ID exam 1 Flashcards
1
Q
xWhat is the goal of PK
A
increase effectiveness of treatment and/or decrease the side effects of the treatment
1
Q
____ is used to develop a model for designing individual drug regimens
A
PK
2
Q
What is PD
A
describe characteristics of interaction between substance, active site, and action (think antimicrobial affect on pathogen)
3
Q
What are the 2 categories that antimicrobial agents are classified as exhibiting
A
concentration dependent activity
non concentration dependent activity
4
Q
What is concentration dependent activity of antimicrobial agents
A
rate/extent of bactericidal activity increases with increasing antimicrobial concentrations
goal to optimize peak: MIC (AUC:MIC)
5
Q
What is non-concentration dependent activity of antimicrobial agents
A
rate/extent of killin do not increase with increasing antimicrobial concentration; instead it is increased by length of exposure
goal to optimize time concentrations remain above MIC (t>MIC)
5
Q
What is the blood culture pathway
A
collection: sample incubated
alert: machine alerts for positive culture
gram stain: tech performs STAT stain
incubation: culture plates
6
Q
What is the timeline for antimicrobial therapy
A
clinical illness
empiric antibiotics
culture processing
ID
targeted antibiotics
7
Q
What is the time frame for gram stain, blood culture, EMR view
A
gram stain: 24-48 h
blood culture: additional 24-48 h
EMR view: additional 24 h
8
Q
What are all the components of targeted antibiotics regimen
A
pathogen
indication/site of infection
dose
route
duration
9
Q
What is MIC (minimum inhibitory concentration)
A
Lowest antimicrobial concentration that inhibits visible bacterial growth
10
Q
What is MBC (minimum bactericidal concentration)
A
lowest antimicrobial concentration that results in microbial death
11
Q
Broth microdilution susceptibility testing
A
inoculation with various antimicrobial concentrations (standard for testing)
12
Q
What drugs focus on the T>MIC (time dependent killing) PD curve
A
beta lactams
tetracycline
oxazolidinones
13
Q
What drugs focus on the AUC/MIC PD curve
A
fluoroquinolones
macrolides
ketolides
glycopeptides
14
Q
What is the goal of beta lactams
A
keep serum concentrations above MIC for at least 40-70% of dosing interval
(max kill at 4-5x MIC, focus on T>MIC)
15
Q
What is the Vd, half-life, and protein binding of beta lactams, excretion
A
Vd: 0.15-0.3 L/kg
half-life: 1-2 hr
protein binding: 25% or less
excretion via glomerular filtration and tubular secretion
16
Q
Critically ill patients may have changed PK derangement what are these principles they effect
A
change in Vd
large volume of fluid resuscitation
vasopressor use
hypoalbuminemia
augmented renal clearance
17
Q
Pharmacy to dose (PTD) - vancomycin PK/PD
A
formal pharmacy consult for pharmacist managed dosing and policy directed management
18
Q
Therapeutic Drug Monitoring (TDM) - vancomycin PK/PD
A
assay procedures to determine drug concentrations in plasma, further interpreted and applied to develop safe and effective regimens
19
Q
What is the difference between C1 and C2 - vancomycin PK/PD
A
C1 peak (1-2 hr after end of infusion)
C2 trough (end interval concentration)
20
Q
What is AUC/MIC
A
integrated quantity of cumulative drug exposure for a defined period of time
average serum drug concentration during time period
21
Q
what is the goal AUC of vancomycin
A
target: 500 mcgh/mL
range: 400-600 mcgh/mL
(500-600 for MRSA, endocarditis, menigitis)
22
Q
Vancomycin MIC <1 and MIC >2 meaning
A
MIC >1 = 100% change of achieving goal AUC/MIC >400
MIC >2 mcg/mL - goal not achievable in patient with normal renal function
23
What is the trough level for vancomycin
15-20 mcg/mL
24
Vancomycin nephrotoxicity levels
AUC/MIC >400
trough <15 mcg/mL
25
Why is AUC in vancomycin a high variability
depends on dose and renal function
