Heterocyclic antibiotics: aminoglycosides, macrolides. Polypeptide antibiotics, polyenes and antitumor antibiotics. Fluoroquinolones as antibiotic drugs.

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Lecture ?18

• Heterocyclic antibiotics aminoglycosides,
  macrolides. Polypeptide antibiotics, polyenes and
  antitumor antibiotics. Fluoroquinolones as
  antibiotic drugs.
• prepared
  ass. Kozachok S.S.

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Aminoglycosides divided on the following groups

• Strepyomycin (separately , NH2- group is
  substituted)
• Aminoglycosides (kanamycin, neomycin, gentamycin,
  monomycin, amikacin)
• Macrolides (erythromycin, oleandomycin,
  roxitromycin, claritromicin, dirythromycin,
  spiramycin, azitromycin)
• Ansamycin (rifampicin)

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Strepyomycin sulfate (Streptomycini sulfas)
Streptomycin sulfate (UP)

• Bis-N,N-bis(aminoiminomethyl)-4-O-5-deoxy-2
  -O-2-deoxy-2-methylamino)-a-L-glucopyranosyl-3-?
  -formyl- a-L -lyxofuranosyl-D-streptamine
  trisulfate

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• Streptomycin, discovered in 1944 by the American
  scientist Waxman.
• Obtaining. Microbiological synthesis from
  Streptomyces griseus actinomycetes.
• Streptomycin glycoside consists of the aglycone -
  streptydin (1,3-diguanidino-2,4,5,6-tetraoxicycloh
  exane) and sugar part-disaccharide
  streptobiozamine (N-methyl-L-glucosamine and
  L-streptose).

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CHARACTERISTICS

• White powder. Hygroscopic . Very soluble in
  water, practically insoluble in ethanol and
  ether.
• Streptomycin has a basic property according to
  the appearance of the nitrogen containing group
  (two guanidins and one N-methylamino) thats why
  easy creates salts.
• In a weak acidic medium streptomycin is stable,
  but in strong acidic and especially in basic
  medium it easy hydrolyzes on a streptydin and
  streptobiozamine, which decomposes on
  N-methyl-L-glucosamine and L-streptos.

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Identification

• TLC.
• Maltol test is caused by the ability of the
  streptose in a basic medium to convert on a
  maltol according to the dehydratation and
  isomerization. At the iron (III) ions interaction
  in an acidic medium maltol forms the violet
  products
• Maltol
  (a-methyl-ß-oxy-?-piron)

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• Sakaguchi reaction on the remnants of guanidines.
  Formation of a violet-red colour, which
  appearances in a basic medium under the action of
  ?-naphthol and concentrated sodium hypochlorite.
  
• Molish reaction on carbohydrates (streptos).
  After acidic hydrolysis the substance does not
  give reaction with ?-naphthol and concentrated
  sodium hypochlorite in a basic solution. Yellow
  colour.
• It gives the reaction of sulfate.

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• Un pharmacopoeia reaction
• Escaping of ammonia by heating of the substance
  with sodium hydroxide (guanidine residues)
• Weber Reagent (it is oxidized by sodium
  nitroprusside NaFe(CN)5NOK3Fe(CN)6NaOH)
  red colour (guanidine residues)
• Brown colour with basic potassium
  tetraiodomerrcurate (Nernst reagent) and red
  sediment with copper-tartrate reagent Feling
  reagent silver mirror reaction (on aldehyde
  group)
• Condensation with phenols in the presence of
  concentrated sulfuric acid aurine dye
• On the aldehyde group of streptos (with a
  hydrazine, a semicarbazide white sediments).

