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Antimicrobial drugs

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Antimicrobial drugs Kharkov National Medical University Department of Pharmacology and Medical Prescription assistant Gordiychuk D. I. Antiseptics and disinfectants. – PowerPoint PPT presentation

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Title: Antimicrobial drugs


1
Antimicrobial drugs

Kharkov National Medical UniversityDepartment of
Pharmacology and Medical Prescription assistant
Gordiychuk D.
  • I. Antiseptics and disinfectants.
  • II. Sulfonamides.
  • III. Synthetic chemotherapeutics.

2
Control of Microbial Growth
  • Sterilizing Agents-- kill everything (e.g. heat,
    radiation)
  • Disinfectants-- kill most things. Too strong for
    living tissues (e.g. lysol, NH3)
  • Antiseptics-- milder in action. Can be used
    topically, but not ingested. (e.g. alcohol,
    iodine)
  • Chemotherapeutics-- can be ingested (e.g.
    penicillin, sulfa drugs)

3
Medicines with an antimicrobial activity are
divided into two groups1 non-selective
antimicrobial agents, causes most destructive
effect on the majority of microorganisms
(antiseptics and disinfectants).2 - selective
antimicrobial drugs (chemotherapeutic agents).
4
ORIGINS OF ANTISEPTICS
  • Joseph Lister (1827 - 1912)
  • Realised that deaths from operations mostly
    occurred from infection contracted during the
    operation as a result of unclean practices.
  • He started using Carbolic acid (phenol) during
    operations to maintain aseptic conditions with
    significant improvements.
  • Like Semmelweiss he initially encountered
    opposition, but use of his methods by the Germans
    during the Franco-Prussian war in 1870 provided
    his major breakthrough and over the next 10
    years, the practise of aseptic surgery became
    accepted.

5
Antimicrobials could be
  • narrow-spectrum and effective only against a
    limited variety of pathogens or broad-spectrum,
    affecting many different types of pathogens
  • bactericidal if they kill the susceptible
    bacteria or bacteriostatic if they inhibit the
    growth of bacteria

6
Antiseptics and disinfectants
  • - a group of drugs that are able to inhibit the
    growth, development or leads to death of
    microorganisms in the environment surrounding the
    patient or on the surface of the body.
  • Antiseptics - (anti- against septicas - putrid).
    This is a group of medicines that are used to
    eliminate pathogens in the wound (skin, mucous
    membranes) in the gastrointestinal tract and
    urinary tract. Causes bacteriocidal or
    bacteriostatic effect depending on the
    concentration.
  • Disinfectants - used for disinfection of medical
    instruments, utensils, facilities, equipment,
    etc. Disinfection - a complex of measures aimed
    at prevention of infection in the wound (in the
    body as a whole) or to prevent the spread of
    infection.
  • Draw a sharp line between antiseptics and
    disinfectants is not always possible, because
    many substances used in low concentrations as
    antiseptics, and higher - for disinfection.

7
Requirements for antiseptics and disinfectants.
  • Must have a broad spectrum of action
  • Rapid onset of action
  • Should have a small latency period
  • Should have a high activity
  • Must be chemically resistant
  • High availability and low cost
  • Lack of local irritant or allergic effects on
    tissues
  • Minimal absorption from the place of their
    application
  • Low toxicity.

8
Sources of antiseptics
  • Early antiseptics were probably vegetable
    extracts
  • Many spices contain antibacterial agents
  • Essential oils extracted from plants often have
    antibacterial properties
  • Lister used carbolic acid which chemically is a
    solution of phenol
  • Phenol was originally extracted from coal tar.
  • Coal tar preparations are still used today in
    therapeutic soaps and shampoos.
  • To characterize the antimicrobial activity of the
    antiseptic agents used phenol ratio which
    indicates action force of the antimicrobial agent
    in comparison with the phenol.
  • The difference between antiseptics and
    disinfectants -The objectives of their
    application.

