Principles 1-4 Flashcards

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1
Q

what are chemotherapeutic agents

A

chemical compounds used to treat disease

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2
Q

what do antimicrobials do

A

destroy pathogenic microbes or inhibit their growth within the host

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3
Q

what do antibiotics do

A

destroy or inhibit bacteria

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4
Q

most antibiotics are ____ or_____

A

microbial products; their derivatives

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5
Q

what antibiotics are used to treat streptomyces spp

A

-amphotericin B
- chloramphenicol
-erythromycin
-kanamycin
-neomycin
-nystatin
-rifampin
-streptomycin
-tetracylcines
- vancomycin

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6
Q

what antibiotic is used to treat micromonospora spp

A

gentamicin

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7
Q

what antibiotics are used to treat bacillus spp

A

bacitracin and polymyxins

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8
Q

what antibiotics are used to treat penicillium spp

A
  • griseofulvin and penicillin
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9
Q

what antibiotics are used to treat cephalosporium spp

A

cephalosporins

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10
Q

what is selective toxicity

A

ability of drug to kill or inhibit pathogen while damaging host as little as possible

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11
Q

what is a therapeutic dose

A

drug level required for clinical treatment

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12
Q

what is a toxic dose

A

drug level at which drug becomes too toxic for patient

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13
Q

what is the therapeutic index

A

ratio of toxic dose to therapeutic dose

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14
Q

what do bacteriocidal antibiotics do

A

kill bacteria

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15
Q

what do bacteriostatic antibiotics do

A

inhibit growth of bacteria

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16
Q

what do broad spectrum antibiotics do

A

attack many different bacteria, gram positive and gram negative

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17
Q

what do narrow spectrum antibiotics do

A

attack only a few different bacteria

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18
Q

what is MIC ( minimal inhibitory concentration)

A

lowest concentration of drug that inhibits growth of pathogen

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19
Q

what is MBC (minimal bacteriocidal concentration)

A

lowest concentration of drug that kills pathogen

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20
Q

what are the two techniques that are normally used to determine MIC and MBC

A

-dilution susceptibility tests
- disk diffusion tests

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21
Q

describe dilution susceptibility tests

A

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

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22
Q

what are dilution suscpetibility tests useful for

A

determining which drug would be best for the patient

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23
Q

describe disk diffusion tests

A
  • disks impregnanted with specific drugs are placed on agar plates inoculated with test microbe
  • drug diffuses from disk into agar, establishing concentration gradient
  • observe clear zones of no growth around disks
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24
Q

what is the 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
- values are plotted and used to determine if concentration of drug reached in body will be effective

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25
Q

what concentrations of a drug at infection site is needed to be effective

A

a concentration greater than MIC

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26
Q

what can be used to determine concentration of drug in blood

A

microbiological, chemical, immunological, enzymatic or chromatographic assays

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27
Q

what are the factors influencing the effectiveness of antimicrobial drugs

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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28
Q

what does the ability of the drug to reach the site of infection depend on

A
  • mode of transmission: oral, topical, parenteral routes
  • drug can be excluded by blood clots or necrotic tissue
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29
Q

what are parenteral routes

A

nonoral routes of administration

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30
Q

what are some factors infleucning ability of drug to reach concentrations exceeding MIC

A
  • amount administered
    -route of administration
    -speed of uptake
    -rate of clearance from body
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31
Q

does a drug required bacterial cell growth to be effective

A

some drugs do

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32
Q

what does the susceptibility of pathogen to drug depend on

A
  • speed of action of a drug
  • if drug requires bacterial cell growth
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33
Q

what are the mechanism of action of antimicrobial agents

A
  • disruption of bacterial cell wall
  • inhibition of protein synthesis
  • inhibition of nucleic acid synthesis
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34
Q

what are the the categories of antimicrobial agents and the specific drugs that disrupt bacterial cell wall

A
  • Beta-lactams: penicillins, cephalosporins, carbapenems and monobactams and beta lactamase inhibitors
  • glycopeptides: vancomycin and teichoplanin
  • polypeptides: bacitracin and polymixins
    -others: cycloserine, isoniazid and ethionamide, ethambutol
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35
Q

what is peptidoglycan made of

A

alternating NAM and NAG sugars

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36
Q

which type of bacteria has a much larger peptidoglycan layer

A

gram positive

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37
Q

describe peptidoglycan synethesis

A

-peptidoglycan repeat unit forms in cytoplasm, involved use of uridine diphosphate (UDP) as a carrier
- repeat unit then transported across membrane by bactoprenol
- repeat unit attached to growing peptidoglycan chain
-cross links formed by transpeptidation

