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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

24
Q

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

A

beta-lactams (penicillin, cephalosporin)

Vancomycin

25
anitbacterial agent mechanisms of action: drugs that are FA inhibitors
Trimethoprim | Sulfonamides
26
anitbacterial agent mechanisms of action: drugs that hinder DNA gyrase
Quinolones
27
anitbacterial agent mechanisms of action: drugs that interfere with DNA-directed RNA polymerase
Rifampin
28
anitbacterial agent mechanisms of action: drugs that interrupt protein 50s synthesis
Chloramphenicol Macrolides Clindamycin
29
anitbacterial agent mechanisms of action: drugs that interrupt protein 30s synthesis
Tetracycline | Aminoglycosides
30
where do beta-lactams live?
in the periplasmic space
31
what are the natural penicillins?
penicillin G | penicillin V
32
penicillin G is administered ___ whilst penacillin V is administered ____. why?
G: IV or IM, because destroyed in acidic environments V: administered orally bc more stable in acidic environments, but on empty stomach
33
aminopenicillin drugs are ___
synthetic
34
what is the mechanism for penicillinase-resistant penicillins?
contain side groups that protect the drugs from being inactivated by bacterial beta-lactamases
35
antipseudomonal penicillins (aka extended spectrum penicillins) are only good for treating what? why?
UTIs, prostatic infections Tx levels are only found in the urinary tract
36
how do irreversible beta-lactamase inhibitors work?
they have no antimicrobial activity themselves combined with penicillin to expand coverage againt beta-lactamase producing bugs
37
what kind of antibiotic resembles penacillin? why is this important? ****
chephalosporins i.e., have beta-lactam backbone pts with penicillin Ax can also be hypersensitive to cephalosporins
38
cephalosporins are excreted by the ____. why is this important? ****
kidney renal toxicity possible, also seizures with new gen; use caution in pts with impaired creatinine clearance
39
cephalosporins are bacteriocidal or bacteriostatic?
bacteriocidal
40
carbapenems are bacteriocidal or bacteriostatic?
bacteriocidal
41
what is the mechanism of carbapenems?
inhibit cell wall synthesis
42
what separates carbapenems from penicillin and cephalosporins?
different chem structure in beta-lactam ring that renders them with PHENOMENAL COSMIC POWER...or resistance to beta-lactamases
43
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?
telavancin vancomycin D-Ala-D-Ala telavancin
44
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(-)?
Cycloserine both
45
what drug is bactericidal to all G(-) but Proteus? what is its mechanism?
Polymixin B detergent that disrupts lipoproteins in bacterial cell wall :: increasing membrane permeability
46
how do antibiotics interfere with protein synthesis?
- interfere with the initiation phase of protein synthesis - binding of mRNA - activities of peptidyl transferase - inappropriate aa insertions
47
what are the three co-mechanisms of aminoglycosides?
1. interfere with formation of the initiation complex 2. misread mRNA and miscode aa 3. cause ribosomes to separate from mRNA
48
aminoglycosides target what?
30s ribosomal subunit
49
because of one of the aminoglycoside mechanisms, blocking the ribosome movement may result in a _____
monosome (a single monosome)
50
what is the mechanism for tetracylines/"cyclines"?
inhibit protein synthesis through reversible binding to bacterial 30s rib subunits; this prevents new aa (with aminoacyl-tRNA chaperone) from binding
51
tetracylines/"cyclines" target what?
30s ribosomal subunit
52
what are the two common mechanisms of tetracycline resistance?
efflux pumps | ribosomal protection
53
tetracycline is are bacteriocidal or bacteriostatic? against what kinds of bacteria?
bacteriostatic G(+) and G(-)
54
why does tetracycline need to be taken on an empty stomach? aka non drug interactions ****
a. chelated to divalent cations - iron - aluminum, mag, Ca antacids - milk b. or bile acid resins
55
how does tetracycline get into G(+) v. G(-) bacteria?
G(+): active diffusion | G(-): passive diffusion
56
what tetracycline-class drug is metabolized HEPATICALLY? why is this useful?****
doxycycline excreted in the feces safest option for renal dysfunction pts

Pharmacology (Sweatman) (3 decks)

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