ANTIMICROBIAL DRUGS

CLASSIFICATION
AND
MECHANISM OF ACTION
• ANTIMICROBIAL DRUGS
DRUGS THAT EITHER KILL THE BACTERIA OR INHIBIT
THEIR GROWTH
• BACTERICIDAL DRUG
THE DRUG THAT KILL THE BACTERIA
• BACTERIOSTATIC DRUG
• THE DRUG THAT INHIBIT THE GROWTH OF BACTERIA
• SELECTIVE TOXICITY
A DRUG THAT IS HARM FUL FOR A MICROBE BUT NOT
OR LITTLE HARMFUL TO THE HOST . AN ABSOLUTE
SELECTIVE TOXICITY NEVER BE ACHIEVED AND MAY BE
RESULT IN ADVERSE EFFECTS
• ADVERSE EFFECT
AN UNWANTED EFFECT OF DRUG ON HOST THAT
MAY BE HARMFUL
• BROAD SPECTRUM ANTIBIOTICS
THE DRUGS , ACTIVE AGAINST SEVSRAL TYPE OF
THE ORGANISMS
• NARROW SPECTRUM
THE DRUGS ACTIVE AGAINST ONE OR VERY FEW
TYPE OF THE ORGANISMS
• PROTOPLAST
DAMAGE OF CELL WALL DUE TO DRUG OR
LYSOZYME RESULT IN FORMATION OF LIVE SPHERICAL
BACTERIA USUALLY G+VE BACTERIA
• SPHEROPLAST
DAMAGE OF CELL WALL DUE TO DRUG OR
LYSOZYME LED TO FORMATIOM OF SPHERICAL LIVING
BACTERIA , USUALLY G-VE BACTERIA
THESE TWO FORMS ARE LIMITED ONLY BY
CYTOPLASMIC MEMBRANE
• CHEMOPROPHYLAXIS
• Administration of antimicrobial drugs to
prevent infection
OR
• Early treatment of an asymptomatic infection
• EXAMPLES
Penicillin G once a month prevent the
re infection of S. pyogenes in rheumatic
patient . This drug also prevent syphilis
Oral Tetracyclines prevent from Plague
Isoniazid 300 mg / day for 6-12 months
used to prevent Tuberculosis
• SYNERGISM
• The use of two or more antimicrobial
drugs to block the microbial metabolic
pathway by two or more different methods
• EXAMPLES------ Septran
TRIMETHOPRIM and SULPHONAMIDE.
Both inhibit the synthesis of bacterial D.N.A
precursor by blocking the synthesis of
FOLIC AID but by different metabolic
pathway . PENICILLINS inhibit the
synthesis of bacterial cell wall and facilitate
the penetration of more GENTAMICIN With
in the bacterial cell
 CLASSIFICATION OF ANTIMICROBIAL DRUGS
ON THE BASIS OF MECHANISM OF ACTION
• ANTIMICROBIAL DRUGS

INHIBIT SYNTHESIS OF CELL WALL

INHIBIT SYNTHESIS OF PROTEIN

ALTER THE CELL MEMBRANE STRUCTURE

INHIBIT THE NUCEIC ACID SYNTHESIS

MISCELLENOUS MODE OF ACTION

 ANTIMICROBIAL DRUGS INHIBIT CELL WALL
SYNTHESIS
• Penicillins (large group)

• Cephalosporins ( large group)

• Monobactam ( Aztreonam)

• Carbepenem( imipenem)

• Vancomycin

• Cycloserine

• Bacitracin
ANTIMICROBIAL DRUGS ALTER THE CELL
MEMBRANE
Polymixins ( Polymyxin – E, Colistin)

ANTI FUNGAL

Amphoteracin B,

Azoles

Imidazoles, Triazoles
 ANTIMICROBIAL DRUGS INHIBIT
PROTEIN SYNTHESIS
• Chloramphenicol

• Macrolides ( Erythromycin, Clarithromycin

Azothromycin, Dirithromycin)
• Lincomycin and Clindamycin
• Tetracyclines ( large group of drugs)
• Amino glycosides ( a large group of drugs)
 ANTIMICROBIAL DRUGS INHIBIT
SYNTHESIS OF NUCEIC ACID
• Quinolones ( large group of drugs)

