antimicrobial drug chart
TRANSCRIPT
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Drug Mechanism of Action
Inhb cell wall synth
Cell wall peptidoglycancross-links
via peptide side-chains(transpeptidation )
PBP init enz actvy by binding to
terminal D-Ala-D-Alaof side-
chains.
PCNs & Cephs = structural analogs
of D-Ala-D-Ala substrate
PCN covalently binds to active
site of PBPs
irrev inhb of transpeptidation
& cell wall synth
cell lysis & death
not p.o. b/c acid labile
C;Penicillins (PCN) = -Lactams Time-dependent BACTERICIDAL (keep C
Route of Admin
Penicillin G
i.v.
cont i.v. infsn common
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Route of Admin Mechanism of Actioni.m.
Inhb cell wall synth
slow release (see PCN)
D-Ala-D-Ala analog irrev bind
to PBP active site
Drug Route of AdminMechanism of
Action Pharmacological Effects
i.v. (see above) NOT degraded by -Lactamase
Benzathine Penicillin G
-Lactamase (Penicillinase) Resistant PCN Broader spectrum PCN
Penicillins (PCN) = -Lactams (contd) Time-dependent BACTERICIDAL
Drug
Procaine Penicillin G
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Designed spcfc
to kill -
lactamase
producing
Staph aureus
Inhb cell wall
synthesis
short t1/2:
D-Ala-D-Ala
analog irrev
bind to PBP
active site
dose q4h/q6h
Oxacillin
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Nafcillin
Oxa, Naf, Diclox > Vancb/c kills
quickly
Dicloxacillin p.o.
Drug Route of AdminMechanism of
ActionPharmacological Effects
Inhb cell wall
synthesisDestroyed by -lactamase!
Aminopenicillins = Extended Spectrum PCN
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(see above)
Combine w/ -lactamase
inhibitors to Rx -lactamase
producing bugs
(e.g. staph aureus)
D-Ala-D-Ala
analog irrevbind to PBP
active site
Ampicillin i.v.
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Combo poss:
Ampicillin + sulbactam(i.v.)
Destroyed by -lactamase!
Combine w/ -lactamase
inhibitors to Rx -lactamase
producing bugs
(e.g. staph aureus
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Combo poss (2nd
line otitis
media):
Amoxicillin + clavulanate(p.o.)
aka Augmentin
p.o. Absorption NOT affected
by presence of food.
Drug Route of AdminMechanism of
ActionPharmacological Effects
Amoxicillin p.o.
Anti-Pseudomonal PCN Kills Pseudomonas aeruginosa (& Enterobacteriacea)
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i.v.Inhb cell wall
synthesisTicarcillin + clavulanate
(see above) (ticar/clav)
esp in ICU
D-Ala-D-Ala
analog irrev
bind to PBP
active site
Piperacillin + tazobactam
(pip/tazo)
broadest spectrum PCN
Drug Route of AdminMechanism of
Action Pharmacological Effects
Ticarcillin
Piperacillin
-Lactamase InhibitorsBroadens spectrum of -lactamase-susceptible PCNs
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Clavulanate
*Co-admin
w/suscep PCN:
protect them
from
inactivation by
-lactamases
&
cephalosporin
ases
aka
Clavulinic Acid
(All Cephs
more resistant
to degradation
by -
lactamases
than some
PCNs)
aka
clav
Tazobactam
Sulbactam
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aka
tazo
Drug Route of AdminMechanism of
ActionPharmacological Effects
Imipenem/
Cilastatin
Inhb cell wall
synth
Metabolized by renal dihydro-
peptidases (DHP)
(carbapenam) (same as PCN)Imipenem must be given in
combo w/ Cilastatin (DHP inhbtr)
D-Ala-D-Ala
analog irrevbind to PBP
active site
Good tissue penetration
Broadest
spectrum
(Must use in combo!!) -lactams
ErtapenemInhb cell wall
synthdoes NOT cover:
Carbapenems & Monobactams i.v. only!!!
i.v.
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(same as PCN) pseudomonas
(carbapenam) acinetobacter
enterococci
Inhb cell wall
synth
Aztreonam (same as PCN)
(monobactam)
D-Ala-D-Ala
analog irrev
bind to PBP
active site
Spectrum
AGs
(e.g.
gentamicin)
i.v.
i.v.
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Drug Route of AdminMechanism of
ActionPharm Effects
1st
:Inhb cell wall
synth1
stgeneration
Cefazolin i.v. (same as PCN) Best against G(+)
D-Ala-D-Ala
analog irrev
bind to PBP
active site
Few G()
Spectrum
varies by gens
(Bactericidal
by gen)
~ Resist
hydrolysis by -lactamases
broader
spectrum >
PCNs
Good distrb in
most body
fluids but NOT
INTRACELLULAR
Cephalosporins
G(+) activity: 1st
gen > 2nd
gen > 3rd
gen G(-) activity: 3rd
gen > 2nd
gen >
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1st
:
Renalelim
dose in pt
w/ poor renal
func (but
cetriaxone
liver)
Cephalexin
2nd
: 2nd
generation
Cefoxitin G() > 1stgen
G(+) < 1st
gen
Anaerobes!!!
2nd
:
Cefotetan
Route of Admin
i.v.
i.v.
p.o.
3rd
:
Ceftaroline
Cephalosporins (continued)
Drug
3rd
:
Ceftazidime
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i.v.
i.m.
p.o.
i.v.
Drug
Doxycycline
(see p. 26)
3rd
:
Cefotaxime
3rd
:
Ceftriaxone
4th
:
Cefepime
3rd
:
Cefpodoxime
3rd
:
Cefixime
3rd
:
Cefdinir
i.v.
p.o.
F=100%
Tetracyclines BACTERIOSTATICRoute of Adm
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Minocyclinep.o.
F=100%
Macrolides (ML)Does NOT cover Enterococcus (espVRE) orMRSA !Drug
(estolate ester= highest F)
Excreted in bile
Erythromycin
i.v. (hurts!)p.o.
(lim p.o. F b/c
acid labile)
Esters less acid labile better F
Azithromycin
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i.v.
p.o.
(F ~ 0.5)
Long t1/2
Large Vd
Clarithromycin
p.o.
Excreted in bile
Ciprofloxacin
i.v.
p.o.
F = 90%
Fluoroquinolones (FQ) Does NOT cover Enterococcus (espVRE) orMRSA !Drug
(F ~ 0.5)
Metab by liver, excreted in urine
* 20% metab by CYP1A2 in liver
FQ chelate oral Fe++
& Ca++
supplements, and Al++
Dairy/food: not affect GI absorbofgemi & levo; d
Ciprofloxacin___________
* Ca++
-fortified milk, anatacids & yogurt F but n
Inhb DNA synth rapidly BACTERICIDAL
(conc-dependent)
Inhb bact topo II & IV
Topo II (DNA gyrase):
Catalyzes relaxn of () supercoiled DNA allows n
Topo IV: Required for separation of replicated DN
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F = 90%
Fluoroquinolones (FQ) (contd) Does NOT cover Enterococcus (espVRE) orDrug
Renal elim no CYP450 interact
Levofloxacin*
i.v.
p.o.
Moxifloxacin*
i.v.
p.o.
F = 90%
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Drug Route of AdminMechanism of
ActionPharmacological Effects
Must giveInhb cell wall
synth G(+) incl anaerobes
Streptomycin
(see TB drugs)
Aminoglycosides (AG) BACTERICIDALDrug
Hepatic metab but no CYP450 drug interactions
Other Antibiotics: Vancomycin BACTERICIDAL
Neomycin
Gentamicin*
Tobramycin*
Amikacin*
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Does NOT
involve PBPs! NO G()s!
i.v.
SLOW
BACTERICIDAL
Big molec penetrn probs (poor
CSF penetrn)
Always use -
lactam to Tx
MSSA instead
Elim by urinary excrtn monitor
renal func & adjust dose in pt w/
renal failure
Lg glycoprot
inhb cell wall
synth b/ccovalently
binds
D-ala-D-ala
terminus of
pentapeptide
side chains of
polysacch
backbone
Poor p.o. absorption!!!
