Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Block 6; Week 4-Michelle > Chemotherapy & Antibiotic Resistance-Kozel > Flashcards

Chemotherapy & Antibiotic Resistance-Kozel Flashcards

1
Q

Why is it that drug developers have little incentive to develop antibiotics even tho they are very much needed?

A

b/c you make it & people don’t use.
it is put in reserve for those with antibiotic resistance
while it is in reserve the patent is pending
eventually you lose your rights & you didn’t make that much money while you had them.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

How long have antibiotics been around?

A

millions of years–in organisms that try to resist microbes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

T/F It takes between 75-100 years for a patient population to develop antibiotic resistance.

A

False. Usu like 10-30 years.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are antibiotics?

A

Chemical substances produced by various species of microorganisms that are capable of inhibiting, in small amounts, the growth of other microorganisms

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the guidelines for an ideal antimicrobial?

A 
Selective toxicity
bactericidal
absence of genetic or phenotypic resistance
the proper spectrum
non-allergenic
minimal side effects
active in body
water soluble
bactericidal levels can be reached in vivo
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is meant by selective toxicity?

A

kill the bug w/o killing the host

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

if an antimicrobial isn’t bactericidal & killing bugs–what is it?

A

bacteriostatic. keeps them from growing

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the options for a proper spectrum? When do you want each kind?

A

Broad Spectrum-like if you don’t know which bug you are trying to kill
Narrow Spectrum-for a more focused approach when you have 1 organism in mind.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Why is it important that an anti-microbial be water soluble?

A

b/c it needs to be able to move around in the body, the blood stream & get to its site of infection.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the 5 sites of antibiotic action? Note: these are used as categories of antibiotics.

A 
Cell wall synthesis
protein synthesis
membrane function or synthesis
nucleic acid synthesis
metabolic pathways
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Why is protein synthesis a good target for antibiotics?

A

b/c bacteria have different ribosomes than humans. Selective toxicity.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the 5 mechanisms of resistance to antibiotics? Note: these are also used to categorize them.

A 
Enzymatic Inactivation
Decreased Permeability
Efflux
Modification of Molecular Target
Failure to Convert Inactivate Precursor to Active Form
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is meant by enzymatic inactivation as a means of antibiotic resistance?

A

microbe makes an enzyme that inactivates an antibiotic. Ex: penicillinase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

There is acquired decreased permeability. But the main mechanism of resistance to antibiotics comes from intrinsic decreased permeability. What is this?

A

Gram negative bacteria are more intrinsically impermeable to antibiotics than gram positive bacteria.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

How is efflux a mechanism of antibiotic resistance?

A

some bacteria actually have pumps that can get rid of antibiotics from the cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What types of things do bacteria do to modify the susceptible molecular target & resist antibiotics?

A

Alteration of antibiotic binding site
Protection of target site
Overproduction of target
Binding-up of antibiotic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are the phases involved in the study of pharmacokinetics of a drug?

A

Absorption
Distribution
Elimination

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is involved in pharmacodynamics of a drug?

A
  • *relationship b/w drug conc’n & toxic effect to host

* *relationship b/w drug conc’n & antimicrobial effect

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What does a good antibiotic need in terms of pharmacokinetics? What is involved in this?

A

Need to be able to get to the microbe.
Involves:
Absorption from the site of administration
Transfer from plasma to site of infection
Elimination from plasma
Elimination from site of infection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is MIC?

A

minimum inhibitory conc’n

the minimum conc’n of antibiotic that will stop bacterial growth

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is MBC? Which types of antibiotics does this apply to?

A

minimum bactericidal conc’n
minimum conc’n to kill bacteria
this only applies to bactericidal antibiotics–about 50% of all antibiotics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What does it mean to be a bactericidal antibiotic?

A

kill the microbe!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are some examples of bactericidal antibiotics?

A 
beta lactams
vancomycin
fluoroquinolones
metronidazole
aminoglycosides
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What does it mean to be a bacteriostatic antibiotic?

A

inhibit the organism-don’t kill it

depend on the host’s mechanisms of killing to clear it out.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What are some examples of bacteriostatic antibiotics?

A

tetracyclines
clindamycin
macrolides
sulfonamides

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What is synergy with respect to antibiotics?

A

this is when a combo of antibiotics produces a larger effect than one alone
in fact-a 2-log10 larger effect!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What is a good example of synergy in antibiotic administration?

A

penicillin + gentamycin
treatment for: viridans strep meningitis
penicillin facilitates the movement of the gentamycin thru the gram positive organisms.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What is the post antibiotic effect?

A

Definition: persistent suppression of growth following exposure to an antimicrobial-even when it gets below the MIC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What are the mechanisms of PAE?

A

slows growth below MIC

alters morphology of the microorganism so that its innate defense mechanisms are altered.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What is Postantibiotic leukocyte enhancement (PALE)?

A

Increases susceptibility to phagocytosis

Increases susceptibility to phagocytic killing

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What are the 3 most used pharmacodynamic outcome parameters?

A

Time>MIC
AUC/MIC
Cmax/MIC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What’s the deal with the time>MIC outcome parameter?

