Chemotherapy of Infection Flashcards Preview

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Flashcards in Chemotherapy of Infection Deck (61):
1

What synthetic chemicals be used to destroy infective agents?

Trypan Red (Trypanosomiasis)
Atoxyl (Trypanosomiasis)
Salvarsan (Syphilis)

2

What must chemotherapy drugs be?

Selective
i.e. drug must kill the pathogen and not the host

3

What was the chemotherpeutic index defined as by Paul Ehrlich?

"minimum curative dose as a fraction of the maximum dose tolerated by patient”

4

What is an example of calculating therapeutic index?

Salvarsan will cure syphilis at a dose of 5mg/kg/day
A dose of 15 mg/kg/day may have severe-to-fatal toxic effects on the patient
The therapeutic index is 3

5

What is chemotherapy?

Use of chemicals, either natural or synthetic to
Kill or inhibit growth of infectious agents
Inhibit the growth of malignant cells
:

6

What are chemotherpeutic agents?

Are intended to be toxic to pathogens or cancer cells
But harmless to the host or normal cell

7

What is selective toxicity?

Acceptable toxicity vs benefit
All toxicity is a matter of dosage

8

What must chemotherapeutic agents be able to do?

Exploit difference between the host and the invading micro-organism
Or between normal cell and cancer cell

9

Why is difficult to achieve selectivity toxicity in cancer chemotherapy?

Cancer cells are too similar to normal host cells
In cancer side effects are more readily accepted

10

What are Protozoa and Helminths?

Eukaryotes

11

What is chemotherapy used to treat infection with?

Bacteria
Viruses
Fungi
Protozoa
Helminths
Ectoparasites

12

What makes a drug selective?

Unique target in pathogen
Different importance of target
Different stability of target protein
Drug has higher affinity for pathogen and host enyme

13

How does a unique target in pathogen make a drug selective?

Identified through comparative genomics
E.g. haemoglobin degradation by Plasmodium (in eukaryote)

14

How does different importance of target make a drug selective?

Target present in host and in pathogen
Essential only in pathogen

15

How does different stability of target protein make a drug selective?

Target present and essential in host and pathogen
Target enzyme quickly replaced by host

16

How does a drug having a higher affinity for pathogen and host enzyme make a drug selective?

Low drug concentrations inhibit pathogen enzymes first

17

What is penicillin?

A naturally occuring substance produced by a micro-organism that killed other microorganisms

18

What is an antibiotic?

Antibiotics are specific chemical substances produced by living organisms for chemically derived from those substances that are capable of inhibiting the life processes of other organisms (kill or inhibiting growth)

19

Why do organisms produce antibiotics?

To defend themselves from micro-organisms such as (other) bacteria, parasites, fungi

20

What do some antibiotics have activity against?

Eukaryotes, parasites and fungi

21

What do antibiotics not work against?

Viruses

22

Are synthetic antibacterials such as sulphanoamide drugs or bleach antibiotics?

No

23

What are limitations of antibiotics?

Ineffective against viruses
Ineffective against most protozoan parasites and helminths
Difficult to synthesise/derivatise
Can be expensive
Antibiotic resistance
Cannot optimise their properties

24

What are the key differences between bacterial and mammalian cells?

Bacterial cels require para-amino nezoic acid (PABA)- mammalian cells do not (need to get in diet, eat green vegetables)
Bacterial cells have cell walls- mammalian cells do not
Bacterial cell ribosomes have 30S and 50S sub-units- mammalian cells have 40S and 60S ribosomal sub-units

25

What do antibacterial agents do?

Deprive bacteria of PABA (Sulphoamides)
Inhibit cell wall synthesis (Penicillin)
Interefere with bacterial protein synthesis (Tetracycline, streptomycin)
Interfere with nucleic acid synthesis

26

What are sulphonamides?

First effective antibacterial agents
Bacterial cells use PABA to synthesis folic acid

27

What can mammalian cells not synthesise?

Folic acid

28

What do bacteria convert PABA into?

Folic acid using the enzyme dihydrofolate reductase

29

What is tetrahydrofolic acid essential for the synthesis of?