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Aurine dye red colour
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• Assay
• Microbiological method (UP).
• Photocolorymetry which is based on the Maltol
  test.
• Cerimetry. Titrant Cerium sulfate. Indicator
  iron (III) chloride. Em ?. m./2

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• Storage
• In the dry place.
• Application
• Broad-spectrum antibiotic.
  Antituberculosis drug. At the treatment of
  pneumonia, peritonitis, , gonorrhea, brucellosis.
• Produced in bottles, sealed with rubber
  stoppers with crimped aluminum caps on 0,25, 0,5
  and 1,0 of the active substance in terms of
  streptomycin-base.
• Inject inner muscular 0,5-1,0 g on a day.
• Side effects. Kidney-and oto-toxic,
  respiratory depression, is rapidly developing
  resistance (2-3 days).

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Aminoglycosides

• The general formula
• Characteristic. According to the physical
  properties aminoglycosides antibiotics are
  powders of white, yellow or creams colors,
  hydroscopic. Freely soluble in water and
  practically insoluble or low soluble in the most
  organic solvents. Optically active .

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Kanamycin monosulfate (UP) (Kanamycini
monosulfas)
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• Composition of Kanamycin is aglucone
  2-deoxystreptomine (meso-1,3-diamino-4,5,6-trioxyc
  yclohexan) and two saccharates -
  3-amino-3-deoxy-D-glucose and 6-?mino-6-deoxy-D-gl
  ucose.
• Drug is obtained by the fermentation of
  Streptomyces kanamycetis at 27-29 ?? and ??7,
  the environment that contains starch and soy
  flour. From the environment Kanamycin A, B and C
  is extracted by an ionchangers.The list toxic
  Kanamycin A has, thats why it composes the mass
  of the drug Kanamycin monosulfate (94 ).
• The semi-synthetic analog of Kanamycin is
  amikacin sulfate. Its main difference from
  kanamycin is a present of 4-?mino-L-2-oxybtyl
  radical. Except aglucone 2- deoxy-D-streptamine
  amikacin has 2-deoxy-L-streptamine.

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Amykacin sulfate (Amy??cini sulfas)
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• Neomycin like Kanamycin is a mixture of two
  stereoisomers ? and ?. Aglucone
  2-deoxystreptamine ties three saccharides.
• The drug is obtained from the liquid Streptomyces
  fradiae culture by the carboxylic cation exchange
  resins. In 1949 neomycin was the first obtained
  by Waxman and le Shatelye.
• Monomycin sulfate drug is a mixture of monomycins
  that are produced by Actinomyces circulatus var.
  monomicini. The difference of the monomycin
  chemical structure from neomycin is a present in
  6 position ??2?? group (paramosa) exept
  CH2NH2.
• Gentamycin is similar to kanamycin. It is a
  metabolizing product of Micromonospora purpurea.
  It is a mixture of

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Neomycin sulfate (Neomycini sulfas)
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Monomycin sulfate (Monomycini sulfas)
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Gentamycin sulfate (Gentamycini sulfas)

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Aminoglycosides identification

• Physical constants melting temperature, UV- and
  Proton Nuclear Magnetic Resonanse-spectroscopy,
  TLC, Liquid chromatography.
• Reaction on the aliphatic amino-group of
  Kanamycin monosulfate at the heating with a
  ninhydrin solution observed violet color.
• Melting temperature of Kanamycin picrate.
• They give reaction of sulfate.
• Bials reaction (pentose opening). For the
  identification of Kanamycin monosulfate and
  neomycin sulfate using a color reaction with a
  alcohol solution of an orcyn (methylresorcinol)
  and concentrated hydrochloric acid at the present
  of iron (III) chloride. Solution gets green color.

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• After acidic hydrolysis kanamycin and amikacin
  give the reaction of the reducing saccharides
  (Feling reagent. Nernst, Tolens).
• Amykacin according to the amide group forms color
  complexes with the hard metals salts (reaction
  with cobalt nitrate after sodium hydroxide
  neutralization violet).
• Amikacin at the heating with concentrated mineral
  acids forms from the saccharides
  5-aminomethylfurfural, which gives the colour
  reaction with antron

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• Assay
• Microbiological method (UP).
• Polarimetry (gentamycin sulfate).
• Photocolorimetry.
• Absorption spectroscopy in UV- and visible
  region.
• Storage
• Protection from light.
• Application
• Broad spectrum antibiotics. For the
  treatment of the gastrointestinal tract diseases,
  tuberculosis and infectious skin diseases,
  sepsis, urinary tract infections.

