Antibiotic presentation

2. PROTEIN SYNTHESIS
INHIBITORS
 substance that stops or slows the growth or proliferation of
cells disrupting the processes that lead directly to the
generation of new proteins.
 usually refers to substances that act at the ribosome level
(either the ribosome itself or the translation factor).
 The bacterial ribosome is smaller (70s) than the mammalian
ribosome(80s).
 The mammalian mitochondrial ribosome more closely
resembles the bacterial ribosomes.
 Although drugs that interact with the bacterial site usually
spare the host cells, high levels of drugs like chlorampenicol or
the tetracyclines may cause toxic effects as a result of
interaction with the mitochondrial ribosomes.

3. PROTEIN SYNTHESIS
INHIBITORS
TETRACYCLINES
AMINOGLYCOSIDE
S
MACROLIDES
CHLORAMPHENICO
L
CLINDAMYCIN
Demeclocycline
Doxycycline
Minocycline
Tetracycline
Amikacin
Gentamicin
Neomycin
Netilmicin
Streptomycin
Tobramycin
Azithromycin Clarithromycin Erythromycin

4. TETRACYCLINES
Demeclomyci
n
Doxycyclin
Minocyclin
Tetracyclin

5. Group of closely related compounds that consist of 4
fused rings with a system of conjugated double bonds.
Small differences in clinical efficacy reflect a variation in
their individual pharmacokinetics due to substitution on
these rings.
Generally bacteriostatic
Drugs of choice for infections for:
 Chlamydial infection
 Rocky mountain spotted fever
 Mycoplasma pneumonia
 Cholera
 Lyme disease
I. TETRACYCLINES

6. Absorption: adequately but incompletely absorbed
after oral ingestion.
Taking these drugs concomitantly with dairy foods
in the diet decreases absorption .
Distribution: concentrate in the liver ,kidney,
spleen, and skin and bind to tissues undergoing
calicification, or tumors that have a high calcium
content.
the parent drug and/or its metabolites are secreted
into the bile: most are reabsorbed in the intestine and
enter the urine by glomerular filtration.
PHARMACOKINETICS

7. Epigastric distress
Deposition in bone and primary dentition occurs
Discoloration and hypoplasia of the teeth
Temporary stunting of growth
Hepatotoxicity
Phototoxicity
Renal damage
Hypersensitivity
Diabetes insipidus ( with demelocycline)
Teratogenecity
Damage to natural gut flora
Vestibular problems (dissiness, bnausea, vomiting)
Pseudotumor cerebri ( benign intracranial hypertension
characterized by headache and blurred vision
Overgrowth of Candida or of resistant staphylococci
ADVERSE EFFECTS

8. Renally impaired patients should not be
treated with any of the tetracyclines except
doxycycline.
May aggravate pre-existing azotemia by
interfering with protein synthesis, thus
promoting amino acid degradation.
Should not be employed in pregnant or
breast-feeding women, or in children under 8
years of age.
CONTRAINDICATIONS

9. TETRACYCLINE DRUGS

10. used to treat a wide variety of bacterial infections, including
those that cause acne, bronchitis and lyme disease.
widely used (though off-label in many countries) in the
treatment of hyponatremia (low blood sodium concentration) due
to the syndrome of inappropriate antidiuretic hormone (SIADH)
when fluid restriction alone has been ineffective.
induces nephrogenic diabetes insipidus (dehydration due to the
inability to concentrate urine).
drug of choice for treating SIADH
contraindicated in children and pregnant ,nursing woman.
interfere with bone development and may discolour teeth.
DEMECLOCYCLINES

11. Acts by binding to the 30S- and 50S-RNA,
which impairs protein synthesis by bacteria.
Bacteriostatic
Impairs the action of antidiuretic hormone,
but it is thought that it blocks the binding of
the hormone to its receptor.
Mode of Action

12. only tetracycline is known to cause
nephrogenic diabetes insipidus.
Adverse Effects

13. Used to treat:
urinary tract infections,
acne, gonorrhea
chlamydia, periodontitis (gum disease)
Also used to treat blemishes, bumps, and acne-like
lesions caused by rosacea. It will not treat facial
redness caused by rosacea.
May be used in combination with other medicines to
treat certain amoeba infections.
Can cause permanent yellowing or graying of the
teeth, and it can affect a child's growth.
DOXYCYCLINE