trough concentration explains 40% of inter0individual variability in AUC
26
For vancomycin what should the loading dose be in patients with severe infections
20-25 mg/kg
27
When to get trough level for vancomycin
30 min -1 hr prior to next dose
must be at least 6 hours after peak level
28
What is the semi-synthetic aminoglycoside
amikacin
(genta and tobra natural)
29
Aminoglycosides consists of _____ sugars joined by _______ bonds to an aminocyclitol nucleus
amino
glycosidic
30
MOA of aminoglycosides (gram negative only)
-inhibit protein synthesis by binding to 16S ribosomal rRNA of 30s ribosome (irreversible bond lead to PAE)
-cause cell damage by mistranslation and incorrect formation of polypeptides
31
Synergy in aminoglycosides
synergy: use with cell-wall active antibiotic to increase aminoglycoside uptake despite small doses
32
Amikacin is resistant to enzyme ____________
inactivation (remains stable against organisms resistant to genta/tobra)
33
Aminoglycoside ADME
a: polar
d: Vd 0.3 L/kg
m: n/a
e: urine, t1/2: 1-4 hr
34
Aminoglycosides are ______________ dependent drugs
concentration (higher peak = better effects) MIC 10:1
35
What is the aminoglycoside dose for hartford? urban-craig nomogram?
hartford: 7 mg/kg
urban-craig: 5 mg/kg
level drawn 8-12 hr after start of infusion
36
What are the common examples of antimicrobial resistance
MRSA
CRE (carbapenem-resistant enterococcus)
VRE (vancomycin-resistant enterococcus)
ESBLs (extended spectrum beta lactamases)
37
What is an efflux pump
antimicrobial actively pumped out of cell
38
What is entry inhibition
antimicrobial actively blocked from entering cell
39
Antimicrobial Resistance inactivation and target site modifcation
inactivation: breakdown of active drug
modification: active drug unable to elicit effect
40
What are gram negative pathogens commonly caused by
intra-abdominal infection (IAIs), urinary tract infections, ventilator-associated pneumonia (VAP), bacteremia
41
Beta-lactamases mechanism of resistance
cleave beta lactam ring to inactivate
ESBL are plasmid encoded
there are different types that are dependent on inactivation/hydrolysis
42
What is horizontal transfer of resistance
transfer of resistance genes from one organism to another
-transduction (bacteriophage/integron)
-conjugation (plasmid)
-transformation (chromosomal DNA/plasmid)
43
ESBLs may have the framework to hydrolyze/inactive all agents with ester/amide bond but what
this is not always the case
44
Efflux pumps/permeability
pumps are proteins w/in membrane that export antibiotics from intracellular matrix
outer membrane porins may decrease entry of antibiotic into cell
45
Target site modification: fluoroquinolone resistance and aminoglycoside resistance
fluoroquinolone resistance: target site protection/modification to alter agent binding
aminoglycoside resistance: alteration of ribosomal proteins that lead to high level resistance
46
Gram positive pathogens common cause
skin and structure infections, bacteremia, hospital/community acquired pneumonia
47
Staphylococci: plasmid-encoded beta lactamase nafcillin/cefazolin generally stable
inactivation
48
Staphylococci: PBP2a has low affinity for beta lactams (show MRSA)
target replacement
49
Staphylococci: leads to linezolid resistance often with other concomitant mutation
target modification
50
Staphylococci: repulusion of antibiotic due to increase in cell envelope charge
drug entry
51
Enterococci: rare-usually found in E. faecalis
inactivation
52
Enterococci: usually acquired resistance may differ depending on enterococcus spp
target replacement
53
Enterococci: reason why cephalosporins do not cover enterococcus spp
target modification
54
Enterococci: repulsion of antibiotic due to increase in cell envelope charge
drug entry
55
Streptococci: type of PBP will determine which beta lactam resistance pattern you will see
