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Drugs and Disease > Chemotherapy of Infection > Flashcards

Chemotherapy of Infection Flashcards

1
Q

What synthetic chemicals be used to destroy infective agents?

A 
Trypan Red (Trypanosomiasis)
Atoxyl (Trypanosomiasis)
Salvarsan (Syphilis)
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2
Q

What must chemotherapy drugs be?

A

Selective

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

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3
Q

What was the chemotherpeutic index defined as by Paul Ehrlich?

A

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

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4
Q

What is an example of calculating therapeutic index?

A

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

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5
Q

What is chemotherapy?

A

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

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6
Q

What are chemotherpeutic agents?

A

Are intended to be toxic to pathogens or cancer cells

But harmless to the host or normal cell

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7
Q

What is selective toxicity?

A

Acceptable toxicity vs benefit

All toxicity is a matter of dosage

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8
Q

What must chemotherapeutic agents be able to do?

A

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

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9
Q

Why is difficult to achieve selectivity toxicity in cancer chemotherapy?

A

Cancer cells are too similar to normal host cells

In cancer side effects are more readily accepted

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10
Q

What are Protozoa and Helminths?

A

Eukaryotes

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11
Q

What is chemotherapy used to treat infection with?

A 
Bacteria
Viruses
Fungi
Protozoa
Helminths
Ectoparasites
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12
Q

What makes a drug selective?

A

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

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13
Q

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

A

Identified through comparative genomics

E.g. haemoglobin degradation by Plasmodium (in eukaryote)

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14
Q

How does different importance of target make a drug selective?

A

Target present in host and in pathogen

Essential only in pathogen

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15
Q

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

A

Target present and essential in host and pathogen

Target enzyme quickly replaced by host

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16
Q

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

A

Low drug concentrations inhibit pathogen enzymes first

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17
Q

What is penicillin?

A

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

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18
Q

What is an antibiotic?

A

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)

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19
Q

Why do organisms produce antibiotics?

A

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

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20
Q

What do some antibiotics have activity against?

A

Eukaryotes, parasites and fungi

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21
Q

What do antibiotics not work against?

A

Viruses

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22
Q

Are synthetic antibacterials such as sulphanoamide drugs or bleach antibiotics?

A

No

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23
Q

What are limitations of antibiotics?

A 
Ineffective against viruses
Ineffective against most protozoan parasites and helminths
Difficult to synthesise/derivatise
Can be expensive
Antibiotic resistance
Cannot optimise their properties
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24
Q

What are the key differences between bacterial and mammalian cells?

A

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

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25
Q

What do antibacterial agents do?

A

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

26
Q

What are sulphonamides?

A

First effective antibacterial agents

Bacterial cells use PABA to synthesis folic acid

27
Q

What can mammalian cells not synthesise?

A

Folic acid

28
Q

What do bacteria convert PABA into?

A

Folic acid using the enzyme dihydrofolate reductase

29
Q

What is tetrahydrofolic acid essential for the synthesis of?

A

Amino acids
Pyrimidine nucleotides (thymidine)
DNA and RNA

30
Q

What structure do sulphonamides resemble?

A

PABA

31
Q

How do Sulphonamides work in the cell?

A

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
Q

What are sulphonamides?

A

Bacteriostatic

33
Q

What is the limits of sulphonamides?

A

Limited use for immune-compromised patients

34
Q

What are examples of sulphonamides?

A

Sulphacetamide

Sulphamethoxazole

35
Q

What was the first antibiotic?

A

Penicillin

36
Q

What is penicillin?

A

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

37
Q

What does penicillin do?

A

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

38
Q

What is the cell wall?

A

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

39
Q

What does penicillin do against cell walls?

A

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
Q

What is peptidoglycan?

A

90% dry weight of gram + bacteria

41
Q

Wha are tetracycline?

A

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
Q

What was one of the first treatments for tuberculosis?

A

Streptomycin and the aminoglycosides

43
Q

What do streptomycin and aminoglycosides contain?

A 
Amino-sugars, bonded by glycosidic linkage
o	Streptomycin
o	Neomycin
o	Kanamycin
o	Gentamicin
o	Neomycin
o	Paromycin
44
Q

What are aminoglycosides?

A

Irreversible inhibitors of bacterial protein synthesis

45
Q

How do aminoglycosides enter gram negative bacteria?

A

Via porin channels in their outer membrane

46
Q

What do aminoglycosides bind to?

A

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

47
Q

What do aminoglycosides do?

A

Interfere with peptide formation
Induce mRNA misreading
Cause breakup of polysomes

48
Q

What is antibiotic resistant?

A

Development of bacterial defences against antibacterial agents

49
Q

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

A

Methicilline-resistance Staphylococcus aureus (MRSA)

Tuberculosis

50
Q

What are mechanisms of development?

A

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
Q

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

A

100 bacterial ones

52
Q

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

A

100,000x

53
Q

What is sulphonamide resistance?

A

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
Q

What is penicillin resistance?

A

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
Q

What were new penicillin’s synthesised to be?

A

Less sensitive to enzyme

56
Q

What do penicillin reversal agents do?

A

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

57
Q

What are ABC transporters?

A

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

58
Q

What can tetracyline not do in a bacterial cell?

A

Accumulate inside in high enough concentrations to inhibit protein synthesis

59
Q

What happens during the intra erythrocytic cycle?

A

70-80% of the host cell Hb is degraded

60
Q

What does haeme undergo?

A

Crystallisation, takes place in the food vacuole

61
Q

What interferes with polymerisation of haem?

A

Quinoline

Drugs and Disease (25 decks)

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