Intro to Antimicrobial Chemotherapy Flashcards Preview

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Flashcards in Intro to Antimicrobial Chemotherapy Deck (33):
1

What is chemotherapy?

+ The use of chemicals (natural or synthetic) to inhibit the growth/replication of 'invading organisms' or cancerous cells within the body

+ Antibiotics and anti-bacterials can be used interchangeably

2

What are features of Salvarsan?

+ Kills trypanosomes
+ Trypanosomes can become resistant (trypanosomes resistant to one agent remain susceptible to others)

3

What is prontosil?

+ A red dye that inbibits bacteria (antibacterial)

+ Metabolises sulphanilamide: not a dye but still reactive to bacteria

4

How was streptomycin discovered?

+ Antibiotic discovery based on theory that soil organisms may have produced agents to kill mycobacteria derived from soil organisms

+ Soil screened for presence of factors that inhibit mycobacteria

+ Mycobacteria discovered

5

What is selective toxicity?

Central to the use of chemotherapeutic agents:

- when drugs intended to be toxic to the invading organism/cancerous cells but be relatively harmless to the host/normal cells

6

What does the approach of using drugs with selective toxicity depend upon?

The existence of biochemical differences between the target group of cells and the host

7

What are examples of different selective toxicity?

+ Penicillins: in the absence of allergy have very low toxicity and high doses can be used

+ Aminoglycosides have a narrow THERAPEUTIC INDEX thus the dose that causes toxicity is very close to the therapeutic dose

+ For anti-tuberculosis drugs such as isoniazid and pyrazinamide a number of patients will develop hepatotoxicity that is not dose related and may require treatment to be stopped

8

What are the main classes of anti-microbial agents?

+ Beta-lactam and cephalosporin

+ Glycopeptide

+ Cyclicpeptide

+ Phosphonic acids

+ Lipopeptides

9

What are the main mechanisms of action of beta-lactam and cephalosporin?

Preventing peptidoglycan cross-linking

10

What is the target of beta-lactam and cephalosporin?

Penicillin bindng proteins

11

What are examples of beta-lactams and cephalosporins?

+ Penicillin G
+ Flucloxavillin
+ Tazobactam

12

What is the main mechanism of action of glycopeptides?

Prevents transglycolation and transpeptidation

13

What is the target of glycopeptides?

C-terminal D-Ala-D-Ala

14

What are examples of glycopeptides?

+ Vancomycin
+ Teicoplanin

15

What is the main mechanism of action of cyclic peptides?

Prevents carriage of building-blocks of peptidoglycan bacterial cell wall outside of the inner membrane

16

What is the target of cyclic peptides?

C55-isoprenyl pyrophosphate

17

What are examples of cyclic peptides?

+ Bacitracin
+ Polymyxin

18

What is the main mechanism of action of phosphonic acids?

Inhibits first stage of peptidolycan synthesis

19

What is the target of phonphonic acids?

murA protein

20

What is an example of a phosphonic acid?

Fosphomycin

21

What is the main mechanism of action of lipopeptides?

Calcium-dependent membrane depolarisation

22

What is an example of a lipopeptide?

Daptomycin

23

What are the different classes of penicillins?

1. Penicillins G and V

2. β-lactamase-resistant penicillins
- cloxacillin, oxacillin, nafcillin, dicloxacillin, methicillin

3. Broad-spectrum penicillins
- ampicillin
- amoxicillin

4. Extended spectrum penicillins
- carbenicillin
- ticaracillin
- azlocillin
- piperacillin

24

How are cephalosporins classified?

By generations in the order in which they were developed:
- 1st, 2nd, 3rd

Now can be termed by means of administration:
- oral (cephalexin)
- parenteral (cefuroxime, cefotaxime)

25

What are bacterial folate antagonists?

Sulphonamides & trimethoprim:

- antibiotics which act through an inhibition of the folate pathway in bacteria

- humans don't have folate (get it via diet)

- this makes bacteria susceptinble to drugs which interfere with folate metabolism: selective toxicity target

26

What is the role of amino glycosides work?

INHIBIT PROTEIN SYNTHESIS

1. Form ionic bonds at cell surface

2. Penetrate cell wall via a transport mechanism across cell membrane

3. Diffuse into cytoplasm then bind to bacterial ribosomes

27

What occurs during the inhibition of protein synthesis by aminoglycosides?

1. Bind to ribosomes
(i) at interface between assembled 30S and 50S units
(ii) directly to individual subunits

2. Inhibits protein synthesis by misreading mRNA

28

What are examples of aminoglycosides?

+ Streptomycin
+ Kanamycin
+ Neomycon
+ Gentamycin

29

What are features of tetracyclines?

1. They prevent attachment of tRNA to acceptor site on mRNA-ribosomal complex

2. This prevents addition of amino acids to peptide chain

3. Weakly bound to ribosomes, unlike aminoglycosides

4. Differences in activity of individual tetracyclines related to solubility in bacteria lipid membrane

30

What is the role of chloramphenicol, erythromycin and clindamycin?

+ Prevent addition of new amino acids to growing peptide chain by binding ribosomes

+ This prevents association of peptidyl-transferase with amino acid and no peptide bond formed i.e no transpepidation

+ May also prevent translocation of ribosome down mRNA template (erythromycin)

31

What are fluoroquinolones?

Synthetic antibiotics

32

What are the classes of fluoroquinolones?

1. Broad spectrum:
- ciprofloxacin, ofloxacin, norfloxacin

2. Narrower-speectrum
- Cinoxacin, nalidixic acid

33

How do fluoroquinolones work?

+ Act by inhibiting bacterial Topoisomerase II (DNA gyrase)

+ This enzyme catalyses introductionof negative supercoil in DNA permitting transcription and replication