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Microbiology > M5: Antibacterials > Flashcards

M5: Antibacterials Flashcards

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1
Q

Antibiotic:

Natural, e.g.

Synthetic, e.g.

Semi-synthetic, e.g.

A

a substance which kills bacteria or inhibits their growth

substance produced by organisms to kill/inhibit other organisms (aminoglycosides)

substances produced and discovered artificially (fluoroquinolones)

substances modified from those found naturally (beta-lactams)

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2
Q

Resistance to antibiotics threatens their success, speaking to the importance of:

Use antibiotics only _

Choose antibiotics _

Choose effective drugs with the _ once an organism has been identified (start _ -> de-escalate to _)

_ appropriately

Limit _ of therapy

A

when necessary (esp for viral infections)

appropriately

narrowest spectrum of activity
broad
narrow

Dose

durations

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3
Q

Points to Consider When Choosing an Antibiotic:

Identify the _ (or identify which _ to target empirically)

Match to _

_

_ / _

A

organism
organisms

antibiotic spectrum of activity

Sensitivity

Pharmacokinetics / Pharmacodynamics

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4
Q

Process of Starting Antibiotics (3)

A

empiric therapy

de-escalation

targeted therapy

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5
Q

Process of Starting Antibiotics:

Empirical Therapy

De-escalation

Targeted Therapy

A

choose antibiotics to cover a broad spectrum of possible organisms

culture & sensitivity data becomes available

choose antibiotics to cover a single pathogen

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6
Q

Antibiotic Classes:

Inhibitors of _ synthesis

Inhibitors of _ synthesis

Inhibitors of _ synthesis

_ damaging agents

_ damaging agents

A

cell wall

protein

DNA & RNA

DNA

cell membrane

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7
Q

Minimum Inhibitory Concentration (MIC):

Determines _

The (highest / lowest) concentration of antibiotic that results in _ (_)

Interpretation: _, _, or _

A

sensitivity

lowest

no visible growth (turbidity)

sensitive, intermediate, or resistant

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8
Q

Pharmacokinetics:

Definition

4 parts

A

the ways the body manipulates a drug

absorption
distribution
metabolism
excretion

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9
Q

Pharmacokinetics:
Absorption:

Bioavailability

Fluoroquinolones are (very / poorly) bioavailable

Vancomycin is (very / poorly) bioavailable

A

Level of drug in blood when given orally/given intraveneously X 100%

very

poorly

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10
Q

Pharmacokinetics:
Distribution:

Measured by _.

Good indicator is to assess concentrations in _ sites (_, _, _, _, etc.)

_ is an unique site, drug penetration depends on a number of factors including _, _, _, and _

Tobramycin: (good / poor) CNS distribution

Rifampin: (good / poor) CNS distribution

A

Volume of Distribution (L/kg)

sequestered
Cerebrospinal fluid, prostate, bone, abscess, etc.

Blood-brain barrier
molecular weight, lipophilicity, plasma protein binding, and active transport mechanisms

poor

good

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11
Q

Pharmacokinetics:
Metabolism:

Aminoglycosides: drugs that are (heavily / minimally) metabolized before being excreted unchanged

Moxifloxacin: drugs that are (heavily / minimally) metabolized

A

minimally

heavily

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12
Q

Pharmacokinetics:
Excretion:

_ vs. _ (e.g., biliary, feces, etc.)

_ eliminated drugs require dosage adjustment in renal failure (_) to avoid toxicity

_ eliminated drugs may not (_)

A

Renal vs. non-renal

Renally
penicillin

Non-renally
moxifloxacin

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13
Q

Pharmacodynamics:

Aspects (3)

A

the biochemical and physiologic effects of the drug and its mechanism of action (effects of the drug on the organism and body)

mechanism of action

toxicities

indices associated w/ optimal activity (concentration vs. time vs. exposure dependent)

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14
Q

Concentration-dependent killing:

The rate of cell killing increases with _

More effective: (400 mg once daily / 100mg four times daily)

Concentration dependent drugs (4)

A

each increase in peak concentration of antibiotic.