Amino acids
Pyrimidine nucleotides (thymidine)
DNA and RNA

30

What structure do sulphonamides resemble?

PABA

31

How do Sulphonamides work in the cell?

Are accepted by the enzyme converting PABA to folic acid
BUT cannot be converted in the next stage
Stop amino acid/purine/pyrimidine/nucleic acid synthesis
Sulphonamides stop bacterial growth but do not kill bacteria

32

What are sulphonamides?

Bacteriostatic

33

What is the limits of sulphonamides?

Limited use for immune-compromised patients

34

What are examples of sulphonamides?

Sulphacetamide
Sulphamethoxazole

35

What was the first antibiotic?

Penicillin

36

What is penicillin?

An organic compound synthesised and released by one micro-organism and which kills other micro-organisms

37

What does penicillin do?

Inhibit cell wall synthesis
Affect only bacteria which are actively growing
Kill bacteria: are bacteriocidal

38

What is the cell wall?

Polymer of glycan units cross-linked by peptides- peptidoglycan wall

39

What does penicillin do against cell walls?

Double activity
Inhibition of the enzyme that cross-links peptide chains in the cell wall
--> inhibition of cell wall construction
Activation of an enzyme involved in cell wall turnover
--> increased cell wall breakdown

40

What is peptidoglycan?

90% dry weight of gram + bacteria

41

Wha are tetracycline?

Inhibits bacterial protein synthesis
Competes with tRNA carrying a new amino acid for its binding site on the 30S sub-unit of the ribosome
Disrupts protein synthesis
Is bacteriostatic

42

What was one of the first treatments for tuberculosis?

Streptomycin and the aminoglycosides

43

What do streptomycin and aminoglycosides contain?

Amino-sugars, bonded by glycosidic linkage
o Streptomycin
o Neomycin
o Kanamycin
o Gentamicin
o Neomycin
o Paromycin

44

What are aminoglycosides?

Irreversible inhibitors of bacterial protein synthesis

45

How do aminoglycosides enter gram negative bacteria?

Via porin channels in their outer membrane

46

What do aminoglycosides bind to?

The 30S (small) ribosomal subunit and disrupt protein synthesis

47

What do aminoglycosides do?

Interfere with peptide formation
Induce mRNA misreading
Cause breakup of polysomes

48

What is antibiotic resistant?

Development of bacterial defences against antibacterial agents

49

What are some drugs that have serious problems for drug treatment of infections?

Methicilline-resistance Staphylococcus aureus (MRSA)
Tuberculosis

50

What are mechanisms of development?

Transfer of resistance genes between bacteria
Main mechanism is by plasmid transfer
Bacteria tha make antibiotics hold resistance genes
Resistance genes already exist- just need to be obtained

51

For every gene in your genome how many bacteria is there?

100 bacterial ones

52

How much faster is bacterial generation time than human cell generation time?

100,000x

53

What is sulphonamide resistance?

Bacteria develop an alternative pathway that bypasses the reaction inhibited by the Sulphonamides
Bacteria develop a Dihydropteroate synthase with normal affinity for PABA but a low affinity for sulphonamides

54

What is penicillin resistance?

Production of an enzyme which destroys the antibiotic- e.g.- beta-lactamase destroys Penicillin’s by breaking the beta lactam ring in the penicillin molecule

55

What were new penicillin's synthesised to be?

Less sensitive to enzyme

56

What do penicillin reversal agents do?

Clauvulanic acid is a mechanism-based B-lactamase inhibitor combined with pencillin group antibiotics to overcome resistance

57

What are ABC transporters?

The bacterium produces proteins in its membrane that pump Tetracyline out of the bacterium

58

What can tetracyline not do in a bacterial cell?

Accumulate inside in high enough concentrations to inhibit protein synthesis

59

What happens during the intra erythrocytic cycle?

70-80% of the host cell Hb is degraded

60

What does haeme undergo?

Crystallisation, takes place in the food vacuole

61

What interferes with polymerisation of haem?

Quinoline