Chemotherapy of Infection Flashcards

(61 cards)

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
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