9
Classification of Antiseptics and Disinfectants
(according chemical structure)
  • I. Inorganic substances
  • 1. Halogens
  • Iodine (2, 3, 5 alcochol solution)
  • Iodinolum
  • Ioddicerinum
  • Povidon-Iod (Betadinum)
  • Iodophorm
  • Lugols solution
  • Chloramine B
  • Chlorhexidine bigluconate
  • Pantocidum (Halazone)
  • 2. Oxidizing agents
  • Hydrogen peroxide
  • Potassium permanganate
  • 3. Acids and alkalis
  • Boric acid
  • Salicylic acid
  • Solution of ammonia
  • 4. Metallic salts
  • Hydrargyri dichloridum
  • Hydrargyri amidochloridum
  • Silver nitrate
  • Copper sulfate
  • Zinc sulfate
  • Zinc oxide

10
Classification continuation
  • II. Organic substances
  • 1. Aldehydes
  • Formaldehyde (Formalinum)
  • Glutaraldehide
  • Hexamethylentetraminum (Methenamine)
  • 2. Alcochols
  • Spiritus aethylicus (Ethyl alcohol)
  • 3. Phenol derivatives
  • Phenol (Phenolum purum,
  • Carbolic acid)
  • Cresol (Tricresolum)
  • Resorcinol
  • Thymol
  • Benzylbenzoat
  • 4. Dyes
  • Methylenum blue
  • Brilliant green (Viride nitens)
  • Etacridin lactate
  • 5. Detergents
  • Aethonium
  • Decamethoxin
  • Roccal
  • Dimexid
  • 6. Tar, resins, products of petroleum
  • Pix liquida Betulae (Birch tar)
  • Ichthyolum
  • Liniment by Vishnevsky
  • 7. Nitrofuran derivatives
  • Nitrofurasone (Furacilinum)
  • 8. Antiseptics from medicinal plants
  • Chlorophyliptum
  • Novoimaninum

11
Halogens
  • Chlorine
  • Discovered in 1774 by a Swede, C.W. Scheele
  • It is a pale green, toxic, reactive gas
  • It is a powerful irritant and toxin
  • Used as a gas warfare agent in WWI
  • very nasty, inflicting lifelong damage on those
    who survived
  • The damaged lungs were possibly a factor in the
    1918 flu pandemic
  • Solution of chlorine in water is both a powerful
    bleach and disinfectant
  • Semmelweis had used chloride of lime as an
    antiseptic

12
Halogens
  • The mechanism of antimicrobial action
  • Denaturation of proteins of the protoplasm of
    microbial cells by reacting with the amino group
    of the proteins, displacing hydrogen.
  • Denatured protein loses its activity.
  • In the presence of organic substances halogens
    antimicrobial effect decreases.

13
Iodines
  • Iodine - active bactericidal element.
  • At a dilution of 1 20 000 - kill vegetative
    forms of bacteria for 1 min,
  • the dispute - 15 min.
  • Alcoholic solution of Iodine 5 (5 g of Iodine,
    KI -2g, ethyl alcohol 95 100ml)
  • An irritant and a distraction action
  • INDICATIONS Disinfection of the surgical field,
    disinfection of wounds, the surgeon's hands, in
    myositis, neuralgia.
  • Iodine is partially absorbed into the blood from
    the skin and exhibits resorptive effects,
    especially in children.
  • SIDE EFFECT Chemical burns, dermatitis.

14
Halogens (Iodine)
  • LUGOL'S SOLUTION (Iodine-1 part, 2 part -KI,
    water-17 part)
  • INDICATION Mucos lubrication in pharynhitis and
    larynhitis.
  • IODDICERINE (Iodine, dimethyl sulfoxide,
    glycerol)
  • Fungicidal, antimicrobial, antiviral,
    antinecrotic, antioxidant effect.
  • !!!The most active Iodine preparation!!!
  • Doesnt irritate tissue, does not cause pain
    reaction, deeply penetrates into the tissue.
  • INDICATION Inflammatory infection (purulent
    wounds, infectious ulcers, sore throats,
    tonsillitis, pulpitis, otitis, pyoderma, erosion
    of the mucous membranes, mastitis, candidiasis,
    inflammatory diseases of the genital organs).
  • Topically in the form of tampons, turundul,
    napkins, irrigation, washing.

15
Halogens (Chlorine disinfectants)
  • CHLORINE - active bactericidal element is active
    in the undissociated form of HOCl when Cl
    dissolved in water at neutral and acidic pH.
  • Bleach - not less than 32 of free Cl.
    Antimicrobial action - fast, but not for long
  • INDICATIONS 0.2-0.5 sol. for the disinfection
    of premises, infective patients discharge (pus,
    sputum, urine, feces).
  • Corrosive to metals.
  • CHLORAMINE B - 25-29 active Cl.
  • INDICATION eye wash, hand disinfection, douching
    (0.25-0.5), treatment of purulent wounds, burns,
    pustular skin diseases (0.5-2). Disinfection of
    premises, health products and non-metallic tool,
    selection of patients (1.5).
  • Deodorizing properties.
  • 4-8mg CHLORAMINE B is able to sterilize 1 liter
    of water for 15-60 min. (Pantocid), if the water
    contains a lot of organic substances.

