Exam 2 - Cushman/Erdman (Drug Classes) Flashcards Preview

Therapeutics V Spring 2019 (P3 Spring) > Exam 2 - Cushman/Erdman (Drug Classes) > Flashcards

Flashcards in Exam 2 - Cushman/Erdman (Drug Classes) Deck (267):
1

Beta Lactam Characteristics: "The 6 things"
They all have the same MOA --- what is it?

inhibit cell wall synthesis

2

Beta Lactam Characteristics: "The 6 things"
They all have the same MORs --- what are they

beta lactamase degradation, PBP alteration, decrease penetration

3

Beta Lactam Characteristics: "The 6 things"
They are (bactericidal or bacteriostatic) in a (time or concentration) dependent matter

*one exception is ___________

bacteriocidal; time dependent


exception: they are NOT bacteriocidal to enterococcus (they are only bacteriostatic to it)

4

Beta Lactam Characteristics: "The 6 things"
They have a (short or long) half life?

short!! (< 2 hours!!!)

5

Beta Lactam Characteristics: "The 6 things"
They are primarily excreted _________
The exceptions are what?

excreted renally mainly

exceptions are Nafcillin, Oxacillin, Ceftriaxone, and Cefoperazone

6

Beta Lactam Characteristics: "The 6 things"
All have Cross-allergenicity (except _______)

aztreonam

7

what are the 4 main groups of beta lactam abx

Penicillins
Cephalosporins
Carbapenems
Monobactams

8

PCNs:
inhibit PBPs and thus inhibit the final ________ step of ________ synthesis

final transpeptidation step
peptidoglycan synthesis

9

What are common bugs that are resistant to penicillins due to alteration in structure of PBPs?

MRSA (methicillin resistant staphylococcus aureus)
and
PRSP (penicillin resistant streptococcus pneumoniae)

10

What drugs are the natural penicillins

Aqueous Pencillin G
Benzathine Penicillin G
Procaine Penicillin G
Phenoxymethyl Penicillin (aka Penicllin VK)

11

what drugs are the Penicillinase Resistant Penicillins

Nafcillin
Oxacillin
Methicillin
Dicloxacillin
Cloxacillin

12

what is another name for the Penicillinase Resistant Penicillins

Antistaphylococcal PCNs

13

why were the Penicillinase Resistant Penicillins developed?

to overcome the penicillinase enzyme of staphylococcus aureus

14

what drugs are aminopenicillins

ampicillin
amoxicillin

15

what drugs are carboxypenicillins

ticarcillin
carbenicillin

16

why were the aminopenicllins developed?

developed in response to the need for agents with some gram negative activity

17

why were the carboxypenicillins developed?

developed in response to the need for agents with some gram negative activity

18

what drugs are ureidopenicillins

Piperacilin, Azlocillin, Mezlocillin

19

why were the ureidopenicillins developed?

developed in response to the need for agents with some gram negative activity

20

what drugs are beta lactamase inhibitors

sulbactam, clavulanate, tazobactam, avibactam

21

PCN and Absorption:
Many penicillins are degraded by _______
Lower concentrations are seen with PO PCN -- therefore they should only be used when the infection is _________

degraded by gastric acid

mild - moderate infections

22

PCN and Distribution:
True or False: PCNs and beta lactamase inhibitors get into the CSF well very well

False!! beta lactamase inhibitors do not

PCNs will get into CSF when doses are high enough!!

23

PCN and Elimination:
PCNs are usually eliminated by the kidney what PCNs are NOT eliminated by the kidney and how are they eliminated

Nafcillin and Oxacillin are eliminated by the LIVER

24

what PCN preparations have a heavy sodium content
*careful with CHF and Renal Insufficiency patients

sodium PCN G
Nafcillin
carbencillin
Ticarcillin (most per gram)
Piperacillin

25

which PCN type should definitely NOT be used for staph infections

natural penicillins (so much resistance has been created against them!!)

26

what PCN types are possibly good for Pseudomonas infections

Carboxypenicillins and Ureidopencillins

27

What are some PCN ADEs?

Neurologic
Hematologic
GI
Interstitial Nephritis

28

What are the Neurologic PCN ADEs?

Irritability, jerking, confusion, and SEIZURES

(seen a lot when renal insufficiency and high doses)

29

What are the hematologic PCN ADEs?

Neutropenia, Thrombocytopenia!!
Hemolysis or anemia

30

Neutropenia and Thrombocytopenia from PCN usually happens with ______ therapy and is (reversible or irreversible?) with discontinuation

happens with prolonged therapy > 2 weeks
is reversible with discontinuation

31

what is interstitial nephritis

immune mediated damage to the renal tubules -- seen by an abrupt increase in SCr
and can lead to RENAL FAILURE

32

Interstitial nephritis seen most commonly with what PCNs?

