Penicillins Flashcards
1
Q
Pure penicillin is ____ to degradation by acids.
A
highly susceptible; pH was 5-7
2
Q
Serial passages of penicillin over ____and ____ results in resistant organisms.
A
staphylococcus; streptococcus species
3
Q
Organisms that are inherently resistant to penicillins
A
Gram - bacilli
4
Q
Peniciilins have a ___ safety margin compared to other available compounds.
A
WIDE
5
Q
Structure of Penicillin: nucleus
A
beta-lactam and thiazolidine rings
6
Q
Nucleus is important because:
A
required for biological activity
7
Q
Breakdown of beta-lactam by beta-lactamase results in
A
loss of activity
8
Q
Acyl side chain modifications
A
change spectrum of activity, stability to enzymes, and pharmacokinetic properties
9
Q
MOA for Penicillin
A
PEN inhibits transpeptidase responsible for cross-linking peptide chains resulting in a dysfunctional wall
10
Q
Normal function of PBP:
A
synthesize peptidoglycan, maintain cell shape, and septum formation
11
Q
Disruption of cell wall stimulates
A
autolysis and cell death
12
Q
Penicillin G could be given:
A
orally, IV, IM
13
Q
Penicillin G benefits over other agents:
A
readily distributed into multiple tissues and wide therapeutic index (safe)
14
Q
Penicillin G challenges:
A
rapid acid degradation, susceptibility to beta-lactamases, narrow spectrum of activity
15
Q
Natural Penicillins oral absorption:
A
PCN VK (60%) >PCN G (30%)
16
Q
Natural Penicillins 1/2 life
A
short
17
Q
Natural Penicillins route of elimination
A
renal
18
Q
Natural Penicillins CSF distribution
A
better into inflamed than non-inflamed but still poor
19
Q
Natural Penicillins protein binding
A
50
20
Q
PCN VK is more/less stable than PCN G
A
more, produces 2-5x greater serum concentration
21
Q
Natural Penicillins can/cannot be removed by hemodialysis
A
can
22
Q
Bacterialcidal activity for beta-lactams is measured by
A
T>MIC; duration of time that free drug levels exceed MIC
23
Q
for stasis:
for cidal:
A
30%
50%
24
Q
Spectrum coverage for Natural PCNs
A
dark purple: streptococcus spp, S. pneumoniae, E. faecalis
light purple: viridans strep
dark red: Neisseria spp
anaerobes: +/- (oral +)
Misc: T. pallidum (syphillis), B. burgdorferi (Lyme)
25
Common indications for Natural PCNs
```
syphilis (dosing depends on stage of syphilis)
neurosyphilis
endocarditis
meningitis
streptococcal pharyngitis
streptococcal toxic shock
```
26
Long acting parenteral agents:
Penicillin G procaine, penicillin G benzathine (Bicillin LA), penicillin G benzathine/procaine (Bicillin CR)
27
Long acting parenteral agents administration
IM; avoid IV due to increased risk of cardiac arrest
28
Purpose for developing PCN long acting parenteral agents
developed in response to short half-life and poor oral absorption of PCN
29
Penicillinase resistant penicillins active against penicillinase producing staph aureus:
Oxacillin and Nafcillin
30
Spectrum coverage for oxacillin and nafcillin:
GRAM + ONLY
dark purple: streptococcus, s.pneumoniae, MSSA/MSSE
light purple: viridans
31
Nafcillin/Oxacillin oral absorption:
poor oral, IV only
32
Nafcillin/Oxacillin 1/2 life:
short
33
Nafcillin/Oxacillin Route of elimination:
hepatic, biliary
34
Nafcillin/Oxacliin distribution
```
skin
joint
lung
urine
CSF with inflammation
bile
peritoneal
```
35
Nafcillin/Oxacliin dosing
the same for both and varies with infection; can be administered as continuous infusion
36
Nafcillin/Oxacliin challenges
poor oral absorption due to gastric acid breakdown
37
Dicloxacillin oral bioavailability
increased 50% from Nafcillin/Oxacliin
38
Dicloxacillin protein binding
high
39
Dicloxacillin 1/2 life
short
40
Purpose of isoxazoyl group in dicloxacillin
mitigates penicillinase and gastric acid breakdown
41
Dicloxacillin used for
treatment of mild bacterial skin/skin structure infections
42
Resistance mechanisms for penicillins
alterations in PBPs (s. pneumo/neisseria, enterococcus)
```
PCN penicillinase (s.aureus)
Oxacillin/methicillin resistance by altering PBP2 (s.aureus)
```
43
Adverse effects for Pencillins
```
well tolerated
neurologic
GI
hepatic
renal
allergy
electrolyte abnormalities
hematologic
thrombophlebitis
```
44
Penicillins have a ____ spectrum of activity
narrow
45
Penicillins are primarily used as ___ therapy
definitive
46
Penicillins are bactericidal/bacteriostatic
bactericidal
47
Extended spectrum penicillins include
aminopenicillins and ureidopenicillins
48
Clinical needs for extended spectrum penicillins
safe antimicrobials
| improved gram - activity by enhancing penetration through outer membrane and having higher affinity for PBP
49
Ampicillin has enhanced cell wall penetration because it is a
zwitterion at neutral pH
50
Zwitterions penetrate through ____ within the cell membrane
porins
51
Ampicillin oral absorption:
50% (fair)
52
Ampicillin elimination:
RENAL
53
Ampicillin 1/2 life:
short
54
Ampicillin is associated with which side effect:
diarrhea
55
Ampicillin has saturable
absoprtion
56
Ampicillin tissue penetration
lung, bone, CNS with inflammation