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38
Q

what is the molecule involved in cross linkage in peptidoglycans in gram negatives

A

DAP and D-ala

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39
Q

what type of bacteria is E coli

A

gram negative

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40
Q

what type of bacteria is staphylococcus aureus

A

gram positive

41
Q

what molecule cross links peptidoglycans in gram positive bacteria

A

D- ala and L-Lys by a peptide interbridge

42
Q

what is transpeptidation

A

the exchange of one peptide bond for another

43
Q

what do Beta lactam antibiotics do

A

inhibit transpeptidation

44
Q

what does penicillin G act on and what is it destroyed by

A

high activity against most gram positive bacteria, low against gram negative, destroyed by acid and penicillinase

45
Q

what does ampicillin act on

A

active against gram positive and gram negative bacteria, acid stable

46
Q

what is methicillin resistant to and is it affected by acid

A

penicillinase, but less active than penicillin G, acid labile

47
Q

what are beta lactamase inhibitors

A

not antibiotics but they help beta lactam antibiotics by preventing their degradation by beta lactamases

48
Q

what are beta lactamases

A

enzymes produced by some bacteria that are resistance to beta lactam antibiotics

49
Q

what are examples of beta lactamase inhibitors

A

clavulanic acid, sulbactam and tazobactam

50
Q

what was the first combination of beta lactam antibiotic and beta lactamase inhibitor and what was it made of

A

-augmentin
- amoxicillin and clavulanic acid

51
Q

what does vancomycin do

A

-binds terminal D- Ala-D-Ala and sterically inhibits addition of peptidoglycan subunits to the cell wall
- binds to existing peptidoglycan chains and inhibits the transpeptidation reaction that crosslinks the chains

52
Q

what infections do vancomycin and teicoplanin treat

A

antibiotic resistance staphylococcal and enterococcal infections

53
Q

what do bacitracins do

A

prevent recycling of lipid carrier

54
Q

what do polymixins do

A

binds phospholipids and disrupts outer and inner membranes of gram negative bacteria

55
Q

why are many polymixins topical

A

its a more general mode of action because they are toxic

56
Q

what is cycloserine used for

A

second line of treatment for mycobacterium tuberculosis

57
Q

what is special about cycloserine

A
  • it is a cyclic analog of alanine
  • crosses blood brain barrier and is an NMDA receptor agonist
58
Q

what do isoniazid and ethionamide do

A

inhibits mycobacteria by affecting synthesis of mycolic acid

59
Q

what is mycolic acid

A

an abundant wax in the cell wall

60
Q

what does ethambutol do

A

inhibits mycobacteria by affecting attachment of mycolic acid in the cell wall

61
Q

describe how proteins are synthesized in ribosomes

A
  • start with free ribosomes and mRNA
  • 30S ribosomal subunit is formed and joined with a charged tRNA molecule
  • initiation factors form the 30S initiation complex
  • initiation factors add a 50S ribosomal subunit to make the 70S initiation complex where the tRNA is in the P site
  • a peptidyltransferase reaction occurs where the amino acid from the A site is added to the growing chain off the tRNA in the P site
  • a translocation reaction occurs where a tRNA in the A site is moved to the P site
62
Q

what makes up the 30S ribosomal subunit

A

16S rRNA and about 20 proteins

63
Q

what makes up the 50S ribosomal subunit

A

23S and 5S rRNA and about 30 proteins

64
Q

what drug falls under the category of oxazolidinones and what does it do

A
  • linezolid
  • binds 23S rRNA and prevents formation of 70S initiation complex
  • inhibition of protein synthesis
65
Q

what do tetracyclines do

A
  • bind 16S rRNA of 30S subunit and prevent binding of aa-tRNA to A site
  • inhibition of protein synthesis
66
Q

what drugs fall under the category of aminoglycosides and what do they do

A
  • streptyomycin
    -amikacin
  • gentamycin
  • tobramycin
  • bind to 30S subunit and distort A site, causing translation misreading which inhibits protein syntheiss
67
Q

what do chloramphenicol and lincosamides do

A

bind to 50S subunit and inhibit peptidyltransferase activity
-inhibition of protein synthesis