Methicillin (why removed from market)
and
Nafcillin

33

what drug(s) are monobactams?

aztreonam

34

what drug(s) are 1st gen cephalosporins (that we need to know)

Cefazolin
Cephalexin

35

what drug(s) are 2nd gen cephalosporins (that we need to know)

Cefuroxime
Cefoxitin
Cefotetan
Cefprozil

("Fur" on a "Fox"
and "fot" the "proz"?
IDK?)

36

what drug(s) are 3rd gen cephalosporins (that we need to know)

Ceftriaxone
Ceftazidime
Cefpodoxime

37

what drug(s) are 4th gen cephalosporins (that we need to know)

Cefepime

38

what drug(s) are the Anti - MRSA cephalosporins (that we need to know)

Ceftraroline

39

what drugs are carbapenems

Imipenem, Mereopenem, Ertapenem, Doripenem

40

what are examples of Cephalosporins with beta lactamase inhibitors

Ceftolozane-tazobactam
Ceftazidime-Avibactam

41

what is an example of carbapenem + a beta lactamase inhibitor

meropenem-vaborbactam

42

PCN vs Cephalosporins:
which has a 5 membered ring and which one has a 6 membered ring next to the beta lactam ring

and what does that difference cause

5 membered: PCN
6 membered: Ceph

the 6 membered ring provides some stability against beta lactamase enzymes

43

what are cephamyacins

a cephalosporin with a methoxy group at position 7 of beta lactam ring AKA the have activity against anaerobes like bacteroides!!! (aka the BDA - below diaphragm aneraobes)

44

Cephalosporins:
Time dependent or concentration dependent?
Bacteriostatic or Bacteriocidal?

time dependent
-cidal!!

45

1st Gen Cephs:
have the most activity against Gram (positive or negative) aerobes than compared to the other Gram type and when compared to other gens of ceph

positive

(out of all gens of Cephs -- 1st is best for Gram positive aerobes!)

46

As you go from 1st gen to 4th gen Cephs:
they lose _______ activity and gain _____ activity

also you gain ______ stability

lost Gram positive; gain Gram negative

gain beta lactamase stability

47

what gram negative aerobes does 1st gen cephs cover

PEK
(Proteus, E. Coli, Klebsiella)

48

cephamyacins are a part of what generation of cephalosporins

2nd gen

49

what drugs are cephamyacins

cefoxitin
cefotetan
cefmetazole

50

what gram negative aerobes do 2nd Gen cephs cover

HENPEK
Haemophilus, Enterobacter, Neisseria
+
(Proteus, E. Coli, Klebsiella)

51

Cephamyacins are useful due to their activity against (aerobes or anaerobes)

anaerobes!! like Bacteroides

52

What 2 drugs are the only cephalosporins that have activity against PRSP (penicillin resistant Streptococcus pneumoniae)

Ceftriaxone
Cefotaxime
*these are 3rd gen cephs!!

53

3rd gen Cephalosporins cover what gram negative aerobes?

HENPECKSSS
(Haemophilus, Enterobacter, Neisseria)
+
(Proteus, E. Coli, Klebsiella)
+
Citrobacter
+
Serratia, Salmonella, Shigella
and Pseudomonas!!!!!

54

3rd gen Cephs: good or poor activity against anaerobes

poor!!!
(2nd gens/cephamyacins are good for anaerobes - but not 3rd gen)

55

what 3rd gen cephs cover Pseudomonas??

Ceftazidime
Cefoperazone

56

the 4th gen ceph (_______)
has similar gram positive coverage as Ceftriaxone (a 3rd gen)
and similar coverage for gram negative aerobes as 3rd generation *most notably this 4th gen drug will cover what 3 bugs?

Cefepime;

3 bugs: Pseudomonas!! annnd
beta lactamase producing Enteroabcter and E. Coli

57

3rd gen or 4th cephs are pretty strong inducers of ESBLs/AmpC?

3rd gen or 4th cephs are weak inducers of ESBLs/AmpC?

strong inducers = 3rd gen

weak inducers = 4th gen

58

Ceftaroline:
it is an Anti _______ Cephalosporin

MRSA!

59

T or F: Ceftaroline will cover Pseudomonas

false!!!

60

The combo cephalosporins and beta lactamase inhibitors spectrum of activity:
Gram + coverage: cover against ______
Gram - coverage: cover against ______

+: streptococci
-: similar to Cefepime + some AmpC producing Pseudomonas!!

61

Overall cephalosporins will not be active against what 3 bugs?

MRSA (exept cetaroline)
Enterococcus
Legionella
C.Diff

62

T or F: None of the cephalosporins reach the CNS

false! some do!
(3rd and 4th gen parenteral ones do as well as parenteral cefuroxime)

63

what cephalosporings reach the CNS?

