Antimicrobial Chemotherapy Flashcards

1
Q

Which are the chemotherapy agents target features found in microbes?

A

Ribosome, cell wall (PG), nucleic acid synthesis, cell membrane

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2
Q

What are the types of antimicrobial agents?

A

Antibiotic drugs (penicillin)
Antiseptics (benzalkonium chloride)
Disinfectants (hypochlorite bleaches)

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3
Q

Name the two types of antimicrobial drugs

A

Bactericidal -> kill infecting bacteria
Bacteriostatic -> halt growth (immune system continues)

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4
Q

What are narrow spectrum and broad spectrum antimicrobial drugs?

A

NS: against limited subset of bacteria
BS: against wide range of bacteria

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5
Q

What are the two types of chemotherapeutic drugs?

A

Synthetic drugs (sulphonamides) -> lab synthesized
Antibiotics (penicilllin) -> natural products

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6
Q

What are the types of inhibitors (antibiotic classes)

A

Inhibitors of cell wall biosynthesis
Disruptors of membrane function
Inhibitors of nucleic acid synthesis
Inhibitors of protein synthesis
Inhibitors of metabolism

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7
Q

What type of inhibitor are beta-lactams?

A

Cell wall biosynthesis inhibitor

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8
Q

True or false: penicillin attacks transglycosylase

A

False: penicillin attacks transpeptidase

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9
Q

What is the mechanism of inhibition of beta-lactams?

A

Structurally analogous to terminal a.a on un-crossed crosslinked pentapeptide PG side chain
Attack different PBPs

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10
Q

Explain glycopeptides

A

Prevent NAM-NAG to be in mesh
Targets substrates not enzymes
Unable to penetrate OM of g.-

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11
Q

What do the two types of vancomycins do?

A

A: Uncrosslinked strands of pre-existing PG
B: Lipid II substrate before polymerisation into PG

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12
Q

True or false: Vancomycin can act on g.+ and g. -

A

False: Vancomycin can only act on g.+

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13
Q

True or false: beta-lactams can act only on g.-

A

False: beta-lactams can act on g.- and g.+

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14
Q

Explain colistin’s disruption of membrane function

A

Target LPS in g.- (destabilises LPS)
Not absorbed by GI so must be topical or IV

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15
Q

What type of inhibitor is Rifampicin?

A

Nucleic acid (transcription) inhibitor

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16
Q

What does Rifampcin?

A

RNA pol. inhibitor
Blocks transcription elongation (initiation) by binding to beta subunit

17
Q

What type of inhibitor are Quinolones?

A

DNA gyrase inhibitors

18
Q

What are two types of Quinolones?

A

Nalidixic acid (g.-)
Ciprofloxacin (broad)

19
Q

True or false: Drugs have high binding affinity for 70S with low affinity for 80S

A

True

20
Q

What type of inhibitors are aminoglycosides?

A

Protein synthesis inhibitors

21
Q

What does Streptomycin (aminoglycoside) do?

A

High affinity to 16S rRNA of 30S ribosomal subunit
Inhibit formation of ribosomal initiation

22
Q

What do tetracyclines (aminoglycoside) do?

A

Bind to 16S rRNA of 30S subunit and block A-site in 70S ribosome

23
Q

What do macrolides (aminoglycoside) do?

A

Inhibit 50S subunit
Blocks elongating peptide exit tunnel

24
Q

How does one determine mechanism of action?

A

Seeing what drug is binding to (biochemical ligand binding assay)
Whole genome sequencing
If it is inhibiting ribosome or inhibiting cell wall

25
Q

What are the types of resistance mechanism?

A

Keep antibiotic outside cell
Modify/mutate molecular target of antibiotic
Destroy/inactivate antibiotic

26
Q

Describe the destroy/deactivate antibiotic resistance mechanism

A

Modify/destroy antibiotic with offensive enzymes

27
Q

Describe the modify/mutate molecular targe of antibiotic resistance mechanism

A

Change structure of ribosomes for ribosome inhibitors so they can’t be bound

28
Q

What are beta-lactamase enzymes?

A

Hydrolytic enzymes that destroy beta-lactam antibiotics

29
Q

From what did beta-lactamase evolve from?

A

PBP’s targets of beta-lactam antibiotic

30
Q

In what ways are beta-lactamase and PBP’s similar?

A

Amino acid sequence similarities -> transpeptidase similar
Gene duplication + mutational remodeling

31
Q

What are the types of spread of AMR genes?

A

Transformation (free DNA)
Transduction (bacteriophage)
Conjugative transfer (plasmid/transposon)

32
Q

How does antibiotic resistance spread?

A

Spread HGT of pre-existing resistance genes (NDM-1)
De novo/in situ evolution of new resistance genes

33
Q

Describes Kirby-Bauer disc diffusion assay

A

Growth inhibited until Minimum Inhibitory Concentration (MIC)
Use of Mast rings

34
Q

Why is keeping PABA free medium important?

A

For microbial growth
Antibiotic diffuses (3D)

35
Q

What is a clinically susceptible organism?

A

High likelyhood of therapeutic success

36
Q

What does MIC determine?

A

Whether a given strain is susceptible or resistant to antibiotic

37
Q

What is MBC?

A

Minimum bactericidal concentration
Lowest concentration of antimicrobial that will kill test organism