A

How long a drug stays above the MIC
Time-dependent killing
Minimal to moderate persistent effects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What’s the deal with the AUC/MIC outcome parameter?

A

Ratio of the 24-hour serum concentration curve to MIC
Total exposure of microbe to antimicrobial agent
Prolonged persistent effects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

What’s the deal with the Cmax/MIC outcome parameter?

A

Maximum serum concentration/MIC
Concentration-dependent killing
Prolonged persistent effects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

What does it mean to be a conc’n-dependent killing agent?

A

Higher drug concentrations have higher rate and extent of bactericidal activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What are the main outcome parameters for conc’n dependent killing agents?

A

Cmax/MIC & AUC/MIC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What are some examples of conc’n dependent killing agents?

A

aminoglycosides
fluoroquinolones
metronidazole

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

What does it mean to be a time-dependent (conc’n independent) killing agent?

A

Bactericidal action is relatively slow
Saturation of killing occurs at low multiples of the MIC
**basically: have slow MOA-want to maximize the time the pt stays just over the MIC. Don’t need a large volume, just long exposure.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

What are the main outcome parameters for time dependent (conc’n independent) killing agents?

A

Time>MIC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

What are some examples of time-dependent (conc’n independent) killing agents?

A

beta lactams

vancomycin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

What are bacteriostatic agents? Do they have a post antibiotic effect?

A

these are antibiotics that only halt the growth of bacteria, don’t kill them.
prolonged PAE

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

What is the main outcome parameter for bacteriostatic antibiotics?

A

AUC/MIC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

What are some examples of bacteriostatic antibiotics?

A

tetracyclines
clindamycin
macrolides
sulfonamides

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

What are antibiotics that are inhibitors of cell wall synthesis?

A

beta lactam antibiotics
cycloserine
bacitracin
glycopeptide antibiotics-vancomycin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Which antibiotics belong in the category of beta lactam antibiotics? What do they all have in common?

A 
natural penicillin
penicillin derivates
cephalosporins
carbapenems
beta lactamase inhibitors
**they all possess the 4-membered beta lactam ring
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

What do beta lactam antibiotics & vancomycin mess with?

A

peptidoglycan cell wall synthesis

prevent the formation of the transpeptide bridge (glycine bridge)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

What are the 2 types of natural penicillins?

A 
Penicillin G (benzyl)
Penicillin V (phenoxymethyl)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

What is the spectrum of natural penicillins?

A

narrow spectrum

mostly gram positives-can’t get thru the outer membrane of gram negatives.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

What is the structure of natural penicillin?

A

4 membered beta lactam ring

next to the 5 membered thiazolidine ring

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

What does a beta lactamase do to penicillin?

A

it destroys penicillin by cleaving the beta lactam ring

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

What does amidase do to penicillin?

A

cleaves the side groups of penicillin

this is actually how you make synthetic derivates

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

To make synthetic derivates of penicillin you start with what?

A

Natural Penicillin! G & V

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

What is the clinical use of natural penicillin?

A

if a pt isn’t allergic-wide use! cheap & works well

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

Which of the natural penicillins-G or V-can be taken orally?

A

Only V can be taken orally.

G is sensitive to gastric acid.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

What are penicillin binding proteins? What is their fcn?

A

these are the target proteins (enzymes) of beta lactam antibiotics
fcn: construction of the pentapeptide-pentaglycine bridges that cross link the peptidoglycan layer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

What are some examples of these penicillin binding proteins-the enzymes that make the transpeptide bridge?

A

Carboxypeptidases
Endopeptidases
Transglycosylases
Transpeptidases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

What is the MOA of penicillin?

A

binds to transpeptide bridge enzymes (penicillin binding proteins)
blocks the cross-linking
bactericidal b/c the cell will eventually lyse from being leaky & having autolytic enzymes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

What kind of a bond is there b/w the penicillin binding protein & penicillin?

A

covalent bond

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

What are some important mechanisms of resistance to penicillin?

A

beta lactamase enzyme
prevent access of antibiotic to PBP
alteration of binding site of PBP-reduces the # & affinity of PBP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

Where is the genetic info to make a beta lactamase enzyme located?

A

plasmid

transposable chromosomal gene

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

How do organisms prevent access of antibiotics to PBP?

A
  • *intrinsic resistance of gram negative bacteria (b/c of their outer membrane)
  • *altered porin in N. gonorrhea so that penicillin can’t penetrate
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

Give some examples of the following type of resistance: Alteration in binding site - reduction in number or affinity of PBP.

A
  • *Newly resistant strains of S. pneumoniae
  • *Some forms of penicillin-resistant N. gonorrhoeae
  • *Methicillin-resistant S. aureus - MRSA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

How can penicillins be manufactured to resist penicillase? What is an example of a drug that has this? What is the tradeoff?

A

you introduce a bulky group near the site of cleavage

ex: methicillin
tradeoff: 1/10 as potent as natural penicillin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

Where does cell wall synthesis occur in gram positive bacteria? What does this mean for penicillin on a mission?

