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ABBEY MSII U6 > Pharm antimicrobials 1 > Flashcards

Pharm antimicrobials 1 Flashcards

1
Q

gram negative organisms vs gram positive

A

gram negative:
-outer membrane (LPS endotoxin, outer membrane proteins for attachement and virulence, and porins)
-thin cell wall
-periplasmic space
gram positive:
-thick cell wall cross-linked by transpeptidase

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2
Q

what is the location of beta lactamase for gram negative? gram positive?

A

gram - : periplasmic space

gram + : secreted outside of cell

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3
Q

which gram - organisms are not covered by your typical drug regimen?

A

pseudomonas

bacilli -> aerobic -> nonfermenters -> oxidase positive

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4
Q

what drugs target the peptidoglycan cross-linking of the cell wall?

A

Beta-lactams (penicillin, penicillinase-sensitive penicillins, penicillinase-resistant penicillins, antipseudomonals, cephalosporins, carbapenems) and monobactams

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5
Q

what is the mechanism of action for beta lactams?

A

bind to penicillin-binding proteins (PBPs) which catalyze polymerization of the glycan strand

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6
Q

what are mechanisms of resistance to beta lactams?

A

enzymatic destruction (gram -‘s - beta lactamase), reduced permeability (porin channel change), target site alteration (PBP change - gram +s)

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7
Q

what do beta lactams have a lack of activity against?

A 
atypical organisms (mycoplasma pneumoniae and chlymydophilia pneumoniae (no cell wall))
MRSA
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8
Q

pharmacokinetics of beta lactams

A

short half lives, polar (go where water is), metabolized in liver, excretion by mostly renal system

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9
Q

side effects of beta lactams

A
  1. hypersensitivity reactions (anaphylaxis, delayed hypersensitivity - rash, drug fever, acute interstitial nephritis, cross-reactivity)
  2. seizures (high doeses in patients with renal dysfunction
  3. GI effects (nausea, vomiting, diarrhea)
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10
Q

what are the natural penicillins?

A

penicillin G (IV and IM) and penicillin V (oral)

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11
Q

what spectrum do the natural penicillins cover?

A

mostly gram-positive aerobic organisms (streptococci, enterococcus, oral anaerobes, clostridium)
also n. meningitidis and t. pallidum (DOC for syphilis)

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12
Q

what are the anti-staphylococcal penicillins (penicillinase-resistant penicillins)

A

nafcillin, oxacillin, dicloxacillin (DON the STAPH!)

i met a nasty ox with a beta lactam ring around its neck

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13
Q

what does the penicillinase-resistant penicillins (anti-staphylococcal penicillins) have that make them penicillinase resistant?

A

bulky side chain sterically shielding the beta lactam ring (preventing degradation from penicillinase and prevents entry into the gram negative cell)

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14
Q

what is the spectrum of anti-staphylococcal penicillins (penicillinase-resistant penicillins)

A

MSSA (methicillin susceptible staph aureus)

streptococci

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15
Q

what is the oral anti-staphylococcal penicillin (penicillinase-resistant penicillin)

A

dicloxacillin

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16
Q

side effects of oxacillin

A

hepatotoxicity and neutropenia

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17
Q

side effects of nefcillin

A

similar to oxacillin (hepatotoxicity and neutropenia) + thrombophlebitis

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18
Q

aminopenicillins chemistry

A

amino group increases hydrophilicity causing improved penetration into gram-negative cell membrane

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19
Q

aminopenicillin spectrum

A
  • gram positives: similar to penicillin with ampicillin as drug of choice for enterococci, listeria
  • poor activity for gram - (still inhibited by penicillinase) covers e coli (some), proteus, salmonella, shigella, som eh influenza
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20
Q

what is the drug of choice for gram-positive enterococcus

A

ampicillin

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21
Q

what are the aminopenicillins?

A

amoxicillin and ampicillin

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22
Q

which aminopenicillin is best given orally?

A

amOxicillin

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23
Q

what are the clinical uses for amoxicillin?

