ANTIBIOTICS 3

(YEAR 1 TERM 2)
(Session 2014-2015)
by
Professor
Dr. Naeem Hasan Khan
17.04.2015
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MACROLIDE ANTIBIOTICS
Are a group of antibiotics with a macrocyclic
lactone structure to which one or more deoxy
sugars are attached.
ERYTHROMYCIN

Binds irreversibly to a site of the bacterial ribosome

thus inhibiting protein synthesis.
Bacteriostatic but acts as bacteriocidal in higher
doses.
Administration:
Erythromycin base is destroyed by gastric acid, thus enteric
coated tablets or esterified forms of the antibiotics are
administered.
I.V. is associated with high incidence of thrombophlebitis. 2
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Conti.,
Distribution :
Erythromycin is well distributed to all body
fluids, except CSF.
Diffuses in the prostatic fluid
Concentrate in liver.

Elimination :
Erythromycin is extensively metabolized.
Inhibit the oxidation of many drugs through
interaction with cytochrome 450.
Interferes with the metabolise of theophylline
and carbamazepin.

Excretion :
Primarily concentrated and excreted in bile.
Inactive metabolites are excreted in urine.
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Conti.,

Antibacterial spectrum of
erythromycin:

Straphylococcus aureus.
Streptococcus pyogenes.
Streptococcus pneumoniae.
Corynebacterium diphtheriae.
Morexella cattarhalis.
Neisseria gonorrhoeae.
Mycoplasma pneumoniae.
Chlamydia trachomatis.
Chalamydia psittaci.

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Conti.,
Uses :
It is a drug of choice for urogenital infections occuring
during pregnancy.
Is very effective in atypical pneumonia.
Is classical drug to use in syphilis when patient is allergic
to penicillins.
Effective against many of same organisms as penicillin.
It may be used in patients with penicillin allergy.
Resistance to erythromycin is becoming a serious problem.

Adverse effects of erythromycin :

Epigastric distress.
Cholestatic jaundice.
Ototoxicity.

Contraindication : in hepatic dysfunction.

Interactions : with digoxin and food, interferes with the
absorption of erythromycin.
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AZITHROMYCIN
Binds irreversibly to a site of the bacterial
ribosome thus inhibiting protein synthesis.
Interfere tranpeptidation.
Bacteriostatic but acts as bacteriocidal in higher
doses.

Antibacterial spectrum of Azithromycin:

Chlamydia trachomatis.
Chalamydia psittaci.
Bordetella pertussis.
Campylobacter influenzae.
Legionella pneumophila.

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Conti.,
Administration :
Azithromycin is stable towards stomach acid.
Adequately absorbed upon oral
administration.
I.V. is associated with much less (1%)
incidence of thrombophlebitis as compared
to erythromycin.

Distribution of Azithromycin :

Concentrate in liver.
Widely distributed in tissues.
Serum levels of azithromycin is low.
Concentrated in neutrophils and fibroblasts.
Longest half-life.

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Conti.,
Elimination of Azithromycin :
As that of erythromycin.

Excretion :
Extensively metabolized and excreted through bile.

Uses:
More active in respiratory infections than
erythromycin.
Less active against streptococci and straphylococci
than erythromycin.
Preferred therapy in urithritis, endocervical and rectal
infections.
Is alternative to tetracyclines.

legionellosis disease.
Adverse effects of Azithromycin:
Is a drug of choice in

Same as for erythromycin.

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Cross resistance occurs with erythromycin.

CLARITHROMYCIN
This antibiotic has the spectrum of
antibacterial activity similar to that of
erythromycin.
It is effective against Haemophilus
influenzae.
A drug of choice, in combination with other
drugs in eradicating Halicobacter pylori
(bacteria in stomach responsible for
production of
high HCL acid, leading to peptic
ulcer).
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Administration and
Fate of some of
macrolide
antibiotics

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10

Some properties
of macrolide
antibiotics

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AMINOGLYCOSIDES
Aminoglycoside
(with 2 amino sugars joined by a glycosidic linkage)
antibiotics had been the mainstays for the
treatment of serious infections due to aerobic Gramnegative bacilli.
However, their use is associated with serious
toxicities, they have been replaced by safer
antibiotics, such as, third and fourth generations of
cephalosporins, Carbapenems and Flouroquinolones.
All members of this group inhibit the bacterial
protein synthesis.
They acts inside the cell by binding to the ribosome.
They are bactericidal
All members of this class resemble one another in
therapeutic, pharmacokinetic and toxic properties.
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Conti.,
Pharmacokinetics :
All aminoglycosides are water soluble and
do nor cross readily cell membrane.
Poor absorption through intestinal tract.
Administered I.V. or I.M.
Distribute mainly to extra cellular fluid.
Less transfer to CSF.
As a single daily dose is the current
practice.