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• Kanamycin monosulfate bottle on 0,5
  and 1,0 g. Inner muscular injection 5-7 days.
  H.d.d. 2 g
• Gentamycin sulfate Solution for
  injection. exports producing. 40 or 80 mg 2,0 ml
  ?10 national (Ukrainian) producing 4 1,0 or 2,0
  ml ?10 cream 0,1 15 ? eye oinment 0,3 5,0 g.
  Average days dose 3 mg/kg, 2-3 times, inner
  muscular injection.
• Amykacin ?? bottle on 0,1 and 0,25
  g. Average days dose 15 mg/kg by 2 times inner
  muscular injections.
• Tergynan vaginal tablets
  (ternidazole, neomycin sulfate, nystatin ,
  prednisolone).
• Side effects Kidney-and oto-toxic action,
  allergy and others.

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Lincomycins

• In medical practical using Lincomycin
  hydrochloride and clindamycin
• Lincomycin hydrochloride (Lyncomycini
  hydrochloridum) (UP)
• Monohydrate methyl-6,8-dideoxy-
• 6-(2S,4R)-1-ethyl-4-propyl-
• pyrrolidinyl-2-carboxamido-
• 1-thio-D-erythro-a-D-galacto-
• octopyranoside hydrochloride

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• Lincomycin hydrochloride used at sepsis,
  staphylococ infections, acute and chronic
  osteomyelitis, purulent skin infections, otitis.
  Externally at purulent diseases of skin and soft
  tissue. Intravenous, inner muscular injection.
  Once dose - 0,5 g, day dose 1,5 g. Capsules on
  0,25 g ?20 solution for injection 30 1,0 or 2,0
  ? 10.
• Contraindications severe liver and kidney
  disease, myasthenia gravis.
• Clindamycin (Dalacin) broad-spectrum ANT.
  Capsule on 150 and 300 mg ? 16 solution for
  injection 150 mg/ml 2,0 or
  4,0 ? 1 vaginal cream and suppositories.

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Macrolides antibiotics

• They contain a lactone ring with 12-17
  carbon atoms, it ties with amino carbohydrates
  (for the amino glycosides type) and neutral
  sugars. Reserve antibiotics.
• Modern classification
• 14 members natural (erythromycin,
  oleandomycin) prodrug (esther and erythromycin
  salts, oleandomycin esthers) semi-synthetic
  (roxithromycin, clarithromycin, dirithromycin,
  josamycin, its active metabolite is 14-hydroxi
  clarithromycin).
• 15 members semi-synthetic (additional nitrogen
  atom azalides - azithromycin (sumamed)
• 16 members natural (spiramycin (rovamycin),
  midecamycin (macropen), semi-synthetic
  (midecamycin acetate (miocamycin).

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• In medical practice the most often used
• Erythromycin phosphate (altrocin S)
• Spiramycin (rovamycin, rovalen)
• Midecamycin(macropen)
• Roxithromycin (roxide, rulid, renicin, rovenal)
• Josamycin (wilprafen )
• Clarithromycin (fromilid , klabax , clacid )
• Azithromycin (Azitrox, Azithro, Zithromax ,
  sumamed ).

