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Cellular Week 3 > Antibacterials I > Flashcards

Antibacterials I Flashcards

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1
Q

cidal - use for deep seated infections

for most healthy people, static is fine

A

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2
Q

antibiogram - resistance patterns in diff areas of the hospital

A

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3
Q

cell wall synthesis:

beta lactams

  • penicillins
  • cephalosporins
  • carbapenems
  • monobactams

glycopeptides (vancomycin)

A

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4
Q

cell membrane inhibitors:

polymyxins
daptomycin

A

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5
Q

periplasmic space:

beta-lactamases

A

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6
Q

folic acid metabolism:

trimethoprim
sulfonamides

A

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7
Q

general resistance mechanims

A

enzymatic destruction
altered target
decreased uptake
increased efflux

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8
Q

beta lactamases break down penicillin and other lactams

A

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9
Q

Penicillin binding protein - overtime this will change shape - example is MRSA!

A

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10
Q

concentration dependent killing

  • higher concentrations result in?
  • efficacy correlates with?
  • ex:?
A
  • higher concentrations result in more rapid, complete cell kill; DECREASED RESISTANCE
  • efficacy correlates with PEAK:MIC
  • ex: aminoglycosides, fluoroquinolones, lipopeptides (daptomycin)

more is better!
time to kill is quicker
MIC = minimum inhibitor concentration

this has bearing on dosing - for ex. aminoglycosides are once a day

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11
Q

time-dependent (concentration independent) killing

  • saturation of killing occurs at..?
  • efficacy correlates with?
  • ex:?
A
  • saturation of killing occurs at low multiples of MIC (4-8 X MIC)
  • efficacy correlates with: Time above MIC (T>MIC), AUC:MIC
  • Ex: beta-lactams (T>MIC for 50% of dosing interval); vancomysin - glycopeptides, most protein inhibitors

MIC = minimum inhibitory concentration

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12
Q

MIC

A

minimum inhibitory concentration
in vitro measure of potency
lowest concentration of the drug that will inhibit the growth of the organism - maybe won’t kill it but it will inhibit it

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13
Q

protein synthesis inhibitors:

50s ribosome

A

macrolides, ketolides
lincosamide (clindamycin)
chlroamphenicol
stretogramins (quinupristin-dalfoprisitn)

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14
Q

30s ribosome inhibitor

A

aminoglycosides

tetracylines

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15
Q

monobactems have a very limited use.. (reserved for severe drug allegry - penicillin)
penicillins and cephalosporins are used most often
reserved use is carbapenems

A

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16
Q

frequently used beta lactamase inhibitor?

A

clavulanic acid

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17
Q

Penicillins have a R group that can be changed to vary their activity range

A

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18
Q

Beta lactam antibiotics

A
  • structually similar to D ala D ala
  • PBPs bind to them (like they would to DalaDala
  • PBPs cleave the Beta lactam bond and form a stable intermediate that does not react further

BETA LACTAMS BIND TO PBP AND RESEMBLE D ALA D ALA

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19
Q

PBPs

A

enzymes that catalyze the last steps of bacterial cell wall biosynthesis
bind to d ala d ala to carry out transpeptidation

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20
Q

Beta lactamases are enzymes in bacteria that have resistance to beta lactam antibiotics. they cleave the ring and the ring is needed to bind to PBP

A

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21
Q

beta lactamase inhibitors

A

available as fixed combinations with certain beta lactams
extends spectrum if inactivity is due to beta-lactamase destruction
they do not inhibit all beta lactamases

ex. clavulanic acid, tazobactam, vaborbactam, sulbactam, avibactam

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22
Q

which drugs are used against extended spectrum beta-lactamases (the inhibitors)?

A

ESBLs

avibactrum and vaborbactam

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23
Q

natural penicillins:
agents/entry?
spectrum?
important uses?

A 
penicillin G (IV, IM)
penicillin VK (oral)

narrow spectrum - streptococci, treponema

important sues - strep endocarditis, meningitis (PCN G), syphilis (PCN G), strep throat (PCN VK)

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24
Q

anti-staphylococcal penicillins:
agents/entry?
spectrum?
important uses?

A

Nafcillin (IV) - important - like methicilin but less toxic
Oxacillin (IV)
Dicloxacillin (PO)

Narrow spectrum!! (Staph - MSSA only)

Important uses - serious MSSA (non-MRSA) infections (skin, blood, lung, etc)