A
  • *occurs at the bottom of the cell wall
  • *nearest the membrane, but outside the membrane
  • *to get to this site, just have to work thru the bulk of the peptidoglycan
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

Where does cell wall synthesis occur in gram negative bacteria? What is the significance of this for penicillin on a mission?

A
  • *synthesis occurs in the periplasmic space

* *it has to cross the outer membrane-tough & resistant to hydrophobic drugs.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

What alterations do broad spectrum penicillins have to be able to penetrate gram negative bacteria as well as gram +?

A

they have charged side groups

they are then hydrophilic & can get thru the pore of the outer membrane of gram negative bacteria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

What is the drawback to the charged structure of broad spectrum penicillins?

A

they have the same sensitivity to penicillinase as natural penicillin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

Give 2 examples of broad spectrum penicillins with charged side groups.

A

Ampicillin: + charge
Carbenicillin: - charge

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
69
Q

Describe the absorption, fate & excretion of penicillin?

A 
vary in oral absorption
rapid renal secretion
well distributed to most tissues
no penetration to BBB usu
time-dependent killing-maximize exposure not conc'n to the drug
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
70
Q

Why does penicillin vary in oral absorption?

A

Some are acid labile-penicillin G & methicillin. These must be injected!
Some are acid stable-penicillin V & semi-synthetic penicillins. These can be taken orally.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
71
Q

How do allergic reactions form to penicillin?

A

the beta lactam ring can open & bind to host proteins-forming a hapten.
then the body is sensitized to the thiazolidine ring that is waving in the wind.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
72
Q

What are the GI consequences of penicillin?

A

disturbs normal flora

most prominent with ampicillin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
73
Q

What is the exception to the rule that penicillin doesn’t go thru the BBB?

A

when there is infection or inflammation in the brain-the BBB becomes more permeable.
So if you have meningitis-you can get that penicillin across!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
74
Q

Is a person who is allergic to penicillin necessarily allergic to cephalosporins?

A

not necessarily

cephalosporins have the beta lactam ring but they don’t have the thiazolidine ring-instead they have a 6 membered ring.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
75
Q

Are cephalosporins sensitive to beta lactamases?

A

generally, they are resistant!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
76
Q

Describe the different generations & types of cephalosporins.

A

1st – Narrow spectrum – Gram positives; some gram negatives
2nd – Expanded spectrum – Gram positives; improved gram negative activity
3rd – Broad spectrum – Gram positives; improved gram negative activity, including Pseudomonas
4th – Extended spectrum – Gram positives; marginally improved gram negative activity
MRSA-active cephalosporins – high affinity for PBP 2a’

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
77
Q

Describe the absorption, fate & excretion of cephalosporins.

A

both oral & injectable forms available for most generations.
some have good CNS penetration
excreted via kidney

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
78
Q

What are the risks or drawbacks of cephalosporins?

A
  • *GI: diarrhea, nausea

* *Superinfections possible with broad spectrum cephalosporins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
79
Q

Describe the multifactorial ways in which an organism can develop resistance to broad spectrum cephalosporins.

A

Altered penicillin binding protein 2 (altered penA gene)
Overexpression of efflux pump (due to mutation in repressor mtrR)
Mutation in porin reduces uptake (penB resistance determinant)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
80
Q

What does the CDC currently recommend for treatment of uncomplicated gonorrhea?

A

ceftriaxone + azithromycin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
81
Q

Where did antibiotic resistant gonococci emerge?

A

Southeast Asia
came over after the vietnam war
**now there are cases of resistance in the Western US & even Norway

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
82
Q

What are 2 examples of carbapenems? Remember: we are still talking beta lactam antibiotics

A

imipenem

muropenem

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
83
Q

What is the structure of carbapenems?

A

beta lactam ring

modified alpha ring-eliminates sulfur; still 5 members

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
84
Q

How do carbapenems work?

A

they have a high affinity for PBPs of most gram positives & gram negatives.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
85
Q

What is the spectrum of carbapenems?

A

broad spectrum

can even penetrate the outer membrane of gram negatives thru a specific OMP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
86
Q

Is carbapenem sensitive to beta lactamase?

A

highly resistant, actually

b/c of the hydroxyethyl group on C6

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
87
Q

Are carbapenems effective against MRSA?

A

no

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
88
Q

So…carbapenems are relatively new. What is their clinical use?

A

useful for a wide array of infections b/c of the broad spectrum
sometimes used for empirical antibacterial therapy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
89
Q

What’s the deal with carbapenem’s absorption, fate, & excretion?

A

needs to be injected, b/c poor absorption if taken orally

hydrolyzed by peptidase in renal tubule

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
90
Q

What is the solution to the problem of the renal peptidase against carbapenems?

A

take it with cilastatin!

this is a peptidase inhibitor that blocks the antibiotic’s renal degradation–it’ll last longer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
91
Q

Do carbapenems have a ton of side effects?

A

not really, pretty well tolerated

can get some allergic reaction via similar mechanism as penicillin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
92
Q

What’s the deal with New Delhi metallo-β-lactamase 1 (NDM-1)?

