Antimicrobial

drugs

I. Antiseptics and disinfectants.

II. Sulfonamides.
III. Synthetic chemotherapeutics.
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)
Medicines with an antimicrobial
activity are divided into 2 groups:

1 – non-selective antimicrobial agents,

causes most destructive effect on the
majority of microorganisms
(antiseptics and disinfectants).

2 - selective antimicrobial drugs

(chemotherapeutic agents).
 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.
 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
 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
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.
 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.
 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
 Lugol’s 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
 Classification continuation
II. Organic substances
1. Aldehydes: 5. Detergents:
 Aethonium
 Formaldehyde (Formalinum)  Decamethoxin
 Glutaraldehide  Roccal
 Hexamethylentetraminum  Dimexid
(Methenamine) 6. Tar, resins, products of
2. Alcochols: petroleum:
 Spiritus aethylicus (Ethyl alcohol)  Pix liquida Betulae (Birch tar)
3. Phenol derivatives:  Ichthyolum
 Phenol (Phenolum purum,  Liniment by Vishnevsky
Carbolic acid) 7. Nitrofuran derivatives:
 Cresol (Tricresolum)  Nitrofurasone (Furacilinum)
 Resorcinol 8. Antiseptics from medicinal
 Thymol
plants:
 Chlorophyliptum
 Benzylbenzoat
 Novoimaninum
4. Dyes:
 Methylenum blue
 Brilliant green (Viride nitens)
 Etacridin lactate
 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
 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 halogen’s
antimicrobial effect decreases.
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.
 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!!!
 Doesn’t 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.
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.
 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.
 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.
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.
 Potassium permanganate
 2KMnO4 + H2O = 2KOH + 2MnO2 + 3O2
It liberates oxygen in atomic form.
 Highly water soluble, used in 1:4000-
1:10000 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.
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.
 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.
 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.
 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.
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).
 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
 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.
 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.
 Ethyl alcohol
 Bactericidal activity starts with 20% alcohol and increases
with concentration. Does not affect on the spore form .
 High concentrations of alcohol in the protein environment
form dense protein aggregates.
 70% - it 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.
 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.
 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.)
 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.
 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.
 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.
 Sulfonamides

 Quinolones and Fluroquinolones

 Nitrofuran derivatives

II. Synthetic chemotherapeutic

agents
 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).

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.
 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.
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
<10 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.
 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.
Mechanism of action
 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.
 SA antimicrobial spectrum
 Currently used SA have broad spectrum, they
inhibit gram-positive and gram-negative
bacteria:Streptococcus pneumoniae, beta-
haemolytic streptococci, E. coli, klebciella,
shigella, salmonella, enterobacter, gonococci,
meningococci, and pneumococci;
 Nocardia,
 Chlamidia,
 Protozoa (toxoplasma and malarial plasmodia).
 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.
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.
 Clinical uses
 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.
 Side effects
- 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.
1. 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.

 Combined sulfa drugs
1 - Combination with 5-aminosalicylic acid:

 SALAZOSULFOPIRIDIN

 SALAZOPIRIDAZIN

2 - combined with Trimethoprim:

 Biseptol (trimethoprim + sulfamethoxazole)

 Sulfaton (trimethoprim + sulfadimezin)

 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.
 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.
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).
 Antimicrobials with different
chemical structure.
FLUOROQUINOLONES:
 mono fluorine • trifluorine substitute
substitute 1. traufloxacin
1. ciprofloxacin 2. gatifloxacin
2. ofloxacin 3. gemifloxacin
3. pefloxacin 4. moxifloxacin
4. norfloxacin
5. enoxacin
 bifluorine substitute
1. lomefloxacin
2. ofloxacin
3. sparfloxacin
 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
 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
 Naphthalidine Derivatives

 nalidixic acid
 oxolinic acid
 pipenamic acid
 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)
 Nitrofurans
(classification)
1. 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
 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
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.
 Derivatives of 8-oxyquinoline
(classification)
1. 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)
 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
 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
 Imidazole derivatives

 Metronidazole

 Tinidazole
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.
 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).
Streptogramins
 quinupristin

dalfopristin
Streptogramins
 Isolated from Streptomyces pristinaespiralis
 Used as oral agents in France since the 1960s
 Dalfopristin and quinupristin are the only parentral
agents
 The combination product (Synercid®) has up to 16 times
the activity of each agent alone
 Streptogramins inhibit bacterial protein synthesis by
irreversibly blocking ribosome functioning
 Each component is bacteriostatic but the combination is
bacteriocidal
 The main reason for development and approval is VRE
Synercid™

Combination of dalfopristin and

quinupristin
administered by intravenous infusion
Metabolism is not dependent on
cytochrome P450. But a major inhibitor of
the activity of cytochrome P450 3A4
isoenzyme
Elimination through fecal excretion
When you may ask for Synercid™

Serious VRE infection

MRSA infection for which you can not use

vancomycin +/- linezolid
Safety of Synercid™

Safe with no major toxicities

Thrombophlebitis, GI
Mostly given through a CVL
Oxazolidinones
Oxazolidinones

Synthetic antibiotics
One approved (Linezolid), some are still
investigational (Eperezolid, furazolidone)
Linezolid
Linezolid
 Approved for use in adults April 2000 and for
pediatrics December 2002
 Works against aerobic gram-positive organisms
 Linezolid inhibits bacterial protein synthesis by
interfering with translation
 binds to a site on the bacterial 23S ribosomal
RNA of the 50S subunit; this action prevents the
formation of a functional 70S initiation complex,
an essential step in the bacterial translation
process
Linezolid
 Linezolid is administered by intravenous infusion
or orally
 oral bioavailability for linezolid is 100%.
 have significant penetration into bone, fat,
muscle, and hematoma fluid
 metabolism is non-enzymatic and does not
involve CYP450
 does not inhibit or induce CYP450 isoenzymes.
 Non-renal clearance accounts for 65% of an
administered linezolid dosage (no adjustment in
renal failure)
Indications of Linezolid

Mainly developed because of VRE

first new antibiotic approved to target
methicillin-resistant staphylococci in 35
years
Resistance to Linezolid

linezolid-resistant VRE organisms were

being discovered in various institutions

Also some MRSA

Safety of Linezolid

linezolid is a non-selective inhibitor of

monoamine oxidase (MAO)
Thank you)))