• Rifampicin

• Pyrimethamine

• Sulphonamides

• Trimethoprim
 ANTIMICROBIAL DRUGS HAVING
DIFFERENT MODE OF ACTION

•
Inhibit synthesis of Mycolic acid
• Pyrazinamide
unknown mode of action
• Metronidazole
Inhibit DNA synthesis or act as electron sink
• Griseofulvin
Anti fungal that prevent formation of Mitotic
spindles
 PENICILLINES
• Called β lactam drug
• Drugs are inactivated when enzymes β-
lactamases cleaved β-lactam ring of the
drug
• Derived from a mould PENCILLINUM
• All Penicillines share same basic
structure (6- amino Penicillanic acid
nucleus)
• Are bactericidal drugs, inhibit the cell
wall synthesis of the growing bacteria
but not act on non growing bacteria
• The effectiveness of the drug can be
enhanced by a series of chemical changes
in the side chain
• Major disadvantage of Penicillines is hyper
sensitivity reaction that includes
ANAPHYLAXIS REACTION,
SKIN RASHS,
HEMOLYTIC ANEMIA ,
NEPHRITIS,
DRUG FEVER.
 Classification of Penicillin
• On the basis of changing in the side chains,
Penicillin are classified into 4 groups
• 1- group –A
Includes Penicillin G that is highly active
against G + ve bacteria and relatively less
active against G- ve bacteria
highly sensitive to HCL of stomach and β-
lactamase enzymes
• 2-group- B
Includes Nafcilin having relatively low
activity against G + ve bacteria but highly
active against G-ve bacteria . These drugs are
relatively resistant to β lactamase
• 3 group-C
Includes Piperacillin, having a broad
spectrum activity i.e. highly active against
G + ve and G - ve bacteria but sensitive to
βlactamase
• 4 group- D
Includes Amoxicillin, Ampicillin. These
drugs are highly resistant to gastric acid but
sensitive to β-. lactamase . The
effectiveness of these drugs can be
enhanced by adding anti β- lactamase drugs
e.g.
AMOXICILLIN + CALUVANIC ACID=AUGMENTIN
 MODE OF ACTION OF PENICILLINS
• Bacteria posses certain receptors on their surface
called PENICILLIN BINBDING PROTEINS (PBP)
some of them are TRANSPEPTIDASE enzymes.
When drug binds with these receptors it inhibit the
final cross linkage step of the cell wall synthesis

• On the other hand Penicillines also activate other

enzyme MUREIN HYDROLASE that lyses the
synthesized cell wall
 CEPHALOSPORINS
Consist of 4 generations
1st generation includes CEPHRADINE , CEPHALEXIN
etc these drugs are very active against G + ve
bacteria except those , produce β-lactamases e.g.
Staph; aureus and Enterococci and are moderately
active against G-ve bacteria except Pseudomonas
SP; and often active against anaerobic bacteria
except Bacteroid fragilis
2nd generation includes CEFOXITIN,CEFUROXIME,
CEFACLOR etc, having broad spectrum activity .
These drugs are more active than the drugs of 1st
generation
3rd generation are includes
CEPHOTAXIME,CEFTRIAXONE, CEFIXIME etc
used successfully against hospital acquired
( nosocomial) infections .
These drugs cross the blood brain barrier and
appear in spinal fluid in sufficient concentration
these drugs are less active against G +ve bacteria
than the G-ve bacteria .

4th generation includes CEFEPIME. This drug is very

active against resistant G - ve rods for e.g.
Pseudomonas aerouginosa
 Monobactam (AZTREONAM)
• Are bactericidal β-lactam drug

• Resistant to βlactamases.

• Active against G – ve bacteria

• These drugs are not active against G + ve and

anaerobic bacteria
 Carbapenem (Imipenem)
• β-lactam drug ,
• Having a very good activity against
G + ve , G-ve and anaerobic bacteria
• This drug is resistant to β-lactamase but
hydrolyzed by DIHYDRO PEPTIDASE in
renal tubules , therefore it is used in
conjunction of peptidase inhibitors
• Excellent penetration in spinal fluid
• Adverse effects includes
Vomiting,
Diarrhoea ,
Skin rashes .
Increased serum level in patients of
renal failure lead to seizures .

