General principle of chemotherapy

General principle of chemotherapy

Chemotherapy

·         Chemo –  Chemical, Therapy – Treatment

·         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.

Antibiotics

·         Antibiotics are the substance produce by microorganism, which selectively suppress the growth or kill other microorganism at very low concentration.

Anti-microbial (Chemotherapeutic agents + Antibiotics)

·         Any substance of natural, synthetic, semisynthetic origin which at low concentrations kill or inhibit the growth of micro-organisms but causes little or no damage of host.

History of chemotherapy

·         Father of chemotherapy – Paul Ehrlich – 1908 (Arsphenamine)

·         Penicillin – Alexander Fleming

·         Gerhard Domagk – Sulfonamide – 1932

Principle of Anti-microbial therapy

1.      Diagnosis

·         Site of infection

·         Organism

·         Drugs (Sensitive)

2.      Treatment (Whether chemotherapy is necessary or not)

·         Acute infection – Require chemotherapy

·         Chronic infection – Poorly respond (Surgery necessary)

3.      Selection of drugs

·         Activity of antimicrobial activity.

·         Pharmacokinetic factor

·         Patient related factor (Allergy, renal disease)

4.      Frequency and duration of drug administration

·         Optimize dose should be used for therapy.

·         Inadequate dose may develops resistance.

5.      Continue therapy

·         Some infection treated within 5-10 days, but some infection need more time to cure.

e.g.      Typhoid fever

            Tuberculosis

            Infective endocarditis (Inflammation of heart valve)

6.      Prophylactic chemotherapy

·         To avoid surgical site infection

Classification of antimicrobial

A.    Chemical structure

B.     Mechanism of action

C.     Types of organism

D.    Spectrum of activity

E.     Types of action (Bacteriostatic and bactericidal)

F.      Source of antibiotic

A.   Chemical structure

1)      Sulfonamides and related drugs:

Dapsone (DDS), Sulfadiazine, Paraaminosalicylic acid (PAS)

2)      Diaminopyrimidines:

Trimethoprim, Pyrimethamine

3)      Quinolones:

Nalidixic acid, Norfloxacin, Ciprofloxacin

4)      Beta lactam antibiotics:

Penicillins, Cephalosporins

5)      Tetracyclines:

Oxytetracycline, Doxycycline

6)      Nitrobenzene derivative:

Chloramphenicol

7)      Aminoglycosides:

Streptomycin, Gentamycin, Amikacin, Neomycin

8)      Macrolides antibiotics:

Erythromycin, Clanthromycin, Azithromycin

9)      Lincosamide antibiotics:

Clindamycin

10)  Glycopeptide antibiotics:

Vancomycin

11)  Oxazolidinone

Linezolid

12)  Polypeptide antibiotics:

Polymyxin-B, Bacitracin, Tyrothricin

13)  Nitrofuran derivatives:

Nitrofurantoin

14)  Nitroimidazoles:

Metronidazole, Tinidazole

15)  Nicotinic acid derivatives:

Isoniazid, Pyrazinamide, Ethionamide

16)  Polyene antibiotics:

Amphotericin-B, Nystatin, Hamycin

17)  Azole derivatives:

Miconazole, Clotrimazole, Ketoconazole, Fluconazole

18)  Others:

Rifampin, Ethambutol, Griseofulvin

B.    Mechanism of action

1)      Inhibition of cell wall synthesis

e.g. Penicillins, Cephalosporins, Cycloserine, Vancomycin, Bacitracin.

2)      Inhibition of protein synthesis

e.g. Tetracyclines, Chloramphenicol, Erythromycin, Clindamycin, Linezolid.

3)      Injury from cell membrane

e.g. Polymyxin-B

4)      Inhibition of synthesis of essential metabolites

e.g. Sulfonamide, Sulfone, PAS, Trimethoprim, Pyrimethamine, Metronidazole

5)      Inhibition of Nucleic acid replication and transcription

e.g. Rifampin. Quinolones.