Antibacterials Reading Flashcards

1
Q

four main mechanisms of antibacterial resistance

A
  1. alterations in receptor target
  2. decreased entry or efflux of drug out of microorganism
  3. alterations in metabolic pathways
  4. drug is inactive
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2
Q

antibacterial resistance: example of alteration in receptor target

A
  • mutations in PBPs (cell wall synthesis inhibition)

- me’lation of ribosomal subunits (protein synthesis inhibitors)

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3
Q

antibacterial resistance: example of decreased entry or efflux

A
  • altered porins (cell wall synthesis inhibitors)

- efflux pumps to remove drug (tetracyclines)

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4
Q

antibacterial resistance: examples of alterations in metabolic pathways

A
  • microorg acquires alt pathway to reroute around blocked pathway (sulfa drugs)
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5
Q

antibacterial resistance: examples of inactive drugs

A
  • failure to convert a prodrug to active form (isoniazid)

- inactovation of drug (penicillins via beta-lactamases)

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6
Q

four mechanisms of action of antibacterial agents

A
  1. inhibition of cell wall synthesis
  2. inhibition of protein synthesis: 30s, 50s
  3. inhibition of folic acid biosynthetic pathways: PABA -x-> DHFA -x-> THFA
  4. inhibition of DNA/RNA synthesis: DNA gyrase, DNA-directed RNA polymerase
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7
Q

drug classes that interfere with cell wall synthesis

A

penicillins
cephalosporins
carbapenems
monobactams

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8
Q

are penicillins are bacteriocidal or bacteriostatic?

A

bacteriocidal

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9
Q

what is the generalized mechanism of action for penicillins? how specifically?

A

generally: interfere with cell wall synthesis by binding to PBPs

specifically:
1. block transpeptidation of peptidoglycan
2. activates autolytic enzymes in cell wall that cause lesions
:: bac death

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10
Q

what crosslinking does penicillin disrupt? by focusing/binding to what enzyme?

A

N-acetyl muramic acid
N-acetyl glucosamine

transpeptidase

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11
Q

what are PBPs? role?

A

penacillin binding proteins

bacterial proteins that are bound/activated by penicillins

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12
Q

name a few ways that PBPs work

A
  • break crosslinking (transpeptidase)
  • break peptide bonds (carboxypeptidase, endopeptidase)
  • hydrolyze components of cell wall (autolysins)
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13
Q

for penacillins to work, they have to do what first?

A

permeate cell wall

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14
Q

four mechanisms of resistance to penicillins

A
  1. modification of PBPs
  2. active efflux/pumping out of drug
  3. cleavage of beta-lactam ring of drug via beta-lactamases
  4. altered porins (G(-) bac only!)
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15
Q

what is the structure in penicillins that bacteria can alter in resistance? what do they do this with? how can you outsmart them?

A

beta-lactam ring

beta-lactamases aka penicillinases

give a second drug that is an irreversible inhibitor of beta-lactamase

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16
Q

drug interactions: penicillin

A
  • bateriostatic drugs (tetracycline)

- oral contraceptives

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17
Q

drug interactions: penicillin and bacteriostatic drugs - why?

A

penicillin needs growing/dividing cell and bacteriostatic drugs stop growth/replication

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18
Q

drug interactions: penicillin and oral contraceptives - why?

A

interferes with enterohepatic circulation

gut bacteria that cleave est-glucuronide, which makes estrogen available for reabsorbtion :: increasing duration of activity, are killed

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19
Q

what penicillin drug interaction (possibly) decreases the half life? of which drug?

A

decreases the half life of oral contraceptive because penicillin interferes with enterohepatic circulation

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20
Q

name the four subclassifications of penicillins

A
  1. natural penicillins
  2. aminopenicillins
  3. penicillinase-resistant penicillins
  4. antipseudomonal penicillins
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21
Q

in general, we use what kinds of penicillins to treat G(+) org? G(-)?

A

G(+): natural penicillins, penicillinase-resistant penicillins

G(-): aminopenicillins, antipseudomonal penicillins [the A’s]

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22
Q

anitbacterial agent mechanisms of action: folate pathway that is blocked

A

PABA -x-> DHFA -x-> THFA

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23
Q

anitbacterial agent mechanisms of action: proteins whose synthesis is disrupted

A

30s

50s

24
Q

anitbacterial agent mechanisms of action: drugs that interfere with cell wall synthesis

A

beta-lactams (penicillin, cephalosporin)

Vancomycin

25
Q

anitbacterial agent mechanisms of action: drugs that are FA inhibitors

A

Trimethoprim

Sulfonamides

26
Q

anitbacterial agent mechanisms of action: drugs that hinder DNA gyrase

A

Quinolones

27
Q

anitbacterial agent mechanisms of action: drugs that interfere with DNA-directed RNA polymerase

A

Rifampin

28
Q

anitbacterial agent mechanisms of action: drugs that interrupt protein 50s synthesis

A

Chloramphenicol
Macrolides
Clindamycin

29
Q

anitbacterial agent mechanisms of action: drugs that interrupt protein 30s synthesis

A

Tetracycline

Aminoglycosides

30
Q

where do beta-lactams live?