400 mg once daily

aminoglycosides
daptomycin
metronidazole
fluoroquinolones

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15
Q

Time-dependent killing:

The rate of cell killing increases with _

More effective: (400 mg once daily / 100mg four times daily)

Time Dependent drugs (3)

A

increasing amount of time that the concentration of antibiotic remains above a certain threshold (the MIC of the organism) for a majority of the dosing interval.

100mg four times daily

beta-lactams
linezolid
trimethoprim/sulfamethoxazole

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16
Q

Exposure Dependent killing:

Based

Exposure dependent drugs

A

neither entirely on peak concentration or time above MIC, rather based on total daily exposure

all other drugs (e.g. vancomycin)

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17
Q

Bactericidal vs. Bacteristatic Antibiotics:

Especially important for _ infections (_and _)

In most infections, _ is sufficient to allow the host immune system to eradicate infection.

A

life-threatening
meningitis and endocarditis

inhibition of growth

18
Q

Bacteristatic:

An antibiotic which _ at usual achievable concentrations.

For (life-threatening / most) infections

Ex. (5)

A

inhibits growth

most

tetracyclines
macrolides (azithromycin, erythromycin)
clindamycin
linezolid
tigecycline
19
Q

Bactericidal:

An antibiotic which _ at usual achievable serum concentrations.

For (life-threatening / most) infections

E.g. (7)

A

kills organism

life-threatening

penicillins
cephalosporins
aminoglycosides
vancomycin
fluoroquinolones
monobactams
daptomycin
20
Q

Inhibitors of cell wall synthesis (3)

A

beta-lactam antibiotics

vancomycin

fosfomycin

21
Q

Inhibitors of cell wall synthesis:
Beta-lactam antibiotics:

E.g. (4)

A

penicillins
cephalosporins
carbapenems
monobactams

22
Q

Inhibitors of cell wall synthesis:
Beta-lactam antibiotics:
Mechanism of action:

The bacterial cell wall is composed of _, assembled in a series of enzymatic steps

The last step is the formation of these cross-links, catalyzed by _

Beta-lactams bind to and inhibit _, thus inhibiting _

This mechanism is part of a pathway that ultimately results in (bacteristatic / bactericidal) activity (except against _)

A

cross-linked peptidoglycans

cross-links
penicillin-binding proteins (PBPs)

PBPs
cell wall synthesis

bactericidal
Enterococcus

23
Q

Inhibitors of cell wall synthesis:
Beta-lactam antibiotics:
Mechanisms of resistance (gram+):

Altered _, which have (increased / decreased) affinity for beta-lactam drug

Mechanism of resistance in gram + organisms (beta-lactam resistance in _, _, and _)

_ (in _ only)

A

PBPs
decreased

Staphylococcus, Enterococcus, and Streptococcus

Β-lactamases
Staphylococcus

24
Q

Inhibitors of cell wall synthesis:
Beta-lactam antibiotics:
Mechanisms of resistance (gram-):

Overexpression of _

Loss of _

_

  1. PBPs that catalyze _
  2. Location is critical to activity
    i. _ space of gram-negatives
    ii. _ cell wall in gram-positives

This renders the antibiotic _ before it reaches the PBP target

A

efflux pumps

porins

β-lactamases
hydrolysis of the β-lactam ring
Periplasmic
Outside

inactive

25
Q

Inhibitors of cell wall synthesis:
Vancomycin:
Mechanism of action:

Vancomycin binds to _, interrupting the chain of events necessary to synthesize _ (occurs one step earlier in pathway than that of the _ mechanism).