Parenteral Cefuroxime (a 2nd gen)
Parenteral 3rd and 4th gen cephs

64

What cephalosporins do NOT get eliminated by the kidneys

Ceftriaxone and Cefoperzone

65

What cephalosporin does NOT need to be redosed/supplemented post hemodialysis

ceftriaxone...

66

Most cephalosporins have a short half life around 2 hours - which one has a longer half life and how long is the half life

Ceftriaxone has a longer 1/2 life - it is around 8 hours and thus can be doses Q12h or Q24h!!!!

67

what ceph is drug of choice for surgical prophylaxis?

Cefazolin

68

T or F: 1st gen cephalosporins cannot reach CNS/should not be used for mennigitis

true

69

what ceph is used as a single IM dose for uncomplicated gonorrhea

ceftriaxone

70

Hypersensitivity rxns to cephalosporins occur most frequently in pts with PCN allergy --- cross reactivity rate is ___ - ___ %

5 - 15%

71

can you give a cephalosporin to someone with a PCN allergy?

give with caution if pt has had just rash/pruritis

if anaphylaxis rxn then NOOOO!!

72

Some cephalosporins have a NMTT side chain that can cause what two ADEs

hypoprothrombinemia (at higher risk for bleeding - bc low vit k production from bacteria in gut)
Disulfiram rxn (alcohol intolerance)

73

what are some hematologic ADEs of cephalosporins?
how do they happen and how to fix them?

Leukopenia, Neutropenia, Thrombocytopenia

occurs mainly in pts getting > 2 weeks of therapy - will be reversed when therapy is discontinued

74

what are some GI ADEs of cephalosporins?

biliary sludging (esp. ceftriaxone therapy)
N/V
transient liver enzyme increase
Pseudomembranous colitis

75

Can cephalosporins cause seizures?

Yepppp

76

Carbapenems - are they bactericidal or bacteriostatic?

bacteriocidal EXCEPT not for enterococcus

77

T or F: Carbapenems are currently the most broad spectrum abx

true

78

what drug class is drug of choice for ESBL and AmpC producing bacteria

carbapenems

79

which carbapenem does NOT cover pseudomonas

ertapenem

80

T or F: Carbapenem will cover anaerobes

true!!! they do super well for anaerobes too

81

What things to Carbapenems NOT cover

MRSA
C.Diff
Atypical Bacteria
Stenotrophomonas maltophilia

82

which carbapenem gets into CSF best?

meropenem

83

which carbapenem has the longest half life out of the 4 of them?

ertapenem (4 hrs)
compared to others of 1 hr 1/2 life)

84

T or F: only 2 of the 4 carbapenems need renal adjustment when renal dysfunction

false! all 4 do.....
(they would all be given AFTER hemodialysis because they would be removed)

85

Imipenem gets hydrolyzed by the kidneys by the ______ enzyme and can make it inactive/or maybe nephrotoxic.

DHP

86

Imipenem is given with a DHP inhibitor called __________ to protect against nephrotoxicity by preventing renal metabolism

cilastatin

87

Do carbapenems have cross reactivity to people with PCN allergies?

yes (same as cephs: 5 - 15%)

88

what are some CNS ADEs of carbapenems?

insomnia, agitation, confusion, dizziness, hallucinations, and depression
and SEIZURES

89

Aztreonam is active against which of the following?
Gram + aerobes
Gram - aerobes
Anaerobes

ONLY gram - aerobes!!

90

T or F: Aztreonam covers pseduomonas strains

true!! (it is a gram - aerobe!)

91

Does aztreonam enter the CSF?

yes

92

does aztreonam have the same hypersensitivity risk as cephs and carabapenems if pt has a PCN allergy

no!
aztreonam is ok if pt has PCN allergy

93

Gram Stain Results:
Gram + = _________ color
Gram - = ______ color

+ = purple
- = red

94

Gram - or gram + bacteria has a periplasmic space

negative

95

T or F: drugs can penetrate out layers of the cell wall in gram + bacteria effectively

true!!
cannot get through gram NEGATIVE (drugs use porins there)

96

Transpeptidase Reaction for Peptidoglycan making:
The enzyme creates a bridge between ______ and _____; the bridge normally consists of 5 _______ (a type of amino acid)

between L-Lys and D-Ala
5 glycine residues

97

MOA of Beta lactams:
Beta lactams inactivate the enzyme by _______ the transpeptidase ____ residue in the enzyme active site - this forms a stable product = inactivates the enzyme

acylating; serine residue

98

why do bacterial transpeptidases NOT catalyze reactions with host cell proteins?

humans do NOT have D-Ala amino acid residues

99

why are penicillins so reactive?

the beta lactam ring is 90 degrees/aka a square and that is not comfortable for the molecule...
the =O part is more like a ketone carbonyl because the Nitrogen next to it that could donate electrons and help is not at a good angle to donate electrons

