01 course introduction.halogen. of alkaline metals

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    LECTURE 1Theme: Course introduction and

    importance of Pharmaceutical Chemistry

    for pharmaceutical analysis. Introductionabout Pharmacopoeia and methods ofdrug analysis.

    Inorganic drugs from group ofhalogenides of alkaline metals.

    Associate prof. Mosula L.M.

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    The plan1. A subject and the contents of pharmaceutical chemistry, its

    interrelation with chemical, medical and biologic and

    pharmaceutical disciplines.2. The State Pharmacopoeia of Ukraine (SPU), the International

    (Ph. Int.), Europian (Ph. Eur.) and British Pharmacopoeias (BP),

    and other analytical normative documentation (AND), which

    regulates high quality of pharmaceutical preparations.

    4. Classification of drugs.

    5. Inorganic drugs from group of halogenides of alkaline metals:

    obtaining, properties (appearance and solubility), identification,

    tests, assay, storage, action and use of preparations of:

    Fluorine (sodium fluoride);Chlorine (sodium and potassium chlorides);

    Bromine (sodium and potassium bromides);

    Iodine (sodium and potassium iodides).

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    Pharmaceutical chemistry is a highly interdisciplinary sciencecombining organic chemistry with biochemistry, inorganic chemistry, analyticalchemistry, pharmacology, pharmacognosy, molecular biology and physical

    chemistry.Pharmaceutical chemistry is the chemistry of drugs and

    pharmaceutical products.

    The aim of pharmaceutical chemistry is the discovery anddevelopment of new therapeutic agents.

    The mission of the Pharmaceutical Chemistry course is tointroduce the structure, properties, and analysis (both qualitative andquantitative) of pharmaceutical agents as well as the fundamental techniquesused for near patient testing in clinical laboratories to the students. Topicsinclude some of the basic concepts in pharmaceutical chemistry as well as

    methods of pharmaceutical analysis such as 1) the drug synthesis, 2) review oforganic functional groups found in drug molecules as well as cations and anionsof the inorganic drugs, 3) physicochemical properties related to drug action, 4)physicochemical and chemical analysis of drugs, 5) methods of identification ofpharmaceutical agents, 6) the storage conditions and use of drugs.

    http://en.wikipedia.org/wiki/Organic_chemistryhttp://en.wikipedia.org/wiki/Biochemistryhttp://en.wikipedia.org/wiki/Computational_chemistryhttp://en.wikipedia.org/wiki/Pharmacologyhttp://en.wikipedia.org/wiki/Pharmacognosyhttp://en.wikipedia.org/wiki/Molecular_biologyhttp://en.wikipedia.org/wiki/Physical_chemistryhttp://en.wikipedia.org/wiki/Physical_chemistryhttp://en.wikipedia.org/wiki/Physical_chemistryhttp://en.wikipedia.org/wiki/Physical_chemistryhttp://en.wikipedia.org/wiki/Molecular_biologyhttp://en.wikipedia.org/wiki/Pharmacognosyhttp://en.wikipedia.org/wiki/Pharmacologyhttp://en.wikipedia.org/wiki/Computational_chemistryhttp://en.wikipedia.org/wiki/Computational_chemistryhttp://en.wikipedia.org/wiki/Biochemistryhttp://en.wikipedia.org/wiki/Organic_chemistry
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    Pharmaceutical Chemistry is a multifaceted discipline that

    encompasses synthetic organic chemistry, inorganic, analytical,

    physical, colloidal, biological chemistry and some disciplines of

    medical and biological profile: biology, normal and pathologicalphysiology, microbiology. The pharmaceutical chemistry is closely

    connected with other profile disciplines: pharmacognosy, technology

    of medicines, the organisation and pharmacy economy,

    pharmacotherapy.

    Pharmaceutical chemistry is a discipline at the intersection of

    chemistry andpharmacology involved with designing, synthesizing

    and developingpharmaceuticaldrugs.

    Compounds used as medicines are overwhelmingly organic

    compounds including small organic molecules and biopolymers.