Sterically
hinders action
of
peptidoglycan
polymerase &
transpeptidase
s
elongation of
peptidoglycan
polymerase
ceases
CANNOT use p.o. for systemic
infxns
Vancomycin
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p.o. Vanc = 2nd
line:
C. diffpseudo-membranous
colitis
*DOC C. diff = metronidazole
Give 2 courses p.o. metronidz. Ifstill C. diff then p.o. Vanc
If still no response fidaxomicin
Drug Route of AdminMechanism of
ActionPharmacological Effects
Clindamycin
(see p. 26) i.v.Inhb protein
synth Excellent G(+)!!
BACTERIOSTAT
IC
- SSTIs (staph aureus & -
hemolytic streps
p.o. - covers MRSA
(same as
macrolides!)
- outpatient Rx of MRSA
cellulitis in adults & children
Also topical
cream
binds 50S
subunit at P
site
Good coverage of G(+)
anaerobes
Other Antibiotics: Clindamycin BACTERIOSTATIC
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(acne) inhb
translocation- aspiration pneumonia
amino acid
most recently
added to
peptide chain
does not move
from A site to
P site
peptide
elongation
stops &
protein synth
terminated
----------------------
Good p.o. F No G(-) coverage!
Penetrates
most body
fluids & tiss
(not CSF &
brain)
Good
intracellularconc
No VRE coverage!
Very hi
bone/serum
conc
Heptaic metab
(NO need to
adjust for
renal func)
Drug Route of AdminMechanism of
ActionPharmacological Effects
Other Antibiotics: Linezolid, Daptomycin, Fidaxomicin
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Excellent G(+) (incl MRSA, VRE
& PCN-resistant strep pnemo)
i.v.
Syntheitic
antiobiotic: 1st
oxazolidione
Min G() actvy
pts on i.v. Vancin hospital
sent home on p.o. linezolid
p.o.Inhb protein
synth
irreversible inhibitor of MAOI
serotonin syndrome if co-
admin w/ SSRI
F = 100%BACTERIOSTATICtho cidal
against some
Bind to unique
site on 23S
ribosomal RNAof 50Ssubunit
block
assembly of
70Sribosomal
complex
needed to init
prot synth
Do NOT need
to adjust dose
for renal func
600 mg dose
Linezolid
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$$$ ($50/pill)
i.v.bind bact mb
depol
no mb
potential
$$$$ cell death
($250-500/d)
Fidaxomicin $$$$Inhibit RNA
synth no
RNA pol
As effective as vanc
Drug Route of Admin Mechanism ofAction
Pharm Effects
Trimethoprim/
Sulfa-methoxazolep.o.
Sulfonamides
= 1st
class
systemic
antibact drugs
Broad spectrum:
aka F = 90% S. aureus incl MRSA
Daptomycin
Other Antibiotics: Trim/Sulfa
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trim/sulfa Synergy: Enterobacter in ICU
akap.o. even in
serious infxns
BacterioSTATI
C alone; E. coli & Klebsiella
BactrimBacterioCIDAL
combo
- drugs * + in urine Rx
uncomplicated UTI in healthy
* Sulfa:
comptv
antagonist of
PABA inhb
dihydropteroa
te synthetase
prevent
DHF synth
DOES NOT cover GAS
i.v. poss
(avoid huge
volumes of i.v.
fluid)
* Triminhb
dihydrofolate
reductase
prevent
conversion of
DHF to THF
* pref inhb
bact enz (w/
little effect on
mammalian
enz)
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Drug Route of AdminMechanism of
ActionPharmacological Effects
p.o.
Macrocrystalli
ne form:
slower absorb
& renal
excretion
* + in urine bactericidal
High F Most active in ACIDIC urine
BACTERIOSTAT
IC (low [ ]) Rx: UTI: G(+) & G(-)
duration
of action in
macro-
crystalline
form
- E. coli
BACTERICIDAL
(high [ ])- Klebsiella
- Enterococcus
Other Antibiotics: Nitrofurantoin
Nitrofurantoin
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*Bact enz
rapidly reduce
nitrofto
reactv
intermed
damages DNA cell death
- some Proteus resistant
Bactericidal Bacteristatic
Aminoglycosides Tetracyclines
PCN Macrolides
Carbepenems Clindamycin
Monobactams
(aztreonam)Linezolid
Cephalosporins
Nitrofurantoi
n (may be
cidal w/ largedose)
Vancomycin Ethambutol
Fluoroquinolones
Nitrofurantion (static
at low [ ]; cidal at high
[ ])
Quinupristin/dalfoprist
in
Metronidazole
INHRifampin
Pyrazinamide
Systemic Antifungals: Polyenes
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Drug Route of AdminMechanism of
ActionPharmacological Effects
Amphotericin B* i.v.
Bind to
ergosterolin
fungal cell
membrane
*Extremely broad spectrum
create
porins
(polyene) topical cell
permeability**Gold standardanti-fungal drug
ions &
macromolec
leak out of cell
cell death
Fungal cell
membrane!
*Do NOT use after Rx w/ azole
b/c azoles take away site of action
of ampho B
Nystatin Oral suspen. Extremely broad spectrum
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(polyene) Topical *Effective against C. albicans
*NOT effective against MET bugs
MET bugs (Dermatophytes)
1. Microsporum 2. Epidermophyton
Systemic Antifungal: Azoles cover: Candida albicans , MET fungi, Pityrosp
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Drug Route of AdminMechanism of
ActionPharmacological Effects
i.v. Most commonly used systemic
antifungal agent
AZOLES: Lacks major toxicity
p.o. p.o. F is excellent
FUNGISTATIC
b/c slow
Pt need patentimm systm
*inhb bact enz
CYP450
lanosterol 14-
demethylase
prevent
ergosterol
formation
accum of
14-
methylsterols
inhb enzy
actvy of
electron
transport
system
block cell
growth
Fluconazole*
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Fungal cell
membrane!
Drug Route of AdminMechanism of
Action
i.v. AZOLES:
topical
FUNGISTATIC
b/c slow
Pt need patent
imm systm
* inhb bact
enz CYP450
lanosterol 14-
demethylase
Systemic Antifungal: Azoles(contd)Candida albicans , MET fungi, Pityros
Pharmacologi
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prevent
ergosterol
formation
accum of
14-
methylsterols
inhb enzy
actvy of
electron
transport
system
block cell
growth
topical
oral trocheFungal cell
membrane!
Clotrimazole Tastes > n
Miconazole
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i.v.
Voriconazole
p.o.
F = 96%
DrugMechanism of
Action
Pharmacological
EffectsTherapeutic Uses
*probably replaced ampho B
Caspofungin
Inhb synth of
1,3--D-
glucan
Big molecule
(key
component
of fungal cell
wall in
Candida &
Aspergillus )
*salvage therapy in pts w/
invasive Aspergillosis who have
NOT responded to ampho B
(echinocandin) No p.o. avail
Systemic Antifungals: Echinocandin
Posaconazole p.o.erratic GI absorption
(need fat!)
* Extended spectrum
Can change from i.v. to p.o. w/o d
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(Diff MOA
from azoles)
*rapidly cidal against Candida ,
even those resistant to
fluconazole
*limited spectrum:
-
Candida- Aspergillus
- Pneumocystis
Drug Route of AdminMechanism of
ActionPharmacological Effects
Flucytosine p.o.(5-FC)
fluorinated
pyrimidine
(5-FC) converted
to 5-FU* rapid absorb
Must be
dosed QID
converted
to 5-FUMP
converted
to FdUMP
* extensive distrb (incl
penetration into CSF)
inhb
thymidylate
synthase
* Renal elim
Lack of
thymidine
inhb DNA
synthesis* Synergy:
5-FC w/ azoles & ampho B
(human cells
do not convert5-FC to 5-FU)
Drug Route of AdminMechanism of
ActionPharmacological Effects
Systemic Antifungals: OTHER
Systemic Antifungals: OTHER (contd)
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Drug accum in:
p.o.
Inhb enz
squalene
epoxidase
prev
ergosterol
synth
- skin
- nails
topical
Accum of
squalene kills
fungal cell.
- fat cells
p.o.
Bind
polymerized
microtubules
Terbinafine
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Inhb fungal
mitosis
ingest w/
fatty foods to
F
Prevents
formation of
cytoplasmic
microtubules
necess forhyphae
growth
topical,
OTC
Drug
Antiprotozoal
Route of Admin
p.o.
