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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
adverse effects of aminopenicillins
GI, hypersensitivity (delayed)
26
what are the antipseudomonal penicillins?
piperacillin, ticarcillin
27
what are antipseudomonal penicillins used in combination with?
beta-lactamase inhibitor to expand spectrum to include beta-lactamase-producing organisms
28
what are the beta-lactamase inhibitors + anti-pseudomonal penicillins effective against?
broad coverage against the beta-lactamase producing gram-positivies (staph aureus), gram-negatives (h influenza) and anaerobes (bacteroides fragilis)
29
what are the beta-lactamase inhibitors?
clavulanic acid, sulbactam, tazobactam
30
what are the penicillins/beta-lactamase resistant combinations?
- amoxicillin and clavulanic acid - ticarcillin and clavulanic acid - ampicillin and sulbactam - piperacillin and tazobactam
31
what are the drug combinations active against pseudomonas aeruginosa?
piperacillin and tazobactam | ticarcillin and clavulanic acid
32
what are the extended-spectrum penicillin/beta-lactamase inhibitor combinations used for clinically?
mixed infections - intra-abdominal infections - diabetic foot - odontogenic infections - animal and human bites - aspiration pneumonia - nosocomial pneumonia
33
which are the only cephalosporins that have activity against pseudomonas aeruginosa?
ceftazidime and cefeprime (cephalosporins)
34
what do cephalosporins lack activity against?
MRSA, enterococcus (except ceftaroline 5th gen) and b. fragilis
35
side effects of cephalosporing
hypersensitivity reactions (less common than penicillins), GI, coagulopathy (cefamandole, cefotetan, cefoperazone), disulfiram-like reaction with ethanole), CNS
36
what advantages do cephalosporins have over penicillins?
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
spectrum of cephalosporins by generation
1. gram-positives 2. even across 3. gram-negative 4. good against gram-negative like 3rd but also good gram + 5. MRSA!!!
38
what are the first-generation cephalosporins
PH!!!! | -cephadroxil, cephalexin, CEFAZOLIN
39
mechanism to generations 1,2,3,4 cephalosporins
form a complex with a PBP, prevent extracellular transpeptidase activity; broader spectrum than penicillins
40
spectrum for first-generation cephalosporins
MSSA, streptococci, UTI bugs (e coli, proteus, klebsiella), mouth anaerobes (although activity against enterobacteriaceae shouldn't be assumed)
41
which first generation cephalosporin can be given IV?
cefazolin (used with surgical prophylaxis and serious MSSA infections)
42
when is cephalexin used?
UTI, SSTI
43
pharmacokinetics of first-generation cephalosporins
do not cross BBB
44
what are the second-generation cephalosporins?
fam, fur, fox, tea | cefamandole, cefuroxime, cefoxitin, cefotetan
45
what is the spectrum for second-generation cephalosporins?
gram-positive organisms (staph, strep) gram negative (h flu, m catarrhalis, gonorrheae) anaerobes -used above and below diaphragm anaerobes
46
what are the third generation cephalosporins?
ceftazadime, ceftriazone, cefpodoxime
47
clinical uses ceftriaxone
- community acquired pneumonia with azithromycin - meningitis - uncomplicated UTI - intra-abdominal infection with metronidazole - CSF lyme - strp endocarditis - gonococcal infection and PID
48
ceftazidime clinical uses
definitive treatment of pseudomonas | -empiric treatment of post-neurosurgical miningitis
49
side effects of third generation cephalosporins
greatest correlation with c. difficile infection than other drugs
50
which third generation cephalosporin should not be used in neonates? why?
ceftriaxone (X FOR BABIES!) | biliary sludging, kernicterus, interaction with calcium-containing solutions causing precipitation
51
third-generation cephalosporins pharmacokinetics
widely distributed (polar) - effective penetration across BBB
52
what is the fourth generation cephalosporin?
cefepime
53
clinical uses of cefepime
nosocomial infections, neutropenic fever, meningitis (CNS*), UTI 3rd generation + staph coverage
54
cefepime side effects
akinetic seizures
55
5th generation cephalosporin
ceftaroline
56
what does ceftaroline cover?
gram + , gram - , MRSA!!!! | lacks activity against pseudomonas
57
cephalosporins/beta-lactamase inhibitor combinations
ceftolozane/tazobactam ceftazidime/avibactam (more against enterobactericeae!!) -increased activity against pseudomonas
58
which cephalosporins have excellent CSF penetration and can cover meningitis causing bacteria?
ceftriaxone (adults) and cefotaxime (children)
59
what are the carbapenems?
imipenem, meropenem, ertapenem, dorpenem
60
what is the class of carbapenems? mechanism?
cell wall syntehsis inhibitor | -similar mechanism to penicillins (attacks PBP)
61
ceftaroline mechanism
possesses a side chain that acts a "trojan horse" allowing access to PBP2a
62
carbapenams spectrum
broad spectrum excluding MRSA - resistant to beta-lactamases
63
what drug must be given with imipenem? why?
cilastatin - normal kidney has a dihydropeptidase that breaks imipenem down - cilastatin is a selective enzyme inhibitor of this dihydropeptidase is given
64
side effect imipenem
higher risk of seizures than other beta-lactams
65
side effects of carbapenams
renal failure if not dose adjusted
66
which carbapenam can be given outpatient due to its long half life?
ertapenem
67
what is the of choice for diabetic foot infections?
ertapenem (not effective against pseudomonas)
68
clinical uses carbapenems
complicated UTI, complicated intraabdominal infection, healthcare-acquired pneumonia, bone and SSTI, bacterial meningitis
69
what do carbapenems have significant interaction with?
valproic acid (VPA) - used to treat seizures
70
what class is aztreonam?
monobactam (cell wall synthesis inhibitor) with similar mechanism to penicillin
71
what is the spectrum of aztreonam?
gram - aerobic bacilli (if a tree falls on your house, you will feel negative) NO GRAM + or ANAEROBES!!!
72
how is aztreonam used clinically?
definitive gram - therapy - not usually used as monotherapy (used with another drug that can cover gram +)
73
which beta-lactam drug can be used in patients with penicillin allergies?
aztreonam!! (the monobactam)
74
what are all the penicillin like drugs that are effective against pseudomonas?
pipercillin/tax, ticarcillin/clav, ceftazidine, cefepime, imipenem, aztretam
75
fourth generation cephalosporin spectrum
excellent activity against enterobacteriaceae (anaerobes) and pseudomonas
76
fourth generation cephalosporin (cefepime) chemistry and why is it beneficial?
zwitterion: neutral molecule with positive and negative charge that permits rapid entry into outer membrane of gram-negative bacteria
77
what are the organisms NOT covered by the 1st-4th generation cephalosporins?
``` LAME listeria atypicals MRSA (ceftaroline covers) enterococci ```
78
what must imipenem be administered with? why?
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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