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Block7 > PDA antibacterials > Flashcards

PDA antibacterials Flashcards

1
Q

What are infections where -cidal drugs have an advantage?

A 
pts with compromised immune system
following in immune-competent pts:
-meningitis
-endocarditis
-deep bone infections
-artificial device implants
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2
Q

What type of antibacterials are preferred for patients with competent immune systems with meningitis, endocarditis, deep bone infections, and artificial device implants?

A

-cidal drugs

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3
Q

What is time dependent killing?

A

amount of time about the MIC

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4
Q

What is concentration-dependent kkilling?

A

peak concentration matters most

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5
Q

What does it mean when drugs are concentration and time dependent?

A

area under curve of concentration over time vs MIC

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6
Q

When do time-dependent killing drugs work on epople?

A

drugs work best when conc. exceeds 4 times the MIC for greater than 50% of total time

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7
Q

What are beta-lactams dependent on for killing with respect to MIC?

A

Time-dependent

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8
Q

What type of depedency do amingolycosides have for killing?

A

concentration dependent and have persistent effect when levels fall below MIC

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9
Q

What type of dependenccy do quinolones have for killiing?

A

concentration x time (area under curve)

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10
Q

Why do beta-lactams requrie more frequent dosing?

A

time dependent killers and they have a shorter half life

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11
Q

Where do penicillins have low penetration?

A

into the csf; although increases during meningitis

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12
Q

How are penicillins eliminated?

A

renally; by anion transport

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13
Q

What are the half lives of penicillins?

A

short 30 minutes to 3 hours

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14
Q

How is penicillin V taken?

A

orally

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15
Q

How is penicllin G taken?

A

IV/IM

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16
Q

What are the spectrum of peniclin V and penicillin G?

A 
anaerobes (mainly gram positivie)
gram positive that are non-beta-lactamase producing
1st line for strep throat
very limited gram negative
-neisseria meningitidis
spirochetes
-syphillis
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17
Q

What penicillins are used for beta-lactamase positive staphylococci?

A

methicillin type drugs; ie oxacillin

MSSA(methicillin sensitive Staph aureus)

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18
Q

What is the spectrum for ampicillin and amoxicillin?

A

maitain gram postiive (Beta lactamase negative)
-enterococcus
expanded gram negative spectrum

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19
Q

What is the drug of choice for otitis media in otherwise healthy children?

A

high dose amoxicillin

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20
Q

What is amoxiciiln an althernate choice for in young children and pregnat/breat-feeding women?

A

Lyme disease

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21
Q

What are 2 important uses for ampicillin that amoxicillin doesnt?

A 
meningitis (neisseria, listeria)
bc available by IV
GI infections;
esp Shigella
bc less abosrbed in orally more avaiable in GI tract
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22
Q

What two penicilins have an extended gram-negative spectrum?

A

ticarcillin and piperacillin

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23
Q

What is the spectrumf or ticarcillin?

A

retain some gram-pos activity
good for some anaerobes
gram neg spectrum extended to include psuedomonas aeruginosa

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24
Q

What is the spectrum for piperacillin?

A

gram negative spectrum like ticarcillin but also some pseudomonas and klebsiella
include those that are ticarcillin-resistant

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25
Q

How can one predict severe allergic reaction to penicillin?

A

pt history
PRE-PEN
-skin test; 90-95% reliable at identifying those at risk for severe allergic reaction

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26
Q

What are the side effects of penicillins?

A 
fever
diarrhea(most common side effect)
enterocolitis (all anti-biotics can causet his due to C diff infection)
elevated liver enzymes
hemolytic anemia
seizures
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27
Q

What are some common properties of cephalosporins?

A

well distributed; although only 3rd gen reach CSF
majority require injection
same mechanism as penicillin

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28
Q

What is teh spectrum for 1st generation cephalosporins??

A

mostly gram positive spectrum
uncomplicated outpatient skin infections
surgical prophylaxis esp for skin flora

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29
Q

What are two cephalosporin 1st generation drugs?

A

cefazolin and cephalexin

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30
Q

What are two examples of second generation cephalosporins?