    However, inorganic compounds and metal-containing compounds

    have been found to be useful as drugs.

    http://en.wikipedia.org/wiki/Chemistryhttp://en.wikipedia.org/wiki/Pharmacologyhttp://en.wikipedia.org/wiki/Drug_designhttp://en.wikipedia.org/wiki/Organic_synthesishttp://en.wikipedia.org/wiki/Pharmaceuticalhttp://en.wikipedia.org/wiki/Medicationhttp://en.wikipedia.org/wiki/Organic_compoundshttp://en.wikipedia.org/wiki/Organic_compoundshttp://en.wikipedia.org/wiki/Small_moleculehttp://en.wikipedia.org/wiki/Biopolymerhttp://en.wikipedia.org/wiki/Biopolymerhttp://en.wikipedia.org/wiki/Small_moleculehttp://en.wikipedia.org/wiki/Small_moleculehttp://en.wikipedia.org/wiki/Small_moleculehttp://en.wikipedia.org/wiki/Small_moleculehttp://en.wikipedia.org/wiki/Small_moleculehttp://en.wikipedia.org/wiki/Organic_compoundshttp://en.wikipedia.org/wiki/Organic_compoundshttp://en.wikipedia.org/wiki/Organic_compoundshttp://en.wikipedia.org/wiki/Medicationhttp://en.wikipedia.org/wiki/Pharmaceuticalhttp://en.wikipedia.org/wiki/Organic_synthesishttp://en.wikipedia.org/wiki/Drug_designhttp://en.wikipedia.org/wiki/Pharmacologyhttp://en.wikipedia.org/wiki/Chemistry
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    Pharmacopoeiain its modern technical sense, is a book containingdirections for the identification of samples and the preparation of compoundmedicines, and published by the authority of a government or a medical orpharmaceutical society.The word derives fromAncient Greek (pharmakopoieia),from -(pharmako-) 'drug', followed by the verb-stem -(poie-)'make' and finally the abstract noun ending - (-ia). These three elementstogether can be rendered as 'drug-mak-ing'.

    The aim of theInternational Pharmacopoeia (Ph. Int.), which is issuedby the World Health Organization as a recommendation, is to achieve a wideglobal uniformity of quality specifications for selected pharmaceutical products,excipients, and dosage forms. The information published in the InternationalPharmacopoeiais collated via a consultative procedure and is based on

    international experience, the monographs being established in an independentmanner. Priority is given to medicines that are widely used throughout theworld. High priority is accorded to medicines that are important to WHO healthprograms, and which may not appear in any other pharmacopoeias.

    http://en.wikipedia.org/wiki/Medicinehttp://en.wikipedia.org/wiki/Pharmaceuticalhttp://en.wikipedia.org/wiki/Ancient_Greekhttp://en.wikipedia.org/wiki/World_Health_Organizationhttp://en.wikipedia.org/wiki/Monographhttp://en.wikipedia.org/wiki/Medicineshttp://en.wikipedia.org/wiki/Pharmacopoeiahttp://en.wikipedia.org/wiki/Pharmacopoeiahttp://en.wikipedia.org/wiki/Medicineshttp://en.wikipedia.org/wiki/Monographhttp://en.wikipedia.org/wiki/World_Health_Organizationhttp://en.wikipedia.org/wiki/Ancient_Greekhttp://en.wikipedia.org/wiki/Pharmaceuticalhttp://en.wikipedia.org/wiki/Medicine
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    The European Pharmacopoeia (Ph. Eur.) of the Council of Europe is apharmacopoeia, listing a wide range ofactive substances and excipients used toprepare pharmaceutical products in Europe[citation needed]. The 2005 editionincludes 1800 specific and general monographs, including various chemical

    substances, antibiotics, biological substances. The European Pharmacopoeia isdeveloped by the European Directorate for the Quality of Medicines (EDQM) andis a part of the Council of Europe, Strasbourg, France. It has been created by theConvention on the elaboration of a European Pharmacopoeiafrom 1964.

