Exam 4 Kays Flashcards
1
Q
what candida species is starting to emerge with multi-drug resistance
A
c. auris
2
Q
why can aspergillus be a problem?
A
Mold can can cause disease in immunocompromised hosts and lead to neutropenia
3
Q
What are endemic (pathogenic) fungi
A
Histoplasma
Blastomyces
Coccidioides
4
Q
Amphotericin B MOA
A
binds to ergosterol and gets inserted into the fungal cytoplasmic membrane –> disruption of the fungal cytoplasmic membrane –> increased cell permeability –> leakage of sodium/potassium/cellular constituents, loss of membrane potential, metabolic disruption –> cell death
5
Q
Is Amphotericin B static or cidal
A
concentration dependent cidal activity
6
Q
Amphotericin B onset of action
A
rapid
7
Q
Amphotericin B DOC
A
Cryptococcus
Histoplasma
Aspergillus
Mucor
8
Q
Amphotericin B Doxycholate dosing
A
Test dose of 0.1mg/kg or 1 mg over 20-30 min
0.3-1 mg/kg/day over 4-6 hours
9
Q
Amphotericin B L-AmB dosing
A
1.5-6 mg/kg daily over 2 hours
10
Q
Amphotericin B ABLC dosing
A
5 mg/kg, infused at 2.5 mg/kg/hr
11
Q
What is Amphotericin B dosing based on
A
ideal body weight or adjusted
12
Q
Amphotericin B Deoxycholate infusion related AE
A
Headache, fever, chills, arthralgias, N/V with infusion
*Pretreat with acetaminophen or aspirin, antihistamines, mepereidine, phenothiazines, hydrocortisone
thrombophlebitis
13
Q
Amphotericin B Deoxycholate non-infusion related AE
A
Nephrotoxicity: direct vasoconstriction –> hypokalemia and hypomagnesia
14
Q
flucytosine MOA proteins
A
5-FC enters fungal cell –> deaminated to 5-FU –> 5FU gets incorporated into fungal RNA –> interference with protein synthesis
15
Q
flucytosine MOA
A
5-FC enters fungal cell –> metabolized to 5-FDUMP –> inhibits thymidylate synthetase –> interfers with DNA synthesis
16
Q
flucytosine MOA
A
cryptococcus neoformans (meningitis)
17
Q
flucytosine excretion
A
85-95% excreted unchanged in urine
18
Q
flucytosine AE
A
hematologic: bone marrow suppression at concentrations >100 ug/ml
19
Q
what is flucytosine dosing based on
A
ideal if non-severe
adjusted if severe
20
Q
flucytosine dosing
A
100 mg/kg/day PO in 4 divided doses
21
Q
Ketoconazole MOA
A
inhibits synthesis of ergosterol via inhibition of the fungal cytochrome p-450 dependent enzyme lanosterol 14-alpha-demethylase
22
Q
Ketoconazole SOA
A
candida albicans
crypptococcus neoformans
histoplasma
dermatophytes
23
Q
Ketoconazole PK
A
absorption is inversely related to gastric pH
24
Q
flucytosine distribution
A
CSF
25
ketoconazole distribution
throughout body minus CSF
26
ketoconazole metabolism
hepatic
27
can ketoconazole be used orally for first line therapy
no due to risk of hepatotoxicity
28
ketoconazole AE
hepatotoxicity
| Endocrine: inhibition of adrenal steroid and testosterone synthesis
29
ketoconazole drug interaction
potent inhibitor of CYP3A4
```
gastric pH meds: decrease bioavailability
anticoag: prolonged PT
Rifampin: decreases ketoconazole
Cyclospoin- increases conce
phenytoin: increased concen
```
30
Itraconazole MOA
inhibits synthesis of ergosterol via inhibition of the fungal cytochrome P450 dependent enzyme lanosterol 14-alpha-demethylase
31
itraconazole SOA
aspergillus
histoplasma
sporothrix
32
itraconazole capsule absorption
good but dependent on gastric acidity (want low pH)
| absorbed better when taking with meal or acidic cola beverage
33
itraconazole solution absorption
absorbed better in fasting state
| not affected by gastric acidity
34
SUBA-itraconazole absorption
not affected by gastric acidity
| give with food
35
are itraconazole capsules and suspensions interchangable
no
36
itraconazole distribution
widely distributed but poor CSF
37
itraconazole metabolism
active metabolite: hydroxyiraconazole
38
itraconazole elimination
hepatic
39
itraconazole clinical use and dosing
histoplasmosis: 200 TID x3 then 200 BID
40
itraconazole adverse reactions
hepatotoxicity
CFH
QTc prolongation
41
itraconazole black box warning
Contraindicated in patients with CHF: may cause negative inotropic effect
42
itraconazole drug interactions
H2 antagonists