• It is now known about 100 macrolide
  antibiotics, the general formula

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Erythromycin(Erythromycinum)
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• Erythromycin is produced from a strain of the
  actinomycete Saccharopolyspora erythraea..
• Erythromycin consists of aglucone erythrolide
  (14-members lactone) and two sugars cladynos
  (3-methyl-3-methoxy-2,6-didedeoxyhexopyranos) and
  deamine (pycrocin, 3- dimethylamino-4,6-
  didedeoxyhexopyranos). Cladynos splits off at the
  interaction with eryehromycin with 0,5 ? ??l
  solution at the cold, and deamine at the
  interaction with eryehromycin with 6 ? ??l
  solution.
• Erythromycin white crystalline substance bitter
  on taste, melting at 190-193 ??, soluble in
  water, freely soluble in ethanol, acetone and
  chloroform.
• With concentrated H2SO4 gives red-brown color,
  and with concentrated HCl orange color that
  transfers into red after puple.
• 1mg of Erythromycin equals 1000 U.A.

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Oleandomycin phosphateOleandomycini phosphas
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Azithromycin (UP) (Azithromycinum)

• Identification IR-spectroscopy
• Assay
• Liquid chromotography

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• Erythromycin is available in enteric-coated
  tablets, slow-release capsules, oral suspensions,
  ophthalmic solutions, ointments, gels, and
  injections.
• Erythromycin tablets on 100000 and 250000 U.A.
  are used for the treatment of pneumonia,
  scarlatina, angina, anthrax etc. For the local
  using at the infection wounds, burns, trophic
  exulcerates, trachoma, bedsores there is
  recommended an ointment Unguentum erythromycini,
  its 1 g contains 10000 U.A.
• Other antibiotics-macrolides are produced as oral
  medicine forms.
• Macrolide antibiotics are used by prescription,
  determine the sensitivity to this group and
  compared with a sensitivity to other groups as
  well as macrolides quickly develop resistance. If
  antibiotics- macrolides are not used
  continuously, the sensitivity of the
  microorganism to them restored.

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Ansamycins antibiotics

• At the core of the structure is aromatic ring,
  coupled with macrocyclic aliphatic chain, called
  Anza-chain. Aliphatic chain does not contain the
  lactone bonds that are typical for macrolides
  antibiotics, it attaches to the core with the
  amide nitrogen atom.
• The following antibiotics belong to ansamycins
  rifampicin, streptovaricin, tolipomicin,
  galomicin, naphtomicin etc.
• Rifampicin and its semi-synthetic analogs are
  used as medicines 3-(4-methyl-1-piperazinyliminom
  ethyl)- rifampicin , rifabutin , rifampitin and
  the combine drugs.
• Ansamycins antibiotics have broud-spectrum
  action and a high efficiency. Prescribed in the
  cases where other antibiotics are ineffective.
  Used for the treatment of all forms of
  tuberculosis, diseases of gastrointestinal tract
  and pyogenic infections on the doses of 0,3-0,45
  g.
• Microorganisms very quick develop the resistance
  to Rifampicin.

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Rifampicins general formula and radicals
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Polyenes antibiotics

• Polyenes antibiotics have an antifungal activity.
  They are mixtures of substances that are very
  close in structure. Molecule of each component
  consists of the aglycone having macrocyclic
  structure, and amino sugars, connected by a
  glycosidic bond. Polyene structure of the
  aglycone has 6-7 double bonds and 35-40 carbon
  atoms.
• In medical practice the following medicines used
  nystatin, Amphotericin ?, levorin, trihmicin,
  candocidin, mycoheptin
• , griseofulvin , amphoglucamin , etc.
• Application. For the treatment of candidiasis,
  dermatomycoses, trichomoniasis, fungal diseases.
• The modern antifungal medicines imidazole
  derivatives Ketoconazole (1-2), Oxiconazole
  (mifungar), Intraconazole (orungal) allylamine
  Terbinafine (lamisil, terbisil, exifine) triazol
  derivatives Fluconazole (diflucan, micosyst).