100

Beta Lactamases:
How do they modify beta lactams?

cut open the ring -- the ring canNOT be fixed/put back together

101

Beta Lactamases:
When they inactivate beta lactams - is the enzyme stuck to drug or does the enzyme get regenerated?

it gets regenerated!! via water rxn

102

How do beta lactams cause allergenicity?

the abx act as a HAPTEN;
ACYLATE host cell proteins (this will cause a raise in antibodies)

103

T or F: you can structurally manipulate beta lactams to get rid of the allerginicity

false!!!
the allergenicity comes from the pharmacophore (aka cant change it or da drug wont work)

104

PCN Degradation:
when in acidic conditions - what are the degradation products
vs
when in basic conditions - what are the degradation products

acidic: benzylPENICILLENIC acid, benzylPENILLIC acid, and benzylPENICILLOIC acid

basic: benzylPENICILLOIC acid

105

T or F: hydrolysis of beta lactams is irreversible

true!!!

106

T or F: hydrolyzed penicillin products have some antibiotic activity

false!! no abx activity

107

What orgo nonsense can help stabilize penicillin from hydrolysis in acidic conditions

an ELECTRONEGATIVE substituent on side chain carbonyl will reduce the nucleophilicity of the side chain

108

PCNs that are hydrophillic or lipophillic will have high protein binding
and higher protein binding will cause ______ bioavailability

lipophillic;

lower bioavailability

109

PCNs are rapidly excreted by the renal route:
most of the excretion is by glomerular filtration or by tubular secretion

tubular secretion is the main mode

110

Tubular Secretion: two mechanisms - one for anions and one for cations: PCNs are anionic or cationic?

anionic

111

Since PCNs are anionic --- if the drug ______ is given with the PCN it will increase the half life of the drug by anion competition

probenecid

112

T or F: PCNs get into the CSF

true!

113

what drug(s) are glycopeptides

vancoymyocin

114

what drug(s) are streptogramins

Synercid (quinupristin-dalfopristin combo)

115

what drug(s) are oxazolidinones

Linezolid (Zyvox)
Tedizolid

116

what drug(s) are Lipopeptides

Daptomyocin

117

what drug(s) are Lipoglycopeptides

Tlavancin
Dalbavancin
Oritavancin

118

MOA of Vancomyocin

inhibits synthesis/assembly during second stage of cell wall synthesis by firmly binding to D-Ala-D-Ala aka will prevent cross-linking/elongation of peptidoglycan

119

MOA of Synercid

they both bind to the 50S ribosomal subunit to inhibit early and late stages of bacterial protein synthesis

120

MOA of the Oxazolidinones

bind to 50S ribosomal subunit byt eh 30S subunit = INHIBITS 70s initiation complex for PROTEIN SYNTHESIS

121

MOA of Daptomyocin

inserts its lipophilic tail into the cell wall and makes a transmembrane channel --> leakage of cellular contents and rapid depolarization of the membrane potential leading to inhibition of protein/DNA/RNA synthesis

122

MOA of Lipoglycopeptides

act a lot like vanco - they interfere with polymerization/cross linking of peptidoglycan by binding to D-Ala-D-Ala
ALSO oritavancin and telavancin have a lipophillic tail that can puncture a whole in the cell wall just like daptomyocin

123

MOR of vancomyocin

modification of the D-Ala-D-Ala vanco binding site of the peptide side chain of peptidoglycan precursors by expression of VanA gene (D-Ala-D-Ala --> D-Ala-D-Lac)

Also VISA happens due to thickening of peptidoglycan layer of the cell wall

124

MOR of Synercid

alteration in ribosomal binding site
- encoded by the erm gene

or enzymatic inactivation

125

MOR of vancomyocin: usually encoded by gene ______
vs
MOR of Synercid: usually encoded by gene ______

vanc: VanA
Synercid: erm

126

MOR of Oxazolidinones

alteration of ribosomal subunit target site (v rare)

127

MOR of Daptomyocin

rarely seen but due to altered cell membrane binding through loss of a membrane protein

128

MOR of Lipoglycopeptides

alteration in peptidoglycan terminus (especially VanA resistance) (aka D-Ala-D-Ala goes to D-Ala-D-Lac)
*seen with telavancin and dalbavancin (this mode of resistance has not seem to affect oritavancin)

129

PK Notes about Vancomyocin:
Bioavailabiity: Goor or Poor?
1/2 Life: short or long?
CSF Penetration?

awful bioavailability (like nothing absorbed systemically)
1/2 life ~ 6 - 8 hours but can be prolonged to 7 - 14 days in ESRD!!!
CSF: "variable penetration" - so no??