PPIs
CYP3A4
43
What drugs does itraconazole increase concentrations of
```
digoxin
quinidine
benzos
statins (minus prava)
rifabutin
cyclosporine
```
44
what drugs decrease concentrations of itraconazole
carbamazepine
phenytoin
phenobarbital
rifampin
45
what drugs increase concentrations of itraconazole
clarithomycin
indinavir
ritonavir
46
fluconazole MOA
inhibit synthesis of ergosterol via inhibition of the fungal cytochrome P-450 dependent enzyme lanosterol 14-alpha-demethylase
47
fluconazole SOA
candida
| cryptococcus
48
what candida is fluconazole not active against
c. glabrata
| c. krusei
49
fluconazole absorption
well absorbed orally independent of gastric acidity
50
fluconazole distribution
good concentration in CSF
51
fluconazole elimination
renal
52
fluconazole oropharyngeal dosing
200mg day 1 then 100-200 qd for 2 weeks
53
fluconazole esophageal dosing
400mg day 1, then 200-400 mg qd for 14-21 days
54
fluconazole vaginal dosing
150mg x1 dose
55
fluconazole prophylaxis dosing
400mg
56
fluconazole candida UTI dosing
100-200 mg qd
57
fluconzole cryptococcal meningitis consolidation therapy dose
400mg QD for 10-12 weeks after CSF negative
58
fluconazole cryptococcal meningitis maintenance therapy dose
200 mg qd for at least 1 year AND remains asymptomatic from infection AND CD4 count >100 for 3 months and suppressed HIV RNA in response to effective antiretroviral therapy
59
what is fluconazole dosing based off of
total body weight
60
fluconazole AE
QT prolongation
61
fluconazole DI
potent inhibitory of CYP2C19
| moderate inhibitor of CYP3A4
62
voriconazole MOA
inhibits synthesis of ergosterol via inhibition of the fungal cytochrome p-450 dependent enzyme lanosterol 14-alpha-demethylase
63
voriconazole SOA
aspergillus
| fusarium
64
voriconazole absorption
Great oral bioavailability
65
is voriconazole absorption affected by acid
NO
66
voriconazole metabolism
significantly metabolized by cyt p450
| metabolism is saturation- non-linear PK
67
when to avoid voriconazole
CLCR <50
68
do you dose adjust for oral dosing of voriconazole
nah
69
voriconazole common dosing
6mg/kg q 12 for first 24 horus for loading
4mg/kg q 12 IV or 200mg Q 12 PO
70
voriconazole AE
visual disturbances
Elevated LFTs
QTC prolongation
71
what drugs decrease voriconazole exposure
rifampin
rifabutin
carbamazepine
72
posaconazole MOA
blocks synthesis of ergosterol
73
posaconazole SOA
aspergillus
| mucor
74
is posaconazole affected by gastric pH
YES for oral suspension
75
when to avoid posaconazole
CrCl< 50 since IV formulation contains cyclodextrin
76
what drugs decrease dose of posaconazole
phenytoin
rifabutin
PPIs
77
posaconazole AE
QTC prolongation
78
how is isavucaonzole different than other azoles
prodrug- metabolized to isavuconazonium sulfate by esterases in blood
79
isavuconazole MOA
inhibits synthesis of ergosterol
80
isavuconazole SOA
aspergillus
mucor
rhizopus
81
isavuconazole PK
linear pk
82
is dose adjustment needed in isavuconazole
no
83
Isavuconazole and QTc
does not cause QT prolongation: can shorten QT interval
84
echinocandin MOA
glucan synthesis inhibit to destroy fungal cell wall
85
are echinocandins cidal or static
cidal
86
echinocandins SOA
aspergillus
87
which antifungal is CI in pregnancy
ibrexafunger
88
What is candida normal flora of
GI tract
89
most common candidasis species
c. albicans
90
What is the primary line of host defenses against superficial candida infections
cell-mediated immunity by CD4 t cells
91
OPC clinical presentation
"cottage-cheese" appearance with yellowish white, soft plaques that are easily removed by vigorous rubbing
92
Treatment duration of OPC
7-14 days but start with shorter time period first
93
OPC mild infection therapy
*Topical
Clotrimazole troche
Nystatin
Miconazole buccal tab
94
When is systemic therapy needed for OPC
Refactory OPC
patients who cannot tolerate topical agents
patients with moderate to severe disease
patients at high risk for neutropenia
95
DOC for systemic therapy OPC
Fluconazole
96
OPC systemic therapy options
fluconazole
itraconazole
