1. INTRODUCTION OF CHEMOTHERAPY

BYBY
Dr.Dr. SAMINATHAN KAYAROHANAMSAMINATHAN KAYAROHANAM
M.PHARM, M.B.A, PhDM.PHARM, M.B.A, PhD
INTRODUCTION OF CHEMOTHERAPYINTRODUCTION OF CHEMOTHERAPY
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NUM CONTENT SLIDE
I DEFINITIONS 4
II HISTORY 7
III MECHANISMS OF ANTIMICROBIAL AGENTS 9
IV MECHANISMS OF ANTIBACTERIAL RESISTANCE 17
V GENERAL PRINCIPLES OF ANTI-INFECTIVE THERAPY 28
VI IDEAL ANTIMICROBIAL DRUG 29
VII PREVENTION OF ANTIBIOTIC RESISTANCE 30
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LEARNING OUTCOME
1. Able to understand and describe about antibiotics.
2. Understand the history of some antibiotics.
3. Abele to demonstrate the various mechanism of antibiotics.
4. Able to describe the antibiotic resistance mechanism and the
types of resistance
5. Able to understand the principles of antibiotic therapy.
6. To gain the knowledge of ideal antimicrobial drug therapy.
7. Able to describe and demonstrate, how to prevent the
antibiotic resistance.
Dr.K.Saminathan.M.Pharm, M.B.A, Ph.D

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I.DEFINITIONS
Chemotherapy is the drug treatment for the
diseases caused by pathologic microorganisms,
parasites, and tumour cells.
“Chemical substance used to kill the
microorganism and cancer cell”
The objective of chemotherapy is to study and to
apply the drugs that have highly selective toxicity to
the pathogenic microorganisms and have no or less
toxicity to the host.
CON ...
4 Dr.K.Saminathan.M.Pharm, M.B.A, Ph.D

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WHAT IS AN ANTIBIOTIC?
“Antibiotic” is from antibiosis, meaning against life.
“Substances produced by various species of microorganisms
(bacteria, fungi, actinomycetes) to kill or suppress the growth of
other microorganisms”
The minimal inhibitory concentration (MIC)
the minimum amount of a drug required to inhibit the growth of
bacteria in vitro.
• The minimal bactericidal concentration (MBC)
the minimum amount of a drug required to kill bacteria in vitro.
TYPE
Natural Antibiotics Antimicrobial drugs produced by microorganisms.
Synthetic Antibiotics Antimicrobial drugs
synthesized in the lab. CON ...

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Antimicrobial spectrum : the scope that
a drug kills or suppresses the growth of
microorganisms.
Narrow-spectrum: The drugs that only act
on one kind or one strain of bacteria.
(isoniazid )
Broad-spectrum: The drugs that have a
wide antimicrobial scope. (tetracycline,
chloramphenicol )
CON ...

II.HISTORY
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1929 Penicillin discovered by
Alexander Fleming
Messy lab, cool damp weather, luck
1940 Florey and Chain mass produce
penicillin for war time use, becomes
available to the public.
1935 Sulfa drugs discovered
1943 Streptomycin discovered
Western civilization fundamentally changed
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III. MECHANISMS OF ANTIMICROBIAL AGENTS
1.INHIBITION OF CELL WALL SYNTHESIS
2.INHIBITION OF FUNCTIONS OF CELLULAR MEMBRANE
3. INHIBITION OF PROTEIN SYNTHESIS
4.INHIBITION OF NUCLEIC ACID SYNTHESIS
5.INHIBITION OF FOLIC ACID SYNTHESIS
CON ...
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BACTERIAL CELL STRUCTURE

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CON ...

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1. Inhibition of cell wall synthesis
– Penicillins and cephalosporins stop synthesis
of wall by preventing cross linking of
peptidoglycan units.
– Bacitracin and vancomycin also interfere
here.
– Excellent selective toxicity
CON ...