130

PK Notes about Vancomyocin:
Route of Elimination?
Renal adjustment?
Removed during hemodialysis?

Route: kidneys via glomerular filtration
Renal adjustment for sure
Vanc is somewhat removed by HD (such a big molecule but some is removed)

131

T or F: Vancomyocin is widely distributed into body tissues

true!! goes into adipose tissues a lot

132

when is it best to take a peak concentration of vanc and why?

ONE HOUR after end of infusion --- want to make sure the drug has had enough time to distribute

133

what weight should be used for dosing vanc and why/

use TBW (total body weight) because since drug goes into adipose tissue (need to account for the adipose tissue that may be present)

*exception if > 120 kg then may overdose them with vanc

134

PK Notes about Streptogramins:
Bioavailabiity: Goor or Poor?
1/2 Life: short or long?
CSF Penetration?

poor - only available parenteral
short 1/2 life (~ 1 hr..)
minimal penetration into CSF

135

PK Notes about Streptogramins:
Route of Elimination?
Renal adjustment?
Removed during hemodialysis?

hepatic clearance/CYP enzymes
no renal adjustment; need to liver adjustments tho
probs not removed with HD? (not sure)

136

PK Notes about Oxazolidinones:
Route of Elimination?
Renal adjustment?
Removed during hemodialysis?

elim: renal and non renal ways...
NO renal adjustment needed
Linezolid IS removed by HD; Tedizolid is NOT removed by HD

137

PK Notes about Oxazolidinones:
Bioavailabiity: Goor or Poor?
1/2 Life: short or long?
CSF Penetration?

amazing bioavailbility!! 100% for linezolid; 91% for tidezolid
t1/2 life: ~ 5 for linezolid; ~ 12 for tedizolid
CSF: ~30% get to brain.... :( ?

138

PK Notes about Daptomyocin:
Bioavailabiity: Goor or Poor?
1/2 Life: short or long?
CSF Penetration?

bioavail: ONLY IV
1/2 life ~ 8 hrs... IS PROLONGED IN RENAL DYSFUNCTION
CSF - not sure....

139

PK Notes about Daptomyocin:
Route of Elimination?
Renal adjustment?
Removed during hemodialysis?

eliminated by KIDNEYS
yes! renal adjust
not sure about HD

140

PK Notes about Lipoglycopeptides:
Route of Elimination?
Renal adjustment?
Removed during hemodialysis?

Elim: Kidneys for telvancin -- not super sure on others??
Adjustment for Telvancin and Dalbavancin
None removed by HD

141

PK Notes about Lipoglycopeptides:
Bioavailabiity: Goor or Poor?
1/2 Life: short or long?
CSF Penetration?

only given IV so probably poor
t1/2:Telvancin: ~ 8 hours; the other 2 are like over 200 hours.....
poor, poor CSF penetration`

142

Major ADEs of Vancomyocin?

Red Man Syndrome (infusion reaction)
Nephrotoxicity and Otoxicity
Dermatologic rxns
Hematologic
Thrombophlebitis

143

for Vancomyocin: what is the preferred route of administration for systemic infections

infusion/IV
NOT IM and NOT Oral

144

what is the DOC for C.diff colitis

ORAL vanc
(NOT IV!)

145

what is red man syndrome

a side effect seen with Vanc and Lipoglycopeptides; it is flushing.pruritis, and rash on face/neck/upper extremities; vasodilation/hypotension occurs

146

how to manage/treat red man syndrome

SLOW DOWN THE INFUSION! *For Vanc: MAX 15 mg per minute!
may give antihistamines/corticosteroids prior to infusion

147

Vanc Nephrotoxicty/Ototoxicty: seen mostly as (monotherapy or polytherapy?)

polytherapy!
esp. when a contaminant nephrotoxin or ototoxin

148

Vanc Nephrotoxicty/Ototoxicty:
Which one is reversible upon discontinuation and which one is irreversible

Nephro: reversible
Ototox: irreversible

149

what things can indicated nephrotoxicity from Vanc

transient elevated in BUN or SCr; sometimes granualr casts in the urine

150

what things can indicated ototoxicity from Vanc

tinnitus and high frequency hearing loss may precede onset of deafness

151

Vanc:
Time or Concentration Dependent?
Bactericidal or Bacteriostatic?
Fast or slow killer?

TIME
-Cidal
so damn SLOW

152

Synercid:
Time or Concentration Dependent?
Bactericidal or Bacteriostatic?

Time dependent
-static (can be cidal if right conditions...)

153

which gram positive abx is a CYP3A4 inhibitor

Synercid

154

what drug-drug interactions of concern with Synercid

Synercid = CYP3A4 inhibitor
Concerned about Statins, Cyclosporine, Tacrolimus, and Carbamazepine

155

Vanc or Synercid has a significant PAE

Synercid

156

ADEs of Synercid

Venous irritation/phelbitis
Myalgias/Arthralgias
GI (N/V/D)

157

Oxazolidinones:
Bacteriostatic or Bacteriocidal?