Tolnaftate unknown
Griseofulvin
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Metab by liver
Cleared by kidney
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Route of Admin
Drug Route of AdminMechanism of
ActionPharm Effects
Antiprotozoal(contd)
Drug
NitazoxanideInterferes w/ pyruvate:ferrodoxin
energy metab
Antimalarial Doxy & Clinda: Also Rx MDR malaria (all)
Pentamidine
Pyrimethamine Sulfadiazine
???
*S inhibits dihydropteroate synthe
*P inhibits dyhydrofolate reductas
*selectively inhibit two enzymatic
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p.o.
Malaria
(Plasmodium
spp)
After parasites
w/in RBCs
digest Hb in
their food
vacuoles
released heme
rendered
nontoxic to
the parasite by
non-enz
polymerizn
into malarial
pigment
hemozoin
qWeek
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Chloroq &
Mefloq
preventspolymerizn
free heme kills
parasite by
oxidative
damage of cell
membranes
Chloroquine
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Drug Route of Admin Mechanism ofAction
Pharm Effects
p.o.MOA
unknown
Mefloquine
Antimalarial(contd) Doxy & Clinda: Also Rx MDR malaria (all)
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(qd)
Gametocide
against ALL
Plasmodium
p.o.Atovaq:
ubiquinone
(qd)
Blocks
cytochrome-
medtd e
transport
destroys mito
mb potential
diff
Primaquine
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Proguanil:
1. Enhances
ability of
Atovaqto
destroy mito
membr
potential
difference
2. Prevents
resistance
Doxycycline(see p. 8)
Clindamycin
(see p.14)
DrugMechanism of
Action
Pharmacological
EffectsTherapeutic Uses
*kills round & tape worms
Atovaquone/
Proguanil
Antihelminitic
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Inhb synth of
microtubules
necess for
glucose
uptake
[glycogen] &
*ATP+
*pinworm (Rx whole family!)
*hookworm
Parasite:
1. Dies
2.
Immobiliz
ed &
cleared
from GI
tract
Also
larvacidal &
ovicidal.
safety
pinworms
bendBroad
spectrumKills all worms in mixed infections
*roundworm
p.o. (low F) *pinworm (Rx whole family!)
Mebendazole
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butb/c
drug just goes
thru GI tract to
kill worms
*hookworm
*threadworm
*tapeworm (cestodes)*flukes (trematodes)
**DOC: mixed infxns
(roundworms & tapeworms)
**DOC:tapeworms
Kills all worms incl larval stage of
pork tapeworms
(cysticercosis calcified larval
cysts in brain focal neuro Sx,
intracran pressure, seizures)
Rx followed by laxatives expel
remaining eggs from GI tract
Ganglionic
nicotiniccholingergic
agonist
musc tetany
*kills round worms
Neuromuscul
ar paralysis
allows
peristaltic
clearance
from GI tract.
*pinworm (Rx whole family!)
*hookworm
Albendazole
Pyrantel pamoate
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DrugMechanism of
ActionPharm Effects Therapeutic Uses
Ivermectin
Releases
GABA &
GABA
binding
facilitate
opening of Cl-
channelsin
NMJ
flaccid
muscle
paralysis in:
**DOC: threadworm
-
helminths
p.o. - insects * River Blindness (onchocerciasis):
-
ectoparasi
tes
Single dose 2/yr kills filarial infxn
Antihelminitic(contd)
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Also poss
tonic
paralysis of
musc in
nematodes
(roundworms
) via Glu-
gated Cl-
channels
found only in
invertb.
*Livestock (e.g. cattle): singledose kills all roundworms &
arthropods (ticks, mites, other
insects) for 30 days
reVolution for benny
iVermectin
FDA has NOT approved ivermRx
scabies but p.o. admin very
effectv
*esp useful Rx scabies in:
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- immunocompromised pts
- pts w/ severely encrusted
scabies
- pts who have failed therapy
w/ topical permethrin
1. Opens
Ca++
channels
musc
tetany
**DOC: Schistosomiasis
2. Spastic
paralysisFlukes (trematodes)
3.
Tegmental
damage Praziquantel
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Activate
host
immune
system
Infxn cannot be transmitted in
US b/c no intermed host (a
snail)
DrugMechanism of
Action
Pharm Effects
Permethrin
1%
permethrin:
pelucidal
**DOC:Pediculosis (lice
infestations)
1% permethrin cream
topical
5%
permithrin:
scabicidal
Head: After shampoo & dry
saturate hair w/ soln for 10 min
rinse drug
Body: Rx clothes
Pubus: cream for 10 min
rinse
Ectoparasites
Therapeuti
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Eyelashes: Rx w/ 1% yellow Hg
oxide ointment
**DOC: scabies (itch mite:
Sarcoptes sabiei)
5% permethrin to entire body
(avoid face, mucus membr &
eyes) for 8-14 h bathe & repeat
if necess
Ivermectin
Releases
GABA &
GABA
binding
facilitate
opening of Cl-
channelsinNMJ
flaccid
muscle
aral sis in:
**DOC: threadworm
-
helminths
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p.o. - insects * River Blindness (onchocerciasis):
-
ectoparasi
tes
Single dose 2/yr kills filarial infxn
Also poss
tonic
paralysis of
musc in
nematodes
(roundworms
) via Glu-
gated Cl-
channels
found only in
invertb.
*Livestock (e.g. cattle): single
dose kills all roundworms &
arthropods (ticks, mites, other
insects) for 30 days
reVolution for benny
iVermectin
FDA has NOT approved ivermRx
scabies but p.o. admin veryeffectv
*esp useful Rx scabies in:
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- immunocompromised pts
- pts w/ severely encrusted
scabies
pts who have failed therapy w/
topical permethrin
Drug Route of AdminMechanism of
ActionPharmacological Effects
Inhb viral
neuraminidas
e Block
release of new
viral particles
Antivirals: Influenza
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Drug Route of AdminMechanism of
ActionPharmacological Effects
Trifluridine
Converted to
trifluridine
tri(PO4) by
host cell
enzymes:
active
metabolite
akaophthalmic
solution
inhibits viral
DNA synthesis
Trifluorothymidine
Antivirals: Herpes keratitis
Oseltamivir p.o.
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Drug Route of AdminMechanism of
ActionPharmacological Effects
p.o.
F = 15-20%Inhb viral DNA
polymeraseA guanosine derivative
Must be phosphorylated 3x
active metabolite: acyclovir
tri(PO4)
i.v.
Virus-specific
thymidine
kinase (found
ONLY in
infected cells)
dose in pts w/ renal failure
produces
acyclovir
mono(PO4)
incidence of resistance is low
topical
phosphorylase
enz of host cell
then produce
acyclovir di- &
tir(PO4)
Acyclovir
tri(PO4):
- Competes
w/ dGTP at
the viral DNA
polymerase
Antivirals: Herpes Simplex (HSV) & Varicella Zoster (VZV )
Acyclovir
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p.o.
- Causes
chain
termination
when incorp
into viral
DNA
Prodrug converted to
acyclovir
F = 48% Rx Vanc (p.o.) *acyclovir+P 3-5x> Rx acyclovir (p.o.)
dose in pts w/ renal failure
inorganic
pyrophosphat
e
Acts directly
to inhibit:
1. viral DNA
polymerase
2. viral RNA
polymerase
Foscarnet i.v.
Valacyclovir
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3. HIV
reverse
transcriptase
No activationvia virus or
host enz
required
Drug Route of AdminMechanism of
ActionPharm Effects
p.o.Inhb viral DNA
polymerase
F = 6-9%
Virus-specific
thymidine
kinase (found
ONLY in
infected cells)
produces
acyclovir
mono(PO4)
i.v.
Antivirals: Cytomegalovirus (CMV)
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phosphorylase
enz of host cell
then produce
acyclovir di- &tir(PO4)
ocular
implant
Acyclovir
tri(PO4):
- Competes
w/ dGTP at
the viral DNA
polymerase
p.o.
- Causes
chain
termination
when incorp
into viral
DNAF = 60%
F by hi fat
meal
inorganic
pyrophosphat
e
Acts directly
to inhibit:
Ganciclovir
Valganciclovir
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1. viral
DNA
polymerase
2. viral RNA
polymerase
3. HIV
reverse
transcriptase
No activation
via virus or
host enz
required
Antisense
oligonucleotide
Binds to mRNA
prevents tsl
prevents
viral
replication
Antivirals: Treatment of HIV
Drug Mechanism of Action
Foscarnet i.v.