• Contraindication hypersensitivity reaction

with Penicillines
 VANCOMYCIN
• Block transpeptidation by binding directly
with D-alanyle-D-alanine portion of
pentapeptide side chain that block the
transpeptidase from binding
• It also inhibit Transglycosylase that use in
the synthesis of Peptidoglycane
• It is the only drug that is used against multi -
drug resistant Staph; aureus,
Enterococci and S. epidermidis but
partial or complete resistant strains are
reported throughout the world
• Cycloserine
similar in structure with D-alanine and
inhibit the formation of D-alanyle-D-
alanine portion of pentapeptide side
chain

• Bacitracin
It prevent the transport of peptidoglycane
across the cell membrane and also
inhibit the regeneration of lipid carrier
molecules
Too toxic for systemic use
 Drugs inhibit Protein Synthesis
• Drugs act on 30 s Ribosomes

AMINOGLYCOSIDES

TETRACYCLINES

• Drugs act on 50 s Ribosomes

CHLORAMPHENICOL

MACROLIDES
 AMINOGLYCOSIDES
• BACTERICIDAL DRUGS
Streptomycin (anti Tuberculosis)
Gentamicin,
Amikacin,
Kanamycin,
Tobramycin,,,
Neomycin,etc
• Active against G-ve bacteria
• Not absorb by GIT
• Poorly penetrate in CSF therefore given
intrathecally in case of G-ve meningitis
• These drugs kill bacteria by acting on 30 s
ribosome by misreading of mRNA and by
inhibition of initiation complex
• toxic effects on
KIDNEYS and
Auditory and vestibular portion of
8TH CRANIAL NERVE
 Tetracycline

• Bacteriostatic drugs
• includes
Tetracycline,
Oxytetracycline,
Doxycycline,
Minocycline,
Demeclocycline etc
• These drugs are active against
G + ve , G - ve bacteria ,
Mycoplasma,
Rickettsiae, and
Chlamydia Sp;
• These drugs inhibit protein synthesis by
acting on 30S ribosome by blocking the
entry of AMINOACYL-TRANSFER-RNA to
the acceptor site
• Adverse effects includes
Diarrhoea,
Brown staining of the teeth in young
children and foetus .
• Contra indicated in pregnancy and in young
children
 Chloramphenicol
• Act on 50 S ribosome
• Broad spectrum ,
• Bacteriostatic
• Bactericidal activity against most commonly
isolated bacteria in cases of meningitis
• It suppress the bone marrow activity.
• It inhibit protein synthesis by blocking the
action of PEPTIDYL-TRANSFERASE on 50 S
ribosome (that yield new peptide bonds)
 Macrolides (Erythromycin)
• Bacteriostatic ,
• Broad spectrum
• Active against
G + ve bacteria ,
Mycoplasma Sp; ,
Legionella Sp;
• Inhibit protein synthesis by acting on 50 S
Ribosomes by blocking the translocation step
• Other drugs of Macrolide group (Clarithromycin,
Azothromycin, Dirithromycin)
have same mode of action but are more
efficient than erythromycin
• Adverse effect includes GIT upset
 DRUGS INHIBIT DNA SYNTHESIS
• SULPHONAMIDES
• Are Synthetic , broad spectrum, Bacteriostatic
drugs
• Used against E.coli, S. pneumoniae,
H. infuenzae, Shigella Sp; , Chlamydia Sp;,
and Nocardia Sp;

• Mode of action
Bacteria synthesize their own Folic acid
where as human required preformed Folic
acid . production of Folic acid in bacteria
inhibited at precursor level
Adverse effects rare drug fever, rashes,
bone marrow depression
• Sulphonamide block the synthesis of
DNA by following steps
Bacteria synthesize Folic acid from
p- aminobenzoic acid (PABA) that form
Di hydro folic acid (precursor of tetra
hydro folic acid that convert into Folic
acid.
• Folic acid is used in synthesis of DNA
precursors Adenine , Guanine and
Thymine
Sulphonamide attach and inactivate the
p-amino benzoic acid
• QUINOLONES
• Bactericidal drugs
Ciprofloxacin,
Norfloxacin,
Ofloxacin,
Pefloxacin,
Lomefloxacin,
Nalidixic acid,
Cinoxacin,
Oxolinic acid
• Some drugs when taken orally not achieve
significant serum level and excreted in urine
therefore use in UTI e.g. Nalidixic acid, Oxolinic acid
etc
• while other drugs achieve useful level in Serum and
Tissues e.g. Ciprofloxacin, Norfloxacin etc
• These drugs actively used against
Faimly Enterobacteriacae,
Nesseria Sp; and
Chlamydia Sp;
Pseudomonas aeruginosa require
large dose of drugs
• These drugs inhibit the synthesis of DNA by
inhibiting the DNA Gyrase
• Adverse effects damage growing bones and
cartilages
• contra indicated in treatment of growing
children and in pregnancy