Transcript Lecture_18.Antibiotics_of_the_heterocyclic_and_other_rows

Lecture №18
Heterocyclic antibiotics: aminoglycosides,
macrolides. Polypeptide antibiotics,
polyenes and antitumor antibiotics.
Fluoroquinolones as antibiotic drugs.
prepared ass. Kozachok S.S.
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)
Strepyomycin sulfate (Streptomycini
sulfas) Streptomycin sulfate* (UP)
Bis-[N,N’-bis(aminoiminomethyl)-4-O-[5-deoxy-2-O-[2deoxy-2-methylamino)-α-L-glucopyranosyl]-3-С-formylα-L -lyxofuranosyl]-D-streptamine] trisulfate
• 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-diguanidino2,4,5,6-tetraoxicyclohexane) and sugar partdisaccharide streptobiozamine (N-methyl-Lglucosamine and L-streptose).
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) that’s
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.
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:
O
O
O
CHO
NaOH, t0C
CH3
OH
CH3
OH
OH
OH
O
Fe3+/3
O
FeNH4(SO4)2
H2SO4
CH3
O
Maltol (α-methyl-β-oxy-γ-piron)
•
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.
O
Br
OH
N
C
N
H
R
NH
•
•
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.
• Un pharmacopoeia reaction :
a) Escaping of ammonia by heating of the substance
with sodium hydroxide (guanidine residues);
b) Weber Reagent (it is oxidized by sodium nitroprusside
Na[Fe(CN)5NO]+K3[Fe(CN)6]+NaOH) – red colour
(guanidine residues);
c) Brown colour with basic potassium tetraiodomerrcurate
(Nernst reagent) and red sediment with copper-tartrate
reagent– Feling reagent; “silver mirror” reaction (on
aldehyde group);
d) Condensation with phenols in the presence of
concentrated sulfuric acid – aurine dye;
e) On the aldehyde group of streptos (with a hydrazine, a
semicarbazide – white sediments).
Aurine dye red
colour
Assay
• Microbiological method (UP).
• Photocolorymetry which is based on the Maltol test.
• Cerimetry. Titrant – Cerium sulfate. Indicator – iron (III)
chloride. Em = М. m./2
O
O
O
OH
- 2e
+ 2H+
1
CH3
CH3
O
O
Ce4++ 1e
Ce3+
2
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).
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
Kanamycin monosulfate (UP)
(Kanamycini monosulfas)
• Composition of Kanamycin is aglucone 2deoxystreptomine (meso-1,3-diamino-4,5,6trioxycyclohexan) and two saccharates - 3-amino-3-deoxyD-glucose and 6-аmino-6-deoxy-D-glucose.
• Drug is obtained by the fermentation of Streptomyces
kanamycetis at 27-29 оС and рН=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, that’s 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-аmino-L-2-oxybtyl radical. Except aglucone 2- deoxy-Dstreptamine amikacin has 2-deoxy-L-streptamine.
Amykacin sulfate
(Amyсаcini sulfas)
NH2
CH2NH2
OH
O
CH2OH
OH
O
OH
OH
O
O
* 2 H2SO4
OH
OH
OH
HN
NH2
C
O
C
H
C
H2
C
H2
NH2
• Neomycin like Kanamycin is a mixture of two stereoisomers В and С.
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 – СН2ОН group (paramosa) exept – CH2NH2.
• Gentamycin is similar to kanamycin. It is a metabolizing product of
Micromonospora purpurea. It is a mixture of:
Neomycin sulfate
(Neomycini sulfas)
H2C
Monomycin sulfate
(Monomycini sulfas)
OH
O
OH
OH
NH2
NH2
OH
H2N
CH2
O
NH2
O
HO
CH2
*nH2SO4
O
O
OH
O
OH
NH2
OH
Gentamycin sulfate
(Gentamycini sulfas)
Aminoglycoside’s 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.
Bial’s 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.
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 metal’s 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:
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.
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 г; eye
oinment 0,3% 5,0 g. Average day’s dose – 3 mg/kg, 2-3
times, inner muscular injection.
Amykacin – КМ – bottle on 0,1 and 0,25 g. Average
day’s 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.
Lincomycins
In medical practical using Lincomycin hydrochloride and
clindamycin
Lincomycin hydrochloride (Lyncomycini
hydrochloridum) (UP)
CH3
CH3
N
C3H7
C
Monohydrate methyl-6,8-dideoxyO
6-[(2S,4R)-1-ethyl-4-propylpyrrolidinyl-2-carboxamido]1-thio-D-erythro-α-D-galactooctopyranoside hydrochloride
HO
C
H
N
H
C
H
O
OH
* HCl * H2O
OH
SCH3
OH
• 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.
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
1. 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).
2. 15 – members: semi-synthetic (additional nitrogen
atom – azalides - azithromycin (sumamed)
3. 16 – members: natural (spiramycin (rovamycin),
midecamycin (macropen), semi-synthetic
(midecamycin acetate (miocamycin).
In medical practice the
most often used :
It is now known about 100
macrolide antibiotics, the
1. Erythromycin phosphate
general formula:
2.
3.
4.
5.
6.
7.
(altrocin –S);
Spiramycin (rovamycin,
rovalen);
Midecamycin(macropen);
Roxithromycin (roxide, rulid,
renicin, rovenal);
Josamycin (wilprafen );
Clarithromycin (fromilid ,
klabax , clacid );
Azithromycin (Azitrox,
Azithro, Zithromax , sumamed ).
Erythromycin(Erythromycinum)
• 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-2,6didedeoxyhexopyranos) and deamine (pycrocin, 3dimethylamino-4,6- didedeoxyhexopyranos). Cladynos splits off
at the interaction with eryehromycin with 0,5 М НСl solution at
the cold, and deamine – at the interaction with eryehromycin
with 6 М НСl solution.
