Principles of antimicrobial chemotherapy

Question 1

Define chemotherapy

Answer 1

The use of chemicals to inhibit the growth or replication of invading organisms or cancerous cells within the body

Question 2

What is selective toxicity?

Answer 2

The concept of drugs being toxic to invading organisms or cancerous cells but relatively harmless to host/normal cells

Question 3

Give some examples that explain selective toxicity

Answer 3

Penicillins (in the absence of allergy) have a very low toxicity can can be used at high doses.
Aminoglycosides have a very narrow theraputic index meaning the dose that causes a toxic effect is very close to that which causes the theraputic effect.
For a number of anti-tuberculosis drugs (isoniazid and pyrazinamide) , patients will develop hepatotoxicity which is not dose related, meaning treatment may have to be stoped.

Question 4

What are the drug classes of the antibiotics active against the cell wall?

Answer 4

Beta-lactam and cephalosporin.
Glycopeptide.
Cyclic peptide.
Phosphonic acids.
Lipopeptides

Question 5

Describe some of the features of beta lactam and cephalosporin

Answer 5

They target penicillin binding proteins which prevents peptidoglycan cross linking. Some examples include penicillin G, Flucloxacillin and Tazobactam

Question 6

Describe some of the features of the glycopeptide drug class

Answer 6

They target the C-terminal of the D-Ala-D-Ala dipeptide (component for peptidoglycans) and this prevents the transglycolation and transpeptidation. Examples include vancomysin and teicoplanin.

Question 7

Describe some of the features of the cyclic peptide drug class

Answer 7

They target the 55th carbon of the isopropyl pyrophosphate chain. It prevents the carriage of building blocks for peptidoglycans from inside the cell.
Examples include Bacitracin and polymyxin

Question 8

Describe some of the features of the phosphonic acid drug class

Answer 8

Targets murA protein and therefore inhibits the first stage of peptidoglycan synthesis.
An example is Fosphomycin

Question 9

Describe some of the features of the drug class Lipopeptide

Answer 9

Targets cell wall stress stimulon which affects the calcium dependant membrane depolarisation.
An example is Daptomycin.

Question 10

What are some examples Beta-lactamase resistant penicillins?

Answer 10

Methicillin, Oxacillin, Nafcillin, Cloxacillin and Dicloxacillin

Question 11

Give two examples of broad spectrum penicillin

Answer 11

Ampicillin and Amoxiciilin

Question 12

Give four examples of extended spectrum penicillin

Answer 12

Carbenicillin, Ticaracillin, Alzocillin and Piperacillin

Question 13

What are some of the features of cephalosprons

Answer 13

They work in the same way as penicillins. Classified in the generations they were developed in.
Now are termed by means of administation. Examples are Cephalexin (oral) and Cefuroxime and Cefotaxime (parenteral)

Question 14

Name some bacterial folate antagonists?

Answer 14

Sulphonamines and Trimethoprim.

Question 15

Describe some of the features of aminoglycosides

Answer 15

They form ionic bonds with the cell surface and penetrate the cell wall by a transport mechanism then diffuse into the cytoplasm and bind to the bacterial ribosomes. Some examples are;
Streptomycin, Kanamycin, Neomycin and Gentamicin

Question 16

Describe the inhibition of bacterial protein synthesis?

Answer 16

The antibiotics bind to the ribosome at the interface between the 30S and 50S subunits. It inhibits protein synthesis by misreading mRNA.

Question 17

Describe some of the features of tetracyclins

Answer 17

The prevent attachment of tRNA to the acceptor site on the mRNA-ribosome complex. This prevents the addition of amino acids to the peptide chain. They are only weakly bound to ribosomes and their activity depends on their solubility.

Question 18

Describe how chloramphenicol, erythromycin and clindamycin work

Answer 18

They prevent the addition of new amino acids to a growing peptide chain by binding to the ribosome. This prevents association of the peptidyl-transferase with the amino acid and no peptide bond is formed.
Only in the case of erythromycin, can they prevent translocation of the ribosome on the mRNA strand

Question 19

Describe some of the features of Fluoroquinolones

Answer 19

These are synthetic antibiotics that act by inhibiting bacteral DNA topoisomerase II also know as DNA gyrase. This enzyme catalyses the production of DNA into a supercoil therefore these antibiotics means that the DNA does not coil up properly.

Question 20

Name some broad spectrum fluoroquinolones

Answer 20

Ciprofloxacin, ofloxacin and norfloxacin

Question 21

Name the narrower- spectrum fluoroquinolone

Answer 21

Nalidixic acid