A

cefuroxime and cefoxitin

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31
Q

What is teh only second gen cephalosporin to penetrate CSF?

A

cefuroxime

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32
Q

What is cefuroxime used to treat?

A

best second for haemophilus but poor against enterics

good tolerance to many gram negative beta lactamases

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33
Q

What is cefotoxin used to treat?

A

similar to many second gen but also good for anaerobes including B. fragilis
good tolerance to many gram-neg beta lactamases

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34
Q

What are two 3rd generation cephalosporins?

A

ceftriaxone and ceftazidime

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35
Q

What cephalosporin is a very good choice for common types of menigitis?

A

ceftriaxone

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36
Q

What is the therapy of choice for gonorrhea?

A

ceftriaxone

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37
Q

What is ceftriaxone used to treat?

A 
common types of meningitis
gonorrhea
sever lyme disease
typhoid fever
surgical prophylaxis GI tract surgery
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38
Q

What is the half life comparison between 3rd generation cephalosporins?

A

ceftriaxone long half life 6-9 hours and ceftazidime shorter half life 90 minutes

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39
Q

What is ceftazimide used to treat?

A

meningitis, brain abcess
pseudomonas aueruginosa esp those resistant ot aminoglycosides
poorest for gram positive

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40
Q

What is the most active 3rd gen cephalosoporin for psuedomonas aeruginosa?

A

ceftazidime

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41
Q

What is teh poorest 3rd gen cephalosoporin for gram positive?

A

ceftazidime

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42
Q

What is a fourth generation cephalosporin?

A

cefepime

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43
Q

What is teh half life of cefepime?

A

2 hours

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44
Q

What is the spectrum of cefepime?

A

similar to ceftazidime except more resistant to inducible chromsomally endoced type 1 beta lactamases so covers mroe gram negative strain

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45
Q

What is cefepime used to treat

A

empirical treatment of serious inpatient infections where both gram positive and gram negative etiologies are possible

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46
Q

What are cephalosporins asa whole bad at treating?

A 
camplobacter
legionella
C. Diff
listeria
Acinetobacter
enterococcus
penicillin resistant strep pneumoniae
MRSA
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47
Q

How are cephalosporins excreted?

A

Renally: GFR and anion secretion

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48
Q

What are teh allergic reactions of cephalosporins?

A

2-10% ( 1-20% pts cross react with penicilin)

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49
Q

What are teh side effects for sephalosporins?

A

allergic rxns
GI issues-generational differences
hepatocellular damage

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50
Q

What do extended spectrum Beta-lactamases inactivate?

A

penicillins as well as drugs considered beta lactamase resistant such as 3rd gen cephalosporins and monobactams

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51
Q

What are the treatment of choice for ESBL (extended spectrum beta lactamase) organisms?

A

carbapenems

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52
Q

What is the spectrum of imipenem?

A

broad spepctrum
gram pos and gram negative
resistant to most beta lactamases including ESBLs

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53
Q

What is imipenem not for?

A

C. diff, MRSA, Enterococcoccus faecium, some psuedomonas, stenophomonas

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54
Q

What class is imipenem?

A

carbapenem

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55
Q

What is imipenem used for therapeutically?

A

ill-defined infections
mixed infections
non-responsive or resistant to other drugs (ESBLs)

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56
Q

Why is imipenem given with cilastatin?

A

to prevent hydrolysis by renal dipeptidases

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57
Q

What are teh side effects of imipenem?

A

allergic rxns
seizures, dizziness, confusion
nausea, vomitin, diarrhea, pseudomembranous colitis, superinfection
thrombophlebitis

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58
Q

What is aztrenoam used to treat?

A

gram negative aerobic rods resistant to many beta lactamases

59
Q

Does aztreonam have allergic cross-reactions with beta-lactams?

A

no

60
Q

What are the side effects of aztreonam?

A

seizures, anaphylaxis, transient EKG changes

  • GI issues
  • hepatiits, jaudice, confusion
61
Q

What is hte mechanism of action of vancomycin?