16
Halogens
  • CHLORHEXIDINE BIGLUCONATE (Bisdiguanidine
    derivative).
  • Has the properties of chlorine and detergent
    compounds.
  • Capable of damaging the plasma membrane of
    microorganisms.
  • Strong antibacterial and fungicidal action.
  • Bactericidal activity against GR, Gr-
    bacterias, active against Treponema, gonococci,
    trichomonas, Proteus.
  • INDICATIONS disinfection of the surgical area,
    the surgeon's hands, tools, burn surfaces, septic
    processes, prevention of sexually transmitted
    diseases. In the form of a tabl. - in infectious
    and inflammatory diseases of the mouth and
    throat. 0.2 solution inhibits the formation of
    plaque and effective in treating gingivitis.
  • SIDE EFFECTS Dry hands, itchy skin, dermatitis.
  • !!!Can not be used in conjunction with IODINE!!!
  • CHLORHEXIDINE is often used as an active
    ingredient in mouthwash pastes to reduce dental
    plaque and oral bacteria.
  • It have an immediate bactericidal action and a
    prolonged bacteriostatic action due to adsorption
    onto the pellicle-coated enamel surface.

17
Oxidizing agents
  • HYDROGEN PEROXIDE
  • It is available as 30 and 3 solution. More
    common 3 solutions is used.
  • H2O2 2H O2
  • It is decomposed with release of molecular
    form of oxygen that is responsible for
    antimicrobial effect
  • Releasing oxygen makes foam that cleans and
    deodorizes putrid wounds and ulcers.
  • Catalases present in tissues speeds decomposition
    and foaming of hydrogen peroxide
  • Hydrogen peroxide is used in treatment of
    infected wounds and to stop small bleeding.

18
Hydrogen peroxide
  • Indications
  • - rinsing the mouth and throat, for the
    treatment of wounds that are infected with
    anaerobic microflora. Concentrated solutions
    (20-30) is indicated for the treatment of warts,
    lichen planus.
  • Side effects
  • - burn mucosa. Not used in deep wounds, and
    not introduced into a body cavity - may cause
    embolism.

19
Potassium permanganate
  • 2KMnO4 H2O 2KOH 2MnO2 3O2
  • It liberates oxygen in atomic form.
  • Highly water soluble, used in 14000-110000
    solution.
  • Higher concentrations cause burns and blistering.
  • It promotes rusting.
  • Clinical uses
  • Gargling, douching, irrigating cavities, urethra
    and wounds.
  • Stomach wash in alkaloid poisoning.
  • In a 2-5 solution is used for burns, bites of
    mosquitoes and snakes, for quick healing of
    wounds.
  • Disinfection of water.

20
Heavy metal compounds.
  • Their mechanism of action is the blocking of
    sulfhydryl, carboxyl and amino groups of proteins
    and enzymes of microorganisms.
  • Metal ions are formed by dissociation of the
    salts, interaction with these active
    biosubstrates functional groups cause their
    denaturation.
  • At a deeper penetration of the substance in the
    tissue causes irritated cells and nerve endings
    effect, and the extreme manifestation of a
    cauterizing effect of metal salts.
  • (Pb, ... Al, Zn, Cu, Ag, ... Hg) In such
    sequence an increases antimicrobial activity. As
    antiseptics most active are metal salts on the
    right side of the row.

21
Heavy metal compounds.
  • With prolonged use of salts of heavy metals can
    be cytotoxic effect due to the inhibition of
    thiol enzymes in the tissues.
  • Symptoms of poisoning with salts of heavy metals
    a chemical burn of GIT mucosa, the weakening of
    cardiac activity, collapse, kidney and liver
    damage.
  • In cases of poisoning gastric lavage with water,
    tea solution with activated carbon, Unithiol.
  • Inside milk, raw eggs, Unithiol or Tetacin
    calcium, Sodium thiosulfate. Symptomatic
    treatment cardiac glycosides, sympathomimetic,
    plasma expanders, vasoconstrictors, narcotic
    analgesics.

