2. Definition of 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

3. Definitions
 Compounds that are used to kill or inhibit growth of
microbial organisms are called ANTIMICROBIALS
 Substances produced by some plants or
microorganisms that can kill or inhibit growth of
other organisms are called ANTIBIOTICS
 ANTIBACTERIALS refer to substances that act
against bacteria

4. Modes of action of Antimicrobials

5. Bactericidal vs Bacteriostatic
antibiotics

6. Antimicrobial targets
The structures in microbes that are mainly targeted by
antimicrobials are
 Cell wall
 Cell membrane
 Cell proteins
 Cell nucleic acids

7. Basic structure of Bacterial cell wall
Therefore it is a N-
G-N-G chains that
are crosslinked
together by
peptaglycine
bridges

9. DNA gyrase DNA-directed
RNA polymerase
Quinolones
Cell wall synthesis Rifampin
ß-lactams &
Glycopeptides
(Vancomycin) DNA
THFA mRNA
Trimethoprim Protein
Ribosomes synthesis
Folic acid inhibition
synthesis DHFA 50 50 50
Macrolides &
30 30 30
Lincomycins
Sulfonamides
PABA
Protein synthesis
Protein synthesis inhibition
mistranslation Tetracyclines
Aminoglycosides

10. Inhibitors of cell wall synthesis
Β-lactam bactericidal drugs;
Examples
Penicillin
Amoxicillin
Ampicillin
Cephalosporins
Vancomycin

11. Modes of action of cell wall
inhibitors
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 (on gram positive bacteria only)

12. Inhibitors of RNA synthesis
Example
Rifampicin
Mode of action
They kill bacteria by inhibiting RNA polymerase
Commonly used in G+ve bacteria especially
Mycobacterium tuberculosis

13. Inhibitors of DNA synthesis
Examples
Fluoroquinolones
Polymixins (Polymixins B, colistin)
Sulphonamides

14. Inhibitors of protein synthesis
Prokaryotic and
eukaryotic ribosomes
are structurally
different
Eukaryotes (80s
ribosomes) contain 60s
and 40s subunits
Prokaryotes (70s
ribosomes) contain 50s
and 30s subunits

15. Inhibitors of protein synthesis
Examples
Aminoglycosides
Tetracyclines
Puromycin
Macrolides

16. BACTERIAL RESISTANCE TO
ANTIBIOTICS
Antibiotic resistance is a type of drug resistance where a
susceptible microorganism is able to survive exposure
to an antibiotic
Human factors that predispose antibiotic resistance
- Under dosage
- Frequent use of antibiotics
- Undirected use of antibiotics
- making poor quality drugs and counterfeit drugs

18. Ability of Bacteria to express
resistance to antibiotics
This basically happens due to structural and
biochemical characteristics that can be due to
- Inherent characteristics
- Adaptive biochemical changes
- Spontaneous genetics changes

19. Mechanisms of Bacterial resistance
to antibiotics
Inherent structural mechanisms
Inherent biochemical mechanisms
Adaptive biochemical mechanisms
Inherent antibiotic resistance genes
Genetic mutations

20. Mechanisms of Bacterial resistance
to antibiotics
Inherent structural mechanism
Some bacteria have cell wall that prevents penetration of
some bacteria
Example; Penicillin can not penetrate wall of G-ve bacteria
because the wall has lipopolysaccharide layer that cover
the site of peptidoglycan synthesis

21. Mechanisms of Bacterial resistance
to antibiotics
Inherent Biochemical mechanisms
Inactivation of drugs – Some bacteria can inactivate
drugs by chemically modifying them
Example; Staphilococcus produce β-lactamase
enzyme which hydrolyses β-lactam ring of drugs like
penicillin
Decreased drug accumulation – some bacteria have
proteins that actively pump out antibiotics
Example; S. aureus has enhanced fluoroquinolone
pumping capability

22. Mechanisms of Bacterial resistance
to antibiotics
Adaptive biochemical mechanisms
Alteration of antibiotic target – Some bacteria alter
the stereochemistry of antibiotic targets hence
antibiotic fails to bind
Example; Chloramphenicol action can be blocked by
changes in bacterial 50s ribosomal unit that prevent it
from binding

24. Mechanisms of Bacterial resistance
to antibiotics
Inherent bacterial resistance genes
Bacteria store genetic information in genes within
chromosomal DNA.
Bacteria has also other extrachromosomal DNA called
PLASMIDS
Of the most important genes in the plasmids, are the
one with information on Antibiotic resistance

26. ANTIBACTERIAL RESISTANCE
PLASMIDS (R-PLASMIDS)
 They are collection of acquired foreign genetic
elements that originated within other bacteria or
fungi
 R-plasmids are capable of combining with other
plasmids, thus resistance to several antibiotics can
reside on one plasmid
 A bacterium may contain as many as 1,000 copies of a
single plasmid
 Bacteria are capable of transferring R-plamids from
one cell to another through a process known as
CONJUGATION

27. Transfer of resistance through
genetic materials
This can happen in
three ways
2. Conjugation
4. Transposons
6. Bacteriophages

28. Mechanisms of Bacterial resistance
to antibiotics
Chromosaomal Genetic Mutations
Spontaneous mutations in bacterial chromosomes can
lead to drug resistance
Basically chromosomal genetic mutations lead to the
changes to structural or biochemical properties of a
given bacteria and this can loose the susceptibility to
a drug.

29. Selection of Antimicrobial agents
This should consider four things;
Identity of the organism and susceptibility to a
particular agent
The site of the infection
The safety of the agent
Patient factors

30. Chemotherapeutic spectra
The chemotherapeutic spectrum of a particular drug
refers to the range of species of microorganisms
affected by the drug
There are
3. Narrow spectrum drugs, eg Isoniazid
4. Extended spectrum drugs, eg Ampicillin
5. Broad spectrum drug, eg Tetracycline and
chloramphenicol

31. Combination of Antimicrobial
drugs
Dynamics of combined antimicrobial action
2. Indifference (2 + 3 = 3)
3. Antagonism (2 + 5 = 4) eg penicillin + tetracycline
4. Synergism (2 + 2 = 5) eg Penicillin + Streptomycin

32. Dynamics of drug combination

33. ANTIBACTERIAL DRUGS
The following are the examples of the common
Antibacterial groups

34. 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

35. Mode of action of Sulfonamides

36. Fluoroquinolones
Mode of Action – inhibit DNA replication. They are
bactericidal
Preparation – Enrofloxacin
- Ciprofloxacin
Spectrum of activity - Broad

37. Penicillins
Belong to β-lactam bactricidal 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
- Semisynthetic penicillins are effetcive
against some G –ve bacteria

38. Penicillins
Preparations (Natural Penicillins)
– Penicillin G, Penicillin C
- Penicillin V
- Penicillinase-stable penicillins
(methicillin, Oxacillin, cloxacillin,
dicloxacillin)
Broad spectrum Penicillins
- Ampicillin, amoxicillin and Hetacillin
- Carbenicillin and Ticarcillin
- Azlocillin, mezlocillin and Piperacillin

39. Cephalosporins
Modes of Action – Inhibit cell wall synthesis (bactericidal)
Preparations
1st Generation cephalosporins (G +ve aerobes)
- cephalexin, cefadroxil, cephaprin, cephalothin,
cefazolin
2nd Generation cephalosporins (G +ve, plus some G –ve)
- cefaclor, cefoxitin
3rd Generation cephalosporins (G +ve, G –ve, resistance to
beta-lactamase, penetrate BBB)
- ceftiofur, moxalactam)

40. Aminoglycosides
Mode of action – Interferes protein syhthesis
(Bactericidal)
Preparations
Natural – Streptomycin and dihydrostreptomycin
- Neomycin
Extended-spectrum
- Gentamycin and amikacin
- Tobramycin
- Kanamycin

41. Tetracyclines
Mode of action – Inhibit Protein synthesis (bond to
30s ribosome)
Spectrum – Broad
Preparations – Tetracycline
- Chlortetracycline
- Oxytetracycline
- Doxycycline

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

43. 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

44. Lincosamides
Mode of action – Bind to 50s of ribosome to inhibit
protein synthesis
Spectrum – effective against G +ve aerobes and
anaerobes, Toxoplasma species, Mycoplasma species
Examples
- Lincomycin
- Clindamycin

45. Miscellaneous Anti-infectious
agents
Metronidazole (Flagyl) – it disrupts DNA.
- it is used in the treatment of bacterial and
protozoal infections (Amoeba, Giardia,
Trichomonas)
Rifampicin – inhibits RNA synthesis
- used in treatmet of Tuberculosis
Tiamulin – inhibits protein synthesis
Others – Bacitracin, Polymixin B.

