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Vet Microbio > Antimicrobial Chemotherapies > Flashcards

Antimicrobial Chemotherapies Flashcards

1
Q

what are chemotherapeutic agents?

A

chemical agents used to treat disease that destroy pathogenic microbes or inhibit their growth within the host

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2
Q

what are most chemotherapeutic agents classified as?

A

antibiotics

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3
Q

what are antibiotics?

A

microbial products or their derivative that kill susceptible microbes or inhibit their growth

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4
Q

how was penicillin discovered?

A

accidentally by Alexander Fleming
observed penicillin activity on a contaminated plate but did not think it could be developed further

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5
Q

what is selective toxicity?

A

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

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6
Q

what is a therapeutic dose?

A

drug level required for clinical treatment

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7
Q

what is a toxic dose?

A

drug level at which drug becomes too toxic for the patient

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8
Q

what is the therapeutic index?

A

ratio of toxic dose to therapeutic dose

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9
Q

what are side effects?

A

undesirable effects of drugs on host cells

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10
Q

what are narrow spectrum drugs?

A

attack only a few different pathogens

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11
Q

what are broad spectrum drugs?

A

attack many different kinds of drugs

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12
Q

what do cidal agents do?

A

kills the target pathogen

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13
Q

what do static agents do?

A

reversibly inhibits growth of microbes

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14
Q

how does the effect of an agent vary?

A

with concentration, microbe, and host

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15
Q

how is effectiveness expressed? (2 ways)

A

minimal inhibitory concentration and minimal lethal concentration

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16
Q

what is minimal inhibitory concentration?

A

lowest concentration of drug that prevents growth of the pathogen

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17
Q

what is the minimal lethal concentration?

A

lowest concentration of drug that kills the pathogen

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18
Q

what are the main modes of action of antimicrobial drugs?

A

inhibitors of cell wall synthesis
protein synthesis inhibitors
metabolic antagonists
nucleic acid synthesis inhibition

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19
Q

how does chromosome replication and partitioning occur?

A

most bacteria have a single circular chromosome

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20
Q

what is the single origin of replication?

A

site at which replication begins

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21
Q

what is the terminus?

A

site at which replication is terminated, located opposite of the origin

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22
Q

what is the replisome?

A

group of proteins needed for DNA synthesis?

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23
Q

what is septation?

A

formation of cross wall between two daughter cells

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24
Q

what are the steps of sepatation (cytokinesis)?

A

selection of site for septum formation
assembly of Z ring (composed of protein FtsZ)
assembly of cell wall-synthesizing machinery
constriction of cell and septum formation

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25
Q

what is the main protein of interest in septation?

A

FtsZ

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26
Q

what are the steps of cell wall synthesis?

A

fliptadase moves the bactoprenol across the membrane and attaches to and moves the NAG-NAM complexes
glycosyltransferase joins all of the sugar layers together
transpeptidase (penicillin binding protein) attaches the amino acid chains and brings the layers together

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27
Q

would cell wall synthesis inhibitors work better against gram positive or gram negative bacteria?

A

gram positive because there is not the protection of the outer membrane that is present in gram negative cells

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28
Q

what is the most crucial feature of penicillin?

A

B-lactam ring

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29
Q

why is the B-lactam ring so important?

A

essential for bioactivity

30
Q

what makes penicillin resistant organisms resistant?

A

many penicillin resistant organisms produce B-lactamase which hydrolyzes a bond in the ring

31
Q

what is the mode of action for penicillin?

A

blocks the enzyme that catalyzes transpeptidation (formation of cross-links in peptidoglycan)
prevents the synthesis of complete cell walls leading to lysis of cell
acts only on growing bacteria that are synthesizing new peptidoglycan

32
Q

what kind of penicillin is narrow spectrum?

A

penicillin V and G are narrow spectrum

33
Q

why do semisynthetic penicillins have a broader spectrum than naturally occurring ones?

A

bulkier side chains make them more difficult for B-lactamase enzymes to degrade

34
Q

what can include in an antibiotic to increase efficiency?

A

B-lactamase inhibitors

35
Q

what are the characteristics of cephalosporins?

A

structurally and functionally similar to penicillin
broad spectrum antibiotics that can be used by most patients that are allergic to penicillin
there are four categories based on their spectrum of activity

36
Q

what are the characteristics of vancomycin?

A

glycopeptide antibiotic
inhibits cell wall synthesis
vancomycin- important for treatment of antibiotic-resistant staphylococcal and enterococcal infections
previously considered “drug of last resort” so rise in resistance to vancomycin is of great concern

37
Q

what do protein synthesis inhibitors do?

A

bind to the bacterial ribosome

38
Q

what are the four steps that can be targeted by PSIs?