target modification
56
BioFire and rapid diagnostic gram negative bacteria
E coli
Pseudomonas aeruginosa
57
BioFire and rapid diagnostic gram positive bacteria
enterococcis faecalis
s. aureus
58
BioFire and rapid diagnostic yeast
candida albicans
candida glabrata
59
BioFire and rapid diagnostic antimicrobial resistance genes
methicillin resistance
-mecA/C
-MRSA
60
In a prospective audit and feedback you reports on the financial impact of interventions and feedback based on what 3 things
dose adjustments
alternative agents
cost of therapy
61
ID pharmacy in policy change
small steps
always identify key stakeholders
implement education and process change
takes time
62
Penicillin MOA
inhibit bacterial cell wall synthesis by binding to penicillin binding proteins
(half liver 1 hour, gets in CNS)
63
Time dependent killing of penicillins
Time > MIC
goal to keep serum concentration above MIC for at LEAST 50-60% OF DOSING INTERVAL)
64
Allergy for penicillin
range in severity
all penicillins may cause neutropenia, neurotoxicity, or renal injury (mainly nadcillin/oxacillin)
65
Cephalosporins MOA
inhibition of bacterial cell wall synthesis by binding to penicillin binding proteins
(half life 1-2 hr, CNS penetration)
66
Time dependent killing for cephalosporins
time > MIC
goal to keep serum concentration above MIC for at least 60-70% of dosing interval
67
Cephalosporins allergy
range in severity
less frequent than penicillins
low rate of cross reactivity especially with higher generations of 2-4
68
Cephalosporins adverse effects
GI
variable association with CDI
neutropenia, neurotoxicity, renal injury
local reactions are common
69
Carbapenems MOA
inhibition of bacterial cell wall synthesis by binding to penicillin binding proteins
(half life 1-2 hr, CNS penetration)
70
Carbapenems time dependent killing
time > MIC
goal to keep serum concentration above MIC for at least 40-50% of dosing interval
71
Carbapenems allergy
low incidence of allergy
minimal cross reactivity
neurotoxicity caution with seizure disorders in general anti epileptic drug drug interactions
72
Aminoglycosides MOA
inhibition of protein synthesis by binding to 30S subunit, leading to misreading in translation process (rapid bactericidal)
1-4 hr half life
73
What adverse effect of aminoglycosides can not be reversed
ototoxicity
(nephrotoxicity can happen and can be reversed)
74
Aminoglycoside concentration dependent killing
peak: MIX/AUC:MIC
goal to maximuze peak/min trough
75
Fluoroquinolones MOA
inhibition of bacterial topoisomerases leading to inhibition of DNA replication and transcription
(4-12 hr half life)
76
Topoisomerase II is gram ________ while Topoisomerase 4 is gram __________
negative
positive
77
Fluoroquinolones concentration dependent killing
AUC:MIC
goal to maximize AUC:MIC ratio based on organism (higher doses for gram negative organisms)
78
Fluoroquinolones adverse effects
GI
CNS
QT prolongation
hypo/hyperglycemia
tendonitis
increase aortic dissection
increase lft
interaction with cation
79
Macrolide MOA
inhibition of RNA dependent protein synthesis bind to 50S ribosomal subunit to prevent bacterial growth
(68-72 hr half life)
concentration dependent killing
80
Macrolide adverse effect
GI
LFT increase
potential headache
CYP3A4 inhibitors (drug-drug interactions with statin, warfarin, azithromycin inhibition weaker)
81
Lincosamide MOA
bind to 50S ribosomal subunit to prevent protein synthesis
half-life 3 hours
concentration dependent killing
82
Lincosamide adverse effects
GI
metallic tase
rash
83
Tetracycline MOA
bind to 30S ribosomal subunit to prevent protein synthesis
half life 12-24 h
concentration dependent killing
90-100 PO absorption
84
Tetracycline adverse effects
NVD
esophagitis
photosensitivity
rash
hepatotoxicity (rare)
deposition into teeth
85
TMP-SMX MOA
