chemistry

1. Chemotherapy &
Antibiotics
- Kalpesh Zunjarrao

2.  Chemotherapy:
The treatment of disease by means of chemicals that have a
specific toxic effect upon the disease-producing
microorganisms or that selectively destroy cancerous tissue
 Antimicrobial Agents:
Compounds that are used to kill or inhibit growth of microbial
organisms
 Antibiotics:
Substances produced by some microorganisms that can kill or
inhibit growth of other organisms.
 Antibacterials refer to substances that act against bacteria

3.  The ability of an antimicrobial to affect an invading
microorganisms without harming the host is referred
to as Selective Toxicity
 Antimicrobials act by exploiting metabolic or
structural differences between host and pathogens.

4. Father of Chemotherapy
Paul Ehrlich [1854-1915]:
• Discovered Salvarsan 606 (derivative of arsenic) sometimes called
as ‘Magic Bullete’
• Salvarsan 606: capable of destroying spirochetes of syphilis.
• Gave rise to new branch of medicine: ‘Chemotherapy’

5. Discovery of 1st Antibiotic
Alexander Fleming [1928]:
• Accidentally discovered Penicillin produced by a fungus
Penicillium
• Left his Staphylococcus culture on an agar plate for 2 weeks →
went on vacation → came back & found mold on his plate which
prevented bacterial growth

6. Important Terminologies:
• Antibacterial spectrum: Range of activity of an
antibiotic
• Broad spectrum Antibiotic: that can inhibit wide range
of Gram positive and Gram negative bacteria.
• Narrow spectrum Antibiotic: active only against a
limited number of bacteria.
• Minimum inhibitory concentration (MIC):
The lowest concentration of antimicrobial that inhibits
the growth of bacterial population

7. Bacteriostatic Vs Bactericidal Antibiotic
Inhibit growth of
microbes Kill microbes

8. Antibiotic combinations:
• Antibiotic synergism: Combination of antibiotics have enhanced
activity when tested together compared with each antibiotic alone
(e.g. 2 + 2 = 6)
e.g. Ampicillin + Gentamicin in entercoccal carditis
• Additive effect: Combination of antibiotics has an additive effect
(e.g. 2 + 2 = 4)
• Antibiotic antagonism: Combination in which the activity of one
antibiotic interferes with the activity of the other (e.g. 2 + 2 < 4)

9. Mechanism of Action of Antibiotics
• Interfering with Cell Wall Synthesis
• Acting on Cytoplasmic Membrane
• Inhibiting Protein Synthesis
• Inhibiting Nucleic Acid function
• Metabolic antagonist

10.  Peptidoglycan: Thick layer in Gram positive
Thin layer in Gram negative
 β-lactam bactericidal drugs
They inhibit bacterial cell wall peptidoglycan synthesis
in growing bacteria.
This leads to the death of the Bacteria
 Vancomycin
They kill Bacteria by interfering with peptidoglycan
polymerization.
Interfering with Cell Wall Synthesis

11. Antibiotics that interfere with cell wall synthesis:
• Penicillin
• Cephalosporin
• Bacitracin
• Vancomycin
• Cycloserine

12.  Certain Antibiotics bind to cell membrane
 Semi-permeability of membrane is lost → loss
of membrane integrity
 Examples:
Polymyxin
Nystatin
Amphotericin B
Acting on Cytoplasmic membrane

13. Inhibitors of Protein Synthesis
Inhibitors of Translation
• Some antibiotics act on 30s or 50s subunits of
ribosome
• Thus can affect Initiation, elongation or termination
of peptide chain formation
• 30S inhibitors: Aminoglycosides, Tetracyclins
• 50S inhibitors: Erythromycin, Chloramphenicol,
Lincomycin

14. Inhibitors of RNA synthesis:
 Rifampicin: They kill bacteria by inhibiting RNA
polymerase
Inhibitors of DNA synthesis:
Examples:
 Novobiocin: inhibits DNA replication
 Metronidazole: damages DNA & inhibits
replication
 Quinolones: block DNA gyrase
Inhibitors of Nucleic acids

15. • Their structure resembles to essential metabolites &
thus can compete with them
• PABA (Para-aminobenzoic acid): essential co-factor
for bacterial cell growth
• Sulphonamides: structure similar to that of PABA
• Other examples:
Sulphones
Trimethoprim
Metabolic Antagonist

16. Antimicrobial Drugs

17. PENICILLINS
 Belong to β-lactam drugs
 Mode of action – Inhibit cell wall synthesis (bind transpeptidase
enzyme involved in cross-linking of peptidoglycans)
 Spectrum:
act against G +ve aerobes and anaerobes
Semi-synthetic penicillins are effetcive against some G –ve
bacteria

18. Preparations (Natural Penicillins)
Penicillin G
Penicillin C
Penicillin V
Penicillinase-stable penicillins
Methicillin
Oxacillin
Cloxacillin
Dicloxacillin
Broad spectrum Penicillins
Ampicillin
Amoxicillin
Hetacillin

19. CEPHALOSPORINS
Modes of Action – Inhibit cell wall synthesis
Preparations
 1st Generation cephalosporins (G +ve aerobes)
- Cephalexin, Cefadroxil, Cephaprin, Cephalothin, Cefazolin
 2nd Generation cephalosporins (G +ve & some G –ve)
- Cefaclor, Cefoxitin
 3rd Generation cephalosporins (G +ve, G –ve, resistance to beta-
lactamase, penetrate BBB)
- Ceftiofur, Moxalactam

