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.

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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).
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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.

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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

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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.

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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.

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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

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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).

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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

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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.

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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.

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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.

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• 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

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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

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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

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Naphthalidine Derivatives

• nalidixic acid
• oxolinic acid
• pipenamic acid

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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)

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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

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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

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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.

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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

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Imidazole derivatives

• Metronidazole
• Tinidazole

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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.

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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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Thank you)))