A

NDM-1 is encoded by the carbapenem resistance gene blaNDM-1
plasmid that carries it found in common enteric bacilli
resistant to almost all usable antibiotics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
93
Q

blaNDM-1 is carried on a plasmid that carries multiple resistance genes. Which things does it resist?

A 
Imipenems
All other beta-lactams
Aminoglycosides
Tetracyclines
Fluoroquinolones
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
94
Q

What was the perfect storm in New Delhi that led to this crazy resistant infection via NDM-1?

A
  • *too many antibiotics used in india
  • *water treatments that allow some spreading of enterics
  • *Note: also seen in elective surgeries in SE Asia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
95
Q

Give 2 examples of beta lactamase inhibitors.

A
  • clavulanic acid

* sulbactam

96
Q

What do beta lactamase inhibitors do?

A

they are suicide inhibitors-inhibit beta lactamase
forms an acyl enzyme intermediate that hydrolyzes slowly
don’t have direct antibacterial action

97
Q

What is the clinical use for beta lactamase inhibitors?

A

used in combo with penicillinase sensitive beta lactams

ex: amoxicillin w/ clavulanate=augmentin

98
Q

What do glycopeptide antibiotics inhibit? What is an example of one?

A

Ex: vancomycin

inhibit cell wall synthesis

99
Q

What is the MOA of vancomycin?

A

bind to the terminal D-ala-D-ala of the peptide bridge to prevent transpeptidation
bactericidal

100
Q

How is resistance to vancomycin carried?

A

plasmid-mediated

involves multiple genes

101
Q

What is the most common form of vancomycin resistance?

A

enterococcus resistance
VRE
lactate substituted for alanine. Alters binding site for vanco & it can’t bind!

102
Q

There are 2 types of staph aureus resistance to vancomycin. Describe the more common of the 2.

A

VISA
Vancomycin Intermediate Staph Aureus
a bunch of terminal alanines instead of just 2.
gets the vancomycin tied up & flustered.

103
Q

There are 2 types of staph aureus resistance to vancomycin. Describe the less common of the 2.

A

VRSA
vancomycin resistant staph aureus
lactate substituted for alanine

104
Q

What is the spectrum of vancomycin?

A

limited to gram positive bacteria

can’t get thru the pores of gram negative bacteria b/c of how large it is

105
Q

What is the clinical use of vancomycin? Is it inexpensive?

A

Expensive drug

used as a last resort & an alternative to penicillin

106
Q

Describe the absorption, fate & excretion of vancomycin (a glycopeptide antibiotic).

A

given via IV
poorly absorbed orally
excreted via kidney

107
Q

When should vancomycin be used orally?

A

to treat C diff

108
Q

What is the clinical significance of vancomycin being mainly excreted by the kidney?

A

the dose is altered in patients with renal insufficiency

109
Q

What are the side effects or toxicity concerns of vancomycin?

A

ototoxicity & nephrotoxicity at high doses

can get red person’s syndrome w/ infusion related reactions

110
Q

Ampicillin and carbenicillin are examples of broad spectrum penicillins in which penicillin has been modified to enhance activity against gram negative bacteria. What is the function of the modifications that achieve the enhanced activity for gram negative bacteria?
A) Facilitates transit through outer membrane porins
B) Enhances binding to LPS in the gram negative outer membrane
C) Enhances affinity for transpeptidases in the cytoplasmic membrane
D) Blocks production of LPS
E) Binds to the terminal alanine during peptidoglycan synthesis

A

A. get thru porins by becoming hydrophilic w/ their negatively or positively charged side groups. Ampicillin + charged.

111
Q

What are 2 types of cell membrane inhibitors that affect membrane function or synthesis?

A

polymyxin

antifungals

112
Q

What is the mechanism of polymyxin?

A

fatty acid tail penetrates the phospholipid bilayer of the outer membrane of gram negative bacteria
leakage of metabolites & disruption of membrane fcn
bactericidal

113
Q

What is the spectrum of polymyxin?

A

gram negative bacteria only

114
Q

What is the clinical use of polymyxin?

A

usu only used in topical creams like neosporin b/c of concerns over toxicity
sometimes IV use of colistin when there is no other alternative

115
Q

What are 3 highly resistant things that polymyxin is used IV to treat?

A

pseudomonas
klebsiella
acinetobacter

116
Q

Can polymyxin be given via oral admin?

A

NO b/c it can’t be absorbed that way.

117
Q

What are some possible adverse side effects of polymyxin?

A

dose-related nephrotoxicity

118
Q

What are the 2 categories of inhibitors of nucleic acid synthesis?

A

Inhibitors of DNA synthesis

Inhibitors of RNA synthesis

119
Q

What are 2 examples of antibiotics that inhibit DNA synthesis?

A

quinolones

metronidazole

120
Q

What is an example of an antibiotic that inhibits RNA synthesis?

A

rifampin

121
Q

What is the basic structure of quinolones & fluoroquinolones? Which is used more clinically?