57
Amoxicillin is administered
orally only in the US
58
Amoxicillin oral absorption
75% so higher than ampicillin
59
Amoxicillin has ____ frequency of diarrhea
reduced
60
Amoxicillin is primarily used for
URI
61
Amoxicillin has activity against ____ so it can be used for URI
s. pneuomoniae
62
Amoxicillin dosing depends on
indication
63
Ampicillin/Amoxicillin spectrum coverage:
dark purple: streptococcus, S. pneumoniae, E. faecalis
light purple: viridans, E. faceium
dark red: Neisseria
light red: H. influenzae, E. coli, P. mirabilis
anaerobes: +/- (oral +)
Misc: L. monocytogenes, H. pylori, Salmonella, Shigella
*** not stable against penicillinase ***
64
Common indications for Ampicillin/Amoxicillin
```
Empiric therapy:
Group A strep
s.pneumoniae (high dose amoxicillin)
H.pylori
Listeria (especially CNS) use ampicillin
```
Definitive therapy:
Enterococcus
S. pneumoniae
H. influenzae (beta-lactamase negative)
65
Sulbactam is added to ampicillin to
minimize impact of beta lactamases
66
Sulbactam is a _____ inhibitor
suicide
67
Suicide inhibitor
permanently inactivates beta-lactamases and cannot be recycled
also has minor PBP inhibitory properties
68
Spectrum of inhibition for ampicillin/sulbactam
penicillinases (MSSA)
cephalosporinases (klebsiella)
broad spectrum beta lactamases (E. coli)
69
Sulbactam has weak intrinsic activity against
Neisseria and acinetobacter
70
Ampicillin/sulbactam oral absorption
50/20
71
Ampicillin/sulbactam 1/2 life
short
72
Ampicillin/sulbactam elimination
RENAL
73
Ampicillin/sulbactam is administered
IV only as combo in 2:1 ratio
74
Sulbactam tissue penetration
CSF- similar to ampicillin in inflamed cases
lung- similar to ampicillin
bone- 15% so less than ampicillin
75
Clavulanate is a ____ inhibitor
suicide
76
Clavulanate extends amoxicillin's spectrum of activity through
inhibition of beta-lactamases
77
Clavulanate does not have activity against
acinetobacter
78
Clavulanate has activity against
s. aureus, h. influenzae, E. coli, klebsiella, p. mirabilis, salmonella, shigella, norcardia, and some mycobacterium
79
Amoxicillin/clavulanate oral absorption
high 75/75
80
Amoxicillin/clavulanate 1/2 life
short
81
Amoxicillin/clavulanate elimination
renal/ hepatic-renal
82
Amoxicillin/clavulanate adverse effects
diarrhea! from clav component and less diarrhea is seen with newer formulations
83
Amoxicillin/clavulanate dosage forms
tablet, ER tablets, liquid
84
Aminopenicillin + inhibitor spectrum coverage:
dark purple: streptococcus, s. pneumoniae, MSSA/MSSE, e. faecalis
light purple: viridans, e. faecium
dark red: Neisseria, h. influenzae, m. catarrhalis, E. coli, klebsiella, p. mirabilis
light red: morganella
anaerobes: ++ (oral and gut b. fragilis)
Misc: similar to ampicillin for acinetobacter
85
Ampicillin/sulbactam indications
empiric use:
surgical prophylaxis for intra-ab surgery
head and neck infections
sinus infections
XDR acinetobacter infections (due to sulbactam activity)
definitive:
- intra-ab infections
- gynecologic infections
- head and neck infections
86
Amoxicillin/clavulanate indications
URI like sinusitis, outpatient community acquired pneumonia, otitis media, strep throat
87
Ureidopenicillins have a ___ spectrum of activity
broader
88
Ureidopenicillins have
enhanced cell wall penetration and improved binding affinity to multiple PBP
89
Ureidopenicillin drug
pipercillin/tazobactam
90
Pipercillin/tazobactam oral absorption
poor
91
Pipercillin/tazobactam administration
IV only
92
Pipercillin/tazobactam 1/2 life
short
93
Pipercillin/tazobactam elimination
renal: 68/80 mostly renal
biliary: 20/20
94
Pipercillin/tazobactam penetration into CNS
not good
95
Pipercillin/tazobactam penetration into tissues
bile, lung, skin, urine, bone, peritoneum
96
Pipercillin/tazobactam spectrum coverage:
dark purple: streptococcus, s. pneumoniae, MSSA/MSSE, E. faecalis
light purple: viridans, E. faecium
dark red: Neisseria, h. influenzae, m. catarrhalis, E. coli, klebsiella, p. mirabilis, morganella, enterobacter, citrobacter, serratia, p. aeruginosa
light red: acinetobacter
anaerobes: ++ oral and gut
Misc: variable activity against ESBL and AmpC
97
Pipercillin/tazobactam indications
healthcare associated infections (suspicion for multi drug resistant organisms)
intra-ab infections
pneumonia
complicated skin/skin structure infections
fever and neutropenia
NOT GOOD FOR CNS/MENINGITIS
98
Pipercillin/tazobactam adverse effects
```
well tolerated
neurologic
GI
hepatic (kcholestatis jaundice is higher than other PCNs)
renal
allergy
electrolyte imbalance (sodium overload)
hypokalemia
hematologic
thrombophlebitis
```
99
Which organism do all PCN drugs not cover?
MRSA/MRSE
100
Which PCN drug/derivative covers p. aeurginosa and acinetobacter?
pipercillin/tazobactam
101
Which PCN drug/derivative covers B. fragilis (gut anaerobes)?
pipercillin/tazobactam and aminopenicillins+inhibitor
102
In the hospital setting _____ is the most used PCN agent due to its broad spectrum of activity
pipercillin/tazobactam