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25
amino penicillins: agents/entry? spectrum? important uses?
ampiciilin (IV) +/- sulbactam amoxicillin (PO) +/- clavulanic acid BROAD SPECTRUM - gram + (not MRSA) and some gram - anaerobes Uses - intra-abdominal, pelvic, skin, pulmonary, bite wounds, some STIs
26
ureido penicillins: agents/entry? spectrum? important uses?
piperacillin + tazobactam (IV) VERY BROAD (enhanced gram - including pseudomonas) pneumonia, bacteriemia, IA, febrile neutropenia, diabetic foot, etc
27
Streptococcus activity for cephalosporin generations
activity generally increases as generation increases
28
staph (MSSA) activity for cephalosporin generations
1st generation has generally best activity for MSSSA
29
staph (MRSA) activity for cephalosporin generations
only 5th generation has any activity against MRSA
30
gram negatives activity for cephalosporin generations
activity generally increases as generation increases
31
1st generation cephalosporins: agents/entry? spectrum? important uses?
cefazolin (IV) cephalaxin (PO) Narrow (gram +) - staphylococci, streptococci cefazolin IV: surgical prophylaxis cephalaxin PO: Skin, UTI, RTI
32
2nd generation cephalosporins: agents/entry? spectrum? important uses?
Cefoxitin (IV) Cefuroxime (IV, PO) broader (also anaerobes) broader cefoxitin - mixed infections cefuroxime IV - meningitis
33
3rd generation cephalosporins: agents/entry? spectrum? important uses?
ceftriaxone (IV, IM) ceftazidime/avibactum (IV) - mainly pseudomonas ceftibuten, cefdinir (PO) broad (enhanced gram - ) pseudomonas (mainly ceftazaidime) meningitis, gonorrhea, serious hospital infections, respiratory
34
4th generation cephalosporins: agents/entry? spectrum? important uses?
cefepime (IV) ceftolozane/tazobactam (IV) very broad enhanced gram -, including pseudomonas and some ESBL's serious hospital infections
35
5th generation cephalosporins: agents/entry? spectrum? important uses?
ceftaroline (IV) broad (MRSA) skin, blood (MRSA)
36
monobactams main agent? spectrum? primary use?
aztreonam spectrum - inhibits gram negatives only! (poor binding to PBP's of gram+) primary use: penicillin, cephalosporin allergy
37
carbapenems agents? spectrum? uses?
imipenem, meropenem, doripenem, ertapenem very stable to most beta-lactamases!! spectrum - very board (more than any other class) severe, life-threatening infections, MDROs (reserved) MDRO = multi-drug resistant organisms drug of choice for ESPL!!
38
beta lactam absorption?
PO forms have modest-good absorption but IV >>PO Most best absorbed on empty stomach Some drugs have IM forms
39
beta lactam distribution?
wide distribution; many beta- lactams PENETRATE THE CNS WITH MENINGEAL INFLAMMATION
40
beta lactam metabolism?
minimal do not adjust in hepatic disease
41
beta lactam excretion?
EXCRETED IN URINE VIA TUBULAR SECRETION (90%) AND GLOMERULAR FILTRATION ADJUST IN RENAL DISEASE
42
Beta lactam adverse effects: common uncommon rare
common - GI - more frequent in PO/higher doses (nausea/loose stools) uncommon - hypersensitivity - non-IgE mediated rashes Rare - hypersensitivity - anaphylaxis, urticarial rashes penicillins >cephalosporins>penems>monobactams
43
imipenem has increased risk for what?
seizures
44
other rare side effects of beta lactams
hematoloigic: neutropenia renal: interstitial nephritis neuro: encephalopathy/seizures
45
5 percent chance of cross-reactivity with cephalosporin and penicillin allergy
..
46
vanco/dapto are both IV
...
47
another name for vancomycin?
vancocin/ Lilly
48
another name for daptomycin?
cubicin, cubist
49
vancomycin characteristics? MoA?
large, tricyclic glycopeptide NOT an aminoglycoside MoA: complexes to DalaDalanine precursor of cell wall pentapeptide interfering with elongation of the peptidoglycan backbone PREVENT ACCESS OF PBPs TO THEIR NATURAL SUBSTRATE! prohibits the chain from being transported to the cell wall for cross linking bactericidal!!
50
all beta lactams and glycopepties are bactericidal!
...
51
vancomycin is bactericidal but it is..
time dependent! needs to be in a certain range for it to work and you try to maintain those levels for as long as possible - monitor trough levels! not a great killer - works slowly
52
vanco: | due to its large molecular size and lipophilicity, only active against what?
gram + bacteria able to diffuse through the highly lipophilic cell wall of gram +
53
what disease is vanco the drug of choice for? resistance?
serious MRSA infections clinical resistance is low!
54
``` vanco: absorption? distribution? metabolism? elimination? monitor what? levels? ```
A - negligible (oral used for C. diff infections) D - does not cross BBB w/o inflamm M - negligible E - primarily filtration, apprx GFR (CrCl) - adjust dosing interval in renal impairment Monitor trough concentrations (10-20 ug/ml) NOT ABSORBED!
55
toxicity of vanco (3)
1. nephrotoxicity (dose/concentration dependent, reversible) 2. red-man (red-neck, red-person) syndrome: - characterized by flushing, erythema, pruritus, angioedema - usually due to rapid infusion, ends after infusion stops - secondary to histamine release, other mediators - not an IgE mediated allergy - slow infusions (1-2h), premeditate with antihistamines 3. ototoxicity - uncommon - high-tone loss, tinnitus, not reversible
56
Cell membrane inhibitor - daptomycin (cubicin) characteristics? moA? type of killing? spectrum?
- circular lipopeptide - MoA - not fully known - binds to gram + via a Ca2+ dependent interaction with membrane disruption and loss of K+ - rapidly cidal, concentration dependent killing - spectrum - gram+ and MRSA
57
daptomycin inactivated by? use? toxicity?
inactivated by pulmonary surfactant - not for pneumonia use - alt to vanco toxicity - myopathy (CPK lvls)
58
cell membrane inhibitor - polymyxins (polymixin B, E [colistin]) chemistry? MoA? type of killing?
chem - cationic, base proteins that act like detergents moA - binds with the anionic LPS molecules by displacing Ca+, Mg2+ from the other men of GRAM NEGATIVE bacteria, leading to permeability changes, leakage, cell death bactericidal, concentration dependent
59
cell membrane inhibitor - polymyxins (polymixin B, E [colistin]) spectrum? use? adverse effects (2)? note?
spectrum - gram negative use - last resort for multi-drug resistant organisms adverse effects: 1) nephrotoxicity (ATN, concentration dependent, reversible) 2) neurotoxicity (facial paraesthesia, dizziness, weakness, vertigo, visual disturbances, confusion, ataxia, neuromuscular blockade, respiratory) 3) NOTE - topical combination products (polysporin, neosporin) are very safe
60
beta lactams SE?
GI, rash/allergy
61
polymixins short SE?
nephroxicity, neurotoxicity

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