A

Quinolones: 2 fused rings
Fluoroquinolones: 2 fused rings + a fluoride group

122
Q

What is the mechanism of quinolones?

A

they inhibit the bacterial DNA gyrase-thus inhibit DNA synthesis
bactericidal

123
Q

Why doesn’t the quinolone affect human DNA synthesis?

A

b/c the DNA gyrase of humans is different than that of bacteria

124
Q

Can resistance to quinolones happen?

A

yes, somewhat common

bacteria will alter its DNA gyrase

125
Q

What is the spectrum of quinolones?

A

both gram negative & gram positive bacteria

126
Q

What are the clinical uses of quinolones?

A

good for UTIs & other bacterial infections

Note: it is excreted in high conc’n in the urine

127
Q

What is the absorption, fate, & excretion of quinolones?

A

oral admin-good absorption

affects the urinary tract b/c renally excreted

128
Q

What are the possible adverse GI effects of quinolones?

A

nausea
vomiting
abdominal discomfort

129
Q

What are the possible adverse CNS effects of quinolones?

A

mild headache

dizziness

130
Q

What are other possible adverse effects of quinolones?

A

achilles tendon damage

ciprofloxacin-cause of C diff

131
Q

What is the structure & form of metronidazole (flagyl)-another inhibitor of DNA synthesis?

A

5 membered ring
made synthetically
prodrug (not active)
activated by ETC in anaerobes or protozoa

132
Q

What does metronidazole produce? What is its spectrum?

A

produces cytotoxic compounds that damage DNA-bactericidal
Spectrum: obligate anaerobes & protozoa
NOT facultative anaerobes or obligate aerobes

133
Q

What is the clinical use of metronidazole?

A

treats anaerobic infections
prophylaxis for colorectal surgery
can treat some protozoan infections like trichomonas vaginalis

134
Q

What is the absorption, fate & excretion of metronidazole?

A

good absorption after oral admin

same w/ IV

135
Q

What’s the toxicity & side effects of metronidazole?

A

well tolerated
nausea, diarrhea
potential mutagenic effects

136
Q

What is the mechanism of rifampin?

A

binds to the DNA-dependent RNA polymerase
blocks chain initiation
**doesn’t affect eukaryotic polymerases
can be either bactericidal or bacteriostatic

137
Q

What is the mechanism for resistance against rifampin?

A

rapid single step mutation in the beta subunit

138
Q

What is the clinical use of rifampin?

A

treatment of TB
leprosy
prophylactic treatment of N meningitis

139
Q

What is the absorption, fate, excretion of rifampin?

A

good absorption after oral admin
good distribution thru body but limited CNS penetration
eliminates in urine & feces (mainly)

140
Q

What are the toxicity & side effects considerations with rifampin?

A

Orange discoloration of tears, sweat, and urine
GI effects most common – cramping, nausea, diarrhea
Hepatic toxicity

141
Q

Rifampin is also an up regulator of cytochrome p450 enzymes. What is the impact of this?

A

Alters hepatic metabolism of hormones and drugs (decreases t1/2)
Examine patient medications for potential interaction

142
Q

What are the 2 main categories of antibiotics that mess with protein synthesis-that is inhibitors of translation?

A

Inhibitors of 30S ribosomal subunit

Inhibitors of 50S ribosomal subunit

143
Q

What are 2 categories of antibiotics that fit under the inhibitors of 30S ribosomal subunit category?

A

Aminoglycosides

Tetracyclines

144
Q

What are 4 categories of antibiotics that fit under the inhibitors of 50S ribosomal subunit category?

A

Chloramphenicol
Lincosamides
Oxazolidinones
Macrolides

145
Q

What are 2 examples of lincosamides?

A

lincomycin

clindamycin

146
Q

What is 1 example of a macrolide?

A

erythromycin

147
Q

Which part of translation do tetracylines affect?

A

they affect the step where the tRNA gets into the A site of the 30S ribosomal subunit.

148
Q

Which part of translation do the chloramphenicols & lincosamides affect?

A

the peptide bond formation b/w the 2 tRNAs

149
Q

Which part of translation do the macrolides affect?

A

peptide bond formation & translocation-where the tRNA in the E slot is booted out

150
Q

What is the mechanism of amino glycosides?

A

they are bactericidal

  • bind 30S subunit
  • deplete ribosomal pool
  • misread the message
  • premature release of ribosome
  • *synergy w/ penicillin & other cell wall active antimicrobials so that it can access gram positives
151
Q

What is an example of an amino glycoside?

A

streptomycin
gentamycin
tobramycin
amikacin

152
Q

What are mechanisms of resistance against amino glycosides?

A

plasmid-mediate enzymatic alteration of the amino glycosides-via acetylation, phosphorylation, or adenylation
**also reduced uptake & intrinsic resistance of anaerobes

153
Q

What is the spectrum of amino glycosides?

A

broad spectrum
gram positives
gram negatives
TB

154
Q

What is the clinical use of streptomycin?

A

2nd line defense for TB
also used for tularemia or plague
pretty toxic

155
Q

What are the clinical uses of gentamycin, tobramycin, amikacin?