    The British Pharmacopoeia(BP)is an annual published collection of qualitystandards for UKmedicinal substances. It is used by individuals andorganizations involved in pharmaceutical research, development, manufactureand testing. Pharmacopoeial standards are publicly available and legallyenforceable standards of quality for medicinal products and their constituents.The Pharmacopoeia is an important statutory component in the control of

    medicines which complements and assists the licensing and inspection processesof the Medicines and Healthcare products Regulatory Agency (MHRA) of theUnited Kingdom. Pharmacopoeial standards are compliance requirements; thatis, they provide the means for an independent judgment as to the overall qualityof an article and apply throughout the shelf-life of a product. Inclusion of asubstance in a pharmacopoeia does not indicate that it is either safe or effective

    for the treatment of any disease.

    http://en.wikipedia.org/wiki/Council_of_Europehttp://en.wikipedia.org/wiki/Pharmacopoeiahttp://en.wikipedia.org/wiki/Active_substancehttp://en.wikipedia.org/wiki/Excipientshttp://en.wikipedia.org/wiki/Pharmaceuticalhttp://en.wikipedia.org/wiki/Europehttp://en.wikipedia.org/wiki/Wikipedia:Citation_neededhttp://en.wikipedia.org/wiki/Monographhttp://en.wikipedia.org/wiki/Antibioticshttp://en.wikipedia.org/wiki/European_Directorate_for_the_Quality_of_Medicineshttp://en.wikipedia.org/wiki/Council_of_Europehttp://en.wikipedia.org/wiki/Strasbourghttp://en.wikipedia.org/wiki/United_Kingdomhttp://en.wikipedia.org/wiki/Medicinalhttp://en.wikipedia.org/wiki/Pharmacopoeiahttp://en.wikipedia.org/wiki/Medicines_and_Healthcare_products_Regulatory_Agencyhttp://en.wikipedia.org/wiki/Medicines_and_Healthcare_products_Regulatory_Agencyhttp://en.wikipedia.org/wiki/Pharmacopoeiahttp://en.wikipedia.org/wiki/Medicinalhttp://en.wikipedia.org/wiki/United_Kingdomhttp://en.wikipedia.org/wiki/Strasbourghttp://en.wikipedia.org/wiki/Council_of_Europehttp://en.wikipedia.org/wiki/European_Directorate_for_the_Quality_of_Medicineshttp://en.wikipedia.org/wiki/Antibioticshttp://en.wikipedia.org/wiki/Monographhttp://en.wikipedia.org/wiki/Wikipedia:Citation_neededhttp://en.wikipedia.org/wiki/Europehttp://en.wikipedia.org/wiki/Pharmaceuticalhttp://en.wikipedia.org/wiki/Excipientshttp://en.wikipedia.org/wiki/Active_substancehttp://en.wikipedia.org/wiki/Pharmacopoeiahttp://en.wikipedia.org/wiki/Council_of_Europe
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    The State Pharmacopoeia of Ukraine (SPU) is a legal

    document which contains the general requirements to

    pharmaceutical preparations, monographies (pharmaceutical

    articles) as well as techniques of quality assurance of medicalproducts. The first edition of SPU was published in 2001. It has

    legislative character and its requirements are obligatory for all

    enterprises and establishments, independently on a form of property

    which develop, keep, supervise, realize and apply medical products.

    Quality assurance of drugs in Ukraine at the state level is

    carried out by Ministry of Public Health. It supervises the service of

    medical products and products of medical appointment, the State

    Enterprise Scientific and Expert Pharmacopoeial Centre, the StatePharmacological Centre, the State Drugs inspection (its structure

    includes the Central laboratory of quality assurance of medical

    products), territorial inspections of quality assurance of medical

    products.

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    Destructive impur ities

    Impurities can be destructive when they obstruct the working nature of

    the material. Examples include ash and debris in metals and leaf pieces

    in blank white papers. The removal of impurities is usually donechemically. For example, in the manufacturing ofiron, calcium carbonate

    is added to theblast furnace to remove silicon dioxide from the iron ore.

    Zone refining is an economically important method for the purification

    of semiconductors.However, some kinds of impurities can be removed by physical means. A

    mixture of water and salt can be separated by distillation, with water as

    the distillate and salt as the solid residue. Impurities are usually

    physically removed from liquids and gases. Removal of sand particles

    from metal ore is one example with solids.