A

aminoacyl-tRNA binding
peptide bond formation
mRNA reading
translocation

39
Q

aminoglycoside characteristics

A

large group, all with a cyclohexane ring, amino sugars
bind to the 30S ribosomal subunit, interfere with protein synthesis by directly inhibiting the process and by causing misreading of the messenger RNA

40
Q

tetracycline characeristics

A

all have a four-ring structure to which a variety of side chains are attached
broad spectrum, bacteriostatic
target the 30S subunit of the ribosome that inhibits protein synthesis

41
Q

macrolide characteristics

A

contain 12- to 22- carbon lactone rings linked to one or more sugars
ex: erythromycin
broad spectrum bacteriostatic
binds to 50S ribosomal subunit to inhibit bacterial protein elongation
used for patients allergic to penicillin

42
Q

metabolic antagonists characteristics

A

act as antimetabolites and are structural analogs

43
Q

what are antimetabolites?

A

antagonize or block functioning of metabolic pathways by competitively inhibiting the use of metabolites by key enzymes

44
Q

what are structural analogs?

A

molecules that are structurally similar to, and compete with, naturally occurring metabolic intermediates to block normal cellular metabolism

45
Q

sulfonamide drug characteristics

A

structurally related to sulfanilamide, a para aminobenzoic analog, which are used for the synthesis of folic aid and is made by many pathogens
makes them selectively toxic due to the competitive inhibition of folic acid synthesis

46
Q

trimethoprim characterisitics

A

synthetic antibiotic that also interferes with folic acid production
broad spectrum
can be combined with sulfa drugs to increase efficacy of treatment
-combo blocks two steps of the pathway

47
Q

what are the two most commonly used antibacterials drugs that inhibit nucleic acid synthesis?

A

fluroquinolones
rifamycins

48
Q

why ae nucleic acid synthesis targeting drugs not as selectively toxic?

A

because bacteria and eukaryotes fo not differ greatly in the way they synthesize nucleic acids

49
Q

fluoroquinolone characteristics

A

synthetic drugs that contain a 4-quinolone ring
act by inhibiting bacterial DNA gyros and topoisomerase II
broad spectrum, bactericidal, treat a wide variety infections

50
Q

what does bacitracin do?

A

inhibits dephosphorylation

51
Q

what does furazolidone do?

A

block DNA transcription

52
Q

what does optochin do?

A

interferes with ATPase and ATP production

53
Q

why has antiviral drug development been slow?

A

because it is difficult to specifically target viral replication bc many target cells are similar to our celss

54
Q

tamiflu

A

anti-influenza agent
neuraminidase inhibitor
shortens course of illness

55
Q

what are nucleoside reverse transcriptase inhibitors?

A

anti-HIV drugs that target and interfere with critical steps in viral replicative processes

56
Q

what are non nucleoside reverse transcriptase inhibitors?

A

prevent HIV DNA synthesis by selectively binding to and inhibiting the viral reverse transcriptase enzyme

57
Q

protease inhibitors

A

block the activity of the HIV protease needed for the production of all viral proteins

58
Q

integrase inhibitors

A

present the incorporation of the HIV genome into the host’s chromosomes

59
Q

fusion inhibitors

A

prevent HIV entry into cells

60
Q

what is the most successful way to avoid resistance with HIV drugs?

A

drug cocktails

61
Q

antifungals

A

fewer effective agents because of similarity if eukaryotic fungal cells and human cells
many have low therapeutic indexes and are toxic

62
Q

superficial mycoses

A

Candida
topical and oral
disrupt membrane permeability and inhibit sterol synthesis
disrupts the mitotic spindle; may inhibit protein and DNA synthesis

63
Q

systemic mycoses

A

difficult to control and can be fatal

64
Q

what are the three common drugs to treat systemic mycoses?

A

amphotericin B-binds sterols in membrane
5-flucytosine-disrupts RNA function
fluconazole- low side effects, used prophylactically

65
Q

examples of antiprotozoan drugs

A

quinine (chloroquine and mefloquine)-malaria
metronidazole- entamoeba

66
Q

what are the three types of drug resistance?

A

intrinsic
acquired
drug-tolerant

67
Q

intrinsic resistance

A

mycoplasma resistance to B-lactam antibiotics and other cell wall inhibitors because they lack a cell wall

68
Q

acquired resistance

A

occurs when there is a change in the genome of a bacterium that converts it from one that is sensitive to an antibiotic to one that is resistant
i.e, plasmids

69
Q

drug tolerant resistance

A

bacteria lacks the mechanisms for antibiotic resistance and ignore the presence of antibiotics
ex: bacteria embedded in biofilms

70
Q

what are the 4 mechanisms of drug resistance?

A

modify the target of the antibiotic
drug inactivation using the enzyme from a plasmid
minimize the concentration of antibiotic in the cell by pumping them out
bypass the biochemical reaction inhibited by the agent or increase the production of the target metabolite

71
Q

how can we overcome drug resistance?

A

give the drug in appropriate concentrations to destroy susceptible microbes and most spontaneous mutants
give two or more drugs at a time
use drugs only when necessary
continue development of new drugs
possibly use bacteriophages to treat disease

Vet Microbio (12 decks)

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