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pharmacology unit 6 > antimicrobial beta lactams > Flashcards

antimicrobial beta lactams Flashcards

1
Q

what essential for the function of beta-lactams

A

the beta-lactam ring

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2
Q

what does the side chain of the beta-lactam determine?

A

the antibacterial spectrum and pharmacological properties

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3
Q

what do beta-lactams bind

A

penicillin binding proteins

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4
Q

what do penicillin binding proteins do?

A

catalyze the polymerization of the glycan strand (transglycosylation) and the cross-linking between the glycan chains (transpeptidation).

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5
Q

what explains the differences in microbial spectrum?

A

the affinity of the PBP for the beta-lactam.

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6
Q

are beta-lactamases PBP? what are they?

A

yes. they are the enzymes responsible for the enzymatic destruction of beta-lactams.

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7
Q

how do the beta-lactam actually cause bacterial death?

A

they cause a build up of peptidoglycan precursors within the bacteria and this initiates autolysins.

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8
Q

where does gram + produce beta-lactamase

A

outside the cell. preemptively stopping the activity of the beta-lactam

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9
Q

where do gram - express beta-lactamase

A

located in the periplasmic space. they allow the beta-lactam into the space and then disable it.

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10
Q

is beta-lactamase a major cause of resistance in gram negative bacteria?

A

yes.

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11
Q

what are two other ways of gram negative beta-lactam resistance

A

alteration of the porins on the surface dont allow the passage of the antibiotic and alterations of PBPs (MRSA and strep. pneumoniae)

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12
Q

what are the natural penicillins

A

G and V

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13
Q

what are the three penicillin-resistant penicillins

A

oxacillin, nafcillin, dicloxacillin

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14
Q

what is another name for the penicillin-resistant penicillins

A

antistaphylococcal penicillins

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15
Q

what are the two aminopenicillins

A

ampicillin and amoxicillin

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16
Q

what are the two carboxy penicillins

A

carbenicillin and tricarcillin

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17
Q

name the ureidopenicillin

A

piperacillin

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18
Q

name the types of the beta-lactam

A

natural, antistaphylococcal, aminopenicillin, carboxypenicillin, ureidopenicillin, cephalosporins, carbapenems, monobactems.

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19
Q

is there a different mechanism for the different types of beta-lactam

A

no. the same. preventing the transpeptidation (cross-linking) of peptidoglycan layers in the cell wall by binding to PBP.

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20
Q

what are the half lives of the beta-lactam

A

short. 20 minutes. this is why they are given so frequently

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21
Q

how are most of the beta-lactams eliminated

A

through the renal route, must take into account renal insufficiency

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22
Q

what are the most common SE of the beta-lactam

A

GI and HSR. acute interstitial nephritis and drug fever. hives and rash.

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23
Q

what is the downfall for the beta-lactam

A

they lack activity against organisms without a cell wall, such as mycoplasma and chlamydia pneumonia.

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24
Q

do the beta-lactam have MRSA activity?

A

no. except for ceftaroline.

