Pharmacology

1. Introduction to Chemotherapy
Prepared by- Shubhangi Buchade

2. Contents
• History
• Definition
• Difference between prokaryotic and
eukaryotic cell
• Mechanism of action of antibiotics
• Mechanism of bacterial resistance
• Principles of antibiotic dosing

3. History
Father of Chemotherapy
• Coined Chemotherapy
and magic bullet
• Discover salvarsan 606
Paul Ehrlich ( 1854-1915 )

4. • Chemotherapy
it means the treatment of systemic/ topical infection with
the drugs that have selective toxicity for an invading
pathogen or selectively destroy cancerous tissue without
harming the host cell
• it require proper dose
• Advantage of biochemical and physiological difference in
prokaryotes and eukaryotes

5. Antimicrobial agents
Antibacterial agents Antibiotics Semisynthetic antibiotics
Synthesized in
laboratory
Obtained from
fermentation of
microorganisms
Chemical structure derived
from microorganism then
modified by attaching
different chemical moieties

6. • Antimicrobials may act as bacteriostatic
or bacteriocidal

7. Difference between prokaryotic and eukaryotic cell

8. Antibiotics
• substances produced
by various species of
microorganism to kill
or supress the growth
of microorganisms

9. Mechanism of action of antibiotics
Inhibition of cell wall synthesis
Alteration of cell membrane integrity
Inhibition of ribosomal protein synthesis
Supression of DNA synthesis

11. Inhibition of cell wall synthesis

13. Alteration of cell membrane integrity

14. Inhibition of ribosomal protein synthesis

17. Supression of DNA synthesis
inhibiting synthesis of folate, purine and pyrimidines
inhibiting DNA/ RNA polymerase
inhibiting DNA gyrase
directly damaging DNA and its functioning

18. inhibiting synthesis of folate, purines and pyrimidines

19. By inhibiting DNA/RNA polymerase

21. By inhibiting DNA gyrase
DNA gyrase
introducing negative supercoils in DNA
cut both strands of DNA
reseal to avoid supercoiling
Fluoroquinolone
Eukaryotic cell do not contain DNA gyrase

22. By directly damaging DNA and its functioning

23. Bacterial resistance to antibiotics
• Antibiotic
resistance: Defines as
microorganism that are not
inhibited by usually acheivable
systemic concentration of an
antimicrobial agent with normal
dosge schedule and / or fall in
the minimum inhibitory
concentration range
Why resistance occurs ?
• resistant organism lead to
treatment failure
• resistant bacteria may spread
in community

24. Antibiotic resistance
Natural Acquired
Genetic methods Biochenical mechanism

25. Genetic method of antibiotic resistance
Genetic method of antibiotic
resistance
Chromosomal
methods: mutation
Extrachromosomal
mechanism:
Plasmid

26. Mutation
• It refers to change
in DNA structure of
a gene
• occcurs at
frequency one per
million cells
• Sensitive bacteria
die but resistant
continue to grow

27. Plasmid
• extrachromosomal
genetic elements can
replicate indepedently
and freely in cytoplasm
• plasmid carry genes
resistant to antibiotic (r-
gene) are called R-
plasmids
• The r-gene transferred
from one R-plasmid to
another plasmid / to
chromosome

28. 1. Transfer of r-genes from one bacterium to another
a. Conjugation
b. Transduction
c. Transformation
2. Transfer of r-genes between plasmids within the
bacterium
a) By Transposons
b) By integrons

29. • Conjugation :
• Transduction

30. Transfer of r-genes between plasmids within the bacterium
Trasposons
 transposons are sequence of
DNA that can move around
different positions within the
genome of single cell
 The donor plasmid conatining
tansposons, co-integrate with
acceptor plasmid. They can
replicate during co-integration.
 Both plasmids then seperate
and carrying r-genes

31.  Integrons
 Large mobile DNA
 Packed with multiple gene casette, eachconsisting of
resistant gene attached to samll recognition site.
 this genes encode several bacterial function like
resistance and virulence

32. Biochemical Mechanism
1. By producing an enzyme that inactivates the antibiotic
2. Prevention of drug accumulation in the bacterium
3. By modification/protection of the target site
4. Use of alternative pathways for metabolic/growth
requirements
5. By Quorum sensing(QS)

33. By producing an enzyme that inactivates the antibiotic
• beta-lactamase enzyme
Inactivation of
beta-Lactam
antibiotics
• chloramphenicol acetyl transferase
Inactivation of
chloramphenicol
• acetyl transferases
• phosphotransferases
• adenyltransferases
Inactivation of
aminoglycoside

34. Prevention of drug accumulation in the bacterium
Prevention of
drug
accumulation
alteration in
the bacterial
outer
membrane
active
transport of
drug ceases
active efflux
of drug

35. modification
of the target
site
Point
mutation
Modified
penicillin
binding
protein
altered
DNA
gyrase
Ribosomal
point
mutation

36. Use of alternative pathways for metabolic/growth
requirements
• resistance can occur by altering pathways
that bypasses the reaction inhibited by the
antibiotic
• Sulfonamide resistance can occur by
overproduction of PABA

37. By Quorum sensing(QS)
Autoinducer
Critical density(quorum)
Quorum sensing (QS)

39. Priciples of antibiotic dosing
Minimum Inhibitory
Concentration
Minimum Bactericidal
Concentration

41. Antibacterial agents ( CDK/TDK & PAE)
• Fluoroquinolones,
Metronidazole, Rifampicicn
CDK with
prolonged PAE
• Beta-lactam antibiotics,
clindamycin, macrolide,
azithromycin
TDK with
shorter PAE
• tracycline, clarithromycin
TDK with
prolonged PAE

42. Antimicrobial spectrum
Narrow
spectrum
Broad
spectrum
Extended
spectrum

43. Superinfection and Pseudomembraneous colitis (PMC)

44. Classification of pathogenic microbes
1. Bacteria
2. Spirochetes
3. Rickettsiae
4. Chlsmydiae
5. Miscellaneous

45. Bacteria

48. Chlamydiae

49. Rickettsiae