14. sold as Minocin, Dynacin, Vectrin, Solodyn and
generic minocycline
kills the acne bacteria more effectively than many
other acne pills and has a separate "anti-
inflammatory" effect
safer than ibuprofen or penicillin
standard treatment for severe acne
MINOCYCLINE

15. hypersensitivity lupus/hepatitis, which
causes severe joint pains
pseudotumor cerebri (an accumulation of
fluid around the brain) that causes
progressively worsening headaches and
vision problems
Adverse Effects

16. AMINOGLYCOSIDES
Tobramycin
Gentamicin
Amikacin
Neomycin
Netimicin
Streptomyci
n

17. mainstays of treatment of serious infections due to
aerobic gram-negative bacilli.
Replaced to some extent by safer antibiotics such
as the third generation drugs:
Cephalosporins
Fluoroquinolones
Imipenem/cilastatin
* Aminoglycosides that are derived from
Streptomyces have “mycin” suffixes , whereas those
from micromonospora end in “micin”.
II. AMINOGLYCOSIDES

18. They bind to the bacterial 30S ribosomal subunit
(some work by binding to the 50S subunit)The
protein synthesis inhibition of aminoglycosides does
not usually produce a bactericidal effect, let alone a
rapid one as is frequently observed on susceptible
Gram-negative bacilli.
Aminoglycosides competitively displace cell biofilm-
associated Mg2+ and Ca2+ that link the
polysaccharides of adjacent lipopolysaccharide
molecules. "The result is shedding of cell
membrane blebs, with formation of transient holes
in the cell wall and disruption of the normal
permeability of the cell wall.
Mode of Action

19. This action alone may be sufficient to kill most
susceptible Gram-negative bacteria before the
aminoglycoside has a chance to reach the 30S
ribosome.The antibacterial properties of
aminoglycosides were believed to result from
inhibition of bacterial protein synthesis through
irreversible binding to the 30S bacterial ribosome

20. Long-term treatment with high doses also entails the
risk of irreversible inner ear lesions (imbalance,
decreased hearing or deafness). According to many
specialists, netilmicin is the aminoglycoside with the
smallest nephrotoxic and ototoxic effect.
Cutaneous and systemic hypersensitive reactions,
gastrointestinal pain, and an increase of liver
enzymes are rare.

21. synthetic derivative of kanamycin.
Nephrotoxic and ototoxic
Many gram negative enteric bacteria are inhibited in vitro
namely:
Proteus
Pseudomonas
Anterobacter
Serratia
*strains of multi-drug resistant Myobacterium tuberculosis,
including streptomycin-resistant strains , are usually
susceptible to amikacin.
AMIKACIN

22. isolated from micromonospora purpurea
Effective against both gram-positive and gram-negative organisms
Inhibits in vitro many strains of staphylococci and coliforms and other
gram-negative bacteria
A synergistic companion with β-lactam antibiotics against:
-- Pseudomonas
-- Proteus
-- Enterobacter
-- Klebsiella
-- Serratia
-- Stenotrophomonas
-- Other gram-negative rods that may be resistant to multiple other
antibiotics
GENTAMICIN

23. Intramuscular or intravenous administration
Topical: gentamicin sulfate: treatment of infected
burns, wounds, or skin lesions and prevention of
catheter infections.
Intrarhecal: Meningitis

24.  Nephrotoxicity (reversible)
 Ototoxicity (irreversible)
 Loss of hearing
ADVERSE EFFECTS

25. active against gram-positive and gram-negative bacteria and
some mycobacteria
♫The widespread use of these drugs in bowel preparation for
elective surgery has resulted in the selection of resistant
organisms and some outbreaks of enterocolitis in hospitals.
poorly absorbed from the GI tract
excreted in feces
excretion of any absorbed drug is mainly through glomerular
filtration in the urine.
too toxic for parenteral use.
NEOMYCIN

26. At higher dose, may produce systemic toxicity
Topical administration : used on infected surfaces or
injected into joints, the pleural cavity, tissue spaces, or
abscess cavities where infection is present.
Oral administration: for preparation for elective bowel
surgery
ADVERSE EFFECTS:
♫prolonged use may result to severe allergic
reactions
♫Auditory function is more affected than
vestibular