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25
what is the antimicrobial spectrum for the natural penicillins
non-beta-lactamase producing gram +. streptococci. anaerobes (actinomyces, clostridium, prevotella, peptostreptococcus), select-gram (-) (neisseria), and syphilis.
26
what are the clinical uses for natural penicillins
streptococcal infections such as pharyngitis, cellulitis, endocarditis (viridans), and syphilis.
27
what are the adverse effects of the natural penicillins
HSR, seizures at high dose.
28
what is the pharmacodynamics of the natural penicillins
ADE -penicillin V is a more stable acid the G. there is wide distribution, and there is renal elimination.
29
antistreptococcal agents
oxacillin, nafcillin, dicloxacillin
30
what is the antimicrobial spectrum for the antistreptococcal
MSSA and strep
31
clinical uses of antistreptococcal
primarily for MSSA. it is actually superior to vancomycin for MSSA.
32
what to watch out for on antistreptococcal
penicillin HSR!
33
what is the adverse effects for oxacillin
hepatotoxicity and neutropenia
34
what are the adverse effects for nafcillin
hepatotoxic and neutropenic and thrombocytopenic.
35
do you take dicloxacillin with food?
no it decreases its availability
36
how are the antistreptococcal eliminated
hepatically
37
how does the antistreptococcal evade the bacterial resistance
they have a bulky side chain that sterically shields the beta-lactam ring. However it also prevents entry into the gram negatives so they are useless there.
38
what are the two aminopenicillins
amoxicillin and ampicillin
39
what is special about the aminopenicillins
the aminogroup aids in the hydrophobicity so that it penetrates the gram (-) cell wall. used against oral anaerobes as well.
40
what is the spectrum for the aminopenicillins
gram (+) (enterococcus, streptococci, and listeria). gram (-) hemophilus and E. coli.
41
are the aminopenicillins good at killing gram negatives
not particularly because of resistance.
42
what are the clinical uses of the aminopenicillins
otitis media, URTIs, UTIs, endocarditis, listeria meningitis
43
what are the aminopenicillins the drug of choice for?
enterococci
44
what are the adverse effects for the aminopenicillins
HSR, rash and GI
45
which of the aminopenicillins has better absorption
amoxicillin
46
how do we use piperacillin and ticarcillin in clinical practice
with a beta-lactamase inhibitor. use them against staph, gram (-) rods, some anaerobes. they are not used often and when they are it is in combination with inhibitor.
47
what is unasyn
ampicillin and sulbactam inhibitor combination.
48
what is augmentin
amoxicillin and clavulanate inhibitor combination
49
what is zosyn
piperacillin and tazobactam inhibitor combination
50
what is timentin
ticarcillin and clavulanate inhibitor combination
51
what are the only inhibitor combinations active against pseudomonas
pip/taz and tic/clav
52
what bugs to the inhibitor combinations have poor activity
MRSA, extended spectrum beta-lactamase GNRs (e coli).
53
what are the clinical uses of the inhibitor combinations
mixed infections, intraabdominal, diabetic foot-ulcerations, nosocomial pneumonia and aspiration pneumonia
54
what are the adverse events for inhibitor combinations
HSR.
55
what are the rare side effects for pip/taz
immune mediated thrombocytopenia, aplastic anemia.
56
are the cephalosporins more resistant to lactamases than beta-lactam?
yes. they are also resistant to penicillinases but susceptible to cephalosporinases
57
are cephalosporins active against MRSA, b. fragalis and enterococcus
no. with one exception: ceftaroline 5th gen. none work against fragilis.
58
what are the adverse effects of the cephalosporins
HSR similar to the penicillins -they have cross-allergenicitiy
59
what are the 1st generation cephalosporins
cefazolin and cefalexin
60
what is the spectrum for the 1st generation cephalosporins
MSSA and strep. some GNR, klebsiella, proteus.
61
what is cefazolin used for
surgical prophylaxis 24hr. (add metrinidazole for colon), MSSA bacteremia, endocarditis, skin and soft tissue. these are suitable for streamlining treatment: broad-spectrum
62
are the 1st generation cephalosporins better tolerated than the antistaphs?
yes.
63
2nd generation cephalosporins agents
these are the true cephs and cephamycins
64
true cephs
