide, and metabolism of other drugs the patient may be taking. Similarly, other drugs may induce metabolism of carbamazepine; the end result is the same as for autoinduction, and the dose of carbamazepine must be readjusted. A common drug–drug interaction is between carbamazepine and the macrolide antibiotics erythromycin and troleandomycin. After a few days of antibiotic therapy, symptoms of carbamazepine toxicity develop; this is readily reversible if either the antibiotic or carbamazepine is discontinued.

• Synthese

  Carbamazepine, 5H-dibenz[b,f]azepine-5-carboxamide (9.5.2), is synthesized by reacting 5H-dibenz[b,f]azepine and phosgene, which forms 5-chlorcarboxy- 5H-dibenz-[b,f]azepine (9.5.1), and its subsequent reaction with ammonia to give the desired carbamazepine (9.5.2) [16]. An alternative method of synthesis is the direct reaction of 5H-dibenz[b,f]azepine with potassium cyanate [17].

  

• Arzneimittelwechselwirkung

  Carbamazepine may be affected by other medicines, such as blood clot preventers and antibiotics. It may also interact with medications used to treat bipolar disorder. Some medications can decrease carbamazepine levels and others can increase carbamazepine levels. Valproate may increase carbamazepine-10,11-epoxide levels, while carbamazepine may decrease the levels of various medications including corticosteroids, clozapine, and lamotrigine. It is important to inform your doctor if you are taking any of these medicines to avoid potential interactions and to ensure carbamazepine works effectively.
  Taking carbamazepine with other medicines and herbal supplements
  What drug-drug interactions should you be vigilant for when someone is prescribed carbamazepine
  https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c13bc0b8-7900-4ef4-98ed-e1315a08d95d

• Environmental Fate

  Carbamazepine is both an important anticonvulsant in therapeutic doses and a powerful proconvulsant in overdose. The therapeutic anticonvulsant mechanism is primarily related to blockade of presynaptic voltage-gated sodium channels. Blockade of the sodium channels is believed to inhibit the release of synaptic glutamate and possibly other neurotransmitters. Carbamazepine is also a powerful inhibitor of the muscarinic and nicotinic acetylcholine receptors, N-methyl-Daspartate (NMDA) receptors, and the central nervous system (CNS) adenosine receptors. In addition, carbamazepine is structurally related to the cyclic antidepressant imipramine and in massive overdose, it may affect cardiac sodium channels.

• Stoffwechsel

  Carbamazepine is metabolised in the liver by cytochrome P450 3A4, where the epoxide pathway of biotransformation yields the 10, 11-transdiol derivative and its glucuronide as the main metabolites. 9-Hydroxy-methyl-10-carbamoyl acridan is a minor metabolite related to this pathway. Other important biotransformation pathways for carbamazepine lead to various monohydroxylated compounds, as well as to the N-glucuronide of carbamazepine produced by UGT2B7. After administration of a single oral dose of 400 mg carbamazepine, 72% is excreted in the urine and 28% in the faeces. In the urine, about 2% of the dose is recovered as unchanged drug and about 1% as the pharmacologically active 10,11-epoxide metabolite.

• Lager

  Store at +4°C

• Toxicity evaluation

  Environmental exposure occurs via direct release into water or via vaporization into the air. It is susceptible to photolysis and is thought to have a half-life of roughly 63 days in lake water in vitro. However, when dissolved and exposed to direct photolysis, it has a half-life of approximately 1 day.

Carbamazepine Upstream-Materialien And Downstream Produkte

Carbamazepin Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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