-static

158

Oxazolidinones or Daptomyocin has a PAE?

Oxazolidinones

159

Oxazolidinones:
which one is pulled of by Hemodialysis?

linezolid

160

Drug interactions with Oxazolidinones?
and why?

SSRIs!!
Oxazolidinones are weak inhibitors of monoamine oxidase -- can lead to increase risk of serotonin syndrome

161

ADEs of Oxazolidinones:

GI
CNS
THROMBOCYTOPENIA/ Anemia

162

ADEs of Daptomyocin

Myopathy/CPK elevation
Acute Eosinophilic Pneumonia***
GI/Headache
Injection site rxns
Rash

163

Drug interactions with Daptomyocin?

statins!! bc increased risk of myopathy

164

Lipoglycopeptides:
Which one(s) need renal adjustment?

Telavancin
Dalbavancin

(NOT oritavancin)

165

Lipoglycopeptides:
which one(s) have a super long 1/2 life

dalbavancin
oritavancin

166

ADEs of lipoglycopeptides

Red man Syndrome
Nephrtoxic
QTc Prolongation
Taste Disturbances

167

Pregnancy Category for Lipoglycopeptides

Telavancin

168

MOA of aminoglycosides:

inhibit protein biosynthesis - by binding to 30S ribosomal subunit
will impair proofread function --> nonsense proteins --> messes with cell wall function --> leakage

169

How are aminoglycosides taken up cellulary?

through cytoplasmic membrane active transport process
done by displacement of Mg2+/Ca2+ ions

170

3 Resistance Mechanisms of for aminoglycosides

-BACTERIA will inactivate aminoglycosides (via acetylation, adenylation, phosphorylation)
-Altered ribosomes
-Altered aminoglycoside uptake

171

Toxicities of aminoglycosides?

Ototoxicity and Nephrotoxicity
Curare-Like effects: Respiratory paralysis

172

Likelihood of aminoglycoside toxicity is increased when what?

if therapy > 5 days; if elderly, if renal function is impaired, and higher doses

173

T or F: Aminoglycosides and beta lactams should be administered in the same arm to increase synergistic effects

FALSE! do not put in same arm!! (they could mix and have a chemical rxn) also do not mix together in same solution!!

174

Aminoglycosides: typically used for Gram + or Gram - bacteria?

Gram -

175

what drugs are aminoglycosides

Amikacin
Tobramycin
Gentamicin
Neomycin
Paromomycin
Streptomyocin
Plaxomicin

176

What drugs are macrolides

Erythromycin
Clarithromycin
Azithromycin

177

what was the 1st drug that could be used to treat tuberculosis

Streptomycin

178

what aminoglycosides are orally used

Neomycin B
Paromomycin

179

why would oral aminoglycosides be used

suppress gut flora for travelers diarrhea and for GI surgery prophylaxis

180

Macrolide abx are known as macrocyclic ______

lactones

181

What is the sugar called that is important for activity for macrolides

desosamine sugar

182

what antibiotic is known as a polyketide?

macrolides

183

what is a polyketide?

alternating methyl groups!
due to sequential addition of propionate groups to a growing chain

184

MOA of Macrolides

inhibit bacterial protein synthesis: bind to the P site of the ribosome/inhibits translocation of peptidyl tRNA from "A" to "P" site

185

what are the 4 resistance mechanisms against Macrolides

- Lactone Ester hydrolase
- RNA methylase drug induced production (the A2058 adenine base gets methylated)
- A2058 site: the adenine gets mutated to a guanine (decreases binding by the abx insanely well)
- efflux pump

186

what drug class gets inactivated by acidic conditions and turns into a ketal formation

Macrolides

187

Why is oral erythromycin put in an enteric coated tablet?

to prevent it from getting degraded by acidic conditions

188

The ketal reaction product form erythromycin in an acid environment is inactive and causes what side effect

GI cramping

189

which macrolide is not possibly able to be made into the inactive ketal shape and why

azithromycin because the O= is actually a N=CH3 (aka not possible... bc orgo science)

190

main route of erythromycin elimination

demethylation by the liver

191

drug interactions for macrolides

they inhibit CYP3A...
thus Drug interactions with CBZ, cyclosporine, disopyramide, quinidine, theophylline, digoxin

192

Odd side effects of Macrolides

Stevens Johnson Syndrome
Reversible cholestatic hepatitis --> jaundice
Pyloric Stenosis in kids that mothers used it while pregnant

193

Aminoglycosides (AGs):
T or F: need to individually dose for every patient

true (bc narrow therapeutic index)

194

AGs:
(polar or non polar) compounds and thus are (soluble or non soluble) in water

polar;
soluble

195

AGs:
good or poor oral aborption?
good or poor CNS penetration?
good or poor lung penetration?

poor and poor and poor (because they are so polar!!)