TMP: bind to dihydrofolate reductase to inhibit formation of folic acid
SMX: inhibit synthesis of dihydrofolic caid
Inhibit DNA synthesis
10 hr half life
90-100% PO absorption
time dependent killing
86
TMP-SMX adverse effects
rash, itching
bone marroe suppression
crystalluria of SMX component in renal tubules
hyperkalemia
caution with DDI: warfarin, anticonvulsants, ACE/ARB
87
Vancomycin MOA
form complex with d-ala-d-ala portion of peptide to prevent peptidoglycan syntheses
AUC: MIC PK
88
Vancomycin ADR
infusion related reaction
nephrotoxicity
ototoxity (rare)
89
Daptomycin MOA
bind to calcium and insertion into cell membrane causing rapid depolarization and cell lysis
8-10 hr half-life
urine secretion
AUC: MIC/ Peak: MIC
90
Daptomycin ADR
myopathies
CK elevation
injection site reaction
91
Linezolid MOA
inhibition of bacterial protein sysnthesis bind to 23S rRNA or 50S subunit to prevent translation complex
half life 5 hr
gets into CNS
92
Linezolid adverse effect
GI
myelosuppression
peripheral neuropathies
serotonin syndroms
93
Metronidazole MOA
intracellular reduction to produce reactive metabolites; damage DNA
half-life 8-10 hr
94
Metronidazole ADR
peripheral neuropathy
metallic taste
disulfiram reaction
95
Amphotericin B killing curve
concentration dependent killing
96
Amphotericin B Infusion Reaction
fever, chills, rigors, N/V, muscle pain
pre-medicate with NSAID, APAP 30-60 min before
(hypotension, bronchospasm, arrhythmia, anaphylaxis)
97
Liposomal amphotericin infusion reactions
Triad
-chest pain, dyspnea, hypoxia
-flank pain, ab pain, leg pain
-flushing, urticaria
Occurs within 5 minutes
-stop infusion
-give diphenhydramine
-slow infusion when re-challenged
98
Amphotericin B nephrotoxicity
tubular dysfunction and vasoconstriction of afferent arteriole
dose limiting toxicity
risk factors:
nephrotoxins, daily dose, cumulative dose, CKD
99
Amphotericin B nephrotoxicity prevention
saline loading with 500-1000 ml 0.9% NaCl before and after administering
adequate hydration
electrolyte correction
using lipid formulation when possible
100
Amphotericin B nephrotoxicity occurrence
Ambisome < Abelcet < Conventional
101
Azole classes
Imidazole (2 nitrogen)
-ketoconazole. topical
Triazoles (3 nitrogen)
-fluconazole, itrazonazole, voriconazole, posaconazole, isavuconazole
102
Azole class adverse effects
N/V
ad pain
headache
rash
hepatotoxicity
QT prolongation
103
Distribution of fluconazole
distributes well into CNS/ vitreous, urinary sources
104
fluconazole monitoring
DDI
QT prolongation
increase LFT
renal
GI
105
Itrazonazole administration
take with food, improves absorption with acid (avoid PPI)
take solution with empty stomach
106
Itrazonazole BBW
caution use in patients with CHF
107
Itrazonazole goal trough
0.5-1
possibily 5 in some literature
108
Voriconazole monitoring
trough levels
DDI
increase LFT
QT prolongation
GI toxicity
109
Voriconazole 30/30/30 rule
30% of patients, 30 min after dose, duration 30 min
abnormal vision, color vision change, photophobia, photopsia
effects subside within 1 week after stopping treatment
110
Recommended intake of fluoride
3-4 mg/d
111
Posaconazole monitoring
trough
DDI
BP
rigors
QT prolongation
112
Monitoring for isavuconazonium
QT shortening**
increase LFT
DDI
GI
electrolytes
113
Echinocandin PK/PD poor penetration in what
CNS
vitreous
urine
114
Echinocandin ADR
infusion related reaction
rash
hepatotoxicity
115
Epidemiology of beta lactam allergies
80% with IgE mediated lose sensitive after 10 years
10% of everyone have allergy reported
116
Caution of beta lactam allergies
avoid penicillin and cephalosporins with documented allergy
117
Inaccurate diagnosis of penicillin allergy
increase medical cost for patient and hospital
increase inappropriate antibiotic use
increase risk of adverse reaction
118
Penicillin cross reactivity
low cross reactivity with cephalosporin groups
