1.4 Flashcards

1
Q

Antibiotics:

A
a class of chemotherapeutic
agents
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2
Q

Chemotherapeutic agents are

A

chemical

compounds used to treat disease

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3
Q

Antimicrobials destroy

A

pathogenic microbes or

inhibit their growth within host

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4
Q

Antibiotics destroy or inhibit

A

bacteria

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5
Q

Most antibiotics are — products or their

derivatives

A

microbial

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6
Q

selective toxicity

A

– ability of drug to kill or inhibit pathogen while

damaging host as little as possible

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7
Q

therapeutic dose

A

– drug level required for clinical treatment

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8
Q

toxic dose

A

– drug level at which drug becomes too toxic for patient

i.e., produces side effects

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9
Q

therapeutic index

A

– ratio of toxic dose to therapeutic dose

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10
Q

Bacteriocidal antibiotics

A

– kill bacteria

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11
Q

Bacteriostatic antibiotics

A

– inhibit growth of bacteria

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12
Q

Broad-spectrum antibiotics

A

– attack many different bacteria (Gram + and Gram -)

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13
Q

Narrow-spectrum antibiotics

A

– attack only a few different bacteria

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14
Q

Determining the Level of
Antimicrobial Activity
• effectiveness expressed in two ways

A

– minimal inhibitory concentration (MIC)

– minimal bacteriocidal concentration (MBC)

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15
Q

– minimal inhibitory concentration (MIC)

A

• lowest concentration of drug that inhibits growth of pathogen

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16
Q

– minimal bacteriocidal concentration (MBC)

A

• lowest concentration of drug that kills pathogen

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17
Q

Dilution Susceptibility Tests

A

• involves inoculating media containing different
concentrations of drug
– broth or agar with lowest concentration showing no
growth is MIC
– if broth used, tubes showing no growth can be
subcultured into drug-free medium
• broth from which microbe cannot be recovered is MBC

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18
Q

Disk Diffusion Tests

A

• disks impregnated with specific drugs are
placed on agar plates inoculated with test
microbe
• drug diffuses from disk into agar,
establishing concentration gradient
• observe clear zones (no growth) around
disks

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19
Q

Kirby-Bauer method

A

• standardized method for carrying out disk
diffusion test
• sensitivity and resistance determined using tables
that relate zone diameter to degree of microbial
resistance
• table values plotted and used to determine if
concentration of drug reached in body will be
effective

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20
Q

Kirby-Bauer method (steps)

A
Inoculate plate
evenly with
bacteria whose
susceptibility is
being studied
Place discs containing
antibiotics or control
solutions onto the plates
Incubate a defined
amount of time at a
defined temperature
Measure zone of inhibition
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21
Q

Measurement of Drug
Concentrations in the Blood
• concentration of drug at infection site must
be > — to be effective

A

MIC

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22
Q

microbiological, chemical, immunological,
enzymatic, or chromatographic assays can
be used to determine

A

concentration of

drug in blood

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23
Q

Factors Influencing the
Effectiveness of Antimicrobial
Drugs (3)

A

• ability of drug to reach site of infection
• ability of drug to reach concentrations in body
that exceed MIC of pathogen
• susceptibility of pathogen to drug

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24
Q

Ability of drug to reach site of
infection
• depends in part on mode of administration (3)

A

– oral
– topical
– parenteral routes

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25
Q

– oral

A

• some drugs destroyed by stomach acid

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26
Q

– parenteral routes

A

• nonoral routes of administration

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27
Q

drug can be excluded by (2)

A

blood clots or necrotic

tissue

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28
Q

Factors influencing ability of drug
to reach concentrations
exceeding MIC (4)

A
  • amount administered
  • route of administration
  • speed of uptake
  • rate of clearance (elimination) from body
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29
Q

Mechanism of Action of
Antimicrobial Agents
• can impact pathogen by targeting some
function necessary for its (2)

A

reproduction or

survival

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30
Q

Ideally, targeted function is very specific to

pathogen =

A

high therapeutic index.

– Not always possible

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31
Q

b-lactams (4)

A

penicillins
cephalosporins
carbapenems & monobactams
(+ b-lactamase inhibitors)

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32
Q

Glycopeptides (2)

A

vancomycin & teichoplanin

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33
Q

Polypeptides (2)

A

bacitracin & polymixins

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34
Q

Others (3)

A

cycloserine
isoniazid & ethionamide
ethambutol

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35
Q
  1. Disruption of bacterial cell wall (2)
A

– Peptidoglycan is unique to bacteria

– Most pathogens contain peptidoglycan

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36
Q

peptidoglycan repeat unit forms in
cytoplasm
• involves use of

A

uridine

diphosphate (UDP) as a carrier

37
Q

repeat unit then transported across

membrane by

A

bactoprenol (“lipid”)

38
Q

repeat unit attached to growing

A

peptidoglycan chain

39
Q

cross-links formed by

A

transpeptidation

40
Q

Transpeptidation creates crosslinks in

A

peptidoglycan

41
Q

Transpeptidation is the exchange of one

A

peptide bond for another

42
Q

b-lactam antibiotics inhibit —

A

transpeptidation

43
Q

penicillin G

A

higher activity against most gram-positive bacteria, low agaist gram negative; destroyed by acid and penicillinase

44
Q

penicillin V

A

more acid restraint than penicillin G

45
Q

ampicillin

A

active against gram-positive and gram-negative bacteria; acid stable

46
Q

carbenicillin

A

active against gram negative bacteria like pseudomonas and proteus; acid stable, not well absorbed by small inteastine

47
Q

methicillin

A

penicillinase-resistant, but less active than penicillin G, acid liable

48
Q

ticarcillin

A

similar to carbenicillin but more active against pseudomonas

49
Q

first generation cephalosporin

A

cephalothin

50
Q

second generation cephalosporin

A

cefoxitin

51
Q

third generation cephalosporin

A

cefoperazone

ceftriaxone

52
Q

Carbapenems and monobactams

A

Two newer classes of b-lactam antibiotics

53
Q

b-lactamase inhibitors

A

Not antibiotics, but help b-lactam antibiotics by

preventing their degradation by b-lactamases

54
Q

b-lactamases are enzymes produced by some bacteria that are

resistant to

A

b-lactam antibiotics

55
Q

Examples of b-lactamase inhibitors: (3)

A

clavulanic acid, sulbactam, and tazobactam

56
Q

Use in combination with b-lactam antibiotic
— was 1st combination
= amoxicillin + clavulanic acid

A

Augmentin

= amoxicillin + clavulanic acid

57
Q

Vancomycin binds terminal D-Ala-D-Ala and sterically inhibits

A

addition of peptidoglycan subunits to the cell wall.

58
Q

Vancomycin binding to existing peptidoglycan chains inhibits

the

A

transpeptidation reaction that crosslinks the chains.

59
Q
vancomycin has been important for treatment of
antibiotic resistant (2)
A

staphylococcal and

enterococcal infections

60
Q

Vancomycin and teichoplanin are —

A

glycopeptides

61
Q

bacitracins

A

Prevent recycling of lipid carrier

62
Q

polymixins

A

Binds phospholipids and disrupts outer
and inner membranes of gram negative
bacteria (topical because of more
general mode of action = toxic)

63
Q

Cycloserine

A

Second line treatment for

Mycobacterium tuberculosis

64
Q

Cycloserine is a cyclic

analog of

A
alanine
- Also crosses blood brain
barrier and is an NMDA
receptor agonist (with
uses and side effects)
65
Q

Isoniazid & Ethionamide
Inhibits Mycobacteria by
affecting synthesis of

A

mycolic
acid (abundant wax in the cell
wall)

66
Q

Ethambutol
Inhibits Mycobacteria by
affecting attachment of

A

mycolic acid in the cell

wall

67
Q

Oxazolidinones

linezolid

A

Binds 23S rRNA and
prevents formation of
70S initiation complex

68
Q

Inhibition of protein synthesis

Tetracyclines

A

Bind 16S rRNA of 30S
subunit and prevent
binding of aa-tRNA to
A site

69
Q

Inhibition of protein synthesis

Aminoglycosides

A

streptomycin
amikacin
gentamycin
tobramycin

Bind to 30S subunit and
distort A site, causing
translation misreading, which
inhibits protein synthesis

70
Q

Inhibition of protein synthesis
Chloramphenicol
Lincosamides

A

Bind to 50S subunit and inhibit

peptidyltransferase activity

71
Q

. Inhibition of protein synthesis

Macrolides

A

Erythromycin, azithromycin, clarithromycin

• Bind 23S rRNA in the 50S subunit
and block the translocation reaction
• also prevent formation of the 50S
subunit

72
Q

Inhibition of nucleic acid synthesis

Quinolones

A

ciprofloxacin and other -floxacins
Interfere with type II topoisomerases
(DNA gyrase or topoisomerase IV) and
stabilize DNA double strand breaks

73
Q

Inhibition of nucleic acid synthesis
Rifampin & Rifabutin
Rifampin

A

Bind to RNA polymerase and prevent

the initiation of transcription

74
Q

Inhibition of nucleic acid synthesis

Metronidazole

A

• a prodrug with no inherent antimicrobial activity
• produces DNA-damaging radicals under anaerobic conditions
via enzymes functioning in anaerobes and microaerophiles

75
Q

Antimetabolites (4)

A

Sulfonamides, trimethoprim, dapsone, and p-aminosalicylic

acid

76
Q

Drug Resistance
Big problem for clinical treatment of —
Resistance can often be transmitted to other —

A

infections

bacteria

77
Q

New mutations of bacterial genes that

encode the targets of —

A

antibiotics

78
Q

Pre-existing resistance genes that are

transmitted from

A

one bacterium to another

79
Q

Plasmids
- some can promote their own
transfer by

A

conjugation

80
Q

Transducing bacteriophage

A
  • can package non-phage DNA

= transfer by transduction

81
Q

Bacterial chromosomal genes (2)

A
  • mutations

- transfer by transformation

82
Q

Transposons

A
  • hop into other genetic elements
83
Q

Integrons (2)

A
  • segments of DNA containing
    complete sets of genes
  • found on plasmids, transposons,
    and bacterial chromosomes
84
Q

Superinfection

A

development and spread of drug-resistant pathogens

caused by drug treatment, which destroys drug sensitive strains

85
Q

Killing of normal flora removes

the

A
inhibitory effect of the
normal flora (which produce
antibacterial substances &
compete for essential nutrients).
This allows for uninhibited
growth of potentially pathogenic
bacteria & fungi
86
Q

Common organisms in Superinfections include: (4)

A

Clostridium difficile (spore-forming agent of pseudomembranous colitis)
MDR (multi-drug-resistant) gram-negative rods
MRSA (methicillin-resistant Staphylococcus aureus)
Candida or other fungi

87
Q

Preventing emergence of drug

resistance (3)

A
  • give drug in high concentrations
  • give two or more drugs at same time
  • use drugs only when necessary
88
Q

possible future solutions (2)

A

– continued development of new drugs
– use of bacteriophages to treat bacterial
disease