196

what drugs are aminoglycosides?

Gentamicin
tobramycin
Amikacin
Streptomycin

197

MOA of AGs?

irreversibly bind to 30s ribosomal subunit = stop protein synthesis

198

AGs:
Slow or fast killers?
Bacteriocidal or Bacteriostatic?
Time or Concentration dependent killer

so fast!!
-cidal!
concentration

199

AGs:
Get through outer membrane of Gram negative cells via porins, once in the periplasmic space - how do they get across the inner membrane?

get through via MEMBRANE potential/ energy dependent

200

AGs:
getting through the inner membrane in gram negative cells require ________ and ______ (thus they are not helpful for ________ bugs)

require: energy and OXYGEN
since needs Oxygen - not good for ANAEROBES

201

AGs:
inner membrane transport requires energy and thus is the rate limiting step:
what things can IMPAIR transfer across the membrane

hyperosmolarity, divalent CATIONS, low pH (more H+), or anaerobiasis
anything that makes the inside of the cell more positive will hinder transport..

202

MOR for AGs?

Synthesis of AG modifying enzymes (plasma mediated)
Alteration in ribosomal binding sites (rare)

203

Which aminoglycoside is "usually" not affected by AG modiyfing enzymes

amikacin

204

why is the MOR of alteration in ribosimal binding sites rare

because the AGs bind to multiple sites

205

Pk/PD parameter for AGs?
and the goal value?

PEAK: MIC;
10:1 is optimal

206

AGs can NEVER be used alone for what infections?

when Gram + aerobes - NEVER US ALONE - dose with cell active agents

207

AGs should use higher doses for what kinds of infections?

for Gram - aerobes

208

AGs do not cover what types of bugs at all?

anaerobes

209

Streptomyocin will cover what type of bacteria?

Mycobacteria - TUBERCULOSIS

210

AGs have synergy with what agents?

cell wall active agents: beta lactams and vanco

211

T or F:
AGs have PAE

truee

212

what two patient variables are important for AG dosing

Volume of distribution
&
Clearance

213

why should IM injections of AGs NOT be used in critically ill pts

critically ill pts = hypotensive = no good perfusion the muscle to disperse the drug

214

T or F:
AGs distributes heavily to the adipose tissue

false!!!
goes to extracellular fluid more NOT adipose tissue (or CSF or sputum)

215

For AGs: TBW or IBW/LBW should be used

IBW! (use AdjBW if > 130% if IBW)
TBW is for Vanc

216

for AGs: use a higher of lower Vd when patient has edema (HF, CKD, hepatic ascites patients)

higher Vd: more fluid = higher Vd!

217

T or F:
AGs do not renal adjustment

false!! they do

218

T or F:
Give supplemental AG doses post Hemodialysis

trueee

219

what AGs are good for Gram negative aerobic bacteria
vs
what AGs + are good for enterococci, viridans streptococci, staphylcocci (aka Gram +)

Negative: Amikacin, Gentamicin, Tobramycin

Positive: use Gentamicin or Streptomycin WITH a cell wall active agent!!

220

ADEs with AGs?

nephrotoxicty and ototoxicity!!!

221

what are the risk factors of getting nephrotoxicity or ototoxicity with AGs

PROLONGED TROUGH CONCENTRATIONS
prolonged therapy (> 2 weeks)
underlying renal insufficiency
advanced age
hypovolemia
use of contaminant nephrotoxins or ototoxins

222

what drugs contaminant drugs could cause ototoxicty with AGs

Loop diuretics - furosemide
Vancomyocin

223

what drugs contaminant drugs could cause nephrtoxicty with AGs

vancomyocin
amphoterocin B
cisplatin
CT contrast

224

what drugs are macrolides

erythromycin
azithromycin
clarithromycin

225

the chemical modifications for clarithromycin and azithromycin have led to what improvements when compared to erythromycin

- better tolerated by patients
- enhance spectrum of activity
- improve tissue penetration
- longer elimination 1/2 lives

226

MOA of Macrolides?

reversibly bind to 50S ribosomal subunit: will inhibit protein synthesis

227

Macrolides:
time or concentration dependent?
bacteriocidal ot bacteriostatic?

time
-static!