has to do with side chain
119
Non professional APCs need a MHC class __ molecule coupled to a beta 2 microglobulin
1
120
The endogenous pathway uses proteosomes and is MHC class __
1
121
The exogenous pathway uses endosomes and is MHC class __
2
122
MHC 1 has 8-10 amino acids with 9 being the most common. MHC 2 has how many amino acids
13-25 (MHC class 2 are larger)
123
Non covalent drug peptide pharmacological interaction model for immune activation goes through the cell while non covalent drug peptide altered peptide repertoire model goes through what
it diffuses and does not have to go through the cell
124
Do quinolones inhibit cutting of DNA
no they inhibit the repair of DNA
125
What does topoisomerase IV do to DNA
relaxes DNA
126
What does topoisomerase II / DNA gyrase do
supercoil DNA
127
RecA causes the LexA repressor to cut itself up which frees the suppressed SOS gene. What does this mean
You activated an inhibitor of an inhibitor to make it work
128
What is the SOS system
Bacteria sees damage and repairs it (gains resistance against quinolones
129
Quinolones bind between the cut ends of DNA and cause what to happen
They do not allow the ends to come back together
130
SAR of quinolone: ketone and carboxylic acid group
essential for gyrase binding and bacterial transport
131
SAR of quinolone: R5 group
controls potency
G(+) activity
132
SAR of quinolone: fluorine
controls gyrase and antibacterial potency
133
SAR of quinolone: R7
controls potency spectrum and PK
134
SAR of quinolone: X
controls PK and anaerobe activity
135
SAR of quinolone: R1
controls potency
some effect on PK
136
SAR of quinolone: R2
close to gyrase binding site
137
What is the pH at which penicillin is stable
NONE
138
In penicillins the side chains slow down or speed up rate of decomposition
slow down rate
(pen G is the first pencillin)
139
Peptides are usually bad leaving groups except for which one
D-alanine transpeptidase
(D-ala-D-ala)
Penicillin is a suicide inhibitor
140
On Dicloxacillin what does the two Cl groups do
they provide steric bluk and stop the ring from spinning
141
Which is these are not an antibiotic: Clavulanic Acid, Sulbactam, Tazobactam
None of them are because none of them have a side chain (dont have amide side chain)
142
How many places can penicillin vary? How many places can cephalosporin vary?
1
2
143
What are the two important counseling points of cephalosporin MTT group
inhibit vitamin K activation (risk of bleeding)
disulfiram like reaction with alcohol (do not drink 3 days before taking and 3 days after taking)
--because of side group
144
Why is there a combination of imipenem and cilastatin
imipenem cause kidney problems in renal tubules
cilastatin helps prevent damage
145
Why is monobactam an inhaler
there is poor absorption from gut
(used for cystic fibrosis)
146
Transfer RNA comes into which site
A site
blocks tRNA binding (tetracyclines)
inhibit translocation (macrolides, clindamycin)
147
Why don't you take doxycycline with calcium
It will cause the drug to not be absorbed
(almond milk, cow milk, etc. NONE)
148
How long is azithromycin in its active form
100% of the time
149
Erythromycin has a ketone in the 9 position and has 6, 12 hydroxy groups what does this have to do with ketals
they have a hemi ketal which can not bind to ribosome to inhibit it
will eventually form a full ketal
Azithromycin lacks a ketone so it does not have this intermediate
150
What are the beta lactam antibiotics
penicillins
cephalosporins
monobactams
carbapenems
151
Beta lactam MOA
interfere with peptidoglycan layer (mainly interrupt gram positive layers)
152
Penicillin binding proteins (PBPs)
High molecular weight PBP (greater than 50 kD) are sensitive to both PCNs and cephalosporins
-less abundant
-activity essential for cell viability
-catalyze transpeptisase activity
153
What are the 3 types of PBPs
