Chemotherapy uses drugs to treat diseases caused by microorganisms, parasites, and tumor cells. The goal is to selectively kill pathogenic microorganisms without harming the host. Antibiotics were discovered starting in the 1920s-1940s including penicillin, sulfa drugs, and streptomycin, which fundamentally changed Western medicine. Antibiotics are substances produced by microorganisms that kill or inhibit other microorganisms. They can be natural, produced by microbes, or synthetic. Antibiotics have mechanisms of action such as inhibiting cell wall synthesis, disrupting cellular membranes, or inhibiting protein, nucleic acid, or folic acid synthesis. Bacteria can develop resistance to antibiotics.
2. Introduction
◦ 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.
3. HISTORY
◦ 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
4. 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
5. 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 )
6. 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
7. 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
8.
9. 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.
10. Inhibition of protein synthesis
◦ Due to differences in ribosomes
◦ – Eukaryotic cells have 80S (60S + 40S subunits) ribosomes.
◦ – Prokaryotic cells have 70S (50S + 30S subunits) ribosomes. – Examples:
◦ • Chloramphenicol, Macrolides and Clindamycin bind to the 50S subunit.
◦ • Tetracycline and Aminoglycosides bind to the 30S subunit
11. 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.
12. RESTRICTION 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
13. .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