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Nystatin Nystatinumtablets, ointment ,
suppository

• Griseofulvin
• Griseofulvinum
• tablets, liniment

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Nystatin (Nystatinum) (UP)

• Identification
• UV-, ?R-spectroscopy
• Substance concentrated hydrochloric acid
  brown color
• Substance concentrated sulfuric acid brown
  color that transfers into a violet
• Liquid chromatography.
• Assay
• Microbiological method
• For a substance that is designed to produce
  medicines for oral use must be withstanded the
  test on abnormal toxicity.

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Amphotericin ?Amphotericinum Bamphomin,
amphotret, fungizome, fungizone

• Yellow or yellow-orange powder. Hygroscopic .
  Sensitive to the action of light and temperature.
  It is easy inactivated in acid and base medium.
• Application - systemic and deep mycoses
  (blastomycosis, criptococoz), mold mycosis,
  chronic and granulomatous forms of candidiasis.
• Intravenous injection, inhalation and topical
  (cream). Used only in hospital settings a highly
  toxic drug, capable to cumulation, kidney
  throtoxic, causes the reducing of potassium
  quantity in a blood.

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Polypeptides antibiotics

• Polypeptides antibiotics according to their
  amino acids composition, chemical structure are
  different from other peptides (proteins). Amino
  acids associate in a cycle.
• In medical practice the following medicines used
  Gramicidin S, Polymyxin M .
• Storage. Protection from light.
• Application. According to a high toxicty of
  polypeptides the are applied outside, at the
  internal using they cause hemolysis of
  erythrocytes. At the heavy septic and
  gastroenteric diseases (as enemas), when other
  antibiotics are uneffective, for washing of
  purulent wounds, ulcers, bedsores, rinse of
  throat.
• Gramicidin S has the spermocidic action (as
  paste).
• Gramidin (tablet fro resorb) Gramicidin S 1,5
  mg and lidocaine h/ch 10 mg.
• Sofradex (drops eye/ears) gramicidin 0,05 mg,
  neomycin 5,0 mg, Dexamethason 0,5 mg.

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Gramicidin S (Gramicidin S)

• Gramicidin S is produced from a bacterial strain
  of the Bacillus brevis, which are in the soil.
  The first it was obtained in USA.

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Antineoplastic antibiotics

• In 1940 actinomycin was obtained by the american
  scientist Waxman, and in 1952 there was
  determined the antineoplastic action of the
  substance.
• Antitumor antibiotics that are used in medical
  practice can be divided into derivatives
• tetracycline (doxorubicin hydrochloride)
• Aurelic acid (olivomycin)
• Anthracycline (rubomycin)
• Quinoline-5,8-dion (?runeomycin ).
• For the analysis of these drugs physical,
  physical-chemical and chemical methods are used.
• Storage. In a well stoppered container in a dry
  place, protected from light at room temperature.

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Doxorubicin hydrochloride(UP)Doxorubicini
hydrochloridumAdriblastin

• Crystalline orange-red powder. Hygroscopic.
• Identifiction ?R-spectroscopy, gives the
  reaction of chloride ions.
• Assay
• Liquid chromatography

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Olivomycin ?
46

• Rubomycin hydrochloride

• ?runeomycin

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• Olivomycin ? yellow powder with a green tint.
  Hygroscopic. Freely soluble in water, alcohol,
  practically insoluble in chloroform, ether.
  Storage as a toxic substance at below 20 ??.
  Using intravenous injection or local (oinmant).
• ?runeomycin (streptonigrin) brown crystalline
  powder. Practically insoluble in water, alcohol,
  soluble in DMFA, pyridine. Storage as a toxic
  substance at below 20 ?? in a dark place. Using
  intravenous injection as a sodium salt,
  hypodermic injection necrosis.
• Rubomycin h/ch red powder. Hygroscopic. Freely
  soluble in water, alcohol, slightly soluble in
  chloroform. The color of medicine in acidic
  medium red, in basic blue. Storage as a toxic
  substance at below 20 ??. Using intravenous
  injection, inner muscular injection or hypodermic
  injection necrosis.