27. primarily suited for the treatment of dangerous
Gram-negative infections, whereby it demonstrates
relatively good tolerance. It is particularly indicated
for septicemias that have been caused by
pseudomonas or gentamicin-resistant germs.
can also be combined with clindamycin or
metronidazole for intra-abdominal and
gynecological infections.
well suited for the treatment of children with Gram-
negative sepsis.
NETILMICIN

28. Netilmicin has proven effective against
pulmonary infections with cystic fibrosis and
— in combination with other antibiotics —
against several other infections (e.g. in
connection with operations or traumatic
wounds, Klebsiella infections).
Urinary tract infections should only be treated
with oral netilmicin, and only if the problems
cannot be solved with better tolerated drugs.

29. binds to bacterial ribosomes and blocks the protein synthesis, which has
bactericidal consequences. It is an antibiotic with a broad spectrum with
respect to Gram-negative bacili. All enterobacteriaceae (E. coli, Klebsiella,
Enterobacter, Serratia, Proteus, etc.) are sensitive. Its activity against
Pseudomonas aeruginosa is particularly useful.
Netilmicin is also active against Staphylococcus aureus; however,
methicillin-resistant staphylococci are often also resistant against
aminoglycosides. Anaerobic germs are also resistant.
causes renal damage particularly in subjects who have been administered
high doses over a long period of time, as well as in patients with pre-
existing renal failure, in combination with nephrotoxic drugs, and in elderly
subjects. Approximately 7 to 8% of the treated subjects experience an
increase of the creatinine levels, proteinuria, cylindruria, etc. If netilmicin is
discontinued promptly renal damages may be reversible.
PHARMACOKINETICS

30.  Isolated from a strain of streptomyces griseus.
 Mainly used as a second-line agent for treatment of
tuberculosis, given intramuscularly or IV.
 Streptomycin plus penicillin is effective for enterococcal
endocarditis and 2-week therapy of viridans streptococcal
endocarditis.
CONTRAINDICATION
-- during pregnancy, can cause deafness in
the newborn.
STREPTOMYCIN

31. Binds to bacterial ribosomes and blocks the protein
synthesis, which has bactericidal consequences
with a broad spectrum with respect to Gram-negative
bacili. All enterobacteriaceae (E. coli, Klebsiella,
Enterobacter, Serratia, Proteus, etc.) are sensitive
activity against Pseudomonas aeruginosa and
Staphylococcus aureus
PHARMACOKINETICS

32. vestibular toxicity (nausea, vomiting, vertigo)
paresthesia of the face
rash
fever
urticaria
angioneurotic edema
eosinophilia
Side effects may be more likely and more severe in
patients with underlying renal insufficiency.
ADVERSE EFFECTS

33. antibacterial spectrum similar to
gentamicin
Pharmacokinetic properties are virtually
identical to those of gentamicin
More against pseudomonas
Ototoxic and nephrotoxic
Formulated in solution for inhalation for
treatment of pseudomonas aeruginosa
Not for patients with pre existing renal,
vestibular, or hearing disorders.
TOBRAMYCIN

34. MACROLIDES
Azithromycin
Clarithromycin
Erythromycin

35. -- Group of antibiotics with a macrocyclic lactone structure.
-- Erythromycin was the first of these to find clinical application
both as the drug of first choice.
-- The new members of this family, clarithromycin and
azithromycin have some features in common with and others
that improve on, erythromycin.
III. MACROLIDES

36. Binds irreversibly to a site on the 50S subunit of
the bacterial ribosome, thus inhibiting the
translocation steps of protein synthesis. Generally
considered to be bacteriostatic, they may be cidal
at higher doses. The binding site is either identical
to or in close proximity to that for lindomycin,
clindamycin, and chloramphenicol.
A. Mode of Action

37. 1. Erythromycin
-- effective against the same organisms as penicillin
G; it is used in patients allergic to the penicillins.
-- used to treat many different types of infections
caused by bacteria. It is also used to prevent bacterial
endocarditis and attacks of rheumatic fever
B. Antibacterial spectrum
AE: Gastrointestinal disturbances, such as diarrhea, nausea, abdominal
pain, and vomiting,

