Chloramphenicol Chemische Eigenschaften,Einsatz,Produktion Methoden
R-Sätze Betriebsanweisung:
R45:Kann Krebs erzeugen.
S-Sätze Betriebsanweisung:
S53:Exposition vermeiden - vor Gebrauch besondere Anweisungen einholen.
S45:Bei Unfall oder Unwohlsein sofort Arzt zuziehen (wenn möglich, dieses Etikett vorzeigen).
Beschreibung
Chloramphenicol was originally produced by fermentation of Streptomyces venezuelae, but its comparatively
simple chemical structure soon resulted in several efficient total chemical syntheses. With two asymmetric
centers, it is one of four diastereomers, only one of which (1R,2R) is significantly active. Because total
synthesis produces a mixture of all four, the unwanted isomers must be removed before use.
Chloramphenicol is a neutral substance that is only moderately soluble in water, because both nitrogen
atoms are nonbasic under physiologic conditions (one is an amide and the other a nitro moiety). It was the
first broad-spectrum oral antibiotic used in the United States and was once very popular. Severe
potential blood dyscrasia has greatly decreased its use in North America. Although its cheapness and
efficiency makes it still very popular in much of the rest of the world where it can often be purchased
over-the-counter without a prescription
Chemische Eigenschaften
Chloramphenicol is a white to grayish-white
or yellowish-white crystalline solid.
Verwenden
Chloramphenicol is unusual nitroaromatic metabolite produced by Streptomyces venezuelae, first published in 1947. Chloramphenicol is a broad spectrum antibiotic with good activity against Gram negative and anaerobic bacteria. Although restricted to ocular use, antibiotic resistance to other classes has refocused attention on this class. Chloramphenicol acts by binding to the 23S sub-unit of the 50S ribosome, inhibiting protein synthesis. Chloramphenicol has been extensively studied with over 35,000 literature citations.
Definition
ChEBI: Chloramphenicol is an organochlorine compound that is dichloro-substituted acetamide containing a nitrobenzene ring, an amide bond and two alcohol functions. It has a role as an antimicrobial agent, an antibacterial drug, a protein synthesis inhibitor, an Escherichia coli metabolite, a Mycoplasma genitalium metabolite and a geroprotector. It is an organochlorine compound, a diol, a C-nitro compound and a carboxamide.
Indications
Resistance to chloramphenicol is usually explained by the presence of a plasmid that
determines the production of chloramphenicol acetyltransferase. This enzyme acetylates
the drug, giving it unable to bind with 50 S subunits of bacterial ribosomes.
Chloramphenicol is a potentially toxic drug and has a few indications for use. It is the drug
of choice for treating typhoid fever, and it is used for treating brain abscesses. Until
recently, it was the drug of choice for therapy of bacterial meningitis in children (in combination with ampicillin). However, third-generation cephalosporins are currently preferred for such purposes. Chloramphenicol is an effective alternative for a number of
infections in situations, where drugs of choice cannot be used for one reason or another.
However, it should never be used for infections that can readily be treated with other
antimicrobial drugs. Synonyms of this drug are levomycetin, amindan, aquamycetin,
chloromycetin, ophthoclor, opulets, leukomycin, and many others.
Weltgesundheitsorganisation (WHO)
Chloramphenicol, an antibiotic isolated from Streptomyces
venezuelae in 1947, first became available for general clinical use in 1948. By 1950
it was evident that its use could cause serious, sometimes fatal, blood dyscrasias.
However, it remains one of the most effective antibiotics for treating invasive
typhoid fever and salmonellosis, some rickettsioses and serious infections caused
by Haemophilus influenzae or anaerobic organisms. This is considered to justify its
retention in the WHO Model List of Essential Drugs.
(Reference: (WHTAC1) The Use of Essential Drugs, 2nd Report of the WHO Expert
Committee, 722, , 1985)
Allgemeine Beschreibung
Synthetic bacteriostatic antibiotic that inhibits the translation of RNA by blocking the peptidyltransferase reaction on ribosomes.
Hazard
Has deleterious and dangerous side effects.
Must conform to FDA labeling requirements. Use
is closely restricted. Probable carcinogen.
Kontakt-Allergie
This broad spectrum phenicol group antibiotic has been
implicated in allergic contact dermatitis. Cross-sensitivity
to thiamphenicol is possible, but not systematic.
Mechanism of action
Chloramphenicol is bacteriostatic by virtue of inhibition of protein biosynthesis in both bacterial and, to a
lesser extent, host ribosomes. Chloramphenicol binds to the 50S subparticle in a region near where the
macrolides and lincosamides bind.