20. AMINOGLYCOSIDES
 Mode of action – Interferes protein synthesis
Preparations
 Natural: Streptomycin & Dihydrostreptomycin
Neomycin
 Extended spectrum:
Gentamicin and amikacin
Tobramycin
Kanamycin

21. TETRACYCLINES
Mode of action – Inhibit Protein synthesis (bind to 30s ribosome)
Spectrum – Broad
Preparations:
Tetracycline
Chlortetracycline
Oxytetracycline
Doxycycline

22. CHLORAMPHENICOL
 Mode of action - Bind to 50s of ribosome
 Spectrum – it is a broad-spectrum antibiotic, and it is
effective against most anaerobic bacteria

23. MACROLIDES
 Mode of action – Inhibit protein synthesis by binding to 50s of
ribosome
 Spectrum – Effective against G +ve aerobes and anaerobes and
Mycoplasma speices
 Examples:
Erythromycin
Tylosin
Tilmicosin

24. FLUOROQUINOLONES
 Mode of Action – inhibit DNA replication. They are
bactericidal
 Preparation –
Enrofloxacin
Ciprofloxacin
 Spectrum of activity - Broad

25. SULFONAMIDES
 Mode of action – interferes Folate synthesis by inhibiting
dihydropteroate synthetase, that incorporates PABA in making
folate
 Spectrum of Action - Broad
 Preparations - Sulfamethazine
- Sulfadimethoxine
- Sulfathiazole
- Sulfachlorpyridazine
- Sulfasoxasole and sulfamethaxazole
- Sulfacetamide
- Sulfasalazine

27.  Permeability:
- Some microbes → alteration in chemical nature of outer
membrane → change cell wall permeability to drug
- Eg: Tetracyclin resistance by Pseudomonas aeruginosa
 Production of enzymes:
- enzymes which can act on drug
- Eg: β-lactamase produced by certain bacteria destroy penicillin
 Altered structure target:
- Aminoglycosides act by attaching to 30S subunit but resistant
bacteria develop altered receptor
 Altered metabolic pathway:
- Drugs inhibit certain pathways
- Resistant bacteria → bypass the reaction
Mechanism

28. Genetic basis of Resistance
Chromosomal Resistance:
Result of spontaneous mutation
Antimicrobial drug:
• Suppress susceptible microbe
• But resistant mutant unnoticed
Eg:
Mutational resistance in Tuberculosis
↓
Two or more anti-tuberculous drugs used for treatment
↓
Multiple drug therapy

29. Extra-chromosomal Resistance:
• Occurs by transfer of plasmid & genetic material
• Drug resistance can be transferred by R-factor
• R-factor: plasmid containing drug resistant genes
• Plasmid codes for enzyme which inactivates drug
• Eg: β-lactamase destroys β-lactam ring present in certain antibiotics

30. Methods of transfer of Plasmid & Genetic material:
1.Transduction:
Plasmid enclosed in bacteriophage → transferred from resistant to
Susceptible Staphylococcus → Acquisition of penicillin resistance
2.Conjugation:
R-factors transferred by conjugation
Common mode of spread of multiple drug resistance
3.Transformation:
Transfer of naked DNA carrying drug resistance genes
4.Transposition:
Certain DNA segments → ability to move around between
chromosomal & extra-chromosomal DNA → Jumping genes

31. Host - Parasite Relationships

32.  Bacteria are consistently associated with the body surfaces of
animals.
 Bacterial cells on the surface of a human body (including the
gastrointestinal tract): More than human cells that make up the
body (60-90 trillion).
 Normal flora:
 The bacteria and other microbes that are consistently associated
with an animal
 “Indigenous microbiota" of the animal.
 These bacteria have a full range of symbiotic interactions with
their animal hosts

33.  Symbiosis: two organisms live in an association with one
another.
 Types of Symbiotic Associations:
1. Mutualism:
 Both members of the association are benefited.
 Eg: In humans, lactic acid bacteria that live on the vaginal
epithelium of a woman.
The bacteria are provided habitat with a constant temperature and
supply of nutrients (glycogen) in exchange for the production of
lactic acid, which protects the vagina from colonization and
disease caused by yeast and other harmful microbes

34. 2. Commensalism:
 There is no apparent benefit or harm to either member of the
association.
 Commensals live in complete harmony with host without causing
any harm
 They constitute normal flora of body
 Eg:
Staphylococcus epidermidis of skin
Escherichia coli of Gastrointestinal tract

35. 3. Parasitism:
 Parasite refers to an organism that grows, feeds on a different
organism while contributing nothing to the survival of the host.
 Parasite: capable of causing damage to the host & may become
pathogenic if the damage to the host results in disease.
 Some parasitic bacteria live as normal flora of humans while
waiting for an opportunity to cause disease.
 Other non-indigenous parasites generally always cause disease if
they associate with a non-immune host

36.  Pathogen is a microorganism that is able to produce disease.
 Pathogenicity is the ability of a microorganism to cause disease
in another organism.
 In humans, some of the normal flora (Eg: Staphylococcus aureus,
Streptococcus pneumoniae, Haemophilus influenzae) are potential
pathogens that live in a commensal or parasitic relationship
without producing disease.
 They don’t cause disease unless they have an opportunity
(compromise or weakness in the host's anatomical barriers, tissue
resistance or immunity.)
 Bacteria which cause disease in a compromised host which
typically would not occur in a healthy host are called as
opportunistic pathogens.

37. Thank you