46. ANTIVIRAL DRUGS
Treatment of viral diseases is difficult because
- Viruses do not have many metabolic processes
- Viruses incorporate into the host cell and uses the
host cell machinery for replication
- Most viruses undergo continuous spontaneous
mutation, leading to the changing of structure
However there have been several drugs for viral
infections with varying mechanisms and effectiveness

47. Mechanisms of action of antiviral
drugs
Inhibition of Penetration to host cell
- Amantidin – Inhibits uncoating
- Gammaglobulins – “neutralize” the virus

48. Mechanisms of action of antiviral
drugs
Inhibition of nucleic acids
Inhibitors of viral DNA polymerase – Acyclovir,
Vidarabine, Foscarnet
Interference with viral DNA synthesis –
Gancyclovir, ribavirin
Inhibitors of Reverse transcriptase – Zidovudine,
Zalcitabine, Didanosine

49. Mechanisms of action of antiviral
drugs
Neuramidase inhibitors
- Zanamivir
- Oseltamivir
Immunomodulators
- Interferons
- Pavilizumab
- Imiquimod

50. Treatment of HIV and AIDS (ARVs)

51. Treatment of HIV and AIDS (ARVs)
ARV Drugs
 Reverse transcriptase inhibitors
 Protease inhibitors
 Fusion inhibitors

52. Treatment of HIV and AIDS (ARVs)

53. Treatment of HIV and AIDS (ARVs)
Protease Inhibitors

54. Treatment of HIV and AIDS (ARVs)

55. Treatment of HIV and AIDS (ARVs)

56. ANTIFUNGAL DRUGS
GRISEOFULVIN
Mode of action; It binds to microtubules to inhibit
spindle formation and mitosis. Fungistatic
KETOCONAZOLE
Mode of action; Inhibits synthesis of ergosterol in
fungal cytoplasmic membranes by blocking
cytochrome P-450 enzymes

57. ANTIFUNGAL DRUGS
AMPHOTERICIN B
Mode of action; Binds to ergosterol of cell membranes
and result to leakage of cell contents. Fungicidal.
FLUCYTOSINE
Mode of action; Inhibits thymidylate synthetase,
thereby inhibiting DNA and RNA synthesis

58. ANTIPROTOZOAL DRUGS
 Anticoccidial drugs
 Antitrypanosomal drugs
 Antitheilerial drugs
 Antibabesial drugs
 Anti-anaplasmal drugs
 Anti-Giardial drugs

59. Anticoccidial drugs
 Amprolium – block thiamine receptors
 Sulfonamides (s/methoxine, s/quinoxaline) – Inhibit
folate synthesis
 Halofuginone
 Sodium inophores (monensin, salinomycin,
lasalocid) – increase intracellular Na+ to impair Mit.
functions
 Decoquinate – inhibit DNA synthesis
 Apronicid – interfere purine metabolism

60. Antitrypanosomal drugs
Human African Tripanosomosis (HAT)
First stage drugs
- Pentamidine
- Suramin
Second stage drugs
- Melasoprol
- Eflornithine

61. Antitrypanosomal drugs
Livestock trypanosomosis
Diminazene (Berenil®, Veriben®)
- bind to kinetoplast and nucleus
Phenanthridinium compounds (Isometamedium,
Homidium)
- inhibit DNA and RNA synthesis
Suramin
Melarsomine
Quinapyramine

62. Antitheilerial drugs
 Halofuginone – destroys parasitized erythrocytes
 Parvaquone – Interferes with electron transport in
mitochondria
 Buparvaquone - Interferes with electron transport in
mitochondria

63. Antibabesial drugs
 Imidocarb (Imizol®) – for therapeutic and prophylaxis
 Diminazine aceturate (Berenil®)

64. Antianaplasmal drugs
 Tetracycline
 Imidocarb
 Dithiosemicarbazones

65. Anti-Giardial drugs
 Metronidazole (Flagyl)
 Tinidazole (Fasigyn)
 Nitazoxanide

66. ANTIHELMINTHIC DRUGS
There are three major groups of helminths
Nematodes (Antinematodal)
Cestodes (Anticestodal)
Trematodes (Antitrematodal drugs)