PBP1: inhibited for cell lysis
PBP2: mediates transpeptidase reactions during specific portion of cell cycle
PBP3: septal peptidoglycan synthesis, blocks seperation and leads to filament formation
154
What are the 4 classifications of penicillins
Pen G and Pen V
resistant to beta lactamase: nafcillin, dicloxacillin
broad-spectrum pen: ampicillin, amoxicillin
extended spectrum pen: piperacillin
155
Beta lactamase ADME
depends on stability in acid and absorption with food
IM or IV
widely distributed
eliminated in kidney, tubular, glomerular, urine
156
PCNs ADR
hypersensitivity reaction
N/V/D
injection site reactions
oral dose C. diff
avoid in people with allergy
157
Injection of PCN D procaine results in what
dizziness, headache, seizures
-due to toxic concentrations of procaine
158
PCNs entrance into CSF is inhibited by what
probenecid competitively inhibits this transport
159
Pen G and Pen V route and dose recommendation
V = oral
G = IM/IV
do not take with food
procaine and benzathine used parenterally as repository forms
not stable beta lactamase
160
What are the class 2 anti-staphylococcal PCNs (beta lactamase resistant and isoxazolyl pen)
Oxacillin (poor absorption)
Dicloxacillin (most active form)
Nafcillin (metabolized in liver no renal adjustment)
161
Isoxazolyl PCN MOA
semistnthetic
resistant to cleavage by beta lactamase
potent inhibitors of growth of beta lactamase producing staphylococci
162
Isoxazolyl PCN Absorption and Distribution
take without food
by liver
no dose adjustment for renal failure or hemodialysis
163
What are the class 3 aminiopenicillins and dosage forms
ampicillin (IV, IM, PO-not for life-theatening infection)
ampicillin/sulbactam (IV, IM)
amoxicillin (oral suspension)
amoxicillin/clauvanate (suspension)
164
aminiopenicillins MOA
destroyed by beta lactamase from both gram positive and gram negative bacteria
165
Amoxicillin ADME
oxidation, hydroxylation, deamination processes
E: urine
co-administer with probenecid delays excretion
166
Augmentin ADME
take with food or snack
167
Class 4 antipseudomonal penicillins
Uredopenicillins (piperacillin)
Carboxypenicillins
168
When to specifically use piperacillin
Klebsiella infection
169
piperacillin and tazobactam ADME
broadest spectrum of activity
high biliary concentration
IV (both), IM (only piperacillin)
hepatic and renal elimination
170
How are cephalosporins classified into generation
based on spectrum of action and beta lactamase stability
has a nucleus with 7-ACA
171
cephalosporins MOA
same as penicillin
inhibits final step of peptidoglycan synthesis
no coverage against enterococci
172
cephalosporins ADME
IM, IV
cross placenta (not for pregnancy)
cross BBB
eliminated in bile
173
cephalosporins ADR
nephrotoxicity with aminoglycosides***
intolerance to alcohol (N/V/D with this)
174
What are the first gen cephalosporins
cephalexin
cefazolin
175
Keflex ADME
oral
good alternative to anti-staphylococcal penicillin
acid stable (without regard to meals)
excreted in urine by glomerular filtration and tubular secretion
176
cefazolin ADME
IM, IV
excreted in urine or biliary
177
cephalexin drug interactions
Metformin
Probenecid
178
What are the second generation cephalosporins
cefuroxime (IV, oral)
cefoxitin (IV, IM)
cefotetan (oral)
cefmetazole (oral)
179
second generation cephalosporins ADR
N-MTT side chain can inhibit vitamin K production which prolongs bleeding
disulfuram-like reaction
180
second generation cephalosporins important point about BBB
do not cross BBB
181
Does cefuroxime need a dose adjustment
yes in renally impaired patients
182
cefuroxime ADR
hypersensitivity
183
Third generation cephalosporins (good against pseudomona)
cefotaxime (IV, IM)
ceftriazone (IV, IM)
ceftazidime (IV)
ceftibuten (oral)
184
Third generation cephalosporins ADR
C. diff
185
cefotaxime drug interactions