posaconazole suspension
97
Treatment duration for fluconazole-refactory opc
>14 days min but up to 28 days
98
Fluconazole refractory OPC treatment options
```
itraconazole
posaconazole
amphotericin B
voriconaole
caspofungin
micafungin
anidulafungin
```
99
what type of therapy is needed for esophageal candidiasis
systemic
100
therapy duration for esophageal candidiasis
14-21 days
101
esophageal candidiasis treatment options
```
fluconazole
itraconazole
echinocandins
voriconazole
posaconazole
amphoteicin B deoxycholate
```
102
therapy duration for esophageal candidiasis fluconazole refractory
21-28 days
103
esophageal candidiasis fluconazole refractory treatment options
```
itraconazole
echinocandins
voriconazole
posaconazole
amphotericin B deoxycholate
```
104
what is uncomplicated VVC
sporadic infection that is susceptible to all forms of antifungal therapy regardless of treatment duration
105
what is complication VVC
recurrent VVC
severe disease
non-candida albicans infection
host factors
106
what is responsible for 80-92% of symptomatic VVC
candida albicans
107
uncomplicated VVC treatment
topical/oral azoles
| nystatin
108
complicated VVC treatment
fluconazole 150mg 2-3 doses 72 hours apart
treatment 10-14 days
109
what is recurrent VVC
>4 episodes within a 12 months period
110
recurrent VVC treatment
topical or oral azole for 10-14 days followed by fluconazole PO once weekly for 6 months
111
antifungal-resistant VVC treatment
boric acid
| flucytosine
112
what are dermatophytoses
superficial mycotic infections of the skin
113
what is tinea pedis
athletes foot
114
treatment duration for tinea pedis
2-4 weeks of topical therapy
115
what is tinea manuum
palmar surface infection
116
what is tinea cruris
infection of the proximal thighs and buttocks
Jock itch
117
treatment duration for tinea cruris
1-2 weeks of topical therapy
118
what is tinea corporis
infection of the skin of the trunk and extremities
119
what is tinea capitis
infection involving the scalp, hair follicles, and adjacent skin
120
how to treat tinea capitis
terbinafine for 4-8 weeks
121
what is tinea barbae
infection of the hairs and follicles of the beard and moustache
122
how to treat tinea barbae
terbinafine for 4-8 weeks
123
what is tinea (pityriasis) versicolor
hyper- or hypopigmented scaly patches on trunk and extremities
124
what is onychomychosis (tinea unguium)
fungal infection of the toe nails (more common) and fingernails
125
onychomychosis (tinea unguium) treatment
Terbinafine
Itraconazole
Fluconazole
126
histoplasmosis pathophys
conidia become aerosolized when soil is distubred --> inhaled and reached bronchiioles and alveoli
organisms are phagocytized by macrophages but not killed and spread via lymph nodes --> creating tissues granulomas with central caseation and necrosis around organs
127
what is important to test for when diagnosing histoplamosis
serologic testing
128
histoplasmosis treatment: immunocompetent host-
| asymptomatic or mild-moderate disease with symptoms < 4 weeks
No therapy required
129
histoplasmosis treatment: immunocompetent host-
| symptomatic with mild-moderate disease with symptoms > 4 weeks
Itraconazole
130
histoplasmosis treatment: immunocompetent host-
| moderately severe-severe disease
lipid amphotericin B + medrol 1-2 weeks THEN
| itraconazole for a total of 12 weeks
131
histoplasmosis treatment: immunocompromised host-
| moderately severe-severe disseminated disease
Lipid amphotericin B for 1 to 2 weeks then itraconazole for at least 12 months
132
histoplasmosis treatment: immunocompromised host-
| less severe disease
itraconazole for 12 months
133
blastomycosis pathophys
pulmmonary infection occurs secondary to inhalation of conidia --> inflammatory response with neutrophilic recruitment to lungs --> dissemination --> cell-mediated immunity --> formation of granulomas
134
pulmonary blastomycosis treatment: immunocompetent host-
| moderately severe-severe disease
Lipid amphotericin B for 1-2 weeks or until improvement, following by itraconazole for 6-12 months
135