22
Acids and alkalis
  • Acids boric acid, salicylic - Shift the pH to
    the acid side ? protein denaturation of microbial
    cell protoplasm. Since proteins of the skin and
    mucous membranes forming dense, insoluble
    albuminates, that is providing anti-microbial,
    anti-inflammatory, antifungal effects.
  • In high concentrations cauterize tissue
    (coagulative necrosis )!
  • Boric acid used for washing and rinsing of the
    mucous membranes of the mouth, diaper rash, acute
    and chronic otitis media, colitis, pyoderma,
    pediculosis.
  • Side effect It penetrates through the skin and
    mucous membranes, especially in children,
    cumulates. With long-term use in patients with
    impaired renal function develops acute and
    chronic poisoning (nausea,vomiting, diarrhea,
    skin rashes, confusion consciousness,
    convulsions, oliguria, sometimes shock.
  • Salicylic acid Weak antiseptic, irritant, low
    concentrations (1-3) keratoplastic, in high (5
    -10) - keratolytic effect.
  • Application Oily seborrhea, acne, eczema,
    psoriasis, ichthyosis, warts, corns, etc.

23
Alkalis
  • Alkalines NaHCO3, sodium tetraborate, sol. of
    ammonia.
  • NaHCO3, sodium tetraborate - melted mucin, a
    softening effect. Inflammatory exudate pH shifts
    to the alkaline side reduces the manifestations
    of inflammation.
  • 10 ammonia solution exhibits antiseptic effect,
    manifests cleaning properties, dissolves fat.
    Given these properties, it is suggested for
    washing hands before surgery (25 ml solution of
    ammonia diluted in 5 liters of water).
  • Inhalation to stimulate the respiratory center.

24
Organic antiseptics
  • Group of (aromatic) phenol, resorcinol, thymol,
    tar, ichthyol, benzylbenzoate.
  • Phenol (carbolic acid) 3-5 solution for
    disinfection of furniture, household items,
    hospital linen, patients discharge.
  • 0.25-1 - sometimes in skin diseases accompanied
    by itching.
  • 0.1-0.5 - conservation of serum and suppository.
  • Readily absorbed through intact skin and mucous
    membranes, causing intoxication (short-term
    stimulation of the CNS, respiratory depression
    and cardiac activity, decrease in body
    temperature, damage of parenchymal organs).

25
Organic compounds  Phenols
  • Resorcinol
  • In small doses has keratoplastic property in the
    more annoying - keratolytic.
  • Used for the treatment of skin diseases (eczema,
    seborrhea), fungal infections (2-5 solutions,
    5-20 ointment, paste).
  • Birch tar
  • Has antimicrobial, keratoplastic, keratolytic
    and irritant effect.
  • Is used to treat a number of skin diseases and
    scabies.
  • Is one of the components of balsamic liniment of
    Vishnevskiy

26
Group of aldehydes and alcohols
  • PREPARATIONS FORMALDEHYDE SOLUTION, LIZOFORM,
    ETHYL ALCOHOL, HEXAMETHYLENETETRAMINE
    (METHENAMINE)
  • Formaldehyde solution (Formalin)
  • Has antimicrobial (vegetative forms and spores)
    and deodorizing effects.
  • MECHANISM OF ACTION dehydration of microbial
    cells protoplasm proteins causing its
    destruction.
  • Is used as a disinfectant and deodorant, skin
    treatment with sweating (0.5-1), disinfection
    tools (0.5). For the preservation of anatomical
    objects.

27
Aldehydes and alcohols (Formaldehyde)
  • If inhaled formaldehyde - tearing, coughing,
    shortness of breath, agitation.
  • In oral poisoning - pain in the mouth, behind the
    sternum, in epigastric region, hematemesis,
    thirst, loss of consciousness, cyanosis, coma.
  • Emergency in poisoning Inhalation of water
    vapor, oxygen saturation, gastric lavage 2.3
    sol. of Ammonium chloride.
  • Inward enter 2-3 tbsp. of activated carbon, 100
    ml of 30 solution of magnesium sulfate.
  • In severe poisoning - forced diuresis, s/c 1 ml
    0.1 solution of Atropine sulfate, Promedol,
    inward - Codeine in tabl.