A

in the periplasmic space

31
Q

what are the natural penicillins?

A

penicillin G

penicillin V

32
Q

penicillin G is administered ___ whilst penacillin V is administered ____. why?

A

G: IV or IM, because destroyed in acidic environments

V: administered orally bc more stable in acidic environments, but on empty stomach

33
Q

aminopenicillin drugs are ___

A

synthetic

34
Q

what is the mechanism for penicillinase-resistant penicillins?

A

contain side groups that protect the drugs from being inactivated by bacterial beta-lactamases

35
Q

antipseudomonal penicillins (aka extended spectrum penicillins) are only good for treating what? why?

A

UTIs, prostatic infections

Tx levels are only found in the urinary tract

36
Q

how do irreversible beta-lactamase inhibitors work?

A

they have no antimicrobial activity themselves

combined with penicillin to expand coverage againt beta-lactamase producing bugs

37
Q

what kind of antibiotic resembles penacillin? why is this important? **

A

chephalosporins

i.e., have beta-lactam backbone

pts with penicillin Ax can also be hypersensitive to cephalosporins

38
Q

cephalosporins are excreted by the ____. why is this important? **

A

kidney

renal toxicity possible, also seizures with new gen; use caution in pts with impaired creatinine clearance

39
Q

cephalosporins are bacteriocidal or bacteriostatic?

A

bacteriocidal

40
Q

carbapenems are bacteriocidal or bacteriostatic?

A

bacteriocidal

41
Q

what is the mechanism of carbapenems?

A

inhibit cell wall synthesis

42
Q

what separates carbapenems from penicillin and cephalosporins?

A

different chem structure in beta-lactam ring that renders them with PHENOMENAL COSMIC POWER…or resistance to beta-lactamases

43
Q

what drugs block by blocking polymerization and crosslinking of peptidoglycan by binding an aa pattern in the cell wall? what is that aa pattern? bonus: which one has additional oopmpf because of a lipophilic chain?

A

telavancin
vancomycin

D-Ala-D-Ala

telavancin

44
Q

what is reserved for treating TB in cases where the pt is resistant to first-line Tx? does it inhibit cell wall synth in G(+) or G(-)?

A

Cycloserine

both

45
Q

what drug is bactericidal to all G(-) but Proteus? what is its mechanism?

A

Polymixin B

detergent that disrupts lipoproteins in bacterial cell wall :: increasing membrane permeability

46
Q

how do antibiotics interfere with protein synthesis?

A
  • interfere with the initiation phase of protein synthesis
  • binding of mRNA
  • activities of peptidyl transferase
  • inappropriate aa insertions
47
Q

what are the three co-mechanisms of aminoglycosides?

A
  1. interfere with formation of the initiation complex
  2. misread mRNA and miscode aa
  3. cause ribosomes to separate from mRNA
48
Q

aminoglycosides target what?

A

30s ribosomal subunit

49
Q

because of one of the aminoglycoside mechanisms, blocking the ribosome movement may result in a _____

A

monosome (a single monosome)

50
Q

what is the mechanism for tetracylines/”cyclines”?

A

inhibit protein synthesis through reversible binding to bacterial 30s rib subunits; this prevents new aa (with aminoacyl-tRNA chaperone) from binding

51
Q

tetracylines/”cyclines” target what?

A

30s ribosomal subunit

52
Q

what are the two common mechanisms of tetracycline resistance?

A

efflux pumps

ribosomal protection

53
Q

tetracycline is are bacteriocidal or bacteriostatic? against what kinds of bacteria?

A

bacteriostatic

G(+) and G(-)

54
Q

why does tetracycline need to be taken on an empty stomach? aka non drug interactions **

A

a. chelated to divalent cations
- iron
- aluminum, mag, Ca antacids
- milk
b. or bile acid resins

55
Q

how does tetracycline get into G(+) v. G(-) bacteria?

A

G(+): active diffusion

G(-): passive diffusion

56
Q

what tetracycline-class drug is metabolized HEPATICALLY? why is this useful?**

A

doxycycline

excreted in the feces

safest option for renal dysfunction pts