A

D-Ala
peptidoglycan
beta-lactam

26
Q

Inhibitors of cell wall synthesis:
Vancomycin:
Mechanism of resistance:

Via : D-alanyl-D- binding site changes to D-alanyl-D-_ or D-alanyl-D-_

Via _, which prevents vancomycin from _

A

an altered binding site
alanine
lactate or serine

a thickened cell wall
reaching its target site

27
Q

Inhibitors of cell wall synthesis:
Fosfomycin:

Mechanism of action:
Inhibits the first step in _ synthesis by binding to the enzyme which catalyzes the formation of _ (a precursor)

Mechanism of resistance:
Decreased _, _ modification and _ inactivation

A

peptidoglycan
N-acetylmuramic acid

drug uptake
target site
enzymatic

28
Q

Inhibitors of protein synthesis:
Mechanism of action:

_ to create proteins

As such, _ results in impaired protein synthesis

e.g. (6)

A

Ribosomes “read” mRNA

inhibition of ribosomal function

aminoglycosides
macrolides
tetracyclines
linezolid
clindamycin
tigecycline
29
Q

Inhibitors of protein synthesis:
50S inhibitors block either:

Initiation of _ (_)

Translocation of _ - inhibits reaction which elongates the peptide chain (_, _)

A

protein translation
linezolid

peptidyl rRNAs
macrolides, clindamycin

30
Q

Inhibitors of protein synthesis:
30S inhibitors:

Block access of _ to ribosome (_, _)

Bind _ component of the ribosome, which leads to protein _ (_)

A

tRNAs
tetracyclines, tigecycline

16S rRNA
mistranslation
aminoglycosides

31
Q

Inhibitors of DNA/RNA synthesis (4)

A

Trimethoprim/Sulfamethoxazole
Rifamycins (rifampin)
Fluoroquinolones (FQ’s)
Fidaxomicin

32
Q

Inhibitors of DNA/RNA synthesis:
Trimethoprim/Sulfamethoxazole:
Mechanism of action:

In combination, act synergistically to _.

TMP is 50-100k times (more / less) active against bacterial enzyme than human

A

inhibit nucleic acid synthesis

more

33
Q

Inhibitors of DNA/RNA synthesis:
Rifamycins (rifampin):

Mechanism of action: inhibits _ (thus inhibiting RNA synthesis)

Mechanism of resistance: _ mutation

A

DNA-dependent RNA polymerase

Target site

34
Q

Inhibitors of DNA/RNA synthesis:
Fluoroquinolones (FQ’s):
Mechanism of action:

_ catalyze reactions which are vital for DNA replication, transcription, recombination, and repair.

FQ’s (enhance / inhibit) the function of these enzymes

A

Topoisomerases

inhibit

35
Q

Inhibitors of DNA/RNA synthesis:
Fidaxomicin:
Mechanism of action:

Inhibiting transcription of _

A

bacterial RNA polymerase

36
Q

DNA damaging agents (2)

A

Nitrofurantoin

Metronidazole

37
Q

DNA damaging agents:
Nitrofurantoin:

Mechanism of action: unclear, but appears that parent compound is reduced to form _

Mechanism of resistance: Mutations resulting in _

A

DNA damaging oxygen radicals

inhibition of reductase activity

38
Q

DNA damaging agents:
Metronidazole:

Mechanism of action: Pro-drug, (aerobic / anaerobic) nitro-reduction to _ that bind to and perturb DNA function

Mechanism of resistance: (common / rare) outside of intrinsically-resistant organisms, multiple mechanisms postulated

A

anaerobic
radical metabolites

rare

39
Q

Cell membrane damaging agents (2)

A

Daptomycin

Polymyxins (Colistin or colistimethate)

40
Q

Cell membrane damaging agents:
Daptomycin:

Mechanism of action:

The antibacterial target of daptomycin in Staphylococcus aureus and other Gram-positive bacteria is the _.

Daptomycin inserts into the CM in a Ca2+-dependent manner, resulting in _ and subsequent _, including K+,Mg2+, and ATP

Mechanism of resistance:

Multiple, and still being studied. Possibly includes _ and _

A

cytoplasmic membrane (CM)

membrane depolarization
loss of intracellular components

thickened cell wall
altered binding site

41
Q

Cell membrane damaging agents:
Polymyxins (Colistin or colistimethate):

Mechanism of action: inserts into membranes, interacting with _; acts as _

Mechanism of resistance: Still being studied. Possibly includes _

A

phospholipids
cationic detergent

altered binding site

Microbiology (36 decks)

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