• Erythromycin – white crystalline substance bitter on taste, melting at
190-193 оС, 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.
Oleandomycin phosphate
Oleandomycini phosphas
H3C
CH3
O
O
OH
H3C
OH
N
O
O
OCH3
H3C
H3C
CH3
*H3PO4
CH3
H2C
O
OH
O
O
O
CH3
CH3
CH3
Azithromycin (UP) (Azithromycinum)
H3C
CH3
O
O
HO
H3C
O
N
O
CH3
H3C
H3C
OH
H3CO
CH3
OH
H 3C
CH3
O
OH
O
•
OH
N
H 3C
CH3
CH3
CH3
Identification: IRspectroscopy
• Assay:
Liquid chromotography
• 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 antibioticsmacrolides are not used continuously, the sensitivity of the
microorganism to them restored.
Ansamycin’s 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
macrolide’s antibiotics, it attaches to the core with the
amide nitrogen atom.
The following antibiotics belong to ansamycin’s : rifampicin,
streptovaricin, tolipomicin, galomicin, naphtomicin etc.
Rifampicin and its semi-synthetic analogs are used as medicines [3-(4methyl-1-piperazinyliminomethyl)- rifampicin ], rifabutin , rifampitin
and the combine drugs.
Ansamycin’s 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.
Rifampicin’s general formula and radicals
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 В, 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).
Nystatin
Nystatinum
tablets, ointment , suppository
CH3
O
OH
NH2
OH
O
H3C
CO
OH
CH3
O
HO
H3C
OH
OH
OH
OH
O
O
OH
OH
OCH3 OH
O OCH
3
• Griseofulvin
Griseofulvinum
tablets, liniment
O
O
H3CO
Cl
CH3
Nystatin (Nystatinum) (UP)
• Identification:
UV-, ІR-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.
Amphotericin В
O
Amphotericinum B
OH
CH3
amphomin, amphotret, fungizome, fungizone
NH2
OH
O
H3C
CH3
O
HO
H3C
OH
OH
OH
OH
O
O
OH
CO
OH
OH
OH
• 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.
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.
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.
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 (Вruneomycin ).
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.
Doxorubicin hydrochloride(UP)
Doxorubicini hydrochloridum
Adriblastin
O
OH
O
OH
OH
• Crystalline orange-red
powder. Hygroscopic.
OCH3
• Identifiction: ІRspectroscopy, gives the
reaction of chloride ions.
• Assay:
OH
Liquid chromatography
H
O
* HCl
OH
O
CH3
NH2
O
O
Olivomycin А
CH3
O
O
O
H3C
C
OCH3
O
OH
OCH3
O
OH
CH3
O
OH
O
OH
OH
OH
CH3
O
O
CH
CH3
O
OH
CH3
OH
C
O
O
O
CH3
H 3C
O
CH3
O
• Rubomycin
hydrochloride
O
OH
COCH3
OH
• Вruneomycin
*HCl
O
OCH3
OHC
3
OH
O
H3CO
O
OH NH2
N
COOH
N
H2N
O
H2N
CH3
OH
OCH3
OCH3
Olivomycin А – 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 оС. Using intravenous injection or local
(oinmant).
Вruneomycin (streptonigrin) – brown crystalline powder.
Practically insoluble in water, alcohol, soluble in DMFA,
pyridine. Storage as a toxic substance at below 20 оС 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 оС. Using
intravenous injection, inner muscular injection or
hypodermic injection – necrosis.
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 ХХ century. The first representative
of this class is nalidyxone acid (nevigramon, negram) and its
analogs is a pipemіdine acid (pipemidine, palin, urosept, pimidel).
These drugs are characterized primarily by the activity to gramnegative 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):
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.
Quinolones have a high effect on aerobic gramnegative 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.
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).
• Norfloxacin
Norfloxacinum
• Ofloxacin
Ofloxacinum
O
O
F
HN
N
COOH
F
COOH
N
H3C
C2H5
N
N
N
O
CH3
1-ethyl-6-fluor-1,4-dihydro-4-оxо7-(1’-piperazinyl)-3quinolinecarboxylic acid
(±) 3-methyl- 7-оxo-9-fluor-10(4’-methyl-1’- piperazinyl)-2,3dihydro-7Н-pirido-1,4benzoxazine -6- carboxylic
acid
• Ciprofloxacin h/ch
(UP 1.2)
Ciprofloxacini
hydrochloridum
• Lomefloxacin
Lomefloxacinum
O
O
F
COOH
F
COOH
H3C
HN
N
N
* HCl * H2O
H 2C
HN
N
N
F
CH
C2H5
CH2
1-cyclopropyl-6-fluorine-4-оxo-7(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid
hydrochloride
1-ethyl-6,8-difluorine-7-(3’methyl-1’- piperazinyl)-4оxo-1,4-dihydro-3quinolinecarboxylic acid
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 Dragendorff’s
reagent,
picric
acid.
Oxo-group is identified by the reactions of the formation
of oxime’s precipitation (reaction with hydroxylamine),
thiosemicarbazone (reaction with thiosemicarbazide)
phenylhydrazone (reaction with phenylhydrazine).
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↓
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- → [FeF6]3- + 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 [ZrF6]2-.
Assay
1. Acidimetry in a non-aqueous medium, a direct titration.
Ем=М.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 UVand
sunlight.
Accumulation in the skeletal system - can not use for
children under 15 years old, pregnant, during
lactation.
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
аmpulla 10 ml. Eye-ear drops 0,3%. Cifran SТ –
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.
Thanx for
attention