Fomivirisenintravitreal
injection
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Fusion Inhibitors
Synthetic peptide binds gp41
Blocks viral/T-cell mb fusion
HIV cannot enter CD4 cell
Enfuvirtide(s.c.)
Maraviroc(p.o.)
Inhibit CCR5 receptor
Blocks gp120 binding to CD4 cell
Zidovudine(AZT, ZDV)
Lamivudine(3TC)
Abacavir(ABC)
NRTI
Nucleoside Rev TSCase Inhibitor
Intracellular kinases convert these nucleosides to
false nucleotides(triphosphates):
1. competitive inhb HIV rev tsc-ase
2. cause chain termination of viral DNA
NRTIs can be incorp into viral DNA
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NNRTI
Non-Nucleoside
Rev TSCase Inhibitor
NO reqd phos to be active
Direct inhb rev tsc-ase stop rep
Bind diff site than NRTIs do NOT compete w/ nt for
binding to rev tsc-ase
NET effect blockage:
Emtricitabine
Tenofovir(TDF, a nt)
Protease Inhibitors
Nevirapine (NVP)
Efavirenz (EFV)
Integrase InhibitorsPrevents viral DNA insertion into human DNA
Raltegravir
1. RNA-dependent DNA pol
2. DNA-dependent DNA pol
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Drug
Atazanavir
Ritonavir*
Lopinavir
Anti-TB (Mycobacterium tuberculosis )R-I-P-Eor R-I-P-SBACTERICIDA
Mechanism of Action Pharmacologi
Block viral protease prevent cleavage of viral
polyproteins into functional subunits necess for
assembly of new virus particles
Inhb cell wall synthesis
BACTERICIDAL for rapidly
dividing
BACTERIOSTATIC
for latent (non-dividing)
- INH antagonizes rxns where B6
- INH = struct sim to pyridoxine (
- Periph neuropathy neuropat
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Active INH metabolite binds
covalently to acyl carrier
protein & -acyl carrier
protein synthetase
Prevents synth of mycolic
acid(a long chain fatty acid
needed to maintain integrity
of Mycobacterium cell wall
Isoniazid (INH)
A prodrug converted into
active form by mycobacterial
catalase-peroxidase
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Drug Mechanism of Action Pharm Ef
Rifampin
Inhibit RNA synthesis
Bind to subunit of bact
DNA-dep RNA polymerase
Do NOT bind to human RNA
polymerase
Anti-TB(contd) R-I-P-Eor R-I-P-SBACTERICIDAL (dividing bacilli)
BACTERICIDAL
Easily penetrate tissues to kill
intracellular mycobact &bugs in abscesses
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Drug
Ethambutol (EMB)
Mechanism of Action
Pyrazinamide
(PZA)Unknown MOA Kills semi-dormant intracellular ba
Rifabutin
Anti-TB(contd) R-I-P-Eor R-I-P-SBACTERICIDAL (dividing bacilli)
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the PCN of TB
Streptomycin
(see AGs)
i.m.
i.v.
AG antibiotic
Inhb protein synth
Primarily against extracellular bacilli
Inhb of cell wall synthesis
Inhb arabinosyl transferase (enz which polymerizes
arabinoglycan)
Arabinoglycan = essential part of mycobacterial cell wall
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Spectrum Drug/Class G() Coverage G(+) Coverage
N AminoPCN E. coli & H. flu
Carbapenem
s (except
ertapenem)
Good Good
Aztreonam Excellent
1st
gen ceph Little Good
Rx of Active TB: R-I-P-E or R-I-P-S
Gold Standard: INH-Rifampin-PZA
& either EMBor streptomycin for 9 months
All 4 drugs given until know susceptibility
(2 wks to culture)
Moxifloxacinshows the greatest activity
versus TB
MDR TB:
Rx for 18-12 mo w/ up to 6 drugs
(tho outcome still not good)
(see FQ)
Ciprofloxacin& levofloxacin
Rx MDR active TB
Rx Mycobacterium avium complex(MAC):
A macrolide (~HIV pts)
Cipro
Rifabutin
EMB
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3rd
gen ceph Good Some (not ceftaxidime)
4th
gen ceph Excellent Moderate
Moderate
(> macrolides)
Little Good
(some w/
clarithromycin
&
azithromycin)
(except Enterococcus)
Fluoroquinol
ones
Vancomycin None Good
Clindamycin None Excellent
B()Aminoglycosi
desHigher doses
Lower doses (combo w/wall synth
inhibitor)
Linezolid None Excellent
B Trim-sulfa Good Good
Nitrofurantoi
n Excellent Excellent
N Macrolides
Definite differences in coverage within this class
2nd
gen ceph Some Good
MB Tetracyclines Moderate
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Pharmacological Effects Therapeutic Uses Mechanism of Resistance
Pen Gt1/2= 30 min **DOC** 1. -lactamase *** (penicillinase)
Probenecid inhb renal transp
systm 1. -hemolytic strepdestroys PCN -lactam ring drug
inactive
Pen G secrtn Group A*, B, C, F, G strepsstaph aureus plasmid encodes -
lactamase
t1/2GAS killed quickly by
Pen G2. drug binding site(G(+))
MRSA/ORSA express an addl -
lactam binding site (bact gene mut)
resistant to ALL -lactams
2. suscep streppneumo
Strep pneumo PBP w/ aff for -
lactams
(but use p.o. amoxicillin)VREs terminus mut D-Ala-D-
lactate
Good distrb in ECFLg dose! If resist Pen G,
also resist 3rd
Ceph3. Drug efflux(G(-))
Will penetrate CSF ifmeninges inflammed
Pseudo & Acinetobacter
Does NOT enter cells3. meningococcalmeningitis (Hi doses!)
S. pneumo marcolides
Renal tubular secrtn ------------------------- 4. Prevent drug entry
Syphilis Pseudo # of porins carbapenams
Ghonorrhea
N. meningitides
NOT staph aureus
(resistant)
> MIC)
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Pharmacological Effects Therapeutic Uses Mechanism of Resistance Good distrb in ECF Depot PCNs (see above)
Will penetrate CSF if
meninges inflammed
Does NOT enter cells prophylax: prev GAS
infxn in military recruits1. -lactamase (PCNase)
Renal tubular secrtn 2. drug binding site (G())
Syphillis 3. Drug efflux (G(-))
(But NOT neurosyph) 4. Prevent drug entry
Therapeutic Uses Adverse Effects/Toxicity
**DOC**
(keep CP> MIC)
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Susceptible staph aureus(MSSA)orsuscep strep
cellulitis, abscesses,
endocarditis, meningitis &
others
(always prefd over broad,
e.g. FQ)
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Cellulitis: always Staph/Strep
unless culture proves
otherwise
--------------------------------
PCNase-prod Staph
soft tissue infxn
Susceptible Strep
infxn
Therapeutic Uses Adverse Effects/Toxicity
**DOC**
1. Enterococcus spp.
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Also for Enterococcus:
Vanc, Doxy, tigecycline,
quinupristin/dalfopristin,
Linezolid, Dapto
2. Listeria spp.
----------------------------
* NOT active against MRSA!
* spectrum extended to cover
G(): E. coli & H. flu
p.o. diarrhea
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b/c better penetration of outer
mb of G() bugs
**DOC**
1. 1st
line: otitis media
If NOT work, give
amox/clav
2. suscep strep pneumo
-------------------------
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Strep Throat
* NOT active against MRSA!
* spectrum extended to cover
G(): E. coli & H. flu
b/c better penetration of outer
mb of G() bugs
Therapeutic Uses Adverse Effects/Toxicity
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**DOC**
Pseudomonas spp.
*excellent anaerobic actvy
*good vs MSSA, S. pneumo
*NEVER use just one drug for
pseudomonas!!!
Therapeutic Uses Adverse Effects/Toxicity
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*** 2ndline otitis media:Amox/clavaka Augmentin
when amox alone fails
**DOC Pseudomonas :
ticar/clav
Given i.v. in ICU
Combo poss:
Ampicillin + sulbactam(i.v.)