pulmonary blastomycosis treatment: immunocompetent host-
| mild-moderate disease
itraconazole for 6 months
136
disseminated or extrapulmonary blastomycosis: immunocompetent host-
CNS disease induction
lipid amphotericin B for 4-6 weeks, followed by an azole as consolidation therapy
137
disseminated or extrapulmonary blastomycosis: immunocompetent host-
CNS disease consolidation
azole for 12 months
fluconazole
itraconazole
voriconazole
138
blastomycosis treatment: immunocompromised host-
| acute disease
lipid amphotericin B for 1-2 weeks or until improvement, then suppressive therapy for at least 12 months
139
blastomycosis treatment: immunocompromised host-
| suppressive therapy
itraconazole for at least 12 months
140
when to treat coccidiomycosis
patients with large inocula, severe infection, or concurrent risk factors
141
coccidiomycosis treatment duration:
| primary respiratory infection
3-6 months
142
coccidiomycosis treatment:
| primary respiratory infection
fluconazole
| itraconazole
143
coccidiomycosis treatment:
| symptomatic chronic cavitary pneumonia
fluconazole
| itraconazole
144
coccidiomycosis treatment:
| diffuse pneumonia with bilateral or miliary infiltrates
Amphotericin B for several weeks; followed by an azole for 12 months total
145
disseminated coccidiomycosis treatment:
| nonmeningeal disease
itraconazole or fluconazole
| amphotericin B
146
disseminated coccidiomycosis treatment:
| meningeal disease
*fluconazole
itraconazole
intrathecal amphotericin B
147
cryptococcal meningitis treatment:
non-HIV infected, non-transplant host-
induction treatment
amphotericin B deoxycholate plus flucytosine for at least 4 weeks
148
cryptococcal meningitis treatment:
non-HIV infected, non-transplant host-
consolidation treatment
fluconazole 400-800 for 8 weeks
149
cryptococcal meningitis treatment:
non-HIV infected, non-transplant host-
maintenance treatment
fluconazole 200mg PO QD for 6-12 months
150
cryptococcal meningitis treatment:
HIV-infected-
preferred induction treatment
liposomal amphotericin B plus flucytosine for at least 2 weeks
151
cryptococcal meningitis treatment:
HIV-infected-
preferred consolidation treatment
fluconazole 400mg PO QD for equal or more than 8 weeks
152
cryptococcal meningitis treatment:
HIV-infected-
preferred maintenance treatment
fluconazole 200 mg to complete at least 1 year of azole therapy
153
cryptococcal meningitis treatment:
organ transplant recipients-
induction
liposomal amphotericin B plus flucytosine for at least 2 weeks
154
cryptococcal meningitis treatment:
organ transplant recipients-
consolidation
fluconazole 400-800mg for at least 8 weeks
155
cryptococcal meningitis treatment:
organ transplant recipients-
maintenance
fluconazole 200-400 mg for at least 6-12 months
156
candidemia treatment DOC non-neutropenic adults
echinocandin
157
candidemia treatment
non-neutropenic adults
alternative as initial therapy in selected patients who are not critically ill and who are unlikely to have fluconazole-reistant candida species
fluconazole
158
candidemia treatment neutropenic adults
echinocandin
| lipid formulation of amphotericin B
159
C. glabrata treatment options
echonocandin
160
c. parapsilosis treatment options
fluconazole or lipid amphotericin B
161
c. krusei treatment options
echinocandin, lipid amphotericin B or voriconazole
162
candidemia treatment duration: neutropenic adults
treat for 14 days after documented clearance of candida from blood, resolution of symptoms, and resolution of neutropenia
163
chronic disseminated (heptasplenic) candidiasis treatment
lipid amphotericin B for several weeks followed by fluconazole
164
invasive pulmonary aspergillosis treatment
voriconazole
165
invasive pulmonary aspergillosis treatment salvage therapy
```
amphotericin B lipid complex
caspofungin
micafungin
posaconazole
itraconazole
```
166
prophylaxis treatment of aspergillosis
posaconazole
167
leading cause of community acquired and hospital acquired bacteremia
staphylococcus aureus
168
what diagnostic evaluation should you do in SAB and why?