A

otitis media, upper and lower respiratory tract infections in children, lyme

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24
Q

what are the clinical uses for ampicillin

A

listeria and enterococcal

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25
Q

adverse effects of aminopenicillins

A

GI, hypersensitivity (delayed)

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26
Q

what are the antipseudomonal penicillins?

A

piperacillin, ticarcillin

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27
Q

what are antipseudomonal penicillins used in combination with?

A

beta-lactamase inhibitor to expand spectrum to include beta-lactamase-producing organisms

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28
Q

what are the beta-lactamase inhibitors + anti-pseudomonal penicillins effective against?

A

broad coverage against the beta-lactamase producing gram-positivies (staph aureus), gram-negatives (h influenza) and anaerobes (bacteroides fragilis)

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29
Q

what are the beta-lactamase inhibitors?

A

clavulanic acid, sulbactam, tazobactam

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30
Q

what are the penicillins/beta-lactamase resistant combinations?

A
  • amoxicillin and clavulanic acid
  • ticarcillin and clavulanic acid
  • ampicillin and sulbactam
  • piperacillin and tazobactam
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31
Q

what are the drug combinations active against pseudomonas aeruginosa?

A

piperacillin and tazobactam

ticarcillin and clavulanic acid

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32
Q

what are the extended-spectrum penicillin/beta-lactamase inhibitor combinations used for clinically?

A

mixed infections

  • intra-abdominal infections
  • diabetic foot
  • odontogenic infections
  • animal and human bites
  • aspiration pneumonia
  • nosocomial pneumonia
33
Q

which are the only cephalosporins that have activity against pseudomonas aeruginosa?

A

ceftazidime and cefeprime (cephalosporins)

34
Q

what do cephalosporins lack activity against?

A

MRSA, enterococcus (except ceftaroline 5th gen) and b. fragilis

35
Q

side effects of cephalosporing

A

hypersensitivity reactions (less common than penicillins), GI, coagulopathy (cefamandole, cefotetan, cefoperazone), disulfiram-like reaction with ethanole), CNS

36
Q

what advantages do cephalosporins have over penicillins?

A
  1. addition of a new basement makes the beta-lactam ring much more resistant to beta-lactamases
  2. new R-group side chain allows for double the manipulations in the lab (more spectrum of activity)
37
Q

spectrum of cephalosporins by generation

A
  1. gram-positives
  2. even across
  3. gram-negative
  4. good against gram-negative like 3rd but also good gram +
  5. MRSA!!!
38
Q

what are the first-generation cephalosporins

A

PH!!!!

-cephadroxil, cephalexin, CEFAZOLIN

39
Q

mechanism to generations 1,2,3,4 cephalosporins

A

form a complex with a PBP, prevent extracellular transpeptidase activity; broader spectrum than penicillins

40
Q

spectrum for first-generation cephalosporins

A

MSSA, streptococci, UTI bugs (e coli, proteus, klebsiella), mouth anaerobes (although activity against enterobacteriaceae shouldn’t be assumed)

41
Q

which first generation cephalosporin can be given IV?

A

cefazolin (used with surgical prophylaxis and serious MSSA infections)

42
Q

when is cephalexin used?

A

UTI, SSTI

43
Q

pharmacokinetics of first-generation cephalosporins

A

do not cross BBB

44
Q

what are the second-generation cephalosporins?

A

fam, fur, fox, tea

cefamandole, cefuroxime, cefoxitin, cefotetan

45
Q

what is the spectrum for second-generation cephalosporins?

A

gram-positive organisms (staph, strep)
gram negative (h flu, m catarrhalis, gonorrheae)
anaerobes
-used above and below diaphragm anaerobes

46
Q

what are the third generation cephalosporins?

A

ceftazadime, ceftriazone, cefpodoxime

47
Q

clinical uses ceftriaxone

A
  • community acquired pneumonia with azithromycin
  • meningitis
  • uncomplicated UTI
  • intra-abdominal infection with metronidazole
  • CSF lyme
  • strp endocarditis
  • gonococcal infection and PID
48
Q

ceftazidime clinical uses

A

definitive treatment of pseudomonas

-empiric treatment of post-neurosurgical miningitis

49
Q

side effects of third generation cephalosporins

A

greatest correlation with c. difficile infection than other drugs

50
Q

which third generation cephalosporin should not be used in neonates? why?