28
Ethyl alcohol
  • Bactericidal activity starts with alcohol 20 and
    increases with concentration. On the spore form
    does not affect.
  • High concentrations of alcohol in the protein
    environment form dense protein aggregates.
  • 70 - it is more deeply penetrates into the
    deeper layers of the epidermis of the skin,
    sebaceous and sweat glands, provides a high
    antiseptic effect (antimicrobial strength of 70
    is equal to 3 phenol sol.).
  • Application disinfection of hands and operating
    field (70).
  • Sterilization of surgical instruments (90-96).
  • Disinfection of the skin before injection (70).
  • Alcohol compresses for children (20), adults
    (40).
  • For the preparation of medicaments.

29
Group of dyes
  • Ethacridine lactate (rivanol), Brilliant green,
  • Methylene blue
  • Antimicrobial activity of this group falls In the
    protein environment
  • The most sensitive Gr bacteria, cocci.

30
  • Ethacridine lactate (rivanol)
  • - used in surgery, gynecology, urology,
    ophthalmology, dermatology. For washing of fresh
    and infected wounds, cavities (pleura,
    peritoneum), bladder, uterus.
  • Brilliant green
  • (1-2 water and alcohol sol.)
  • - for the treatment of skin with scratches,
    pyoderma, blepharitis, and others.
  • Methylene blue
  • - used internally for urinary tract infections
    (cystitis, urethritis).
  • - I/V 1 sol. 50-100 ml in case of poisoning
    with hydrocyanic acid or salts (in large doses
    translates hemoglobin to methemoglobin which
    comes into contact with a non-toxic form of
    cyanide complex cyanmethemoglobin).
  • - When administered I/V in small doses (0.1-0.15
    ml/kg 1 sol.) contrary methylene blue restores
    methemoglobin in the hemoglobin (with nitrite
    poisoning, aniline, and others.)

31
Nitrofuran derivatives (furacillin, furazolidone)
  • Spectrum of action Gr-, Gr bacteria
    (staphylococci, streptococci, dysentery bacillus,
    intestinal coli, Salmonella paratyphi, the
    causative agent of gas gangrene, etc.) and
    protozoa (Trichomonas, Giardia).
  • Pharmacodynamic influenced microbes reductase,
    there is a restoration of the nitro group and
    their transformation into toxic products for
    cells (inhibition of the respiratory chain, the
    destruction of the microbial wall).
  • In the presence of pus does not lose
    effectiveness.
  • Apply for external treatment of wounds, skin,
    mucous membranes, wash serous and joint cavities,
    otitis media, conjunctivitis and others. Eye
    diseases and orally for the treatment of
    bacterial dysentery.

32
Detergents
  • Detergents - a substances with a high surface
    activity.
  • Show antiseptic and cleansing action.
  • Distinguish anionic and cationic detergents.
  • Anionic detergents include ordinary soaps (sodium
    or potassium salts of fatty acids).
  • As antiseptics mainly used cationic surfactants
    benzalkonium chloride, cetylpyridinium chloride,
    miramistim.
  • Benzalkonium chloride has antibacterial,
    antiprotozoal and spermicidal action (spermicidal
    effect develops in two stages first - the
    destruction of the flagellum, and then - the gap
    of the sperm head, which makes it impossible to
    fertilization).
  • Used for treatment of skin, mucous membranes,
    wounds, rinsing the bladder, urethra, and for
    contraception in women.

33
  • Miramistim
  • Antiseptic, antiviral, antibacterial agent
  • Gr-, Gr , anaerobes, fungi.
  • Reduces the resistance of bacteria and fungi to
    antibiotics.
  • Application used as a 0.01 solution as an
    antiseptic in dental practice for the treatment
    of infected wounds, burns, infections of upper
    respiratory tract, urogenital system, stimulates
    local non-specific immunity, accelerates
    regeneration.
  • Cetylpyridinium chloride
  • in the composition of the drug "Tserigel" is used
    for hand washing before surgery.

34
II. Synthetic chemotherapeutic agents
  • Sulfonamides
  • Quinolones and Fluroquinolones
  • Nitrofuran derivatives

35
Sulfonamides
  • Sulfa drugs (SA) - synthetic chemotherapeutic
    agents, which are derivatives of sulfanilamide,
    or amides of sulfonic acid.