nephrotoxicity aminoglycosides
cause seizures in renally impaired patients
cause GI problems
186
Ceftriazone ADME
CSF penetration
longer half life
187
Do you need dosage adjustment for ceftazidime
yes for renally impaired patients
188
Ceftazidime ADR
hypersensitivity reaction
189
Ceftazidime drug interactions
chloramphenical is antagonistic to beta lactam antibiotics
nephrotoxicity with aminoglycosides
190
Ceftibuten ADR
hypersensitivity
191
Ceftazidime drug interactions
antacids reduce effectiveness of ceftibuten
192
What are the 4th generation cephalosporins
cefepime (IV, IM)
193
cefepime ADME and ADR
in urine
require dose adjustment
local reactions
seizure with renal insufficiency
194
5th generation cephalosporines
Ceftaroline (IV)
dose modification needed for renal impairment
hydrolysis metabolism
excreted in urine
195
Monobactams (Aztreonam) ADME
active only against gram-negative bacteria
No cross sensitivity with PCNs
adverse effect: gram positive superinfection
dose adjustment for renal impairment
196
What are the carbapenems drugs
Imipenem
Meropenem
Ertapenem
Doripenem
197
carbapenems MOA
same as beta lactam antibiotics
used for serious nosocomial infections resistant to other beta lactams
(IV in hospital setting)
198
carbapenems ADR
painful injection
allergic reaction
superinfection
seizure (unless other CNS disorders are present)
199
Cilastatin is an inhibitor of what
dipeptidase
200
Imipenem and Cilastatin drug interactions
cross allergy to other beta lactam antibiotics
local anesthetics
Probenecid
Valproic acid
201
Meropenem considerations
not sensitive to renal dipeptidases (given alone, does not need cilastatin)
not for pregnancy
202
Meropenem metabolism
liver to open beta lactam form (inactive)
203
Ertapenem consideration
allows for once daily dosing
IM
good activity
204
Doripenem ADME
dose adjustment for renal impairment
IV
metabolism occurs by dehydropeptidase-1
205
Fluoroquinolones MOA
inhibit DNA topoisomerase (leading to breaks in DNA and death of cell)
206
Fluoroquinolones ADME
no metabolism
elimination through kidneys
dose adjustment in renal dysfunction EXCEPT moxifloxacin
207
Fluoroquinolones ADR
boxed warning for tendon rupture
208
Tetracycline MOA
bind to bacterial ribosome at 30S subunit preventing docking of tRNA carrying new amino acid for addition to elongating protein chain
209
Tetracycline ADR
photosensitivity
discoloration of teeth
chelate cations (do not mix with calcium, iron, antacids, multvitamins)
210
Doxycycline ADME
100% bioavailability
with or without food
bile concentration
excreted in urine, feces
long half life
211
Macrolides MOA
bind to 50S subunit of bacterial ribosome, preventing ribosome from shuffling along and adding new amino acids to the elongating protein chain
212
Macrolides ADR
NVD
QT prolongation
potent inhibitors of drug-metabolizing cytochrome P450 enzymes
213
Macrolide ADME
oral
Azithromycin not metabolized extensively
elimination in bile***
long half life
214
Aminoglycosides have a narrow therapeutic window which causes what
high risk of toxicity (nephro and ototoxicity)
also neurologic disorders
215
Aminoglycosides MOA
bind to bacterial ribosome 30s subunit causing mis reading of genetic code leading to incorrect proteins formation and interruption of protein synthesis
216
Aminoglycosides important fact
have to monitor peak and through levels for correct dosing
217
Sulfonamide is a general term used to describe any derivative of what
para-aminobenzene-sulfonamide
(para-NH2 group essential)
218
TMP exerts a __________ effect when used with sulfamethoxazole
synergistic
(inhibitor of microbial dihydrofolate reductase which produces tetrahydrofolate)
219
MOA sulfonamide
interfere with single carbon transfers
-folate synthesis
-de-nove purine biosynthesis
-thymidylate synthesis
220
SMX common side effect
crystalluria (drink with water)