38. 2. Clarithromycin
-- effective against Haemophilus influenzae
-- Its activity against intracellular pathogens such as
Chlamydia, Legionella and Ureaplasm is higher than that
of erythromycin
-- used to treat pharyngitis, tonsillitis, acute maxillary
sinusitis, acute bacterial exacerbation of chronic
bronchitis, pneumonia

39. 3. Azithromycin
-- less effective against streptococci and staphylococci
than erythromycin
-- far more active against respiratory infections due to
Haemophilus influenzae and Moraxella catarrhalis
-- it is now the preferred theraphy for urethritis caused by
Chlamydia trachomatis
-- its activity against Mycobacterium avium intracellular
complex has not proven to be clinically important, except in
AIDS patients with disseminated infections.

40. 1. ADMINISTRATION:
-- the erythromycin base is destroyed by gastric acid; thus
either enteric coated tablets or esterified forms are
administered.
-- All are adequately absorbed on oral administration
-- Clarithromycin and azithromycin are stable to stomach
acid and are readily absorbed
-- intravenous administration of erythromycin is associated
with a high incidence of thrombophlebitis.
2. DISTRIBUTION:
-- Erythromycin distributes well to all body fluids except the
cerebrospinal fluid (CSF)
-- Clarithromycin and azithromycin are widely distributed in
tissues.
PHARMACOKINETICS

41. 3. METABOLISM:
-- Erythromycin is extensively metabolized and is known
to inhibit the oxidation of a number of drugs through its
interaction with the cytochrome P-450 systems
-- Clarithromycin is oxidized to the 14-hydroxy derivative,
which retains antibiotic activity
-- Azithromycin does not undergo metabolism
4. EXCRETION
-- Erythromycin and azithromycin are primarily concentrated
and excreted in an active form in the bile.
-- Clarithromycin and its metabolites are eliminated by the
kidney as well as the liver.

42. 1. Epigastric distress
2. Cholestatic jaundice
3. Ototoxicity
CONTRAINDICATIONS: Patients with hepatic dysfunction
should not be treated with erythromycin, since the drug
accumulates in the liver.
E. Adverse Effects

43. -- active against a wide range of gram-positive and gram-
negative organisms, but because of its toxicity, its use is
restricted to life-threatening infections in which there are no
alternatives
IV. CHLORAMPHENICOL

44. The drug binds to the bacterial 50S
ribosomal subunit and inhibits protein
synthesis at the peptidyl transferase
reaction. Because of the similarity of
mammalian mitochondrial ribosomes to
those of bacteria, protein synthesis in
these organelles may be inhibited at high
circulating chloramphenicol levels,
producing bone marrow toxicity.
A. Mode of action

45. CHLORAMPHENICOL
-- a broad spectrum antibiotic
-- active not only against bacteria but
also against other microorganisms such
as rickettsiae.
-- has excellent activity against
anaerobes
-- either bactericidal or
bacteriostatic, depending on the organism
B. Antimicrobial spectrum

46. -- it may be administered either intravenously
or orally
-- completely absorbed via the oral route
because of its lipophilic nature and is widely
distributed throughout the body.
-- excretion of the drug depend on its
conversion in the liver to a glucuronide that is
then secreted by the renal tubule.
D. Pharmacokinetics

47. The clinical use of Chloramphenicol is limited because of
the serious adverse effects associated with its
administration. In addition to gastrointestinal upsets,
overgrowth of Candida may appear on the mucous
membrane.
1. Anemias
2. Gray baby syndrome
3. Interactions: Chloramphenicol is able to inhibit
some of the hepatic mixed function oxidases and thus can
block the metabolism of suc drugs as warfarin, phenytoin,
tolbutamide and chlorpropamide.
E. Adverse Effect

48. -- has a mechanism of action that is the same as that of
erythromycin.
-- employed primarily in the treatment of infections caused by
anaerobic bacteria, such as Bacteroides fragilis.
-- significantly active against nonenterococcal, gram-positive
cocci.
-- well absorbed by oral route
-- In addition to skin rashes, the most serious adverse effect is
potentially fatal pseudomembranous colitis caused by
overgrowth of Clostridium difficile.
V. Clindamycin