Principles of chemotherapy

1. Mrs Mwila. Dip Pharm ,Bpharm, MClinPharmacology

2. Learning objectives:
At the end of this session, YOU should be able to:
1. Understand the general principles of
infectious/cancer disease chemotherapy.
2. Understand the pharmacology of different classes
of chemotherapeutic agents
3. Apply principles of chemotherapy to treatment of
infectious/cancer diseases

3. CHEMOTHERAPEUTIC AGENTS
• Chemical substances of known structure when
administered to a living organism produce biological
effect.
• May cause change in an organism’s physiology or
correct to a disorder resulting in treatment

4. Introduction
What is Chemotherapy?
Application of chemical substances (chemotherapeutic
agents ) for treatment that are 'selectively toxic' to invading
prokaryotic micro-organisms while having minimal effects
on the host
Principle also applied to cancerous cells

5. Chemotherapy includes:
1. Antimicrobial agents:
Antibacterial drugs
Antifungal drugs
Antiviral drugs
N.B: - Antibiotics are antimicrobial agents derived from living organisms.

6. 2. Anti-Parasitic agents
Antihelminthic drugs
Antiprotozoal drugs
3. Anticancer chemotherapy.

7. General Principles of Chemotherapy
1. Targeted treatment: Chemotherapeutic agents should
only be given when necessary and after confirmatory
susceptibility test whenever possible;
2. Pharmacokinetics of the drug should be taken into
consideration in association with hepatic and renal functions
of the patient

8. General Principles of Chemotherapy
3. MIC: Effective dosing of chemotherapeutic agent requires
attainment of MIC for antimicrobial effect
• (MIC) – The MIC is defined as the lowest
concentration of antibiotic that completely inhibits
growth of the specific organism being tested.
4. Avoid relapse: continue antimicrobial agent for at least 3
days after apparent cure is achieved

9. 5. Avoid emergence of resistant strains: administer
adequate dosage and adopting proper synergistic regimens

10. Classification of antimicrobial according to
time and concentration
Time dependent antimicrobial
• Concentration independent (Time dependent) means that the
rate and extent of microorganism killing remain unchanged
regardless of antimicrobial concentration:
• Examples of concentration independent antimicrobials
include: beta-lactams, vancomycin, macrolides, aztreonam,
carbapenems, clindamycin, tetracyclines,
quinupristin/dalfopristin, flucytosine, and azole antifungals

11. Concentration dependent
• Concentration dependent (time independent) means that the rate
and extent of microorganism killing are a function of the
antimicrobial concentration (increase as the concentration
increases).
• Examples of concentration dependent antimicrobials include:
fluoroquinolones, aminoglycosides, and amphotericin B.

12. Question
Which of the following antimicrobial agent(s) is (are)
concentration dependant?
a. Penicillin's
b. Azoles antifungal
c. Aminoglycosides
d. Vancomycin
e. Fluoroquinolones

13. Antibacterial Chemotherapy

14. Guidelines:
Appropriate choice of chemotherapy depends
on:
1. Type of infecting organism and antimicrobial
susceptibility
2. Type of infection (e.g. bacteremia, meningitis, urinary tract
infection, abscess, etc)
3. Host factors (e.g. neutropenia, immune deficiencies, concurrent
illnesses, age, drug allergies, renal function, pregnancy, etc)

15. Guidelines:
4. Antimicrobial agent (e.g., dosage, drug interactions, serum
levels and tissue penetration, potential toxicities, cost, etc)
5. Public health considerations (e.g. widespread resistance)

16. Antibacterial Drugs Can Be divided As
Follows:
1. According to effect on bacteria:
Bactericidal
Kill micro-organism and eradicate
infection with no need for body
defence mechanisms e.g. Penicillins,
Aminoglycosides, etc
Bacteriostatic
Stop growth & multiplication of
micro-organism then body defence
mechanism eradicate the infection
e.g. Tetracyclines, Chloramphenicol, etc

17. 2. According to spectrum of activity
Broad spectrum
Effective against both G(-) & G(+) e.g. Broad spectrum
Penicillins, Cephalosporins, Tetracyclines, Chloramphenicol,
Cotrimoxazole and Quinolones
Narrow spectrum
Effective against G(-) only (e.g. Aminoglycosides, Polymyxin,
Metronidazole, etc) or G(+) only (e.g. Vancomycin, etc) or
specific species only (e.g.antimycobacterial, etc)

18. 3. According to mode of action
 Inhibitors of bacterial cell wall synthesis
e.g. β-lactam antibiotics, Vancomycin, etc
 Inhibitors of protein synthesis e.g. Tetracyclines,
Aminoglycosides, Macrolides, Chloramphenicol, etc
 Inhibitors of nucleic acid synthesis e.g. Quinolones
and Rifampicin, etc
 Inhibitors of metabolic pathways: Folate antagonists
e.g. Sulphonamides, Trimethoprim, Co-trimoxazole, etc
 Drugs affecting cell membrane permeability e.g.
Polymyxins, etc

20. Questions
Inhibitor(s) of the cell wall synthesis include :
a. Tetracyclines
b. Penicillins
c. Aminoglycosides
d. Vancomycin
Inhibitor (s) of nucleic acid synthesis include
a. Quinolones
b. Chloramphenicol
c. Rifampicine
d. sulphonamides

21. Inhibitor of folate synthesis:
a. Macrolyde
b. Sulphonamide
c. Trimethoprime
d. Tetracycline