Elimination :
All of them are eliminated unchanged
mainly by glomerular filtration and attain
high level in urine.
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Administration
and fate of
Aminoglycosides

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Conti.,
Antibacterial spectrum of
Aminoglycosides :
Staphylococci.
Aerobic Gram-negative bacteria (All
Enterobacteriaceae).
Bacterial resistance of aminoglycosides is
increasing due to variable problems.

Uses :
Gram-negative bacillary infections (septicaemia,
renal, pelvic and abdominal sepsis).
Bacterial endocarditis.
Tuberculosis and plague.
Topical use.
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Conti.,

Adverse activity of
Aminoglycosides :
Aminoglycoside toxicity is a risk at high doses
or longer duration.
Ototoxicity.
Nephrotoxocity.
Neuromuscular blockade.
Rashes.
bone marrow depression.
Haemolytic anaemia.
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GENTAMYCIN
is a bactericidal antibiotic that works by irreversibly
binding the 30S subunit of the bacterial ribosome,
interrupting protein synthesis. This mechanism of
action is similar to otheraminoglycosides.
Used against infections, particularly those caused
byGram-negative organisms.
However, Gentamicin is not used forNeisseria
gonorrhoeae and N. meningitidis.
Gentamicin is alsoototoxicandnephrotoxic ( with
this toxicity remaining a major problem in clinical
use).
Gentamicin is one of the few heat-stable antibiotics
that remain active even afterautoclaving.
Patients with cyctic fibrosis eliminate Gentamycin
rapidly.
When applied to eyes, give effective corneal concentration.
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STREPTOMYCIN
Streptomycin is a bacterial protein synthesis inhibitor, binds to
the small subunit of the bacterial ribosome.
Superseded as a first line choice for tuberculosis against
Mycobacterium tuberculosis and Staphylococcus aureus.
Infective endocarditis caused by enterococcus when the
organism is not sensitive to Gentamycin.
Plague has historically been treated with it as the first-line
treatment.
In veterinary medicine, streptomycin is the first-line antibiotic
for use against Gram-negative bacteria in large animals.
It is commonly combined with procaine penicillin for I.M. route.
Traditionally is given by I.M. but may also be administered by
I.V. route.
Side effects are tinitus, vertigo, nephrotoxicity, fetal toxicity,
neuromuscular paralysis, and ataxia.
Streptomycin is also used as a pesticide.
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AMIKACIN
Acts by binding to the bacterialribosomalsubunit,causing
the bacterium unable to synthesizeproteins
Is expensive.
Amikacin is most often used for treating severe, hospitalacquired infections withresistant Gramnegativebacteria.
Amikacin may be combined with a-lactam antibiotic.
Is usually used as a last-resort medication against
multidrug-resistant bacteria.
Administered by I.V. orI.M.routes or vianebulization.
Side-effects of amikacin are similar to those of other
aminoglycosides.

Effective against :
Pseudomonas aeruginosa, Pseudomonas aeruginosa
Serratia marcescens and Serratia marcescens
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NEOMYCIN
Principally used for topically for skin, eye and ear
infections.
Neomycin is not absorbed from the
gastrointestinal tract.
Similar to other aminoglycosides, neomycin has
excellent activity againstGram-negative and
Gram-positive bacteria.
It is relatively toxic to humans, and many people
have allergic reactions to it (hypersensitivity).
neomycin is known for its ability to bind to duplex
RNA with high affinity.

Spectrum:
Enterobacter cloacae.
Escherichia coli.
Proteus vulgaris.
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TETRACYCLINES
The first member of the group discovered was
Chlortetracycline derived from a golden-colored,
fungus-like, soil-dwelling bacterium
namedStreptomyces aureofaciens.
Oxytetracycline was discovered shortly afterwards
from Streptomyces rimosus.
Later on Tetracycline was developed and so on............
Tetracycline antibiotics (as a group) areprotein
synthesis inhibitors, inhibiting the binding
ofaminoacyl- t RNA to themRNA-ribosome complex.
Tetracyclines have been found to
inhibitmetalloproteinases.
Tetracycline inhibits cell growth by
inhibitingtranslation.

Translationis the process in which cellular ribosome create

protein.

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CLASSIFICATION OF TETRACYCLINES
Naturally occurring

Tetracycline.
Chlortetracycline.
Oxytetracycline.
Demeclocycline.

Semi-synthetic

Momcycline.
Lymecycline.
Meclocycline.
Methacycline.
Minocycline.
Rolitetracycline.

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Conti.,

Short acting

(half life is 6-8 hours)

Tetracycline.
Chlortetracycline.
Oxytetracycline.

Intermediate acting
12 hours)

(half life is about

Demeclocycline.
Methacycline.