Resistance is mediated by several R-factor enzymes that catalyze acetylation of the secondary and, to some
extent, the primary hydroxyl groups in the aliphatic side chain. These products no longer bind to the
ribosomes and so are inactivated. Escherichi a coli frequently is resistant because of chloramphenicol's lack
of intercellular accumulation.
Sicherheitsprofil
Confirmed human
carcinogen producing leukemia, aplastic
anemia, and other bone marrow changes.
Experimental tumorigenic data. Poison by
intravenous and subcutaneous routes.
Moderately toxic by ingestion and
intraperitoneal routes. Human systemic
effects by an unknown route: changes in
plasma or blood volume, unspecified liver
effects, and hemorrhaging. Experimental
teratogenic and reproductive effects. Human
mutation data reported. An antibiotic. When
heated to decomposition it emits very toxic
fumes of NOx and Cl-. See also other
chloramphenicol entries.
mögliche Exposition
An antibiotic derived from streptomyces venezuelae. A potential danger to those involved in the
manufacture, formulation, and application of this antibiotic
and antifungal agent
Carcinogenicity
Chloramphenicol is reasonably anticipated to be a human carcinogen, based on limited evidence of carcinogenicity from studies in humans.
Environmental Fate
As an antibiotic, chloramphenicol enters the target cells by
facilitated diffusion and binds reversibly to the 50S ribosomalsubunit. This prevents the interaction between peptidyl transferase
and its amino acid substrate, which results in the inhibition
of peptide bond formation. Indeed, it is an inhibitor of
protein synthesis in the bacteria and to a lesser extent, in
eukaryotic cells. Chloramphenicol can also inhibit mitochondrial
protein synthesis in mammalian cells particularly erythropoietic
cells, which are sensitive to the drug.
Stoffwechselwegen
Six metabolites of chloramphenicol are identified,
among which the sulfate conjugate is characterized in
goat urine.
Stoffwechsel
When given orally, it is rapidly and completely absorbed but has a fairly short half-life. It is mainly excreted
in the urine in the form of its metabolites, which are a C-3 glucuronide, and, to a lesser extent, its
deamidation product and the product of dehalogenation and reduction. These metabolites are all inactive.
The aromatic nitro group also is reduced metabolically, and this product can undergo amide hydrolysis. The
reduction of the nitro group, however, does not take place efficiently in humans but, rather, primarily occurs
in the gut by the action of the normal flora. Chloramphenicol potentiates the activity of some other drugs by
inducing liver metabolism. Such agents include anticoagulant coumarins, sulfonamides, oral hypoglycemics,
and phenytoin.
Versand/Shipping
UN3249 Medicine, solid, toxic, n.o.s., Hazard
Class: 6.1; Labels: 6.1-Poisonous materials. UN2811 Toxic
solids, organic, n.o.s., Hazard Class: 6.1; Labels: 6.1-
Poisonous materials, Technical Name Required.
läuterung methode
Purify chloramphenicol by recrystallisation from H2O (solubility is 2.5mg/mL at 25o) or ethylene dichloride as needles or long plates, and by sublimation at high vacuum. It has A 1cm 298 at max 278nm, and it is slightly soluble in H2O (0.25%) and propylene glycol (1.50%) at 25o but is freely soluble in MeOH, EtOH, BuOH, EtOAc and Me2CO. [Relstock et al. J Am Chem Soc 71 2458 1949, Confroulis et al. J Am Chem Soc 71 2463 1949, Long & Troutman J Am Chem Soc 71 2469, 2473 1949, Ehrhart et al. Chem Ber 90 2088 1957, Beilstein 13 IV 2742.]
Inkompatibilitäten
Compounds of the carboxyl group react
with all bases, both inorganic and organic (i.e., amines),
releasing substantial heat, water, and a salt that may be
harmful. Incompatible with arsenic compounds (releases
hydrogen cyanide gas), diazo compounds, dithiocarbamates,
isocyanates, mercaptans, nitrides, sulfides (releasing heat,
toxic, and possibly flammable gases), thiosulfates, and
dithionites (releasing hydrogen sulfate and oxides of sulfur).
Waste disposal
It is inappropriate and possibly
dangerous to the environment to dispose of expired or waste
pharmaceuticals by flushing them down the toilet or discarding them to the trash. Household quantities of expired or
waste pharmaceuticals may be mixed with wet cat litter or
coffee grounds, double-bagged in plastic, discard in trash.
Larger quantities shall carefully take into consideration applicable DEA, EPA, and FDA regulations. If possible return the
pharmaceutical to the manufacturer for proper disposal being
careful to properly label and securely package the material.
Alternatively, the waste pharmaceutical shall be labeled,
securely packaged, and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.
Chloramphenicol Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