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2. Inhibition of functions of cellular
membrane:
– The bacterial cell membrane is also called
cytoplasmic membrane. Its main compounds
are proteins and lipids.
– Polymyxins can selectively combine with
phosphatide in the cell membrane and cause
the increase of membranous permeability. As
the result, some important materials will
outflow from bacterial cells and result in
death of bacteria. CON ...

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3. Inhibition of protein synthesis
– Due to differences in ribosomes
– Eucaryotic cells have 80S (60S + 40S subunits)
ribosomes.
– Procaryotic cells have 70S (50S + 30S subunits)
ribosomes.
– Examples:
• Chloramphenicol,Macrolides and Clindamycin
bind to the 50S subunit.
• Tetracyclines and Aminoglycosides bind to
the 30S subunit.
CON ...

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4. Inhibition of nucleic acid synthesis
– Stop DNA replication
• Example: Quinolones-inhibiting DNA
gyrase; Metronidazole???-DNA
Polymerase
– Or stop RNA synthesis
• Example: Rifampin -binds to the bacterial
DNA-dependent RNA polymerase.
CON ...

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5. Inhibition of folic acid synthesis
A drug mimics a normal metabolite and
acts as a competitive inhibitor.
– Enzyme of cell recognizes the drug instead of
the normal metabolite-Pathway stops.
– Example: Sulfonamides and trimethoprim are
similar to PABA (para aminobenzoic acid).
inhibit folic acid synthesis by blocking
dihydrofolic acid synthase and reductase
respectively. CON ...

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IV.RESISTANCE TO ANTIBACTERIAL AGENTS
• Drug resistance is the phenomenon that
susceptibility of pathogenic microorganisms
to drugs becomes lower or even loses after
the microorganisms contact with drugs many
times.
• When the bacteria show resistance to one
drug, they are also resistant to some other
drugs. This phenomenon is called cross
drug resistance. CON ...

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MECHANISMS OF ANTIBACTERIAL RESISTANCE
1.Inhibition of drug uptake or blocking the
entry (Change their cell membrane and cell
wall permeability to the drug)
2. Produce enzymes that destroy the chemical
structures of drugs
3.Alter or modified the target molecule.
4. Activation of drug efflux pump.

RESISTANCE TO ANTIBIOTICS
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1. Mechanisms of antibacterial resistance
Structurally modified antibiotic target site,
resulting in:
– For example, as the receptor protein on the
30s ribosomal subunit may be deleted or
altered as a result of mutation, some
aminoglycosides cannot combine with the
bacteria.
CON ...

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• Antibiotic inactivation
– bacteria acquire genes encoding
enzymes that inactivate antibiotics
• Examples include:
– b-lactamases
– aminoglycoside-modifying enzymes
– chloramphenicol acetyl transferase CON ...

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3.Mechanisms of antibacterial resistance
Develop an altered metabolic pathway
– Bacteria can develop an altered metabolic
pathway that bypasses the reaction inhibited
by drugs.
– For example, sulfonamide resistance my
occur as a result of mutations that cause
over-production of PABA or cause production
of a folic acid-synthesizing enzyme that has
low affinity for sulfonamides.
Mechanisms of antibacterial resistance
PABA, p-aminobenzoic acid

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Altered uptake of antibiotics, resulting in:
– decreased permeability
– increased efflux
– For example, gram-negative bacillus can
induce some special proteins to block porin
channels in cell wall and prevent tetracyclines
into the bacillus.
CON ...

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A) TRANSFERMATION
When naked DNA (Antibiotic-resistance Gene) is released on
lysis of an organism and is taken up by another organism.
B) TRANSDUCTION
Antibiotic-resistance genes are transferred from one bacterium
to another by means of bacteriophages.
C) CONJUGATION
Direct contact between two bacteria:
Plasmids form a mating bridge across the bacteria and DNA is
exchanged, which can result in acquisition of antibiotic-
resistance genes by the recipient cell. Transposons can also
carry antibiotic-resistance genes
GENETIC TRANSFER

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COMMON ANTIMICROBIALS AND METHODS OF
RESISTANCE
ANTIBIOTIC
METHOD OF
RESISTANCE
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 Tetracycline
B-Lactams
Sulfonamides
Fluoroquinolones
Aminoglycosides
Active efflux from cell
Hydrolysis or protein
binding
Overproduction of
antibiotic target
Modification of
antibiotics binding site
Enzymatic modification
antimicrobial
27Dr.K.Saminathan.M.Pharm, M.B.A, Ph.D

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V. GENERAL PRINCIPLES OF ANTI-INFECTIVE
THERAPY
Selection of an appropriate anti-infective agent
① Identification of the infecting organism should
precede antimicrobial therapy when possible.
② The pathogenic microorganism susceptibility to
antimicrobial agents should be determined, if a
suitable test exists.
③ Factors that influence the choice of an
antiinfective agent or its dosage for a patient
include the age, renal and hepatic function,
pregnancy status, and the site of infection, etc.

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VI. IDEAL ANTIMICROBIAL DRUG
Have highly selective toxicity to the pathogenic
microorganisms in host body
Have no or less toxicity to the host.
Low propensity for development of resistance.
Not induce hypersensitive in the host.
Have rapid and extensive tissue distribution
Be free of interactions with other drugs.
Be relatively inexpensive29 Dr.K.Saminathan.M.Pharm, M.B.A, Ph.D

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VII. PREVENTION OF ANTIBIOTIC RESISTANCE
Patients :
•Take antibiotics exactly as the doctor prescribes.
•Do not skip doses.
•Complete the prescribed course, even when you feeling better.
•Only take antibiotics prescribed for you.
•Do not save antibiotics for the next illness.
•Discard any leftover medication once the treatment is completed.
•Do not ask for antibiotics to your doctor.
•Prevent infections by practicing hygiene and recommended vaccines.
Health professionals:
•Do not treat viral infections with antibiotics.
•Prescribe antibiotics only when they are absolutely necessary –
giving them at the right dose and only for as long as they are needed.
•Avoid unnecessary overlaps in antibiotics.
•Become familiar with resistance trends in your region. END

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“A drug is a chemical substance that has known
biological effects on humans or other animals”
DRUG IS THE CHEMICAL SUBSTANCE AND USED TODRUG IS THE CHEMICAL SUBSTANCE AND USED TO
1.PRIVANT DISEASE1.PRIVANT DISEASE ( vaccine)( vaccine)
2.IDENTIFIED DISEASE2.IDENTIFIED DISEASE (diagnostic kit)(diagnostic kit)
3. REDUCE/SUPPRESS DISEASE3. REDUCE/SUPPRESS DISEASE (pain killer)(pain killer)
4. CURE DISEASE4. CURE DISEASE ( kill the microbes)( kill the microbes)
5. CHANGE THE PSYCHOLOGY MOOD5. CHANGE THE PSYCHOLOGY MOOD
(sleeping tablets)(sleeping tablets)
DRUG

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MINIMAL INHIBITORY
CONCENTRATION

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THE MINIMAL BACTERICIDAL CONCENTRATION

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Sir Alexander Fleming, FRSE, FRS,
FRCS was a Scottish biologist,
pharmacologist and botanist. He
wrote many articles on
bacteriology, immunology, and
chemotherapy.
Born: August 6, 1881, Lochfield
Died: March 11, 1955,
London, United Kingdom
Education:
St Mary's Hospital Medical School
(1903–1906),
Awards:
Nobel Prize in Physiology or Medicine
, John Scott Legacy Medal and
Premium
Children: Robert FlemingDr.K.Saminathan.M.Pharm, M.B.A, Ph.D

PENICILLINS
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CEPHALOSPORINS

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POLYMYXIN

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CHLORAMPHENICOL

1. INTRODUCTION OF CHEMOTHERAPY

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