A

used empirically if you suspect aerobic, gram - bacteria.

used specifically if you know

156
Q

How is neomycin used?

A

often used in topical ointment, like neosporin w/ polymyxin

157
Q

Are amino glycosides effective w/ gram positives?

A

yes, but need to be in combo w/ a cell wall active agent to get inside

158
Q

What’s the deal with the absorption, fate & excretion of amino glycosides?

A

not really GI absorbed-need to use IM or IV
excreted via the kidney
conc’n dependent effect-Cmax/MIC predictor

159
Q

What are the possible adverse effects of amino glycosides? How often do these happen?

A

Nephrotoxicity – 5-25%
Ototoxicity – irreversible - 2-10%
Neuromuscular blockade - rare

160
Q

What is the structure of tetracycline?

A

4 fused rings

161
Q

What is the mechanism of tetracycline?

A

blocks binding of aminoacyl tRNA to A site of ribosome
reversible binding
bacteriostatic!

162
Q

What are possible mechanisms of resistance against tetracycline?

A

active efflux pump-pumps the antibiotic outside of the bacterial cell
**also cytoplasmic proteins bind ribosome to protect it from the antibiotic

163
Q

What is the spectrum of tetracycline?

A 
broad!
gram positives
gram negatives
anaerobes
spirochetes
mycoplasma
rickettsiae
chlamydia
164
Q

What is the clinical use of tetracyclines?

A

1st line for chlamydia, rickettsia, spirochetes-primary drug for lyme disease
2nd line for other things b/c of toxicity possibilities

165
Q

What is the absorption, fate, & excretion of tetracyclines?

A

variable
impaired by certain cations, including milk!
excreted via kidney & bile

166
Q

What are the possible toxicities & side effects of tetracyclines?

A 
Photosensitivity in skin
GI disturbances
Nephrotoxicity
Stains teeth and bones during early development; not recommended for children under 8 years
Superinfection
167
Q

What’s the deal with the availability of chloramphenicol-inhibitor of 50S ribosomal translation?

A

no longer available in the US
very toxic, including bone marrow toxicity
but still sold OTC in Mexico.

168
Q

Lincosamides are a part of which antibiotic category? What is an example of one of these?

A

Inhibitors of Translation-50S ribosomal subunit

Ex: clindamycin

169
Q

What is the mechanism of lincosamides?

A

blocks peptidyl transferase

bacteriostatic

170
Q

Is there resistance against lincosamides?

A

yes, plasmid mediated methylation of ribosome–so the antibiotic can’t bind!
**methylation of the target

171
Q

What is the spectrum of lincosamides?

A

aerobic gram + cocci
anaerobes
NOT gram negatives

172
Q

What is the clinical use of clindamycin?

A

anaerobe infections
good alternative to penicillin
can help some strains of MRSA

173
Q

What is the absorption, fate & excretion of clindamycin?

A

oral commonly
could be IV
excreted via urine & feces
if have renal failure-increased half life-dosage adjustment required

174
Q

What are the toxicity considerations for clindamycin?

A

GI: diarrhea, nausea, vomiting, cramps

Pseudomembranous colitis-C diff

175
Q

What antibiotic category do oxazolidinones fall into? What is an example?

A

inhibitors of translation-50S ribosomal subunit

Ex: linezolid

176
Q

What is the mechanism of oxazolidinones?

A

binds 50S
prevents formation of 70S complex
effective against resistant bacteria
bacteriostatic

177
Q

What is the spectrum of oxazolidinones?

A

active against any gram +

limited activity w/ gram negative

178
Q

What is the clinical use of oxazolidinones?

A 
MRSA (but not FDA approved for it)
Multi-drug resistant strep pneumonia
vancomycin resistant entercocci
other difficult bacteria
**used as a reserve antibiotic
179
Q

What is the absorption, fate & excretion of oxazolidinones?

A

used IV or oral
great bioavailability
excreted in urine

180
Q

What are the toxicity & side effects of oxazolidinones?

A 
well tolerated
GI-diarrhea, nausea, vomiting
myelosuppresion with long term use
inhibitor of monoamine oxidase
**shouldn't be given with SSRIs
181
Q

What category of antibiotics do macrolides fall into? What are some examples?

A

inhibitors of translation
50S subunit
Ex: erythromycin, azithromycin, & clarithromycin

182
Q

What is the MOA of macrolides?

A

binds 50S ribosome
blocks peptidyl transferase & translocation
bacteriostatic

183
Q

What is the resistance mechanism against macrolides?

A

plasmid mediated methylation of ribosome (target)

cross resistance to lincomycin & clindamycin w/ methylation of ribosome-nothing can bind!

184
Q

How do macrolides get their name?

A

their large cyclic structure

185
Q

What is the spectrum of macrolides?

A

broad

active against aerobic & gram positive bacteria

186
Q

What is the clinical use of macrolides?

A

primary for mycoplasma, legionella

alternative to penicillin

187
Q

What is the absorption, fate & excretion of macrolides?