    No matter what method is used, it is usually impossible to separate an

    impurity completely from a material. What technicians can do is to

    increase the purity of a material to as near 100% as possible or

    economically feasible.

    http://en.wiktionary.org/wiki/ashhttp://en.wikipedia.org/wiki/Debrishttp://en.wikipedia.org/wiki/Metalshttp://en.wikipedia.org/wiki/Ironhttp://en.wikipedia.org/wiki/Blast_furnacehttp://en.wikipedia.org/wiki/Silicon_dioxidehttp://en.wikipedia.org/wiki/Orehttp://en.wikipedia.org/wiki/Zone_refininghttp://en.wikipedia.org/wiki/Salthttp://en.wikipedia.org/wiki/Distillationhttp://en.wikipedia.org/wiki/Residue_(chemistry)http://en.wikipedia.org/wiki/Residue_(chemistry)http://en.wikipedia.org/wiki/Distillationhttp://en.wikipedia.org/wiki/Salthttp://en.wikipedia.org/wiki/Zone_refininghttp://en.wikipedia.org/wiki/Orehttp://en.wikipedia.org/wiki/Silicon_dioxidehttp://en.wikipedia.org/wiki/Blast_furnacehttp://en.wikipedia.org/wiki/Ironhttp://en.wikipedia.org/wiki/Metalshttp://en.wikipedia.org/wiki/Debrishttp://en.wiktionary.org/wiki/ash
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    There are two types of impurities: generaland specific.The sources of general impurities are equipment, solvents, auxiliary

    materials, and ofspecific onesby-products, semiproducts of synthesis of

    substances of medicinal forms and compounds which are formed in medical

    products at their wrong storage.The State Pharmacopoeia of Ukraine, other Analytical Normative

    Documentation (AND) on the basis of experimental researches regulate

    specific impurities and their quantity for each preparation.

    For revealing the impurities in the medical products and their approximate

    quantitative estimation use standard solutions (standards).Standard solution is a chemical term which describes a solution of

    known concentration of testing impurity. The concentration of the solution

    is normally expressed in unit ofppm (parts-per-million, ppm = 106) (One

    part permillion (ppm) denotes one part per 1,000,000 parts, one part in 106,

    and a value of 1 106.). For standards (standard solutions)preparationuse chemically pure initial substances (mother substances).

    Presence of impurities defines by means of such methods:nephelometry

    and colorimetry.

    At the revealing same impurities use instrumental methods of analysis (atomic

    absorption spectroscopy, spectrophotometry, chromatography, etc.).

    http://en.wikipedia.org/wiki/Solutionhttp://en.wikipedia.org/wiki/Concentrationhttp://en.wikipedia.org/wiki/Millionhttp://en.wikipedia.org/wiki/Millionhttp://en.wikipedia.org/wiki/Concentrationhttp://en.wikipedia.org/wiki/Solution
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    The proposed program will you prepare to fully and

    confidently participate in health and biomedical careers.

    Pharmaceutical companies need employees with strong

    skills in modern chemical techniques as well as a good

    understanding of biomedical issues such as drug action, drug design

    and drug development. Students are increasingly careeroriented and

    are motivated by early exposure to applications of their studies.

    Pharmacists are health professionals who practice the

    science ofpharmacy. It is very important propfession.

    http://en.wikipedia.org/wiki/Health_professionhttp://en.wikipedia.org/wiki/Pharmacyhttp://en.wikipedia.org/wiki/Pharmacyhttp://en.wikipedia.org/wiki/Health_profession
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    Browse: British Pharmacopoeia 2009SPU, add. 1

    Sodium ChlorideGeneral Notices

    (Ph Eur monograph 0193)

    NaCl58.44

    DEFINITION

    Content99.0 per cent to 100.5 per cent (dried substance).

    CHARACTERS

    Appearance

    White or almost white, crystalline powder or colourless crystals or white or almostwhitepearls.

    SolubilityFreely soluble in water, practically insoluble in anhydrous ethanol.

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    OBTAINING:1. From water of lakes and the seas by evaporation.

    2. Clarification of technical mineral salt NaCl from impurity, which

    carry out consistently. Addition of a solution barium chlorideCl2 is precipitates by sulphates and phosphates:

    Precipitate filter off, and to filtrate add excess of Na2CO3 forprecipitation of impurities of Mg, Ca, Ba salts.