**DOC Pseudomonas :
pip/tazo
Diarrhea
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Given i.v. in ICU
Therapeutic Uses Adverse Effects/Toxicity
Cover many nosocomial G()
rods (incl Pseudomonas ),
anaerobes & G(+)
seizurecillin esp hi
doses in pts w/ poor renal
func & neurosurg pts
pt w/ PCN allergy:
BEWAREmore cross-
reactv than cephs
Multi-drug resistant bugs
Last resort drug after pt fails
pip/tazoor cefepime
pip/tazo, cefepime> carbap
for Pseudomonas
polymicrob, life-threat
infxns
e.g. intra-abdominal trauma
& nosocomial infxns by
Citrobacter, Enterobacter,
etc.
Use pip/tazoor cefepime
for febrile neutropenic pt
instead
Tx pts w/PCN allergy
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Very good G() actvy (incl
Pseudo , actvy comparable to
ceftazidime)
Little allergic cross-
reactivity w/ other
-lactams
NOT clinically useful against
G(+) (incl MRSA) & anaerobes
Severe G() infxn in pt w/
PCN allergy
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Mechanism of Resistance
(same as PCN)
1. PBP site!
2. Bugs begin to make cephalo-
sporinases
Cheap & good tissue penetration
1st
line: non-MRSA SSTIs
(better than vanc!)
1st line: mild PCN allergy
Rx: pyelonephritis in pregnant
MS-Staph Aureus & strep
1st
genNo activity against Enteroccocci, MRSA, Listeria, or PCN-resist
strep pneumo!
***DOC: Surgicalprophylaxis
Therapeutic Uses
Do NOT cover Enterococci orMRSA!!!!
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MSSA SSTIs, strep
Safe for pregnant
Binds mutated PBP binding site in MRSA
Inhb cell wall synth
Mechanism of Action
Spectrum varies by gens (cidal by gen)
(same as PCN)
D-Ala-D-Ala analog irrev bind to PBP active site
intra-abdominal infxns
pelvic inflamm disease (PID)
surgicalprophylaxis
**DOC: intra-abdominal
Not used much anymore, replaced by 3rd
gen
Do NOT cover Enterococci orMRSA!!!!
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~ Resist hydrolysis by -lactamases spectrum > PCNs
Good distrb in most body fluids, but NOT INTRACELLULAR
Renalelim dose in poor renal func (cetriaxonehas liver elim)
Cefepime:
resist to degradtn by -lactamases
Good CNS penetr Rx bact meningitis
1. Ceftazidime
2. Cefotaxime
3. Ceftriaxone
4. Cefepime
in Mechanis
Inhb protein synth
BACTERIOSTATIC
Bind 30Ssubunit of bact ribosome blo
subunit
Oral bioavailb = 100%
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- Albumin (in serum)
Long t1/2 & slow elim dosed bid
High [ ] in bile check liver func tests (L
-
alkaline phosphatase
- AST & ALT transaminases
BACTEROSTATIC
Mechanism of A
- Bilirubin
Inhb protein synth
BACTERIOSTATIC
Bind 50Ssubunit at peptidyltransferase
inhb translocation
(most recently added amino acid to peptide
to P site)
Peptide elongation stops, protein synth st
----------------
Good G(+) incl MSSA & strep pneumo
- Also CAP Rx: morax, H flu
- Intracellular: Legionella & Chlamydia
Some G(-)
(esp Clarith & Azith)
Good tissue penetration
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(except brain & CSF)
BACTERICIDAL
Mechanism of Action
Mg++
antacids cations GI absorb
lay moxiabsorb
t dietary Ca++
ormal gene tsc & DNA replication
into daughter cells
--------------------
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MRSA ! BACTERICIDAL
Mechanism of Action
Inhb DNA synth rapidly BACTERICIDAL
(conc-dependent)
Inhb bact topo II & IV
Topo II (DNA gyrase):
Catalyzes relaxn of () supercoiled DNA allows normal gene tsc &
Topo IV: Reqd for separation of replicated DNA into daughter cells
--------------------
FQ chelate oral Fe++
& Ca++
supplements, and Al++
& Mg++
antacids
absorb
Dairy/food: not affect GI absorbofgemi & levo; delay moxiabsorb
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Therapeutic Uses Adverse Effects/Toxicity
***DOC:severe MRSA infxns *ototoxicity deafness
Route of Admin
AG does NOT distrb in fat use adjusted body weight for obese pt
Elim by renal filtration
give i.v. for systemic infxns
Must
Poor GI absorb
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* Amp-resistant enteroccoci:
(rare w/o excessive
plasma [ ] or prolonged
use
50% E. faecium resist to Vanc
E. faecalis ~always suscept to Amp *renal toxicity (overstated)
*PCN-resistant strep pneumo: poss renal func
Do NOT use Vanc.
FQ instead (if not meningitis)
Tox ~b/c co-Rx w/ other
nephrotox drugs
*G(+) MDR bugs
(!enterococci)
interstitial nephritis poss,
but very rare
MDR strep pneumo (FQ>Vanc)
* Hospital MRSA infxns
(min Rx: 14 days of i.v. Vanc)
red-man syndrome
* Empiric: bact meningitis(~strep pneumo)
NOT ALLERGIC RXN!
Ceftriaxone + Vanc(Vanc for PCN
resist); add i.v. Ampfor Listeria if pt
< 2 y.o. or elderly
1st
i.v. dose too rapid
massive histamine release
flushing in neck & head
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*Empiric: febrile neutropenia
Prevent by slow infusion
(1-2h) or pre-Rx w/ Lg
dose antihistamine
(diphenhydramine)
Need bactericidal Rx G(): pip/tazo
or cefepime. Add Vancif evid ofG(+)/waiting for Cx results (esp if see
port wine skin)
*Empiric: G(+) bacteremia *allergic rxns & rashes
Init need Vanc b/c risk of MRSA.
Then do NOT use Vanc unless staph
in multiple blood Cx.#1 cultured from blood: coag(-)
staph epidermidis (90% skin
contaminant)
Therapeutic Uses Adverse Effects/Toxicity
*reasonable choice for anyPCN or sulfonamide-allergic
pts who need G(+) coverage
*Rash
*excellent for SSTI infxn, esp
in pt w/ PCN or sulfonamide
allergy
*Diarrhea
due to change in
composition of bowel
flora
*Pulmonary anaerobic infxns
(e.g. aspiration pneumonia &
penetrating abdominal
wounds)
*C. dificile
pseudomembranous
colitis
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*good for outpatient Rx of
comm-acq MRSA adults &
kids
Rx w/ p.o. metronidazole
*Cream (topical): Rx acne
* MDR malaria: RBC form of
ALL Plasmodium
Therapeutic Uses Adverse Effects/Toxicity
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*Rx MDR G(+) bugs ~well tolerated but N/V
*Reversible bone marrow
suppression 25%
platelet suppressionn in
25% pt when Rx 10 days
*Rx VRE, esp E. faecium (but
bacteriostatic)
(No prolonged Rx, Not in
bone marrow transpl pt)
Monitor platelets & CBC
Rx MRSA when pt cant tol
Vanc (but bacteriostatic)
* periph neuropathy
*Rx complicated SSTIs
* optic neuritis
(irreversible)
*Drug interactions:
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*Does NOT work in deep
seated infxns (e.g.
endocarditis & osteomyelitis)
b/c bacteriostatic
irreversible inhbr of MAOI
serotonin syndrome if
co-admin w/ SSRI
* 2nd
line: MRSA N/V
(behind vanc) Sk mm tox
* NOT for MRSA pneumo
(inactivated by surfactant) or
SSTIs (too expensive)
(poss rhabdomyolysis)
* VRE
C. diffafter metronidazole &
vanc both fail
Therapeutic Uses Adverse Effects/Toxicity
**DOC: Pneumocystis
jiroveci (PCP)
All S/E mainly occur w/
large doses & long term
use.
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**DOC: Nocardia (esp
immune-compromised host)
HIV pt req larger dose
S/E more likely
*Stenotrophomonasmaltophilia : when ICU &
resist carbapenems
* Sulfonamide-inducedallergic rxn of skin
(hives)
- rash
*Staph aureus (incl MRSA) - fever
Outpatient MRSA: - photosensitivity
-clinda> trim/sulfaor doxy
b/c clinda covers GAS/GBS;
trim/sulfa not cover GAS
- urticaria
-
works well after abscessdrainage
-
erythemamultiforme
-MSSA: use -lactam p.o.
instead
- exfoliative
dermatitis
Inpatient MRSA:
- Stevens-Johnson
syndrome (bad rash
widespread skinsloughing)
-clinda, trim.sulfa, or doxy
-critical: i.v. Vanc 1st
line* blood dyscrasias (Lg
dose)
-Linez/Daptofor pt Vanc-intol
or Rx few days for uncomplic
MRSA infxn
- Thrombocytopenia
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- Leukopenia
* Enterobacterin ICU
- Hemolytic anemia,
esp in pt w/ genetic
deficiency of G-6-P
dehydrogenase
* E. coli& Klebsiella* hyperkalemia: trim acts
as K+-sparing diuretic
Drugs * + in urine Rx un-
complicated UTIin healthy
* Toxoplasmosis (prophylaxis
in AIDS pt)
Therapeutic Uses Adverse Effects/Toxicity
Effects lim to urine! urine brown
*UTI: G(+) & G(-) * Prolonged Rx:
- heptatitis
*uncomplicated UTIs - neuropathies
- pulm fibrosis
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*safe in preg
(amox & cephalexinalso safe
for preg )
*Does NOT Rx: pyelonephritis
or prostatitis (cannot
penetrate tissue)
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Therapeutic Uses Adverse Effects/Toxicity
*Also interacts w/chol in
humans (massive IFN- &
IL-6 ):
*Do NOT use after Rx w/azole b/c azoles take away
site of action (ergosterol) of
ampho B
- arthralgia/myalgia
- fever
- malaise
*Nephrotoxic (dose-dep& transient)
Lipid Ampho B:Exacerbated by other
nephrotox drugs
- Enclosed in liposome Renal wasting of K
+&
Mg++
- Same MOA
No permanent renal
damage in pts w/ norm
renal func before Rx
- Still toxic but delayed
Renal damage
lessened by giving 1L
saline i.v. prior to
ampho B Rx
- $$$$$$$$$$$$$$*shake & bake
syndrome
- fevers & chills!
- caused by IL-1, IL-6,
TNF, IFN-
*oropharyngeal/esophageal
Candida (thrush):
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Neonates, children, 90%
of HIV pts, asthmatics using
ICS
swish & swallow oral
suspension (3-4 days &
every other day for 2 wks)
Replaced by clotrimazole
(oral troche) b/c better taste
rum orbiculare ( tinea versicolor)
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Mechanism of Resistance
1.Mut of binding to demythylase
Lanoesterol can still bind but azoles
cannot.
C. cruseiresist fluconazolebut notvorcionazole
* Candida vulvovaginitis (CVV) 150 mg tablet (p.o.)takes 48h to improve Sx tho few S/E
*If CVV ~ everytime, single p.o. dose after ABX Rx 48 hrs
Candida colonizes genital tract of 20-50% healthy
(70-75% of all healthy will 1 ep)
~ C. Albicans
Most common in :
-taking antibiotics
Therapeutic Uses
* very actv against C. albicans
* weakness: narrow spectrum
- Not C. crusei
- No anti-mold activity
- Not Aspergillus, etc.
-pregnant
-diabetes mellitus (DM)
symptoms:
-vaginal d/c
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Therapeutic Uses Mechanism of Resistance
orum orbiculare ( tinea versicolor)
al Effects
-phys exam: white d/c & erythema
* tinea capitus
- (p.o. 2 wks) = efftv griseo& fewer S/E
- any azole: topical in very young pt
*Athletes foot & jock itch
Any azoletopical (or terbinaf)
-pruritus (severe itching)
-discomfort/pain during sex
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*oropharyngeal/esopha
geal Candida (thrush):
Neonates, children, 90%
of HIV pts, asthmaticsusing ICS
1. Mut of binding to demythylase
swish & swallow oral
suspension (3-4 d & qod x
2 wks)
Oral troche replaced
nystatinb/c better taste
Lanoesterol can still bind but azoles
cannot.
* Candida vulvovaginitis(CVV)
200 mg suppository (3 d,
bedtime)
C. cruseiresist fluconazolebut not
vorcionazole500 mg vaginal tablet (1 d,
bedtime)
(see flucon)
statin
* Candida vulvovaginitis
(CVV) 200 mg suppository (3d, bedtime) (see flucon)
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***DOC: systemic
Aspergillus infxns
(Voricon > ampho B)
*Fusarium spp. (pt needs
WBCs!)*Scedosporium
apiospermum
*Candida (incl C. crusei.
Otherwise use flucon,
cheaper)
Not effectv against C.
glabrata?
Adverse Effects/Toxicity Mechanism of Resistance
~None
No cross-resistance w/
azoles
*well tolerated w/ excellent
pharmokinetics
Covers voricon+
zygomycetes
se adjustment
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*few drug-drug interactions
b/c it does NOT induce or
inhibit CYP450
Therapeutic Uses Adverse Effects/Toxicity
* narrow spectrum:* bone marrow
suppression
- Cryptococcus neoformans - leukopenia
- some Candida - thrombocytopenia
(GI bact convert 5-FC 5-
FU)
* 5-FC+ ampho Bor itracon
in selected fungal infections
*Beware impaired renal
func
Therapeutic Uses
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- age - Diabetes mellitus
- - Periph vascular Dz
- Nail trauma - Immunosuppression
- Tina pedis
- Chronic exposure of
nails to H2O Candida
infxn
-
Poor hygiene
toenails: qd x 12 wks but S/E
2x >
Risk factors:
*Athletes foot & jock itch : topical (or azole )
* tinea capitus (p.o. x 2 wks) = efftv griseo& fewer S/E
* Preg : category B
**DOC:nail fungus
(dematophyte, yeast, or mold)
Rx: 250mg/d same week each month for 3 consecutive
months (cure rate 80%)
fingernails: qd x 6 wks but S/E
***DOC:Covers all tineas
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Mechanism of Action
Kills directly!!!
Pharmacological Effects
* MET fungi
* P. orbiculare
*safe for children
griseo use b/c replaced by terbinafine & itracon
(tinea capitus : ringworm of scalp & hair b/c
Trichophyton invades hair shaft & follicle)
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Bugs electron transport chain
contains ferredoxins(donate
electrons to metronidazole
form a highly reactive nitro
radical
Nitro radical attacks protozoal
DNA
destroys helical struct
cell death
*pregnancy category B (but avoid during 1st
trimester)
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Aerobic organisms do NOT
produce the toxic metabolite
from the prodrug
metronidazole
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Therapeutic Uses Adverse Effects/Toxicity
Mechanism of Action Therapeutic Uses
xidoreductase-dep e
transfer rxn, reqd for anaerobic
Giardiasis(Giardia lamblia ) = beaver fev
Pentamless efficacious & more toxic
**DOC: Toxoplasmosis (Toxoplasma go
immunocompetent pt
2nd
line for: Pneumocystis jiroveci (PCP)
Fungus but anti-protozoal drugs work
(trim/sulfa is DOC)
tase
teps in folate synth in Plasmodium spp.
Cryptosporidiosis(Cryptosporidium spp.
***DOC: Cryptospoidiosisin AIDS pts
combo w/ paromomycin & azithromycin
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* Kills erythrocytic/RBC stage:
1. P. vivax*
2. P. ovale*
3. P. malariae (cure)
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4. Senstv strains of P.
falciparum (cure)
* No effect on
exoerythrocytic (hepatic)
stage
* Prophylaxis in Chloriq-
senstv areas:
Rx 2 wk before travel &
continue 4 wk after leaving
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Safe in children
*frequent (~difficult to
disting fr early stage ofPlasmodium fxn):
*~ Only drug able to suppress
& cure infxns by MDR P.
falciparum
- n/v
- diarrhea
* Prophylaxis in Chloriq-
resistant areas:- abdominal pain
Rx 2 wk before travel &
continue 4 wk after leaving
- dizziness
Safe in children - dysphoria
*50% of pts (~ mild & self-
lim):
- ataxia
- headache
- visual/auditory
hallucinations
- dizziness
*rare :
- disorientation
- seizures
- neurotic/psychotic Sx
Therapeutic Uses Adverse Effects/Toxicity
*Rx ALL Plasmodium
*pts w/ genetic deficiency
of G-6-P dehydrogenase
(~Mediterannean/Asian):
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w/o enz
RBCs cant synth
reducing eqv
(NADPH) to protect
cell membr fr
oxidative damage
*Only drug that kills hepatic
form (liver hypnozoites) of
P. vivax & P. ovale
hemolytic
anemia oxidatv
damage to RBC cell
membr
*Test pt for deficiency of G-6-
P dehydrogenase prior to
primaq Rx
*Normal pts:
methemoglobinemia
*Prophylaxis in Chloriq-
resistant areas:
*Avoid in preg : fetus
doesnt have well
developed G-6-P
dehydrogenase
Rx 2 wk before travel
& continue 4 wk after
leaving
Safe in children
*Rx of drug-resistant P.
falciparum
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*Prophylaxis in Chloriq-
resistant areas:
Rx 2 wk before travel
& continue 4 wk after
leaving
Best tolerated
* active vs all erythrocytic
Plasmodium
* MDR malaria
Adverse Effects/Toxicity
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*abdominal pain
*reversible alopecia
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eased LFT
( AST & ALT)
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Adverse Effects/Toxicity
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Adverse Effects/Toxicityc Uses
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Therapeutic Uses Adverse Effects/Toxicity
Influenza A & B!
duration/severity of Sx
by 1 d
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Rx NOT incidence of
complications
Avian H5N1still ~susceptible
to neuraminidase inhibitors
Therapeutic Uses Adverse Effects/Toxicity
* herpes keratitis
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Therapeutic Uses Adverse Effects/Toxicity
* fever blister: Rx ASAP
* 1oor recurrent genital HSV * N/V
* suppressive Rx for recurrent
genital HSV
* HSV proctitis * diarrhea
* herpes zoster (VZV)
* prophylaxis of CMV retinitis
in pts w/ transplanted organs* headache
b/c inhb DNA synth NOT
effectv against non-
replicating, latent viruses
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* HSV & VZV strains resistant
to acyclovir
* CMV strains resistant to
ganciclovir& cidofovir
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Therapeutic Uses Adverse Effects/Toxicity
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* HSV & VZV strains resistantto acyclovir
* CMV
* CMV
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* CMV strains resistant to
ganciclovir& cidofovir
Pharmacological Effects Therapeutic Uses
* CMV
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CCR5-tropic pts (HIV tropism test needed
prior)
* Rx for sero(+) HIV pt offered when:
3.Prevent development of resistance to antiviral drugs
high viral loads despite contd Rx w/
other drugs
*** HAART ***
1. NNRTI-based (preferred)
Abacavir + lamivudine + zidovudine
Combo: (TZV) one log in 2-8wks
Not detectable (55,000 copies/ml
* Efficacy of Rx determ by viral load
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MDR HIV infxns
*Many CYP450 interactions
PI (lopin) + PI (riton) + NRTI (lamiv) + NRTI (stavu, zido)
or
3. NRTI based regimen
Not effect if viral load >100,000)
Abacavir+ lamivudine+ zidovudine
(Trizivir)
NNRTI (efav) + NRTI (lamiv)+ NRTI (zido, stavu,
tenofovir)
or
2. PI-based
Often effectv when HIV resistant to NRTIs
affects CYP450 multiple drug
interactions
*Used w/ NRTI b/c diff MOA
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(dividing bacilli)
al Effects Therapeutic Uses Adverse Effects/Toxicity
*1st
obligatory drug for Rx
TB
*NEVER used alone to Rx
active TB b/c rapid
development of
resistance
*Healthy people PPD(+) &
CXR(-): (Not active TB)
INHsingle agent Rx b/c
pt immun systm inhb
growth of bact (esp if
seroconvernsion w/in
previous 2 yrs)
is a cofactor
Vit B6)
* riton as pharmaco-kinetic enhancer inhb CYP450 hepatic clear of
lopin daily maintn dose
* riton = substrate & inhbtr of CYP3A4
(& CYP450)
y by B6 deficiency
*metabolized by hepatic N-acetylation
slow acetylator pt thought to be at
neuro- & hepatotoxicity
*hepatotoxicity
- Lower risk in younger adults
- ETOH hepatotox by INH
- 20% pt 3-4x AST & AGT but
necess to stop Rx
w/o Rx: ~5-15% lifetime
risk of developing TB
disease
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- Rx: daily dose of B6 prevents & r
neuropathy
*neurotoxicity
- INH = struct sim topyridoxine (Vit B
- INH antagonizes rxns where B6 is a
- Periph neuropathy (axonal sensori
polyneuropathy) neuropathy by B6
- ~preceded by paresthesias of hand
If pt 35 y.o. &serconversion date
unknown: do NOT use
INH.
Use Rifampininstead
- ~1% pt severe hepatitis (jaundic
quad pain, n/v) STOP Rx else deat
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ects Therapeutic Uses
*Rifampin + INH: preg category C Be
should > risk to fetus
*pt > 35 y.o. on INH: carefully monitor
*Drug regimens w/ rifampinclear mycobact fr sputum ~2wks
faster than regiments w/o rifampin
*NEVER used alone to Rx active TB b/c rapid development of
resistance
*2nd
obligatory drug for Rx TB
*TB prophylaxis: alternative to INH
-
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Pharm Effects Therapeutic Uses Adverse Effects/Toxicit
*NEVER used alone to Rx active TB b/c rapid dev of resistance
illi in macrophages
*ocular damage
*Also Rx M. avium (MAC)
*Replacement for rifampinin HIV pts (b/c only 50% of CYP
induction caused by rifampin)
*NEVER used alone to Rx
active TB b/c rapid
development of
resistance
*50% resist INH-Rifampin also resistant to PZA
*Used as 3rd
drug w/ INH& Rifampin
*PCN-resistant strep pneumo
*MRSA
*Can elim meningococcal carrier state
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2. mycobact
disseminated infxn
1. mycobact
meningitis
*Given i.m. or i.v. Rx:
- poss serious retrobulbar neuritis
abnormal red/green vision
- Must obtain a basal vision exam be
- Visual exam q4-6 wks recommende
*No clin significant drug interactions
*Used as 4th
drug w/ INH-
Rifamp-PZA
Streptomycin-resist TB
poss susceptible to
Amikacin(see AGs)
*Also Rx M. avium (MAC)
*~80% resist INH-
Rifampin also
resistant to EMB
*~80% resist INH-
Rifampin also
resistant to streptomycin
*sometimes replaces
EMBin TB combo Rx: INH-
Rifamp-PZA
*greater vestibular toxicitythan the oth
loss of balance
*less auditory toxicity than the other AG
*less renal toxicity than the other AGs
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Anaerobic Coverage
Good
Twice/wkly INH& Rifampin
Directly Observed Therapy (DOT)
1st
2 weeks after actv disease detected:
Daily R-I-P-E@ home or hospital
Weeks 3-8 (pt should be smear (-) for b
Twice/wkly R-I-P-Ebut
INHdose & PZA-EMB
Weeks 9-26:
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Cefoxitin
Cefotetan
Good
Good
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-
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-
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-
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-
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-
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-
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-
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Bactericidal bygeneration.
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ceftriaxone-resis strep pnuemo & MR
NOT for enterococcus
Pharm Effects
3rd
generation
Excellent G()
Moderate G(+)
Pseudomonas
(Always combo: e.g. -lactam & AG, gent)
No G(+) actvy (incl strep pneumo CAP)
Bactericidal bygeneration.
