Chemotherapy & Classification of Antimicrobials

Chemotherapy

• It is the branch of Pharmacology which deals with drugs which selectively inhibit or destroy specific pathogenic organisms like bacteria, viruses, fungi and parasites.
• This term is extended to the use of drugs in the treatment of neoplastic diseases because of similarity between the malignant cells and the pathogenic microbes.
• The term was first used by Paul Ehrlich in 1913 to describe drugs which attack invading organisms without harming the host.

Terms and Concepts

Chemotherapeutic Agents

The drugs used to interfere with the functioning of foreign cells.

Antibiotics

Chemical substances produced by various micro organisms that kill or suppress growth of other micro organisms.

Antimicrobials

All chemical substances whether natural, synthetic or semi-synthetic that kill or suppress the growth of micro organisms

Selective Toxicity

It is the ability of an antimicrobial agent to kill an invading microorganism without harming the cells of the host.

Antimicrobial Activity

Refers to the ability of a compound to react with the microbial cell molecules in a way that interferes with growth and multiplication of microorganism or causes killing of the microorganism

Bacteriostatic Activity

It is the ability of the antibacterial agent to inhibit the growth and multiplication of bacteria.

Bactericidal activity

It is the ability of an antimicrobial agent to cause the death of the bacteria.

Antimicrobial Spectrum

Refers to the range of pathogenic organisms against which an antimicrobial agent is active.

B.S.A.M. are active against a wide variety of organisms.

N.S.A.M. are active against a few or a class/type of organisms.

Narrow Spectrum

Active against a few or class/type of organisms e.g, G + ve or G-ve.

Broad Spectrum

Active against a wide variety of organisms e.g.  both G + ve & G-ve.

Potency

Defined as the antimicrobial activity per miligram (microgram) of a chemotherapeutic agent

Expressed in:

MIC, MBC, MAC

All are determined in vitro.

Minimum Inhibitory Concentration (MIC)

It is the lowest concentration which prevents visible growth of bacteria when grown on serial dilutions in vitro.

Minimum Bactericidal Concentration (MBC)

Lowest concentration which kills the bacteria

Minimum Antibiotic Concentration (MAC)

Concentration which reduces the growth of an organism in vitro by factor of 10 (e.g. one log)

Used to express the activity of some drugs that exert antimicrobial action in vivo at conc. Below the MIC

Post Antibiotic Effect (PAE):

Effect even after antibiotic is out.

Biphasic (EAGLE) Effect

Effect at low doses but not at high doses

Properties of an ideal Antimicrobial Agent (AMA)

• Powerful action against micro organisms
• Selective toxicity
• Slow metabolism
• Well distributed in the body
• Good oral bio availability
• Long elimination half life
• No bacterial resistance or cross resistance
• No effect on the host immune system
• No adverse drug interaction
• No/Short withdrawal period in food producing animals
• Economical and easily available

Classification of antimicrobial agents

Based on Mechanism of Action

Inhibit Cell Wall Synthesis: Penicillin, cephalosporin, cycloserine, bacitracin, vancomycin & clotrimazole.

Inhibit Cytoplasmic Membrane Function: polymyxins, amphotericin B & nystatin.

Inhibit protein synthesis: Chloramphanicol, tetracycline, macrolides and aminoglycosides.

Interfere with Intermediary Metabolism: sulphonamides, trimethoprim and sulphons.

Affect nucleic acid metabolism and synthesis: quinolones, rifampicin, and acyclovir

Based on Chemical Structure

Sulphonamides:

sulphadimadine, sulphadiazine, sulphanilamide, sulphaquinoxalone.

Diaminopyrimidines:

Trimethoprim, ormetoprim and baquiloprim

Quinolones:

Nalidixic acid, enrofloxacin, difloxacin and ciproflaxocin

Beta-lactam antibiotics:

Penicillin G, ampicillin, cloxacillin, cephazolin, cephalexin

Aminoglycosides:

streptomysin, gentamicin, amikacine, tobramycin

Tetracyclines:

Oxytetracycline, tetracycline, doxycyline, minocycline

Macrolide Antibiotics:

Erythromycin and Azithromycin

Nitrofuran – Derivatives:

Nitrofurantoin and furazolidone

Nitroimidazole:

Metronidazole and Imidazole

Polypeptide Antibiotics:

Polymyxin B, Colistin and bacitricin

Polyene Antibiotics

Nystatin and amphotericin B

Imidazole derivatives

Ketoconazole, fluconazole and clotrimazole

Based on Therapeutic Uses (Type of Organism)

Anti-bacterial:

Penicillin, aminoglycosides, tetracycline, & chloramphenicol,

Anti-fungals:

Amphotericin B, griseofuvin and ketoconazole

Anti-virals:

Idoxuridine, vidarabine, zidovudine, and ribavirin

Anti-protozoals:

Metronidazole, quinapyramine and diminazine

Anthelmintics:

Albendazole, levamisole, niclosamide and praziquntel

Ectoparasiticides:

Cypermethrin, lindane, amitraz and ethion

Based on Spectrum of Activity

Narrow spectrum antimicrobials:

Penicillin G, streptomycin, erythromycin and vancomycin

Broad Spectrum Antimicrobials:

Tetracycline, chloramphenicol, cephalexin, gentamycin, ampicllin

Based on type of Action

Bacteriostatic

Sulphonamides, chloramphenicol, erythromycin, trimethoprim, clindamycin

Bactericidal

Penicillin G, cephalexin, streptomycin, vancomycin, bacitracin and  potentiated  sulphonamides

Based on Source

Natural and Semi-synthetic

Fungi:

Penicillin G, griseofulvin and cephalexin

Actinomycetes

Streptomycin, tetracycline, erythromycin and    chloramphenicol

Bacteria:

Polymyxin B, Colistin and bacitracin

Synthetic:

Sulphonamides, trimethoprim, quinolones, nitrofurans and nitro-imidazoles