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6 Fluoroquinolones

• Antibiotics of a 4-quinoline
  derivatives, which in the 6-th position contain
  Fluorine atom, and in the 7-th position -
  piperazine cycle.
• Their precursors such as derivatives of
  quinoline and naphtiridin, are started to use in
  60 years of ?? century. The first representative
  of this class is nalidyxone acid (nevigramon,
  negram) and its analogs is a pipem?dine acid
  (pipemidine, palin, urosept, pimidel). These
  drugs are characterized primarily by the activity
  to gram-negative microorganisms, the rapid
  development of resistance to these antibiotics
  causing their using only for infectious diseases
  of the urinary tract.
• Nalidyxone acid
• (belongs to naphtiridines)

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• Fluoroquinolones began to be introduced
  into medical practice in 80 years of the last
  century. Introduction of fluorine atoms in the
  molecule of quinoline derivatives and naphtiridin
  leds to a group of drugs with fundamentally new
  pharmacological properties. Fluoroquinolones are
  a highly active antimicrobial compounds, which
  are used at severe infections of the different
  etiology and localization (respiratory tract
  infections, skin and soft tissues, bones and
  joints, gastrointestinal tract, postoperative
  infections, other chronic inflammatory
  processes).            The mechanism of
  fluoroquinolones action they affect on the
  metabolism of bacterial DNA by inhibiting the
  enzyme in bacterial cells, DNA gyrase, which
  controls the structure and function of DNA.
  Inhibition of DNA gyrase leads to destruction of
  the bacteria (bactericidal effect). Antibacterial
  activity of quinolones is also connected with the
  effect on RNA synthesis of bacteria and bacterial
  proteins, the stability of membranes and other
  vital processes of the bacterial cells.

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• Quinolones have a high effect on
  aerobic gram-negative bacteria and have little
  effect on anaerobic bacteria. They are rapidly
  absorbed from the gastrointestinal tract and are
  effective at the inside administration.          
    Quinolones inhibit the oxidazing enzymes of
  liver and can increase the effects of drugs
  (increase the side effects of theophylline).     
         The quinolones activity increases when
  administered in their molecules of two
  (lomefloxacin) or three (hemafloxacin) fluorine
  atoms.            Replacement of the ethyl
  radical in norfloxacin on cyclopropyl leads to
  the increasing of the substances activity
  (ciprofloxacin) by 3-8 times.            Some
  drugs of this group after extensive clinical
  using have been banned because of serious side
  effects.

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Fluoroquinolones classification

• The first generation
• Pefloxacin (Abactal, Unikpef, Peflox-400)
• Norfloxacin (Norbactin, Negaflox, Nalicin,
  Norilet, Renor) is the active metabolite of
  pefloxacin
• The second generation
• Ciprofloxacin (Ciprinol, Ciprobay, Cyprohexal,
  Cyprolet, Cyfran, Ciprom, Cipronat)
• Ofloxacin (Zinocin, Oflohexal, Ofloxin, Geoflox,
  Zanocin, Zoflox, Tarivil,)
• Lomefloxacin (Lomaley, Maxacvin, lomflox, Oxacin)
• The third generation
• Levofloxacin (Locsof, Tavanic, Leflox) left
  rotation isomer of ofloxacin
• Moxifloxacin (Avelox)
• Gatifloxacin (Zicvin, Terbis)
• Sparfloxacin (Omniflox).