Common properties of SA - Sulfa nucleus -
Mechanism of action - Spectrum of antibacterial
action.
The first preparation of SA Red Streptocid
(1935).
36
Classification of SA
  • 1. Preparations with the resorptive (system)
    actions which are well absorbed in the intestine,
    creating high concentrations in the blood and
    other tissues
  • short-acting drugs (period of half of absorption
    less than 10 hours are applied 3-4 times per day,
    sometimes even 4-6 times a day in an amount of
    4-6 g/day)
  • - Sulfadimezin
  • - Etazol
  • - Norsulfazol
  • - Urosulfan.

37
Classification of SA
  • drugs with intermediate action (t1/2 10 -24
    hours)
  • - Sulfazin
  • - Sulfamethoxazole.
  • long-acting (t 1/2 24-28 hours)
  • - Sulfadimetoxin
  • - Sulfapiridazin
  • - Sulfamonomethoxine.
  • extremely long-acting (t 1/2 of 48 hours)
  • - Sulfalen.

38
Classification of SA
  • 2. Preparations of the intestinal action, which
    are slowly and incompletely absorbed from the
    GIT, they are use for the treatment of intestinal
    infections (t 1/2 lt10 hours).
  • - Ftalazol
  • - Sulgin
  • - Ftazin
  • 3. SA for topical application (readily soluble in
    water and is used topically in the eye drops for
    the prevention and treatment of gonococcal eye
    disease in newborns, as well as for the treatment
    of conjunctivitis, blepharitis, corneal ulcers
    and other pathologies of the eye).
  • -Sulfacil-sodium.

39
Mechanism of action
  • Certain microbes require paraaminobenzoic acid
    (PABA) to synthesize dihydrofolic acid which is
    required to produce purines and ultimately
    nucleic acids.
  • Sulfonamides, chemical analogs of PABA, are
    competitive inhibitors of dihydropteroate
    synthetase.
  • Sulfonamides therefore are reversible inhibitors
    of folic acid synthesis and bacteriostatic not
    bacteriocidal.

40
Mechanism of action
41
Conditions necessary for the manifestation of the
antibacterial action of the SA
  • - microorganisms can use SA instead of PABA in
    the case when the concentration of the drug in
    tissues in 2000-5000 times higher than the
    concentration of PABA
  • - SA efficiency sharply decreases in the presence
    of pus, blood and tissue breakdown products due
    to the PABA high concentration in these products
  • - SA have antimicrobial action only against those
    microorganisms which are themselves synthesized
    DHFA
  • - In SA resistant microorganisms observed
    increased synthesis of PABA
  • - The use of the SA in low concentrations
    contributes to the formation of resistant strains
    of microorganisms and leads to inefficiency of
    the SA.

42
SA antimicrobial spectrum
  • Currently used SA have broad spectrum, they
    inhibit gram-positive and gram-negative
    bacteriaStreptococcus pneumoniae,
    beta-haemolytic streptococci, E. coli,
    klebciella, shigella, salmonella, enterobacter,
    gonococci, meningococci, and pneumococci
  • Nocardia,
  • Chlamidia,
  • Protozoa (toxoplasma and malarial plasmodia).

43
SA pharmacokinetics
  •        Absorption. Slightly in the stomach and
    mainly in the small intestine. Within 30 minutes
    after the administration of the SA are found in
    urine. The bioavailability is 70-90.
  •      Biotransport. Reversibly bind to serum
    albumin, an agent which is directly proportional
    to the degree of hydrophobicity of the molecule
    of the drug. SA can displace from its association
    another protein drugs, particularly NSAIDs and
    endogenous substances (bilirubin).
  •      Distribution. Pass through the blood-tissue,
    placenta and blood-brain barriers. Also passes
    into breast milk.
  •      

44
SA pharmacokinetics
  •  Biotransformation.
  • Phase I reactions - acetylation, hydrogen
    substitution in the group NH2-acetic acid
    residue, thereby forming acetylated derivatives
    which do not have antimicrobial activity in an
    acidic medium and form crystals that disrupts the
    function of the kidney (crystalluria).
  • Reaction Phase II formation of double
    binding with glucuronic acid.
  • Excretion. Advantageously, urine, saliva, to a
    lesser extent and intestinal contents, but also
    breast milk.
  • Are displayed in the form of metabolites and
    unchanged.

45
Clinical uses of SA
  • Infections of urinary tract
  • GIT infections
  • Respiratory tract infection
  • Pharingitis, gingivitis
  • Chlamidial infections
  • Wounds, burns
  • Toxoplasmosis
  • Malaria
  • For systemic treatment cotrimoxazole is more
    often used nowadays
  • Sufonamides are used for prevention of
    infections.