228

MOR of Macrolides?

active efflux by "mef" gene
alteration in binding site by "erm" gene

229

the erm gene causes resistance via what mechanism

methylation to 50s binding site/altered ribosomal binding site

230

when the erm gene is active - what drugs are affected by resistance

macrolides
clindamycin
synercid
(bc all bind to 50S binding site)

231

Macrolides:
what notable organisms do they NOT cover

NOT PRSP, MRSA< or Enterobacteriaceae

232

what 3 drug classes DO cover atypical bacteria

Fluroquinolones
macrolides
tetracyclines

233

T or F:
Macrolides cover anaerobes

true!
"above the diaphragm"

234

which macrolide(s) have lower bioavailability when food is present

which macrolide(s) bioavailability is not affected if food is present

lower bioavail: erythromycin

not affected: clarithromycin, azithromycin

235

Macrolides:
Get into CSF well?
Get into tissues well?
Get into serum/systemic system well?

CSF: NO
Tissues: YES
Serum: NO --> NOT GOOD FOR BACTEREMIA

236

Macrolides:
which macrolide(s): needs renal adjustment when CrCl < 30 mL/min

renal: clarithromycin

237

Macrolides:
which macrolide(s): are CYP450 inhibitors

erythromycin
clarithromycin

238

Macrolides:
which macrolide(s): is NOT known to be associated with CYP450 drug-drug interactions

azithromycin

239

ADEs of Macrolides:

GI: epigastric distress (like acid burn)
Cholestatic hepatitis
Thrombophlebitis/infusion site irritaiton
Allergic Rxns
Ototoxicity
QT prolongation

240

Macrolides:
which macrolide causes the worse epigastric pain

erythromycin

241

what drugs will have the serum levels increase if taken at the same time as erythromycin or clarithromycin

Theophylline
Carbamazepine
Valproate
Cyclosporine
Digoxin
Phenytoin
Warfarin

*if see these drugs -- ok to use AZITHROMYCIN THO

242

T or F:
macrolides cover atypical bugs

true!!

243

what drugs are Fluroquinolones (FQs)

Ciprofloxacin
Levofloxacin
Moxifloxacin
Delafloxacin

244

Original prototype of the FQs

nalidixic acid

245

MOA of FQs

binding/inhibiting bacterial topoisomerases II and IV

topo II = gyrase

246

FQs:
Gram negative bacteria inhibited by primary target of ________
vs
Gram positive bacteria inhibited by primary target of ________

negative: gryase/topo II


positive: topo IV

247

MOR of FQs:

alteration in binding sites
active efflux
alteration in cell wall permeability
cross resistance is seen with FQs

248

FQs:
which FQ(s) are older?
which FQ(s) are newer/"respiratory"

older: ciprofloxacin
newer/respiratory: levofloxacin; moxifloxacin,

also Delafloxacin is new and exists

249

Ciprofloxacin:
better for gram positive or negative aerobes

gram NEGATIVE

250

FQs:
which FQs(s) cover MRSA

ONLY delafloxacin

251

FQs:
which FQ(s) cover PRSP

ALL
except CIPRO!!!

252

FQs:
which FQ(s) cover Pseudomonas aeruginosa

Cipro, Dela, and Levo

253

which FQ does NOT cover pseudomonas

moxifloxacin or gemifloxacin

254

T or F:
FQs have little affect on atypical bacteria

FALSE!
they are super good for atypical;

255

FQ(s):
slow or rapid killing?
time or concentration dependent?
PAE - yes or no?

RAPID!!
Concentration
yes, PAE

256

FQ(s):
poor or good bioavailability

good

257

FQ(s):
do they get into the CSF?

yes --- when meninges are inflamed

258

T or F:
FQs are not good for UTIs

FALSE! they are great for them
(EXCEPT moxi and gemi do not get into the urine enough)

259

FQ(s):
Renal adjustment - yes or no?

yes
*cipro and dela have both renal and hepatic elimination

260

FQ(s):
Removed by HD- yes or no?

NOOOO

261

ADEs of FQs

GI - CDF
Neurologic: Seizures AND PERIPHERAL NEUROPATHY
QT prolongation
Articular damage -- avoid in KIDS and pregnant/breastfeeding pts
Tendonitis/Tendon Rupture
(Phototoxicity --- for weird FQs tho)

262

what cardiac related reasons should FQs be used with caution

hypokalemia
concomitant use of amiodarone/sotalol (antiarrhythmics)
preexsiting QT prolongation

263

Drug interactions for FQs?

divalent/trivalent cations ("ZICAM" - zinc, iron, Ca2+, Al, Mg2+, antacids, sucralfate (has Aluminum), enteral feeds
warfarin

Theophylline and cyclosporine -- only with CIPRO

264

what is the issues with warfarin and FQs

increasing bleeding risk/longer prothrombin time

265

what are the two drug interactions for FQs that is really only with cipro

theophylline
cyclosporine

266

why are divalent/trivalent cations a problem for FQs

they chelate to the drug and prevent them from working

267

how to get around the divalent/trivalent cation drug interaction

take FQ 2 hours before other drugs
(best to take FQ first -- because abx are best)
or take FQ 2 - 6 hours after these agents