A

binds to free carboxl end of D-ala-Dala of the pentapetptide interferes with cross–linking of petidoglycan chain

62
Q

What is vancomycin used to treat?

A 
gram positives only
staph, incl MRSA
strep pneuomniae; hemolytic strep
enterococcus (20-30% resistant VRE)
C. dif enterocolitis
63
Q

How is vancomycin administered?

A

IV for systemic infection
limited pen into CSF
oral for C. diff eneteroclitis

64
Q

How is vanocmycin used to treat meningitis?

A

poor pen without inflamed meninges so used as a second line for cephalosporin resistant by combining 3rd gen cephalosporin and vancomycin together

65
Q

What are the side effects of vancomycin?

A 
nephrotoxicity
red man syndrome
ototoxicity
phlebitis
hypersensitivity, skin rashes, neutropenia
66
Q

What is the use of fosfomycin?

A

uncomplicated UTIs caused by E. coli and enterococcus

67
Q

What are the side effects of fosfomycin?

A

headache, diarrhea, nausea, vaginitis

dizziness, rash

68
Q

What is the mechanism of bacitracin?

A

interferes with cell wall syntehsis by interfereing with carrier that moves early wall components through membrane

69
Q

What is bacitracin used for?

A

topical only and used only against the gram positive spectrum

70
Q

What is the side effect of bacitracin?

A

allergic dermatitis

71
Q

What are drugs that target cell membrane?

A

polmyxin B and E

daptomycin

72
Q

What is the mechanism of polymyxin B?

A

branched chain decapeptides; act as cationic detergents taht binds LPS in outer membrane of gram negatives

73
Q

What are the side effects of polymyxin B?

A

topical use-few probelms, allergies

systemic use-potential for serious nephrotoxicity and neurotoxicity

74
Q

What is the mechanism of daptomycin?

A

binds to bacterial cytoplasmic membrane causing rapid membrane depolarization
stops essential metabolic and catabolic steps
rapidly bactericidal

75
Q

What is the spectrum of daptomycin?

A

gram positive spectrum

no cross resistance

76
Q

What is the use of daptomycin?

A

for complicated skin and skin structure infections
MRSA
Streptococcus
Enterococcus (vancomycin-susceptile only)
bacteremia
not for pneumonia

77
Q

What are the side effects of daptomycin?

A

nausea, diarrhea, GI flora alterations
including C. Diff enterocolitis
muscle pain and weakness
fever, headache, rash, dizziness, injection site rxn

78
Q

What is the mechanism of action of quinolones?

A

inhibits alpha and possibly beta subunit of DNA gyrase, thereby interfering with control of DNA winding
bactericidal

79
Q

How is killing by quinolones best predicted?

A

AUC24/MIC
more frequent doses
more drug per dose
longer half life

80
Q

What is the norfloxacin used for?

A

prototype quinolone for urinary infections

limited use at other sites

81
Q

What is ciprofloxacin used for?

A 
useful for infections at many sites
UTI
infectious diarrhea
bone and joint infections
skin infections
not best choice for gram positive infections
chlamydia
haemophilus
anthrax
82
Q

What is better against gram positive than cirpofloxacin used for?

A

moxifloxacin and levofloxacin

83
Q

Quinolones administered how?

A

oral some also IV

84
Q

How is quinolones distributed?

A

many fluorinated drugs are well-distributed

some and the nonfluorinated agents achieve therapeutic concentration onsly in urinary tract

85
Q

What are the quinolones side effects?

A 
nausea, vomitting, abdominal paiin
rare seizure
dizziness, headache, restlesness, depression
rashes, some serious potentially fatal
EKG iregullariteies, arrythmias
peripheral neuropathy; rapid onset
children cartilage damage cautioned
precautions those with seizure disorder and pregnancy
arthropathy-tendon rupture
86
Q

What is the mechanism of nitrofurantoin?

A

itroreductase enzyme converts tehse drugs to reactive compounts whch ccan damage DNA

87
Q

What does nitrofurantoi treat?

A

UTI lower only not renal

88
Q

What are teh side effects of nitrofurantoin?