46
Side effects of sulfonamides
  • - occur in 3 - 5 of patients and more frequently
    in children and the elderly. Complications due to
    overdose, and patients with hypersensitivity to
    the SA.
  • The central nervous system nausea, vomiting,
    dizziness, headache (central genesis),
    depression, increased fatigue.
  • 2. Blood leukopenia, thrombocytopenia,
    agranulocytosis, methemoglobinemia, hemolytic
    anemia.
  • 3. Kidneys oliguria, proteinuria, hematuria,
    crystalluria.
  • 4. Allergic reactions fever, itching, rash, pain
    in the joints.
  •           
  •  Prevention of crystalluria
  • - Drink plenty of liquids (3-5 liters per day)
  • - drink alkaline mineral water or milk during SA
    using.
  • Contraindications Toxic and allergic reactions
    to drugs.

47
Combined sulfa drugs
  • 1 - Combination with 5-aminosalicylic acid
  • SALAZOSULFOPIRIDIN
  • SALAZOPIRIDAZIN
  • 2 - combined with Trimethoprim
  • Biseptol (trimethoprim sulfamethoxazole)
  • Sulfaton (trimethoprim sulfadimezin)

48
Combined sulfa drugs (BISEPTOLUM).
  •  The mechanism of action of the combined drug on
    the principle of combined violations of nucleic
    acid synthesis in two points
  • 1. at the level of DHFA inclusion in PABA
    synthesis
  • 2. at the level of THFA formation from DHFA.

49
Combined sulfa drugs (BISEPTOLUM).
  •   The second (additional) mechanism is achieved
    by use of Trimethoprim (TMP) - antimalarial drug.
  •   TMP has a similar antimicrobial activity with
    the SA and is superior in activity in the 20-100
    times. The most justifiable is a combination of
    TMP with sulfamethoxazole in the ratio of 1 5.
  •   Thus, the combined preparation Biseptol-480
    created, which is a combination of TMP with
    sulfamethoxazole 1 5 (80 mg 400 mg).
  • This combination has a bactericidal effect,
    although each of the components exhibits -
    bacteriostatic.

50
Features of combined SA drugs
  • - Effective even in the case of resistance to SA
  • - Resistance to the combined drugs develops
    slowly
  • Side effects
  • 1. Dispepsia
  • 2. Skin rash
  • 3. Sometimes superinfection
  • 4. The reduction in reproductive function (rare).

51
Antimicrobials with different chemical structure.
  • FLUOROQUINOLONES
  • mono fluorine substitute
  • ciprofloxacin
  • ofloxacin
  • pefloxacin
  • norfloxacin
  • enoxacin
  • bifluorine substitute
  • lomefloxacin
  • ofloxacin
  • sparfloxacin
  • trifluorine substitute
  • traufloxacin
  • gatifloxacin
  • gemifloxacin
  • moxifloxacin

52
FLUOROQUINOLONES
  • The spectrum of action
  • wide, including Pseudomonas aeruginosa,
    Chlamydia, Giardia, Trichomonas, Yersinia,
    anaerobes, anthrax.
  • Mechanism of action
  • block the enzyme DNA-gyrase, responsible for
    supercoiling of the DNA molecule, as well as
    block the enzyme topoisomerase type 4, is
    responsible for the compact folding of the DNA
    molecule. This leads to an uncoiling of DNA and
    the microorganism death.
  • Type of antimicrobial action
  • bactericidal

53
FLUOROQUINOLONES
  • Indications trichomoniasis, giardiasis, plague,
    anthrax, gonorrhea, anaerobic infections,
    Legionnaires' disease.
  • Side effects
  • Excitation of the central nervous system,
    anxiety, in large doses - convulsions (disrupt
    the synthesis of GABA in the CNS).
  • Dyspepsia, drug-induced hepatitis, swelling of
    the tongue
  • Tachycardia, shortness of breath
  • Anemia, leukopenia
  • Photodermatitis, itching
  • Disturbances of cartilage in children, so
    containdicated for children under 12 years.
  • Hypothyroidism
  • Allergic reactions