A

ceftriaxone (X FOR BABIES!)

biliary sludging, kernicterus, interaction with calcium-containing solutions causing precipitation

51
Q

third-generation cephalosporins pharmacokinetics

A

widely distributed (polar) - effective penetration across BBB

52
Q

what is the fourth generation cephalosporin?

A

cefepime

53
Q

clinical uses of cefepime

A

nosocomial infections, neutropenic fever, meningitis (CNS*), UTI
3rd generation + staph coverage

54
Q

cefepime side effects

A

akinetic seizures

55
Q

5th generation cephalosporin

A

ceftaroline

56
Q

what does ceftaroline cover?

A

gram + , gram - , MRSA!!!!

lacks activity against pseudomonas

57
Q

cephalosporins/beta-lactamase inhibitor combinations

A

ceftolozane/tazobactam
ceftazidime/avibactam (more against enterobactericeae!!)
-increased activity against pseudomonas

58
Q

which cephalosporins have excellent CSF penetration and can cover meningitis causing bacteria?

A

ceftriaxone (adults) and cefotaxime (children)

59
Q

what are the carbapenems?

A

imipenem, meropenem, ertapenem, dorpenem

60
Q

what is the class of carbapenems? mechanism?

A

cell wall syntehsis inhibitor

-similar mechanism to penicillins (attacks PBP)

61
Q

ceftaroline mechanism

A

possesses a side chain that acts a “trojan horse” allowing access to PBP2a

62
Q

carbapenams spectrum

A

broad spectrum excluding MRSA - resistant to beta-lactamases

63
Q

what drug must be given with imipenem? why?

A

cilastatin - normal kidney has a dihydropeptidase that breaks imipenem down - cilastatin is a selective enzyme inhibitor of this dihydropeptidase is given

64
Q

side effect imipenem

A

higher risk of seizures than other beta-lactams

65
Q

side effects of carbapenams

A

renal failure if not dose adjusted

66
Q

which carbapenam can be given outpatient due to its long half life?

A

ertapenem

67
Q

what is the of choice for diabetic foot infections?

A

ertapenem (not effective against pseudomonas)

68
Q

clinical uses carbapenems

A

complicated UTI, complicated intraabdominal infection, healthcare-acquired pneumonia, bone and SSTI, bacterial meningitis

69
Q

what do carbapenems have significant interaction with?

A

valproic acid (VPA) - used to treat seizures

70
Q

what class is aztreonam?

A

monobactam (cell wall synthesis inhibitor) with similar mechanism to penicillin

71
Q

what is the spectrum of aztreonam?

A

gram - aerobic bacilli (if a tree falls on your house, you will feel negative)
NO GRAM + or ANAEROBES!!!

72
Q

how is aztreonam used clinically?

A

definitive gram - therapy - not usually used as monotherapy (used with another drug that can cover gram +)

73
Q

which beta-lactam drug can be used in patients with penicillin allergies?

A

aztreonam!! (the monobactam)

74
Q

what are all the penicillin like drugs that are effective against pseudomonas?

A

pipercillin/tax, ticarcillin/clav, ceftazidine, cefepime, imipenem, aztretam

75
Q

fourth generation cephalosporin spectrum

A

excellent activity against enterobacteriaceae (anaerobes) and pseudomonas

76
Q

fourth generation cephalosporin (cefepime) chemistry and why is it beneficial?

A

zwitterion: neutral molecule with positive and negative charge that permits rapid entry into outer membrane of gram-negative bacteria

77
Q

what are the organisms NOT covered by the 1st-4th generation cephalosporins?

A 
LAME
listeria
atypicals
MRSA (ceftaroline covers)
enterococci
78
Q

what must imipenem be administered with? why?

A

cilastatin - inhibitor of renal dehydropeptidase I (with imipenem “the kill is lastin’ with cilastatin”)
-imipenem is inactivated by dehydropeptidase I otherwise

ABBEY MSII U6 (18 decks)

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