    For deleting of exess of Na2CO3 to filtrate add HCl:Na2CO3 + 2HCl = 2NaCl + H2O + CO2

    SO42

    + Ba2+

    BaSO4

    HPO42

    + Ba2+

    BaHPO4

    Mg2+

    + CO32

    MgCO3

    Ca2+

    + CO32

    CaCO3

    Ba2+ + CO32 BaCO3

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    IDENTIFICATION

    A. It gives the reactions of chlorides(2.3.1).

    Chlorides:A. (BrPh, SPU, add. 1). Reaction with solution of

    AgNO3 in the nitric-acid medium.Dissolve in 2 ml ofwater R a quantity of the substance to be examined

    equivalent to about 2 mg of chloride (Cl) or use 2 ml of the prescribed solution.

    Acidify with dilute nitric acid R and add 0.4 ml ofsilver nitrate solution R1.Shake and allow to stand. A curdled, white precipitate is formed. Centrifuge and

    wash the precipitate with three quantities, each of 1 ml, ofwater R. Carry out this

    operation rapidly in subdued light, disregarding the fact that the supernatant

    solution may not become perfectly clear. Suspend the precipitate in 2 ml ofwater

    R and add 1.5 ml ofammonia R. The precipitate dissolves easily with thepossible exception of a few large particles which dissolve slowly.

    NaCl + AgNO3 AgCl +NaNO3;

    Cl+ Ag+ AgCl

    curdled, white precipitate

    AgCl + 2NH4OH [Ag(NH3)2]Cl + 2H2O

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    B. (BrPh, SPU, add. 1).Reaction with oxidizers inthe acid medium with the next identification of toxic gas

    Cl2.Introduce into a test-tube a quantity of the substance to be examined equivalent toabout 15 mg of chloride (Cl) or the prescribed quantity. Add 0.2 g ofpotassiumdichromate Rand 1 ml ofsulphuric acid R. Place a filter-paper strip impregnated with0.1 ml ofdiphenylcarbazide solution Rover the opening of the test-tube. The paperturns violet-red. The impregnated paper must not come into contact with the potassiumdichromate.

    6NaCl + K2Cr2O7 + 7H2SO4 = 3Cl2 + Cr2(SO4)3 + K2SO4 + 3Na2SO4 + 7H2OCr2O72 + 14H+ + 6 2Cr3+ + 72

    2Cl 2 Cl2

    diphenylcarbazide diphenylcarbazonediphenylcarbadiazone

    (colourless) (orange-yellow) (violet-red)

    O C

    NH NH C6H

    5

    NH NH C6H5

    CL2

    O C

    N N C6H5

    NH NH C6H5

    CL2

    O C

    N N C6H5

    N NC

    6H

    5

    -2 HCl

    -2 HCl

    + +

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    B. It gives the reactions of sodium(2.3.1).Sodium and Sodium Salts:

    A. (BrPh, SPU, add. 1).Reaction with potassium pyroantimonate

    solution.

    Dissolve 0.1 g of the substance to be examined in 2 ml ofwater R or use 2 ml of theprescribed solution. Add 2 ml of a 150 g/l solution ofpotassium carbonate R and

    heat to boiling. No precipitate is formed. Add 4 ml ofpotassium pyroantimonate

    solution R and heat to boiling. Allow to cool in iced water and if necessary rub the

    inside of the test-tube with a glass rod. A dense white precipitate is formed.

    NaCl + K[Sb(OH)6] Na[Sb(OH)6] + KClNa+ + [Sb(OH)6] Na[Sb(OH)6]

    dense white precipitate

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    B. Reaction with methoxyphenylacetic reagent.Dissolve a quantity of the substance to be examined equivalent to about 2 mg of sodium

    (Na+) in 0.5 ml ofwater R or use 0.5 ml of the prescribed solution. Add 1.5 ml of

    methoxyphenylacetic reagent R (it is solution ofmethoxyphenylacetic acid in the

    tetramethylammonium hydroxide solution and ethanol) and cool in ice-water for 30

    min. A voluminous, white, crystalline precipitate is formed. Place in water at 20 C

    and stir for 5 min. The precipitate does not disappear. Add 1 ml ofdilute ammonia

    R1. The precipitate dissolves completely. Add 1 ml ofammonium carbonate solution

    R. No precipitate is formed.

    white, crystalline precipitate

    Other reaction:

    SPU, N. Pyrochemical reaction.Sodium salt, wetted with hydrochloric acid

    and brought in a colourless flame, paints its in yellow colour:

    Na+ + h *Na+ Na+ + h1.