A

erythromycin-inactivated by gastric acid-need to coat if given orally
azithromycin-acid stable
distributes well except to CNS
primarily biliary excretion

188
Q

What are the toxicity & side effects considerations with macrolides?

A

hepatotoxicity
Gi motility increases-diarrhea, nausea, ab pain
inhibitor of cyt p450
cardiac arrhythmias

189
Q

Rifamycins are highly effective against staphylococci. However, use of rifampin as a single agent for treatment of Staphylococcus aureus infections is limited due to the high rate of development of rifampin resistance during therapy. What is the most likely mechanism for resistance to rifampin?
A) Mutation in one of the penicillin binding proteins
B) Mutation in binding sites on the 30S ribosomal subunit
C) Mutation in binding sites on the 50S ribosomal subunit
D) Mutation in DNA gyrase
E) Mutation in the DNA-dependent RNA polymerase

A

E. Mutation of the target of the antibiotic!

190
Q 
Cycloserine is an antibiotic that is a competitive inhibitor for incorporation of the terminal alanine into the pentapeptide that is attached to N-acetyl muramic acid in peptidoglycan. Which of the following antibiotics also targets the terminal alanine in the peptide attached to MurNAc?
A)	Penicillin
B)	Imipenem
C)	Polymyxin
D)	Bacitracin
E)	Vancomycin
A

E. Binds to the terminal alanines

  • *penicillin blocks enzymes
  • *polymyxin affects cell membrane
  • *bacitracin is cell wall but different mechanism
191
Q

Patients with possible exposure to Bacillus anthracis during the bioterrorism attack in 2001 were treated for 40 days with ciprofloxacin. What is the mechanism of action of ciprofloxacin?
A) Blocks cell wall synthesis
B) Disrupts membrane integrity
C) Inhibits subunit A of DNA gyrase
D) Inhibits the action of the DNA-dependent RNA polymerase
E) Blocks binding of aminoacyl-tRNA to the 30S ribosomal subunit

A

C.

192
Q

What are 3 metabolite analogs that are antibiotics? Which 2 have a similar mechanism?

A 
Similar Mechanism: 
sulfonamides
trimethoprim
Other Mechanism:
isoniazid
193
Q

How do sulfonamide drugs act in bacterial metabolism?

A

they affect folic acid metabolism by acting as a competitive inhibitor in the formation of dihydrofolic acid. They mimic PABA.

194
Q

How do trimethoprim drugs act in bacterial metabolism?

A

they affect folic acid metabolism by acting as a competitive inhibitor in the formation of tetrahydrofolic acid
they mimic dihydrofolic acid

195
Q

Sulfonamides are analogs of what exactly? Are they bactericidal or bacteriostatic? What is the name of the first one of this type to be used? Which type is common today?

A

analogs of p-aminobenzoic acid
bacteriostatic
First one used: sulfanilamide
Primary One: sulfamethoxazole

196
Q

How does resistance form against sulfonamides?

A

plasmid mediated production of dihydroptroate synthetase w/ decreased affinity for sulfa
OR just more dihydropteroate synthetase
**either way makes the competitive inhibitor less effective

197
Q

What is the spectrum for sulfonamides?

A

BROAD
gram - & +
Nocardia
Chlamydia

198
Q

What is the clinical use of sulfonamides?

A

UTIs

other special applications

199
Q

What is the absorption, fate & elimination of sulfonamides?

A

oral admin-absorbed via GI

mainly excreted in urine

200
Q

What are the types of side effects that are possible with sulfonamides?

A

disorder of hematopoietic system
hypersensitivity reactions-rash, hives
Stevens Johnson Syndrome

201
Q

What types of hematopoietic disorders can result from adverse response to sulfonamides?

A

hemolytic anemia
agranulocytosis
aplastic anemia

202
Q

What is Stevens-Johnson Syndrome?

A

immune rxn

confluent epidermal necrosis-dermatological emergency

203
Q

What is trimethoprim an analog of?
It is a synergist with what drug?
What is its spectrum?

A

analog: dihydrofolic acid
synergistic w/ sulfonamides
spectrum-broad, similar to sulfa

204
Q

What are the clinical uses of trimethoprim?

A
  • *used w/ sulfamethoxazole=bactrim or septa
  • *used for UTIs
  • *some gram - infections
  • *best drug for pneumocystis jirovecii (fungus)
  • *w/ sulfa used w/ MRSA
205
Q

What is the absorption, fate & elimination of trimethoprim?

A

oral admin

high levels in urine

206
Q

What are the toxicity possibilities with trimethoprim?

A

hypersensitivity

impaired folate usage

207
Q

What is the mechanism of isoniazid (INH)?

A

prodrug-activated inside bacteria

inhibits the synthesis of mycolic acids

208
Q

What is the spectrum of isoniazid?

A

only mycobacteria

209
Q

What’s the deal with resistance against isoniazid?

A

common!

deletion of gene encoding activating enzyme of INH

210
Q

What is the clinical use of INH? What is the pharmacology of INH?

A

best drug for TB

well absorbed orally or IM

211
Q

What are the side effects of INH? Why are they important to consider?