68
Q

what drugs fall under the category of macrolides and what do they do

A
  • erythromycin, azithromycin, clarithromycin
  • binds 23S rRNA in the 50S subunit and block the translocation reaction
  • also prevent further formation of the 50S subunit
  • inhibition of protein synthesis
69
Q

what drugs fall under the category of quinolones and what do they do

A

-ciprofloxacin and other -floxacins
- interfere with type II topoisomerases such as DNA gyrase or topoisomerase IV and stabilizes DNA double strand breaks
- inhibition of nucleic acid synthesis

70
Q

what do rifampin and rifabutin do

A

bind to RNA polymerase and prevent the initiation of transcription

71
Q

what does metronidazole do

A
  • a prodrug with no inherent antimicrobial activity
  • produces DNA damaging radicals under anaerobic conditions via enzymes functioning in anaerobes and microaerophiles
  • inhibition of nucleic acid synthesis
72
Q

what are drugs that fall under the class of antimetabolites and what do they do

A

-sulfonamides, trimethoprim, dapsone, and p-aminosalicyclic acid
- prevents formation of precursors of folic acid

73
Q

do humans make folic acid? do bacteria?

A

humans dont bacteria do

74
Q

drug resistance can often be transmitted to_____

A

other bacteria

75
Q

what are the resistance mechanisms of bacteria to antibiotics

A
  • impermeable barrier
  • target modifications
    -antibiotic modification
  • efflux pump mechanism
76
Q

how does the impermeable barrier confer drug resistance

A

the bacterial cell membrane develops an impermeable barrier which blocks antibiotics

77
Q

how does target modification confer drug resistance

A

modification of components of the bacteria which are targeted by the antibiotic, meaning the antibiotic can no longer bind properly to its target in order to destroy the bacteria

78
Q

how does antibiotic modification confer drug resistance

A

the cell produces substances (usually an enzyme) that inactivate the antibiotic before it can harm the bacteria

79
Q

how does the efflux pump mechanism confer drug resistance

A

antibiotic is actively pumped out of the bacteria so that it cannot harm the bacteria

80
Q

are penicillins and cephalosporins plasmidborne and what is their resistance mechanism to antibacterial agents

A
  • yes
  • hydrolysis of beta lactam ring by beta lactamase
81
Q

is methicillin plasmidborne and what is its resistance mechanism to antibacterial agents

A
  • no
  • change in penicillin binding protein
82
Q

are tetracycline plasmidborne and what is its resistance mechanism to antibacterial agents

A
  • yes
  • efflux pump pushed drug out of cell
83
Q

are oxazolidinones plasmidborne and what is its resistance mechanism to antibacterial agents

A

-no
- mutation in 23S rRNA

84
Q

are quinolones plasmidborne and what is its resistance mechanism to antibacterial agents

A
  • no
  • mutations in genes encoding DNA gyrase and topoisomerase IV
85
Q

what is the origin and transmission of drug resistance

A
  • new mutations of bacterial genes that encode the targets of antibiotics
  • pre-existing resistance genes that are transmitted from one bacterium to another
86
Q

what are the genetic elements involved in resistance gene spreading (dissemination)

A
  • plasmids
  • transducing bacteriophage
  • bacterial chromosomal genes
  • transposons
  • integrons
87
Q

how do plasmids transfer

A

conjugation

88
Q

how do transducing bacteriophages transfer and how

A

transduction by packaging non-phage DNA

89
Q

how do bacterial chromosomal genes transfer and how

A

transformation by mutations

90
Q

how are transposons involved in resistance gene dissemination

A

hop into other genetic elements

91
Q

what are integrons and where are they found

A
  • segments of DNA containing complete sets of genes
  • found of plasmids, transposons, and bacterial chromosomes
92
Q

what is superinfection and what causes it

A

development and spread of drug resistant pathogens caused by drug treatment which destroys drug sensitive strains

93
Q

what does the killing of normal flora result in

A

uninhibited growth of potentially pathogenic bacteria and fungi

94
Q

what does normal flora produce

A

antibacterial substances and competes with pathogenic bacteria for essential nutrients

95
Q

what are the common organisms in superinfections

A
  • clostridium difficile
  • MDR (multi drug resistant) gram negative rods
  • MRSA (methicillin resistant staphylococcus aureus
  • candida or other fungi
96
Q

what is clostridium difficile

A

spore forming agent of pseudomembranous colitis

97
Q

how can you prevent emergence of drug resistance

A
  • give drug in high concentrations
    -give two or more drugs at the same time
  • use drugs only when necessary
98
Q

what organisms are antibiotic resistant public health threats

A
  • clostridium difficile
  • carbapenem resistant enterobacteriaceae
  • neisseria gonorrhoeae
    -fluconazole resistant candida