Echocardiography to check for infective endocarditis
169
when to perform echocardiography in SAB
5-7 days after onset of bacteremia
170
catheter and prosthetic device management in SAB
consider all IV catheters and prosthetic devices to be infected in patients with SAB until infection ruled out
attempt to remove all prosthetic devices or use rifampin
171
empiric treatment of SAB
empirically cover MSSA/MRSA
vanc 15-20 mg/kg IV q 8-12
vanc 6-10 mg/kg IV q 24
172
Treatment of MSSA bacteremia
*cefazolin 2g Q8
nafcillin 2 g Q4
oxacillin 2 g Q8
173
Treatment of MRSA batceremia
Vanc 15-20 mg/kg IV q8-12 h
| Daptomycin 6mg/lV q 24
174
Treatment of PVE
Vanc+rifampin for 6 weeks
| gent for first 2 weeks
175
duration of treatment of uncomplicated SAB
14 days from first negative blood culture
176
duration of treatment of complicated SAB
4-6 weeks
177
what is bacteremia
presence of viable bacteria (fungi) in the blood
178
what is an infection
inflammatory response to invasion of normally sterile host tissue by the microorganisms
179
what is SIRS
systemic inflammatory response to a variety of severe clinical insults manifested by 2 or more of the following conditions
180
2 or more of the following conditions of SIRS
```
Temp >38 or <36
HR > 90 bpm
RR >20 bpm
PaCO2 <32 mmHg
WBC >12,000, <4000
```
181
what is sepsis
life-threatening organ dysfunction caused by a dysregulated host response to infection
182
what is septic shock
subset of sepeis in which underlying circulatory, cellular, and metabolic abnormalities are associated with higher risk of mortality than sepsis alone
183
sepsis characteristics
Pts requiring vasopressors to maintain a MAP of > 65 mm Hg and serum lactate >2 mmol/L
184
what is multiple organ dysfunction syndrome
presence of altered organ function in an acutely ill patient so that homeostasis cannot be maintained without intervention
185
What gram negative bacteria are causative pathogens in sepsis and septic shock
enterobacteriaceae (e. coli, klebsiella)
| p. aeruginosa
186
What gram positive bacteria are causative pathogens in sepsis and septic shock
staphylococci
187
what drugs target exotoxins
clindamycin and linezolid
188
complement systemic mechanism
Activated of C3a and C5a induce vasodilation and increase vascular permeability --> hemodynamic changes na platelet aggregation and activation of neturophils
189
kallikrein/bradykinin system
fluid leakage into interstitial space due to vasodilation --> prominent feature of sepsis/septic shoc
190
macrophage role in sepsis
1. phagocytic cells remove and destroy bacteria and bacterial products
2. produce potent mediators of inflammation
191
tumor necrosis factor role in sepsis
increases vascular permeability
cause cellular damange
produce fever
primary mediator of sepsis- concentrations correlated with severity of sepsis
192
IL-1 role in sepsis
activate monocytic cells, neutrophils, B and T lymphocutes
| produce endogenous pyrogenic effect, lypolysis, cachexia
193
IL-6 role in sepsis
stimulated the production of platelets
| induces elevation in body temperature
194
neutrophils role in sepsis
contributes to vascular and tissue injuries by releasing oxygen metabolites and lysosomal enzymes or by causing microemboli after aggregation
195
what is the key target for inflammatory mediators and important producer of active mediators
endothelial cells
196
general variables for sepsis
```
Fever >38.3 or hypo <36
HR >90
Tachypnea
Altered mental status
Edema
Hyperglycemia
```
197
inflammatory variables for sepsis
WBC >12,000
WBC <4,000
10% immature forms
Plasma CRP more than 2SD above normal value
198
Community acquired infection Empiric therapy of sepsis in adults:
CAP non-neutropenic
Cefrtiaxone + Azithromycin
| Ceftriaxone + moxi/levo
199
Community acquired infection Empiric therapy of sepsis in adults:
urinary tract source non-neutropenic
3rd/4th gen ceph +/- AG
| Pip/tazo +/- AG
200
Community acquired infection Empiric therapy of sepsis in adults:
intra-abdominal non-neutropenic
pip/tazo
carbapenem
3rd/4th gen ceph + flagyl
cipro/evo + flagyl
201
Community acquired infection Empiric therapy of sepsis in adults:
skin/soft tissue infection non-neturopenic
vanc
dapto
linezolid
202