hematological reactions
221
TMP/SMX ADME
widely distributed
highly absorbed
limited hepatic metabolism
222
Urinary tract antiseptics inhibit the _______ of many species of ________
growth, bacteria
(cant be used systemically)
223
Nitrofurantoin ADME
rapidly absorbed
discolors urine (brown color)
activity higher in acidic urine
metabolites are in active
224
What are the two reasons why macrobid is selectively toxic
concentrations of nitrofurantoin are higher in microbial than mammalian cells
higher nitrofuran reductase activity in microbial cells
225
Nitrofurantoin contraindications
pregnant women
children
226
Fosfomycin used to treat and how to take
UTI and cystitis
come as granules and mixed with cold water
227
Fosfomycin MOA
phosphoric acid derivative that inactivates the enzyme pyruvyl transferase, which inhibits bacterial wall synthesis
228
Nalidixic acid MOA
inhibit bacterial DNA gyrase and topoisomerase IV
229
Nalidixic acid pharmacokinetics
hepatic metabolism
urine excretion and 10 times concentration in plasma (local effect)
230
Nalidixic acid ADR
GI
photosensitivity
231
What are the types of UTIs
pyelonephritis
ureteritis
cystitis
prostatitis
232
What are the three types of pathophysiology of UTIs
Ascending: bacteria from urethra up
Descending: blood stream
Lymphatic: bowel and kidney
233
Risk factors for UTIs
female
previous UTI
sex
change in vaginal flora
pregnancy
structural abnormalities
poor hygiene
234
Pathogens of community acquire UTIs
E. Coli (80-90%)
Klebsiella species
Staphylococcus saprophyticus
Enterococcus faecalis
235
Clinical presentation of community acquires UTI
urgency
frequency
burning pee
-cloudy urin
-pelvic pressure
236
What are the 4 urinalysis suggestive of UTI
bacteriurea
pyuria: WBC > 10mm^3
Nitrate positive
Leukocyte esterase positive
237
What are the two types of urinalysis
Rapid
Complete
238
What is the amount of CFUs for clinical presentation of UTI
>100,000 CFU
<100,000 and symptoms
-urinalysis PRIOR to treatment
239
Definition of uncomplicated UTI
acute cystitis in female without pregnancy, catheter, obstruction
240
Non pharm treatment for UTI
cranberry juice (prevention only, contains proanthocyanidin)
probiotics - lactobacillus (prevention only, lower pH)
hydration
241
OTC product for uncomplicated UTI
Azo, stops burning, preventative
242
What are the treatments for uncomplicated UTI
nitrofurantoin: 5 days (contraindicated if CrCl <60)
bactrim: 3 days (local resistance <20)
fosfomycin: 1 day
beta lactam: 3-7 days
243
What medication to use in pregnancy for UTI
beta lactams
244
What is recurrent cystitis referred to as
2 episodes within the last 6 months or 3 episodes within 1 year
245
Complicated UTI risk factors
colonization of indwelling catheter (contamination, catheter into bladder)
anatomical (VUR)
retention urine/incomplete voiding
246
Most common pathogens in hospital acquired UTI
E. Coli
Pseudomonas aeruginose
protus vulgonis
enterobacter species
enterococcus species
247
Acute complicated cystitis treatment
cipro: 5-7 d (renal adjusted)
bactrim: 7 d
beta lactam: 7 d
fosmycin: 7 d (ESBL e coli only)
macrobid: 7 (ESBL e coli only)
248
Clinical presentation of pyelonephritis
fever/chills
N/V
hematuria
249
Phelonephritis treatment non hospitalized
cipro: 3 d
bactrim: 14 d (IV first)
beta lactam: 10-14 d (IV first)
250
Phelonephritis treatment hospitalized
fluoroquinlones (>10% give IV)
aminoglycoside
cephalosporin
cabapenems (ESBL organisms)
251
Clinical presentation prostatitis
fever
N/V
pain
dysuria
frequency
urgency
nocturia
retention
252
prostatitis common pathogens
E. coli
Klebsiella spp
PROTUS
enterococcus spp
253
prostatitis treatment
2-4 weeks
fluoroquinolones
bactrim (gram negative pathogens)
254
Pregnancy treatment of UTI
cephalexin (5-7 d, preferred)
augmentin (5-7 d)
macrobid and fosfomycin (avoid use in pyelonephritis)