Long acting

(half life is +16 hours)

Doxycycline.
Minocycline.
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TETRACYCLINES
Mechanism action of Tetracyclines:
Tetracycline antibiotics (as a group) areprotein
synthesis inhibitors, inhibiting the binding
ofaminoacyl- t RNA to themRNA-ribosome
complex. By this mechanism bacterial protein
synthesis is inhibited.

Antibacterial spectrum :
Tetracyclines are broad spectrum bacteriostatic
antibiotics.
Effective against Gram-negative and Grampositive
bacteria.

Resistance:
The most commonly encountered, naturally occuring
resistance factor confers an inability of the organism
to
accumulate the drug, thus producing resistance. 24
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PHARMACOKINETICS OF TETRACYCLINES
Absorption :
Most tetracyclines are adequately, yet incompletely
absorbed after oral ingestion.
However, taking these drugs with dairy foods in the
diet, decreases the absorption due to formation of
non-absorbable chelates of the tetracyclines with
calcium ions.
These chelates are also formed with iron,
magnesium and aluminium ant-acids.
Doxycycline and Minocycline are almost totally
absorbed by oral route.
Currently Doxycycline is preferred for parenteral
administration and Minocycline is available I.V. as
well.
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 Administration and
fate of Tetracyclines.
In tetracycline
preparations,
stability must be considered
in order to avoid formation
of toxic
epi-anhydrotetracyclines.
(Fanconis syndrome)
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IMPORTANCE OF DOXYCYCLINE
A single dose of 200 mg can prevent development
of tick bite disease.
(TICKS are external parasites living on the blood of
mammals,
birds, reptiles and amphibians, e.g. castor bean
tick).
Best used against Mycoplasma pneumoniae

(skin lesion, headache, fever followed by encephalomeningitis).

In the treatment of cholera.
In sexually transmitted
diseases.
Of choice in rocky mountain
spotted fever.
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Conti.,
Distribution:
Tetracyclines concentrate in the liver, kidneys,
spleen and skin.
They bind to tissues undergoing calcification.
Penetration in the body fluids is adequate.
All Tetracyclines enter CSF with the exception of
Minocycline.
Minocycline is not effective in C.N.S. infections.
All Tetracyclines cross the placental barrier and
concentrate in fetal bones and teeth.

Elimination:
They are metabolized and conjugated to form
soluble glucuronides.
Are secreted in bile.
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Tetracyclines are also excreted in breast milk.

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Conti.,
Adverse effects:
Gastric discomfort (Nausea, vomiting, dizziness).
Phototoxicity.
Effects the calcified tissues.
Fatal hepatotoxicity.
Intracranial hypertension.
Superinfection (overgrowth of Candida in vagina).

Contraindications of Tetracyclines:
In patients with renal problems (high urea )
except Doxycycline.
Should not be administered in pregnancy, breast
feeding and children under 10 years of age
( permanent yellow-gray staining ).
In myasthenia gravis.
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CHLORAMPHENICOL
Chlroamphenicol is active against a wide range of
Gram-positive and Gram-negative organisms. Because
of its severe toxicity, its use is restricted to lifethreatening infections for which no alternatives exist.

Mechanism of action:
The drug binds to the bacterial 50S ribosomal subunit
and inhibits protein synthesis in higher circulating
chloramphenicol levels, producing bone marrow
toxicity.
Inhibits cytochrome P450 system.

Antimicrobial spectrum of chloramphenicol:

Is a broad spectrum antibiotic (bacteriostatic or
bactericidal)
Is active against bacteria and other microorganisms.
Has excellent activity against anaerobes.
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Inhibition of the cytochrome P450

system by chloamphenicol

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Mechanism action of
Chloramphenicol

Administration and fate

of Chloramphenicol
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Conti.,
Resistance :
Is conferred that codes acetyl coenzyme A
tranferase.
When there is inability of drug to penetrate the
organism.

Pharmacokinetics:
May be administered I.V. or orally.
Completely absorbed by oral route (lipophilic
nature).
Widely distributed in body fluids.
Enters CSF.
Metabolized in liver and excreted through renal
tubules.
It is also secreted into breast milk.
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Conti.,
Adverse effects of Chloramphenicol:
G.I.T. upset and overgrowth of Candida
albicans.
Anaemias (haemolytic and aplastic).
Gray baby syndrome. This occurs in neonates
because they have decreased ability to excrete
the drug. This leads to poor feeding, depressed
respiration, cardiovascular collapse, cyanosis
(gray baby) and death.
Very high doses in adults may cause the above
toxicity.

Interactions:
Blocks the metabolism of warfarin, phenytoin,
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tolbutamide and chlorpropamide.

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THANKS FOR BEING

ATTENTIVE
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