cefuroxime, cefaclor, loracarbef, cefprozil
65
cephamycins
cefoxitin and cefotetan
66
what is the spectrum for the true cephs
gram (+) (strep pneumoniae), gram (-) (H. flu, gonorrhea, catarhalis, some enterobacteraciae).
67
spectrum for the cephamycins
less active against gram (+) than 1st gen. gram (-) (more active against klebsiella and e coli, but less active against H. flu. than the 1st gen).
68
what are the true cephs used for clinically
community acquired respiratory infections
69
what are the cephamycins used for clinically
intraabdominal infections, pelvic and gynecological infections, mixed aerobic/anaerobic infections and surgical prophylaxis.
70
3rd generation cephs
cefotaxime, ceftriaxone, ceftazidime, cefdinir, cefpodoxime, ceftibutin, cefixime
71
what is the spectrum of the 3rd generation cephs
pseudomonas aeruginosa (ceftazidime), streptococci, MSSA.
72
what do the 3rd gens have NO activity against
MRSA, enterococcus, stenotrophamonas, listeria. b. fraglais
73
what do the 3rd gens have limited activity
anaerobes
74
what is ceftriaxone used for clinically
CA pneumonia, complicated UTI, CA meningitis, CSF Lyme, strep endocarditis, gonococcal and PID, intraabdominal infection with metronidazole
75
what is cefotaxime used for
similar to ceftriaxone. preferred in neonates.
76
what is ceftazidime used for
pseudomonal infections post-neurosurgical meningitis,
77
what is ceftazidime a poor choice for
CA meningitis
78
what are the adverse effects for the 3rd gener
correlation with c diff. | ceftriaxone causes biliary sludging
79
which 3rd gens cross the BBB
ceftriaxone, cefotaxime, ceftazidime
80
which 3rd gener can be problematic in neonates and why
ceftriaxone because of biliary sludging. also interacts with calcium containing medications to form crystals.
81
what is special about the 4th gener
they are zwitterion so the neutral charge passes the gram(-) barrier. they also have relative resistance to ampC beta-lactamases.
82
what is the spectrum of the 4th gens.
gram (-) excellent activity against enterobacter and pseudomonas. gram (+) high afinity for PBP of +'s MSSA and strep pneumoniae,
83
what do the 4th gens not have activity against
MRSA, fragalis, listeria.
84
what are the clinical uses of the 4th gens
neutropenic fever, meningitis, ceftazidime resistant enterobacter, similar to the 3rd gens.
85
what are the 5th gen agentds
ceftaroline and ceftobiprole.
86
what is unique about the 5th gens
they have a side chain that mimics part of the cell wall and acts as a trojan horse.
87
what is the spectrum for the 5th gens
gram (+): MRSA, MSSA, strep, faecalis. gram (-): H flu, catarrhalis, enterobacter.
88
what are the 5th gens NOT active against
poor anaerobes, and no pseudomonas.
89
what are the clinical uses of the 5th gen
complicated skin and soft tissue. off label
90
how can staph become resistant to 5th gens
alterations of the ceftaroline binding pocket.
91
monobactam agents
aztreonam
92
spectrum for aztreonam
only gram (-) enterobacter and pseudomonas
93
what is aztreolam ineffective at treating?
gram (+)'s and anaerobes.
94
what is the clinical use for azteonam
almsot never used as a monotherapy unless the infection is known to be gram (-). pneumonia, UTI, surgical wounds (gram (-)). used in patients requiring gram (-) activity with penicillin allergy and unable to use aminoglycosides
95
what are the carbapenem agents
imipenem/cilastatin, meropenem, ertapenem, doripenem.
96
what is the spectrum for the carbapenems
broad spectrum against (+), (-), and anaerobes, some types of MDR gram (-) rods,
97
what are the carbapenems not useful for
MRSA, stenotrophomonas, not ideal for enterococcus, or coagulase negative staph.
98
what can we not use ertapenem for
pseudomonas, acinetobacter
99
what do we use ertapenem for
CA intraabdominal infection.
100
what do we use meropenem for
hospital acquired infection, intraabdominal, HAP, VAP, post-neurosug meningitis, ESBL-producing GNR.
101
what do we use imipenem for
similar to meropenem
102
what do we use doripenem for
same as meropenem.
103
what are the adverse effects of the carbapenems
similar to the other betas
104
what is unique about the SE of imipenem
it causes more seizures than the others. watch out for the renal failure patient.

pharmacology unit 6 (45 decks)

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