54
Naphthalidine Derivatives
  • nalidixic acid
  • oxolinic acid
  • pipenamic acid

55
Naphthalidine Derivatives
  • The spectrum of action
  • narrow (only Gr- microorganisms)
  • Mechanism of action
  • blocks the enzyme DNA gyrase, as a consequence
    despiralization DNA and death of microorganisms.
  • Indication
  • when introduced into the body does not leave the
    bloodstream, excrited with the urine in unchanged
    form, so used in infectious diseases of the
    kidneys and urinary tract infection
    (pyelonephritis, cystitis, urethritis,
    prostatitis).
  • Type antimicrobial action
  • Bactericidal
  • (Side effects see FLUOROQUINOLONES)

56
Nitrofurans(classification)
  • The drug is used topically for treatment of
    wounds and hands, with anaerobic infections
  • FURACILLIN
  • FURAZOLIDONE
  • 2. The drug is used in infectious diseases of
    the GIT
  • FURAZOLIDONE
  • 3. The drug is used in infectious diseases
    caused by protozoa
  • FURAZOLIDONE
  • 4. The drug is used in infectious diseases of the
    kidneys and urinary tract
  • FURAGIN
  • FURADONIN
  • SOLOFUR

57
Nitrofurans
  • The spectrum of action
  • Gr , protozoa
  • and anaerobic.
  • Mechanism of action
  • are acceptors of H ions and enter into
    competition with the natural acceptors in the
    chain of tissue respiration, as a consequence of
    violating the microbial cell respiration and
    death.
  • Type of antimicrobial action
  • bactericidal

58
Nitrofurans
  • Side effects
  • Peripheral paresthesia and paresis
  • Hypotension (donors are NO)
  • Nausea, diarrhea, vomiting, epigastric pain,
    anorexia
  • Anemia and leukopenia
  • Allergic reactions
  • Indications see classification.

59
Derivatives of 8-oxyquinoline(classification)
  • The drug is used topically for treatment of
    wounds and hands
  • SAPROSAN
  • HLORHINALDON
  • 2. The drug is used in infectious diseases of the
    gastrointestinal tract
  • ENTEROSEPTOL
  • MEXAZA
  • INTESTOPAN
  • 3. The drug is used in infectious diseases caused
    by protozoa
  • ENTEROSEPTOL
  • QUINIOFON
  • DIYODOHIN
  • 4. The drug is used in infectious diseases of the
    kidneys and urinary tract
  • NITROXOLIN (5-NOC)

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Derivatives of 8-oxyquinoline
  • The spectrum of action
  • Gr , fungi, protozoa and anaerobic
  • Mechanism of action
  • Disrupt the synthesis of NA in the microbial
    cell
  • Uncouple oxidative phosphorylation processes
  • Communicating with iron enzymes and break
    breathing activity of microbial cells
  • All this leads to the death of microorganisms.
  • Type of antimicrobial action
  • bactericidal
  • Indication
  • see. classification

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Derivatives of 8-oxyquinoline
  • Side effects
  • Peripheral paresthesia and paresis, polyneuritis,
    headache, optic nerve damage (irreversible
    blindness).
  • Dyspepsia, anorexia, itching in the anal area.
  • Hyperthyroidism, iodine phenomenon (iodine
    poisoning a runny nose, nasal congestion, cough,
    conjunctivitis, acne-like skin rash, treatment -
    the NaCl solution).
  • Allergic reactions

62
Imidazole derivatives
  • Metronidazole
  • Tinidazole

63
Imidazole derivatives
  • The spectrum of action
  • anaerobes, Giardia, amoeba, balantidiums, some
    protozoa, Helicobacter pilory
  • Mechanism of action
  • penetrate into the cells, where the enzymatic
    action of metalloproteases separates nitro from
    them, which causes the death of the
    microorganism.
  • Nature of antimicrobial action
  • bactericidal
  • Indication
  • generalized anaerobic infection, amoebiasis,
    amoebic dysentery, giardiasis, trichomoniasis,
    balantidiazis, peptic ulcer and duodenal ulcer.

64
Imidazole derivatives
  • Side effects
  • Peripheral paresthesia and paresis, headache,
    dizziness
  • Dyspepsia, drug-induced hepatitis, a metallic
    taste in the mouth
  • Photodermatitis
  • Antabuse like syndrome (when co-administered with
    alcohol patients have hypotension, tachycardia,
    weakness, dizziness, nausea, uncontrollable
    vomiting, fear of death, allergic reactions).

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