hospital acquired infection Empiric therapy of sepsis in adults:
HAP/VAP
Antipseudomonal beta lactam + AG or
| AP FQ + vanc or linezolid
203
hospital acquired infection Empiric therapy of sepsis in adults:
urinary tract source non-neutropenic
cefepime + tobra or FQ
| Pip/tazo + tobra or FQ
204
hospital acquired infection Empiric therapy of sepsis in adults:
intra-abdominal non-neutropenic
pip/tazo
| carbapenem
205
hospital acquired infection Empiric therapy of sepsis in adults:
skin/soft tissue infection non-neturopenic
vanc + pip/tazo (+ clinda if necrotizing fascitis)
206
hospital acquired infection Empiric therapy of sepsis in adults:
neutropenic patient
pip/tazo +/- AG
AG Carbanepen +/- AG
Ceftazidime or cefepime +/- AG
207
Empiric therapy of sepsis in adults:
| thermal injury to at least 20% of body surface area
AP BL + AG+ vanc
208
Empiric therapy of sepsis in adults:
| suspicion of indwelling vascular catheter infection
vanc
dapto
linezolid
209
sepsis duration of therapy
7-10 days
210
Antibiotics are strongly discouraged when PCT is < _____
0.25 ng/dL
211
Antibiotics are strongly encouraged when PCT is > _____
1 ng/dL
212
Principle of sepsis therapy
early initiation (within first hour) of aggressive antimicrobial therapy- 1 or more drugs with in vitro activity against the most likely pathogens and that penetrate to the site presumes to be the source of sepsis
213
What should be completed in the first 3 hours of septic shock presentation
1. measure lactate concentration
2. blood cultures prior to antibiotics
3. give broad-spec antibiotics
4. Give 30 mL/kg crystalloid (NS,LR)
214
What should be completed in the first 3 hours of septic shock presentation
Add vasopressors
| norepinephrine first line
215
MAP initial resiscitation goal
MAP >65 mm Hg
216
Is acyclovir a prodrug?
Yes- must be converted to acyclovir-TP by thymidine kinase in HSV
217
acyclovir MOA
inhibits viral DNA polymerase to inhibit viral replication and is incorporated into viral DNA to cause premature chain termination
218
Mechanisms of resistance for acyclovir
Absence or partial or altered production of viral thymidine kinase
Altered viral DNA polymerase
219
Acyclovir SOA
HSV
| VZV
220
Acyclovir bioavailability
Oral bioavailability 10-20% (not affected by food)
| Dose-dependent oral absorption (bioavailability decreases with increasing dose)
221
Acyclovir distribution
widely distributed in tissues and body fluids
222
Acyclovir metabolism/elimination
Eliminated renal --> adjust for renal dysfunction
223
Acyclovir AE
N/V
Nephrotoxicity
Neurotoxicity
Thrombophlebitis with IV form
224
Is valacyclovir a prodrug
Yes- a L-valyl ester prodrug of acyclovir
225
Valacyclovir MOA
inhibits viral DNA polymerase to inhibit viral replication and is incorporated into viral DNA to cause premature chain termination
226
Valacyclovir SOA
HSV
| VSV
227
Valacyclovir vs Acyclovir bioavailability
Relative bioavailability of acyclovir is 3-5 times greater with valacyclovir and may be given without regards to meals
228
Is famciclovir a prodrug
Yes- a diester prodrug of penciclovir
229
Is penciclovir a prodrug
Yes- becomes penciclobir triphosphate
230
Famciclovir SOA
HSV
| VZV
231
Which is more potent: penciclovir or acyclovir
Acyclovir
232
famciclovir oral bioavailability
Well absorbed orally but food does slow absorption but may be administered without regards to food
233
Famciclovir excretion
Renal thus dose reduction is recommended in renal dysfunction
234
famciclovir Ae
Headache
| Nausea
235
Special SOA of ganciclovir
CMV
236
is ganciclovir a prodrug
Yes- in CMV infected cells, ganciclovir is mono-phosphorylated by a CMV encoded protein kinase UL97 gene then to the di- and triphosphate forms by cellular kinases
237
ganciclovir MOA
inhibits viral DNA polymerase and/or incorporation into viral DNA to inhibit viral replication
238
ganciclovir resistance
UL97 gene mutation which leads to viral kinase deficiency or altered viral DNA polymerase
239
ganciclovir bioavailability
low oral bioavailability --> use IV formulation
240
ganciclovir spread
CSF
| Brain tissue
241
acyclovir spread
brain, spinal card
| CSF
242
ganciclovir elimination
kidney --> adjust dose for renal dysfunction
243
ganciclovir AE
bone marrow suppression