A

hepatitis
inhibitor of cytp450-therefore possible drug interaction
**important to consider side effects b/c you use these drugs for a long period of time!

212
Q

What is the mechanism of resistance against beta lactam antibiotics?

A

enzymatic alteration of antibiotic

altered target binding site

213
Q

What is the mechanism of resistance against glycopeptide antibiotics?

A

altered target binding site

214
Q

What is the mechanism of resistance against quinolone antibiotics?

A

altered target binding site

215
Q

What is the mechanism of resistance against rifampin?

A

altered target binding site

216
Q

What is the mechanism of resistance against amino glycosides?

A

enzymatic alteration of antibiotic thru phosphorylation, adenylation, or addition of nucleotides

217
Q

What is the mechanism of resistance against tetracycline?

A

formation of an efflux pump in bacteria to get rid of the antibiotic

218
Q

What is the mechanism of resistance against macrolides & lincosamides?

A

altered target binding site on ribosome-works on both!

219
Q

What is the mechanism of resistance against sulfonamide & trimethoprim?

A

altered target binding site

220
Q

T/F Precise targeting is better than shotgun when you are prescribing antibiotics.

A

TRUE

221
Q

T/F It is better to use the longest course of antibiotics that have clinical efficacy.

A

False. If it is effective-the shorter the better.

222
Q

T/F It is best to use antibiotic combos whenever possible.

A

False. This increases resistance, so only do it when you have to.

223
Q

T/F It is terrible to prescribe empirically & terrible to depend on a microbio lab.

A

False & false.

224
Q

What are 3 forms of antibiotic sensitivity testing?

A
  • diffusion tests
  • dilution tests
  • automated tests
225
Q

What’s the process of using diffusion tests for antibiotic sensitivity testing?

A

Spread patient isolate on agar plate
Place antibiotic disc on plate
Antibiotic sets up concentration gradient on plate
Incubate; read diameter of inhibition zone
Use zone diameter and standard tables to estimate minimum inhibitory concentration (MIC)

226
Q

What are the advantages to using diffusion tests?

A

simple
inexpensive
widely used

227
Q

What are the disadvantages to using diffusion tests?

A

non-quantitative interpretation
doesn’t measure bactericidal activity
bad for slow growers & slow diffusers bacteria

228
Q

What’s the deal with dilution tests?

A

Prepare serial dilutions of antibiotic
Inoculate with standardized inoculum of clinical isolate
Calculate minimal concentration needed to inhibit growth

229
Q

What are the advantages to doing dilution tests?

A

Provides quantitative results
Not influenced by growth rate
Avoids problems with diffusion properties of antibiotics
Allows for determination of minimum bactericidal concentration (MBC)

230
Q

What are the disadvantages to dilution tests?

A

expensive
time consuming
requires rigid quality control

231
Q

What is the automated test?

A

mechanized version of dilution test
Bacterial growth determined by reduction in light transmittance or increase in light scattering
look for turbidity-means that an organism is growing!

232
Q

What are the advantages to the automated test?

A

Better standardization
Usually produces more information
Rapid results

233
Q

What are the disadvantages to the automated test?

A

initial expense

promotes blind dependence on machines

234
Q

The patient is a 32-year old gardener who was treated with streptomycin for ulceroglandular tularemia. Midway through the treatment, the infection stopped responding to the antibiotic. Further study might show that the bacterium had
A) Acquired an altered penicillin binding protein
B) Acquired a plasmid that produced an altered 50S ribosomal subunit
C) Undergone a mutation in the DNA-dependent RNA polymerase
D) Acquired a plasmid that encoded an enzyme that phosphorylated the antibiotic
E) Acquired a plasmid that encoded an efflux pump

A

D. This is for amino glycosides.

235
Q

Widespread use of tetracyclines for human therapy and in animal feeds has led to an increased number of resistant strains. Which of the following is a common mechanism for resistance to tetracycline?
A) Mutation in DNA gyrase
B) Mutation in RNA-dependent DNA polymerase
C) Production of altered outer membrane porins
D) Mutation in target proteins on the 50S ribosomal subunit
E) Acquisition of an efflux pump

A

E.

236
Q 
A 6-year-old child was diagnosed with strep throat. The patient is allergic to penicillin and was treated with an antibiotic of this class that binds to the the bacterial 50S ribosomal subunit.
A)	Cephalosporin
B)	Quinolone
C)	Rifampin
D)	Tetracycline
E)	Macrolide
A

E. Binds 50S ribosomal subunit

237
Q 
CDC’s Strategic National Stockpile includes enough antibiotics to treat several large cities at the same time in the event of a bioterrorism attack. One of the antibiotics in the stockpile is this antibiotic that would be used to treat individuals exposed to anthrax. In 2011, the FDA included a black box warning for this antibiotic due to the possibility of spontaneous tendon ruptures.
A)	Penicillin G
B)	Rifampin
C)	Sulfamethoxazole
D)	Ceftriaxone (a cephalosporin)
E)	Ciprofloxacin
A

E.

Block 6; Week 4-Michelle (5 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions