Chemotherapy and Drug Resistance
Chemotherapeutic agents and antibiotics.
Modes of action of antibiotics on microorganisms
Amjad Khan Afridi
Lecturer,
Department of Health & Biological Sciences
Abasyn University Peshawar

• The use of drugs to treat a disease
• Selective toxicity:
– A drug that kills harmfulmicrobes without
damaging the host
Chemotherapy

Antibacterial spectrum
Range of activity of an antibiotic.
A broad spectrum
Antibiotic that can inhibit wide range of G- positive and
G- negative bacteria e.g. Carbapenems, 3-4th
generation cephalosporins, quinolones.
A narrow spectrum
Antibiotic that is active only against a limited number of
bacteria e.g. penicillin G, 1-2nd generation
cephalosporins, oxazolidone.
Terminologies

Effects of Combinations of Drugs
•Synergism occurs when the effect of two
drugs together is greater than the effect of
either alone.
•Antagonism occurs when the effect of two
drugs together is less than the effect of either
alone.

Effects of Combinations of Drugs

Antibiotic/Antimicrobial
• Antibiotic:
– Chemical produced by a microorganism that
kills or inhibits the growth of another
microorganism
• Antimicrobial agent:
– Chemical that kills or inhibits the growth of
microorganisms

AntimicrobialAgents
• Disinfectant:
•Antimicrobial agent used only on inanimate
objects
• Chemotherapeutic agent:
•Antimicrobial agent that can be used internally
• Bactericidal:
•Agent that kills bacteria
• Bacteriostatic:
•Agent that inhibits the growth of bacteria

II.HISTORY
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 1929 Penicillin discovered by Alexander Fleming
 1940 Florey and Chain mass produce penicillin for war time use,
becomes available to the public.
 1935 Sulfa (sulfonamide-prontosil rubrum) drugs discovered by
Gerhard Domagk in 1935.
 1943 Streptomycin (aminoglycoside drugs) discovered by
Selman Waksman.

• Bacteria have their own enzymes for
√ Cell wall formation
√ Protein synthesis
√ DNA replication
√ RNA synthesis
√ Synthesis of essential metabolites
Mechanisms of Antimicrobial Action

Modes of Antimicrobial Action

Basic mechanisms of antibiotics

Inhibition of cellwallsynthesis
–Penicillins and cephalosporins stop synthesis of
cell wall by preventing crosslinking of
peptidoglycanunits.
–Bacitracin and vancomycinalsointerfere here.
– Excellentselectivetoxicity
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 The bacterial cell membrane is also called cytoplasmic
membrane. Its maincompounds are proteins andlipids.
 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 cellsandresult in death ofbacteria.
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Inhibition of functions of cellularmembrane

Acting on DNA
replication
Quinolones
Ciprofloxacin
Metronidazole
Quinolones
Fluoroquinolones
Inhibition of nucleic acid synthesis
Acting on RNA
synthesis
Rifampin
Rifabutin

 Dueto differences inribosomes
 Eucaryotic cellshave80S(60S+40Ssubunits) ribosomes.
 Procaryotic cellshave70S(50S+30Ssubunits) ribosomes.
 Examples:
 Chloramphenicol, Macrolides and Clindamycin bind to the
50Ssubunit.
 Tetracyclines andAminoglycosides bind to the 30S
subunit.
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Inhibition of protein synthesis

Sulfonamides
Dapsone
Trimethoprim
Para Aminosalicylic acid
Antimetabolites

 Drug resistance is simply defined as the ability of
disease-causing microorganisms to continue multiplying
despite the presence of drugs that usually kill them.
 When the bacteria show resistance to one drug, they
are also resistant to some other drugs. This
phenomenon is called cross drug resistance.
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Resistance To Anti Bacterial Agents

1. Inhibition of drug uptake or blocking the entry (Change
their cell membrane and cell wall permeability to the drug)
2.Produceenzymes that destroy the chemical structures of drugs
3. Alter or modified the target molecule.
4. Activation of drug efflux pump.
Active efflux is a common resistance mechanism in a wide range of bacterial
pathogens. It is responsible for the transport of such toxic compounds as drugs,
toxins, and detergents.
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Mechanisms of Antibacterial Resistance

 Havehighly selective toxicity to thepathogenic
 Microorganismsin hostbody
 Haveno or lesstoxicity to the host.
 Lowpropensity for development ofresistance.
 Not induce hypersensitive in thehost.
 Haverapid and extensive tissuedistribution
 Befree of interactions with other drugs.
 Be relatively in expensive
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Ideal Antimicrobial Drug

Prevention of Antibiotic Resistance
Patients :
• Take antibiotics exactly as the doctor prescribes.
• Donot skip doses.
• Complete the prescribed course, even when you feeling better.
• Onlytake antibiotics prescribed for you.
• Donot save antibiotics for the nextillness.
• Discard any leftover medication once the treatment is completed.
• Donot ask for antibiotics to yourdoctor.
• Prevent infections by practicing hygiene and recommended
vaccines.
Health professionals:
•Prescribe antibiotics only when they are absolutely necessary –
giving them at the right dose and only for as long as they areneeded.
•Avoid unnecessary overlaps in antibiotics.
•Become familiar with resistance trends in your region.

Minimal Inhibitory Concentration

Thank You

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