    CH

    O

    C

    O

    OHCH3

    CH3

    4

    NOH CH

    O

    C

    O

    CH3 ON(CH

    3)4

    +

    CH

    O

    C

    O

    O

    CH3

    CH

    O

    C

    O

    CH3

    Na

    ONa

    + +

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    ASSAY

    (BrPh, SPU, add. 1). Argentometry, direct titration

    with potentiometric fixation of end-point.Dissolve 50.0 mg in water R and dilute to 50 ml with the same

    solvent. Titrate with 0.1 M silver nitrate determining the end-point

    potentiometrically (2.2.20).

    1 ml of0.1 M silver nitrate is equivalent to 5.844 mg of NaCl.NaCl + AgNO3 = AgCl + NaNO3

    m(NaCl) = M. m.

    Other methods:1.SPU, add. 1. Thiocyanatometry.

    2. SP X. Argentometry, direct titration (Morh method).Indicator K2CrO4.3. Argentometry, back titration (Volhard method) (see thiocyanatometry). Toinvestigated solution add double excess of standart solution of AgNO3.

    NaCl + AgNO3 = AgCl + NaNO3AgNO3 + NH4SCN = AgSCN + NH4NO3

    3NH4SCN + (NH4)Fe(SO4)2 = Fe(SCN)3 + 2(NH4)2SO4

    m(NaCl) = M. .

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    NaCl + AgNO3 = AgCl + NaNO3

    m(NaCl) = M. .

    2NaCl + g(NO3)2 = gCl2 + 2NaNO3

    m(NaCl) = M. .

    O C

    N N C6H5

    NH NH C6H

    5

    Hg(NO3)2 O C

    N N

    C6

    H5

    NH N

    C6H

    5

    Hg

    N

    N

    C6H

    5

    C6H

    5

    N

    NH

    C O HNO3

    2 + + 2

    Argentometry, direct titration (Fajance method).

    Indicatorfluoresceine.

    5. Mercurymetry, direct titration.

    Indicatordiphenylcarbazone.

    To titrate until changing of colouring solution from yellow-red to dark blue colour.

    In the equivalence point excess drop of titrant g(NO3)2 interaction with indicator of

    diphenylcarbazone and formation of dark blue complex.

    Ley e ing

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    Ley e ing where applicable, that the substance is suitable for use in the manufacture ofparenteral dosage forms; where applicable, that the substance is suitable for use in the manufacture ofperitoneal dialysis solutions, haemodialysis solutions or haemofiltration solutions.

    Action and useUsed in treatment of electrolyte deficiency.Plasma substitute.Ions Na + are basic extracellular Ions. It is the basic component of all saltsolutions, which are applied as plasma substitutes.Isotonic (0,9 %) a solution of sodium chloride (Soluto Natr chlordsotonca pro

    njectonbus) apply hypodermically, intravenously (more often drop method) and in clysteras antitoxic means and at organism dehydration, at bleedings, a shock (sometimes - to 3 L).Introduction of great volumes of this solution can lead chloride acidisis, hyperhydrations,

    strengthening of conclusion of Potassium from an organism.

    PreparationsCompound Glucose, Sodium Chloride and Sodium Citrate Oral SolutionOral Rehydration Salts

    Potassium Chloride and Sodium Chloride Intravenous InfusionPotassium Chloride, Sodium Chloride and Glucose Intravenous InfusionSodium Chloride Eye DropsSodium Chloride Eye LotionSodium Chloride Intravenous InfusionSodium Chloride and Glucose Intravenous InfusionSodium Chloride Irrigation SolutionCompound Sodium Chloride MouthwashSodium Chloride Oral Solution

    Sodium Chloride SolutionSodium Chloride Tablets

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    Thanks for attention!