A 
nausea, vomiting, diarrhea
hypersensitivity, fever, chills
peripheral neuropathy
acute and chronic pulmonary reaction
acute and chronic liver damage
granulocytopenia, leukopenia, megaloblatic anemia
acute hemolytic anemai
89
Q

What is the mechanism of rifampin?

A

binds to and inhibits RNA pollymerase Beta
inhibits RNA synteshis
bacteriacidal

90
Q

What is rifampin used for?

A

tuberculosis
meningitis prophylaxis
difficult infections

91
Q

Wha are the side effects of rifampin?

A

serious hepatotoxicity
strongly induces many other enzymes including CYP3A
orange color to excrement
may others

92
Q

What is the mechanism of fidaxomicin?

A

non competitive inhibitor of RNA polymerase

93
Q

What is fidaxomicin used for?

A

clostridium dif infxn; 3rd line

bacteria cidal

94
Q

What is the spectrum of fidaxomicin?

A

narrow gram pos mainly clostridium
oral admin, poorly absorbed
limited impact on normal GI flora

95
Q

What are fidaxomicin side effects?

A

GI upset, GI bleed, neutropenia

96
Q

What is the mechanism of action of metronidazole?

A

anaerobes reduce the nitro group resuting produc damages and disrrupts DNA
bacteriacidal

97
Q

What are the uses of metronidazole?

A

anaerobes
C. diff enterocolitis
H. pylori combo therapy
bacterial vaginosis

98
Q

What are the side effects of metronidazole?

A

nausea, vomiting, anorexia, diarrhea
transient leukopenia, neutropenia
thrombophlebitis after IV infusion
bacteria and fungal superinfection

99
Q

Aminoglycosides are unique how?

A

only protein synthesis inhibitors that are bactericidal

100
Q

What is teh mechanism of aminoglycosides?

A

transported into bacteria by energy-requirng aerobic procesc

bind to several ribosomal sites; stop initiation, cause mRNA misreading

101
Q

What is the primary use of aminoglycosides?

A

primarily for gram negative aerobic bacilli

poor activity against anaerobes

102
Q

How do you use aminoglycosides with gram positive bacteria?

A

cell wall inhibitors plus aminoglycosides lead to increased permeability and death of aminoglycosides

103
Q

Aminoglycosides have post-antibiotic effect?

A

sustained activity for several hours after aminoglycoside concentraion ahd dropped below effective levels
concentration dependent killing

104
Q

Aminoglycosides are restricted to what type of infections?

A

serious infections

105
Q

What are teh three aminoglycosides?

A

gentamicin, tobramycin, amikacin

106
Q

What ist he choice agent for gentamicin and tobramycin resistant straing?

A

amikacin

107
Q

What are the two classic side effects of aminoglycoides?

A

nephrotoxicity-mostly reversible
ototoxicity-mostly irreversible
neuromuscular blockade-less common; associated with intraabdominal infection

108
Q

Tetracyclines are what type of mechanism?

A

transported into cells by protein carrier binds aminoacyl-tRNA to 30S ribosomal subunit

109
Q

What is teh most common for of resistance to tetracyclines?

A

drug efflux pumps, resistance to one tetracycline implies resistance to all

110
Q

Use of tetracycline is the preffered agent for what?

A 
unusual bugs
rickettsia
lyme disease
chlamdia, mycoplasma, ureaplasma(atypical)
chancroid (haemophilus ducreyi)
111
Q

What are the two tetracyline examples?

A

doxycycline and minocycline

112
Q

What is doxycycline used for?

A

alternative for penG-sens syphilis

uncomplicated N. gonorrheae

113
Q

What is unique about doxycycline among tetracyclines?

A

has the least affinity for calcium

114
Q

Binding calcium does what to tetracycline?

A

inhibits it’s absorption

115
Q

What are the side efffects of tetracycline?

A 
GI disturbance
photosensitization
cadida infection
teeth discoloration- avoid use in you children
contraindicated in pregnancy
116
Q

Tigecycline is used when?

A

increased risk of death makes it a last line drug when nothing else is working

117
Q

Chloramphenicol has what mechanism of action?

