Prepared By:-

Meraj Khan
Assistant Professor
Sop, ITMBU
 Chemotherapy
Chemotherapy is defined as the use of drugs to eradicate pathogenic organisms
or neoplastic cells in the treatment of infectious diseases or cancer.

Chemotherapy is based on the principle of selective toxicity.

According to this principle, a chemotherapeutic drug inhibits a vital function of

invading organisms or neoplastic cells without damaging host cell.

The chemotherapeutic drugs include antimicrobial drugs, antiparasitic drugs, and

antineoplastic drugs.
 History of chemotherapy:-
THE HISTORY OF CHEMOTHERAPY MAY BE DIVIDED INTO 3 PHASES.

(a) The period of empirical:-

 Use of ‘mouldy curd’ by Chinese on boils

 Chaulmoogra oil by the Hindus in leprosy
 Chenopodium by Aztecs for intestinal worms
 Mercury by Paracelsus (16th century) for syphilis
 Cinchona bark (17th century) for fevers.
(b) Ehrlich’s phase of dyes and organometallic compounds (1890–1935):-

Ehrlich toyed with the idea that if certain dyes

could selectively stain microbes, they could also
be selectively toxic to these organisms.

He tried methylene blue, trypan red, etc. He

developed the arsenicals—atoxyl for sleeping
sickness, arsphenamine in 1906 and neo
arsphenamine in 1909 for syphilis.

He coined the term ‘chemotherapy’

(c) The modern era of chemotherapy:-

It was ushered by Domagk in 1935 by

demonstrating the therapeutic effect of Prontosil, a
sulfonamide dye, in pyogenic infection.

It was soon realized that the active moiety was

para-amino benzene sulfonamide, and the dye
part was not essential.

Sulfapyridine was the first sulfonamide to be

marketed in 1938.
The phenomenon of antibiosis was
demonstrated by Pasteur in 1877: Growth of
anthrax bacilli in urine was inhibited by air-
borne bacteria.

Alexender Fleming (1929) found that a

diffusible substance was elaborated by
Penicillium mould which could destroy
Staphylococcus on the culture plate.
He named this substance penicillin
 CLASSIFICATION OF ANTIMICROBIAL DRUGS
a) On the basis of Chemical structure
b) On the basis of Mechanism of action
c) Type of organism against which primarly active
d) On the basis of spectrum activity
e) On the basis of type of action
f) On the basis of source of antibiotics

A. Chemical structure:-
1. Sulfonamides and related drugs:- Sulfadiazine and others, Sulfones,Dapsone
(DDS), Paraaminosalicylic acid (PAS).
2. Diaminopyrimidines: Trimethoprim, Pyrimethamine.
3. Quinolones: Nalidixic acid, Norfloxacin, Ciprofloxacin, Gatifloxacin, etc.
4. β-Lactam antibiotics:- Penicillins, Cephalosporins, Monobactams, Carbapenems.
5. Tetracyclines: Oxytetracycline, Doxycycline, etc.
6. Nitrobenzene derivative: Chloramphenicol.
7. Aminoglycosides: Streptomycin, Gentamicin, Amikacin, Neomycin, etc.
8. Macrolide antibiotics: Erythromycin, Clarithromycin, Azithromycin, etc.
9. Lincosamide antibiotics: Lincomycin, Clindamycin.
10. Glycopeptide antibiotics: Vancomycin, Teicoplanin.
11. Oxazolidinone: Linezolid.
12. Polypeptide antibiotics: Polymyxin-B, Colistin, Bacitracin, Tyrothricin.
13. Nitrofuran derivatives: Nitrofurantoin, Furazolidone.
14. Nitroimidazoles:- Metronidazole, Tinidazole, etc.
15. Nicotinic acid derivatives: Isoniazid, Pyrazinamide, Ethionamide.
16. Polyene antibiotics: Nystatin, Amphotericin-B, Hamycin.
17. Azole derivatives: Miconazole, Clotrimazole, Ketoconazole, Fluconazole.
18. Others: Rifampin, Spectinomycin, Sod. fusidate, Cycloserine, Viomycin,
Ethambutol, Thiacetazone, Clofazimine, Griseofulvin.
B. Mechanism of action:-
1. Inhibit cell wall synthesis:- Penicillins, Cephalosporins, Cycloserine,
Vancomycin, Bacitracin.
2. Cause leakage from cell membranes: Polypeptides—Polymyxins, Colistin,
Bacitracin. Polyenes—Amphotericin B, Nystatin, Hamycin.
3. Inhibit protein synthesis: Tetracyclines, Chloramphenicol, Erythromycin,
Clindamycin, Linezolid.
4. Cause misreading of m-RNA code and affect permeability:
Aminoglycosides—Streptomycin, Gentamicin, etc.
5. Inhibit DNA gyrase: Fluoroquinolones— Ciprofloxacin and others.
6. Interfere with DNA function: Rifampin, Metronidazole.
7. Interfere with DNA synthesis: Acyclovir, Zidovudine.
8. Interfere with intermediary metabolism: Sulfonamides, Sulfones, PAS,
Trimethoprim, Pyrimethamine, Ethambutol.
C. Type of organisms against which primarily active:-

