Exam 2 - Cushman/Erdman (Drug Classes) Flashcards
1
Q
Beta Lactam Characteristics: “The 6 things”
They all have the same MOA — what is it?
A
inhibit cell wall synthesis
2
Q
Beta Lactam Characteristics: “The 6 things”
They all have the same MORs — what are they
A
beta lactamase degradation, PBP alteration, decrease penetration
3
Q
Beta Lactam Characteristics: "The 6 things" They are (bactericidal or bacteriostatic) in a (time or concentration) dependent matter
*one exception is ___________
A
bacteriocidal; time dependent
exception: they are NOT bacteriocidal to enterococcus (they are only bacteriostatic to it)
4
Q
Beta Lactam Characteristics: “The 6 things”
They have a (short or long) half life?
A
short!! (< 2 hours!!!)
5
Q
Beta Lactam Characteristics: “The 6 things”
They are primarily excreted _________
The exceptions are what?
A
excreted renally mainly
exceptions are Nafcillin, Oxacillin, Ceftriaxone, and Cefoperazone
6
Q
Beta Lactam Characteristics: “The 6 things”
All have Cross-allergenicity (except _______)
A
aztreonam
7
Q
what are the 4 main groups of beta lactam abx
A
Penicillins
Cephalosporins
Carbapenems
Monobactams
8
Q
PCNs:
inhibit PBPs and thus inhibit the final ________ step of ________ synthesis
A
final transpeptidation step
peptidoglycan synthesis
9
Q
What are common bugs that are resistant to penicillins due to alteration in structure of PBPs?
A
MRSA (methicillin resistant staphylococcus aureus)
and
PRSP (penicillin resistant streptococcus pneumoniae)
10
Q
What drugs are the natural penicillins
A
Aqueous Pencillin G
Benzathine Penicillin G
Procaine Penicillin G
Phenoxymethyl Penicillin (aka Penicllin VK)
11
Q
what drugs are the Penicillinase Resistant Penicillins
A
Nafcillin Oxacillin Methicillin Dicloxacillin Cloxacillin
12
Q
what is another name for the Penicillinase Resistant Penicillins
A
Antistaphylococcal PCNs
13
Q
why were the Penicillinase Resistant Penicillins developed?
A
to overcome the penicillinase enzyme of staphylococcus aureus
14
Q
what drugs are aminopenicillins
A
ampicillin
amoxicillin
15
Q
what drugs are carboxypenicillins
A
ticarcillin
carbenicillin
16
Q
why were the aminopenicllins developed?
A
developed in response to the need for agents with some gram negative activity
17
Q
why were the carboxypenicillins developed?
A
developed in response to the need for agents with some gram negative activity
18
Q
what drugs are ureidopenicillins
A
Piperacilin, Azlocillin, Mezlocillin
19
Q
why were the ureidopenicillins developed?
A
developed in response to the need for agents with some gram negative activity
20
Q
what drugs are beta lactamase inhibitors
A
sulbactam, clavulanate, tazobactam, avibactam
21
Q
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 _________
A
degraded by gastric acid
mild - moderate infections
22
Q
PCN and Distribution:
True or False: PCNs and beta lactamase inhibitors get into the CSF well very well
A
False!! beta lactamase inhibitors do not
PCNs will get into CSF when doses are high enough!!
23
Q
PCN and Elimination:
PCNs are usually eliminated by the kidney what PCNs are NOT eliminated by the kidney and how are they eliminated
A
Nafcillin and Oxacillin are eliminated by the LIVER
24
Q
what PCN preparations have a heavy sodium content
*careful with CHF and Renal Insufficiency patients
A
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
| imipenem--relebactam
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