A

binds 50S subunits to prevent protein use

118
Q

Chloramphenicol has what major side effect and used for what?

A

very serious can result in bone marrow suppression
alternative in those with serious cephalosporin meningitis
brain abcesses (often anaerobes)

119
Q

What are the major side effects of chloramphenicol?

A

Gray baby
bone marrow suppression
-fatal aplastic anemia (1 in 30000)
optic neuritis and blindness

120
Q

What are the macrolides?

A

erythromycin, clarithromycin, azithromycin

121
Q

What is the mechanism of macrolides?

A

bind 50S subunit and blocks translocation

122
Q

What is erythromycin used for?

A

primarily against gram positive
2nd line against strep in allergic
also effective against atypical bugs
-mycoplasma, chlamydia, brdetella, legionella

123
Q

What is erythromycin side effects?

A

rapid vomitting and nausea from enhacned GI motility
inhibits CyP3A metabolism
increased risk of arrythmias and cardiac arrest
-doubles risk on its own
5 fold on other CYP3A inhibitors

124
Q

What is Clarithromycin role?

A

most expensive macrolide; similar mechanism
also some CV risk
prolongs QT interval
but less GI motility, wider antibacterial spectrum

125
Q

What is the use of clarithromycin?

A 
same as erythromycin plus:
haemophilus influenzae, moraaxella
pneicillin resistant strep pneuoniae
atypical mycobacteria
liscened for heliobacter pylori
3 drug combos are becoming standard
126
Q

Heliobacter approved eradication include what?

A

combination with 2 antibiotcs + acid blocker most efective combination

127
Q

What is the role of azithromycin

A

very common for outpatient respiratory tract infections

also genita infections-chlamydia and 2nd line for N. gonorrhea

128
Q

Azithromycin has what adverse reactions?

A

fewer
still QT prolongation
fewer effects on CYP3A4

129
Q

What is clindamycin mechanism of action?

A

binds to 50S ribosomal subunit

130
Q

What is clindamycin famous for?

A

causing C. diff infections

131
Q

What is the use for clindamycin?

A

Strep and MSSA (gram pos cocci)
suppresses bacterial toxin production
many anaerobes including bacteroides flragiles

132
Q

What are the side effects of clindamycin?

A

liver damage
colitis
GI problems

133
Q

What is the mechanism of linezolid?

A

binds to 50S ribosomal subunit and interferes with formation of 70S initiation complex

134
Q

Linezolid is used for what?

A 
gram positive spectrum
Vancomycin resistant Enterococcus
Staph Aureus including MRSA
Strep
Nosocomial pneuomniae
135
Q

What are the side effects of linezolid?

A

non-selective inhibitor of MAO
diarrhea, eneterocolitis
headache, nausea/vomiting
bone marrow suppresion

136
Q

What are the anti-folates?

A

inhibit folate synthesis
sulfamethoxazole
sulfadiazine
trimethoprim

137
Q

What is mechanism of action of sulfonamides?

A

competitive analogs of p-aminobenzoic acid, a precursor in folate synthesis

138
Q

Sulfonamides are used how?

A

wide spectrum but high resistance

used in combination with others

139
Q

What is silver sulfadiazine used for?

A

used topically for infection prevention in burn pts

large amount of its effect is silver

140
Q

What are the side effects of sulfonamides?

A 
hypersensitivity
sunlight makes rashes worse
renal damage (crystalluria)
potentiate actions of other drugs
inhibit CYP2C9 therefore ave an effect on warfarin
141
Q

Sulfonamides plus trimethorpim has waht sort of effect

A

-cidal effect; unusual bc its two statics

142
Q

what is trimethorprim used for?

A 
in combo wit sulfamethoxazole
used for uncomplicated UTIs
-E.coli and coagulase negative staph
upper respiratory tract, ear infections
GI infections
1st line in pneumocytis jiroveci
143
Q

What are the side effects of the TMP/SMX side effects?

A

all of the sulfa side effects
bone marrow suppression
GI effects

144
Q

What is one common use of empiric therapy?

A

uncomplicated cstitis in nonpregnant women

Block7 (10 decks)

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