1. Antibacterial: Penicillins, Aminoglycosides, Erythromycin, etc.

2. Antifungal: Griseofulvin, Amphotericin B, Ketoconazole, etc.
3. Antiviral: Acyclovir, Amantadine, Zidovudine, etc.
4. Antiprotozoal: Chloroquine, Pyrimethamine, Metronidazole, Diloxanide,
etc.
5. Anthelmintic: Mebendazole, Pyrantel, Niclosamide, Diethyl carbamazine,
etc.
D. Spectrum of activity:-
1. Narrow-spectrum:- Penicillin G , Streptomycin, Erythromycin
2. Broad-spectrum:- Tetracyclines Chloramphenicol
E. Type of action:-

Primarily bacteriostatic:-
Sulfonamides, Erythromycin, Tetracyclines, Ethambutol, Chloramphenicol,
Clindamycin ,Linezolid

Primarily bactericidal:-
Penicillins, Cephalosporins, Aminoglycosides, Vancomycin, Polypeptides,
Nalidixic acid, Rifampin, Ciprofloxacin, Isoniazid ,Metronidazole, Pyrazinamide
,Cotrimoxazole
F. Antibiotics are obtained from:-
Fungi:- Penicillin, Griseofulvin, Cephalosporin
Bacteria:- Polymyxin B, Tyrothricin, Colistin Aztreonam, Bacitracin
Actinomycetes
Aminoglycosides:- Macrolides, Tetracyclines, Polyenes, Chloramphenicol
 TERMINOLOGY

Bactericidal or Bacteriostatic Effect:-

A bactericidal drug kills sensitive organisms so that the number of viable

organisms falls rapidly after exposure to the drug.

In contrast, a bacteriostatic drug inhibits the growth of bacteria but does not
kill them

(The same principle applies to a drug that kills or inhibits the growth of fungi
and is referred to as a fungicidal drug or a fungistatic drug, respectively.)
Spectrum of activity:-

Antimicrobial agents that are active against a single species or a limited

group of pathogens (e.g., gram-positive bacteria) are called narrow
spectrum drugs.

An
An agents that are active against a wide range of pathogens are called
broad-spectrum drugs.

Agents that have an intermediate range of activity are sometimes called

extended-spectrum drugs.
Drug Resistance:-

Drug resistance in bacteria may be natural or acquired.

Development of acquired resistance may be due to single step mutation (as seen
with streptomycin and rifampicin) or multi step mutation (erythromycin,
tetracycline and chloramphenicol).

Drug resistance can be transferred from one microorganism to other by gene

transfer (also called infectious resistance) via conjugation, transduction or
transformation
I. Conjugation:-
It is due to the physical contact between bacteria and is responsible
for multidrug resistance.
This is a very important mechanism for the development of resistance against
chloramphenicol and streptomycin.

II. Transduction:-
It is the transfer of resistance gene through bacteriophage e.g. penicillin,
erythromycin and chloramphenicol.

III. Transformation:-
It is the transfer of resistance gene through environment and is not significant
clinically e.g. penicillin G.
Super-infection:-

It refers to the appearance of a new infection as a result of antimicrobial therapy.

Normal microbial flora contributes to host defense by development of

bacteriocins.

Pathogens also have to compete with the normal flora for nutrients.

Broad spectrum antibiotics (tetracyclines, chloramphenicol, clindamycin,

aminoglycosides and ampicillin) may kill the normal flora and result in the
development of new infection.
Superinfection is more commonly seen in immunocompromised patients.
Factors Affecting the Choice of an Antimicrobial Agent:-

1. Age:-
Chloramphenicol in new born may cause grey baby syndrome.
Sulfonamides in new born may cause kernicterus.
Half life of aminoglycosides is prolonged in the elderly.
Tetracyclines are contra-indicated in children below 6 years because it
accumulates in the developing teeth and bone.
2. Pregnancy:-
All antibiotics pose risk to the fetus when used in pregnancy.
Penicillins, most cephalosporins and macrolides (PCM) appear safe.

3. Impaired Host Defenses:- Bactericidal drugs are must in

immunocompromised patients.
4. Renal function:-
Drugs contraindicated in Renal Failure Dose required to reduce in Renal
Cephalothin Aminoglycosides
Cephaloridine Amphotericin B
Nitrofurantoin Vancomycin
Nalidixic acid Ethambutol
Tetracyclines (except doxycycline)

5. Liver function
Drugs contra-indicated in liver disease Dose reduction required in liver failure
Erythromycin estolate Chloramphenicol
Tetracyclines Isoniazid
Pefloxacin Rifampicin
Pyrazinamide Clindamycin