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• Norfloxacin
• Norfloxacinum
• 1-ethyl-6-fluor-1,4-dihydro-4-?x?-7-(1-piperaziny
  l)-3-quinolinecarboxylic acid

• Ofloxacin
• Ofloxacinum
• () 3-methyl- 7-?xo-9-fluor-10-(4-methyl-1-
  piperazinyl)-2,3-dihydro-7?-pirido-1,4-benzoxazine
  -6- carboxylic acid

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• Ciprofloxacin h/ch (UP 1.2)
• Ciprofloxacini hydrochloridum
• 1-cyclopropyl-6-fluorine-4-?xo-7-(piperazin-1-yl)-
  1,4-dihydro-quinoline-3-carboxylic acid
• hydrochloride

• Lomefloxacin
• Lomefloxacinum
• 1-ethyl-6,8-difluorine-7-(3-methyl-1-
  piperazinyl)-4-?xo-1,4-dihydro-3-quinolinecarboxyl
  ic acid

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• Fluoroquinolones characters
• Pale yellow crystalline powder,
  norfloxacin and ciprofloxacin - hygroscopic. Very
  slightly or practically insoluble in water,
  soluble in alcohol and acetone. Norfloxacin is a
  photosensitive. Chlorides of ofloxacin and
  ciprofloxacin are soluble in water and
  practically insoluble in alcohol, acetone and
  methylene chloride. Fluoroquinolones
  identification
• IR, UV spectroscopy, TLC.
• Heterocyclic nitrogen atom is determined by
  Dragendorffs reagent, picric acid.Oxo-group is
  identified by the reactions of the formation of
  oximes precipitation (reaction with
  hydroxylamine), thiosemicarbazone (reaction with
  thiosemicarbazide) phenylhydrazone (reaction with
  phenylhydrazine).

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• Chlorides containing salts give the reaction of
  chloride.
• Formation of the chelate complexes of a dark-red
  color with Fe3 ions
• For the determining of fluorine atom the
  mineralization is carried out in order to obtain
  the F- ion, a) after pre-mineralization with a
  mixture for sintering. The residue was dissolved
  at pH 4,0-5,0, to add a solution of calcium
  chloride, observed opalescence (precipitate
  CaF2) 2F- Ca2 ? CaF2?

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• b) After the combustion with oxygen in the
  presence of hydrogen peroxide. Fluorides are
  formed discolor red solution of iron (III)
  thiocyanate
• Fe(SCN)6 6F- ? FeF63- 3(SCN)-
• b) after the mineralization of the substance
  under the influence of molten sodium metal.
  Fluorides destroy the zirconium-alizarin red
  complex, according to that extract a free
  alizarin is a yellow color
• Extracted at this case a white precipitate
  zirconium (IV) fluoride is dissolved at the same
  time in excess of fluoride with the formation of
  a colorless anion ZrF62-.

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Assay

• 1. Acidimetry in a non-aqueous medium, a direct
  titration. ???.m.
• 2. Hydrogen chloride salts are determined by a
  liquid chromatography .
• Storage
• Protection from light.
• Side effects
• Fluoroquinolones cause photosensibilization
  (sensitivity to light), so we can not at the time
  of acceptance of this group of drugs irradiate
  with UV-and sunlight.Accumulation in the
  skeletal system - can not use for children under
  15 years old, pregnant, during lactation.

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• Producing
• Pefloxacin tabl. on 04 g ampulla on 5 ml
  (0,4g).
• Norfloxacin and Lomefloxacin tabl. on 0,4 g.
• Ofloxacin tabl on 0,2 g.
• Ciprofloxacin tabl. on 0,25 g 0,5 g 0,75 g
  0,2 solution for infusion on 50, 100 ml 1
  solution for injection ?mpulla 10 ml. Eye-ear
  drops 0,3. Cifran S? ciprofloxacin 500 mg
  tinidazole 600 mg.
• Levofloxacin tabl. 0,25 g 0,5g ?5 solution
  for infusion 0,5 g on 100 ml ?1.
• Moxifloxacin tabl. 0,4 g ?5 solution for
  infusion 0,4 g on 250 ml ?1.
• Gatifloxacin tabl. 0,2 and 0,4 g ?10 solution
  for infusion 0,4 g on 200 ml ?1.
• Sparfloxacin - tabl. 0,2 g ?10.

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Thanx for attention