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Cefotaxime & ceftriaxone:
Good G(+) actvy despite 3rd
gen
Ceftriaxone _
Single large i.m. dose for gonorrhea
**DOC: strep pneumo , effctv against PCN G-r
Meningitis (strep pneumo & Neisseria)
Strep: strep pn meng & - hemolytic stre
CAP(H flu, strep pneumo & Moraxella),
add ML (e.g. azithromycin) for atypical bugs
Cefotaxime _
Comm Acq Meningitis (H flu, Neisseria
Otitis media: After 2 fails w/ amoxor am
4th
generation
1st+ 3rd= 4thgen
Excellent G()
UTI by E. Coli
Pedi/adultUTI
1 p.o. dose for uncomplicated gonorrhea
of Action Pharmacological Effects
Moderate G(+)
> ceftazidime
Pseudo. aeruginosa & inpt strep pneu
G() meningitis (good CNS penetratio
Febrile neutropenic pt
Critically ill pts (ICU)
polymicrobial infxns & unknown infxn
ck aminoacyl tRNA access to A site of 30S
- do NOT use for infxns
- G(-) > macrolides
Moderately broad spectrum
Moderate G(+)
- 65% S. aureus suscept
- Strep (but not GBS)
- Avoid use in serious SSTI but can be used for co
Moderate G()
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Ts )
(Borrelia burgdorferi)
Relapsing fever
(Borrelia recurrentis)
Plague (Yersinia pestis)
Malaria
(Entamoeba histolytica & Plastmodium falciparum)
- Good for outpt G(-) infxns
Good INTRACELLULAR
Mycoplasma, Chlamydia, Rickettsia
Lyme Disease
ction Pharmacological Effects
site (P site)
chain does not move from A site
ps
---
Erythpads topically Rx acne
***DOC: atypical outpt CAP
-
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**DOC: outpt CAPb/c hi intracellular (atypical) & extracellula
(& low risk of MDR strep do not need to use FQ)
b/c intracellular [ ]
azith> clarith= eryth
**DOC: Cryptosporidiosis in AIDS pt
Combo Rx w/ paromomycin
Azith NOT good for extracellular pathogens
Pharmacological Effects
Anaerobes
moxi> levo= cipro
But use metronidazole or pip/tazoinstea
levo= cipro> moxi = gemi
Need culture for senstvy & need add pip/
Limited G(+)
moxi= gemi > levo> cipro
spectrum b/c overuse
Good G()
* Pseudomonas :
FQ only p.o. Rx for pseudo.
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(e.g. atypical CAP)
Good Intracellular!
Pharmacological Effects
DNA replication
cations GI
***DOC:
***DOC: i
*** 1st lin
(clarith)
*** 1st lin
- urinary
- , preg
- Upper
Good Intracellular! (e.g. atypical CAP)
Anaerobes
moxi> levo= cipro
But use metronidazole or pip/tazoinstead of FQ
FQ only p.o. Rx for pseudo.
levo= cipro> moxi = gemi
Need culture for senstvy & need add pip/tazo
Limited G(+)
moxi= gemi > levo> cipro
spectrum b/c overuse
Good G()
* Pseudomonas :
- Bact m
* Diarrhea
* MDR TB
* greatest
***DOC:
***DOC: i
*** 1st lin
(clarith)
*Systemic
* Diarrhea:
Avoid fo
-
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Mechanism of Action
Broad G(-) spectr
bactericidal
Will cover G(+) if
synthesis
G(-) = high doses
-
Add another dru
G(+) = low doses
Bind to 30Sbact ribosomal subunit:
1. Block init of peptide synth
2. misread mRNA codons incorrect amino acid added
nonfunc prot
3. prevent mRNA tsl b/c func polysomes broken into nonfunc
monosomes
Seldom used ALONE
~ Always combo w/ c
Synergy:
PCNs, cephs , & Vanc
penetrate G(-) cell
Irrev inhb of prot synth
but BACTERICIDAL
[ ]-dep & post-ABX effect
Cp rate & effic of killing large doses, less often
* Enter G(-)cell via aq porin chan in outer mb of cell wall
* Deeper penetration thru cell mb req actv Xport via O 2-dep
process involving H+grad
* Low O2tension (anaerobic cond) or low extracellular pH
cell wall Xport
- Never AG alone!
- Rx: endocarditis
-
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-
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-
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-
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-
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-
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-
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-
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-
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-
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-
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-
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-
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-
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Therapeuti
c Uses
*Anaero
bic
bacteria :
Adverse Effects/Toxicity
*common:
- n/v
-
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Bac
ter
oid
es
fragili
s
Clo
stri
diu
m
diff
icil
e
**DOC:
Trichom
oniasis(cure 80-
90%)
: p.o. &
topical
: p.o.
**DOC:
Giardiasis
(children
& adults)
Beaver
fever,
campers
fever
- dysguesia
-
xerostomia (dry mouth)
- abdominal pain
*uncommon:
- leukopenia
- dizziness
- headache
- metallic taste
-
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**DOC:
Amebias
is
(b/c
metron =
mixed
amebicid
e kills
luminal &
systemic
organism
s)
Rx may
be
followed
w/
luminal
amebicid
e e.g.
paromo
mycin)- ataxia
- seizure
bleeding w/ warfarin
Ingestion of ETOH
- n/v
- abdominal pain
- flushing (disulfiram-like
rxn)
*Monitor CBC & LFT w/
prolonged Rx of chronic
recurrent trichomoniasis
*Avoid 1st
trimester of
pregnancy
*Drug interactions:
- urticaria
- vaginal candidiasis
- peripheral neuropathy,
- pancreatitis
-
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Adverse
Effects/Tox
icity
Mechanism
of
Resistance
S/E
ab pain
diarrhea
headache
nausea
er, campers fever
Disulfiram inhb acetaldehyde
dehydrogenase (ADH)
acetaldehyde accum in blood
dii) in
)
-
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-
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-
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-
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-
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Mechanism
of
Resistance
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*No cross
resistance
w/ other
antiretrovi
ral classes
pt can
have
dual/mixe
d CXCR4-
tropic HIV
*Some
cross
resistanc
e in this
class b/c
each
drug has
slightly
diff MOA
-
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*Resistan
ce
quickly
develops
w/
monothe
rapy b/c
these
drugshave
same
MOA
*Resistan
ce to one
=resistanc
e to all
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risk for
NOT
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everses
6 )
cofactor
otor
deficiency
& feet
, upper rt
-
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Adverse
Effects/Toxicity
nefit
- Skin
- Saliva
-
Tears
- Skin
*Flu-like syndrome
*Drug interactions
(many drugs):
Strong inducer ofCYP450
Enhances hepatic
clearance of HIV
drugs (NNRTIs &
protease inhibitors)
*turn ORANGE
(annoying but
harmless):
- Urine
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Hepatitis: LFTs
are the norm but
disappear w/
continued Rx
*50% CYP450
induction of
Rifampin
Enhances hepatic
clearance of HIV
drugs (NNRTIs &
protease inhibitors)
*harmless yellow
discoloration of the
skin
*polymyalgias
*uveitis
*Rifampin + INH:
preg category C
Benefit should >risk to fetus
*N/V
*hepatoxicity (1-
5%)
*No clin significant
drug interactions
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impaired vision &
fore Rx
d
r AGs vertigo &
s
-
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Chemopro
phylaxis
Seroconve
rsion
(w/in 2
yrs):
300 mg
INHdaily
for 9
months
50%
probabilit
y of
developin
g active
TB
Avoid
ETOH b/c
risk of
hepatotox
.
cilli:
-
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-
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-
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A
Therapeutic Uses Adverse Eff
*thrombophlebitis: (uncommo
ceftoxitin
*superinfections esp w/ broad
*cross-reactv in pts w/ PCN alle
cross-reactv w/ later gen
1st
(5-10%)
3rd
/4th
(1-2%)
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(regens reduced Vit K for synth
prolonged PT bleeding(rar
b/c cephs inhb Vit K epoxide re
(cervical, urethral, orophryg, rectal)
esist strep pneumo & potent (low MIC)
strep pneumo)
ox/clav
Therapeutic Uses
mo
n)
**DOC: Rickettsia infxns
Covers 95% of MRSA
CAP (esp doxy)
Cheap & effectv Rx
Typicals (extracellular) munity-acq MRSA b/c drugs
- Strep pneumo
- H flu
- Moraxella catarrhalis
GI pro
- N/V
Do NOT gi
- milk -
- MulVi
- Ca++
-
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Partially metab by liver
MRSA & Actinobacter
-
Legionella
Very effectv against Chlamydia & Mycoplasma
pneumo
Rx: acne (esp Mino)
Doxycyline________
**DOC:pt w/ renal dysfunc b/c elim by fecal
excretion
Minocycline_________
Atypicals (intracellular)
- Mycoplasma pneumo
- Chlamydia
Superi- Disturb
- Oral, an
- C. diff p
Tetrac
- newly-f
- newly f
Photo
Hepat
Nephr
- Epiga
- Ab cr
- Diarr
GI prob
Therapeutic Uses
- Mycoplasma
- Chlamydia
Reasonable alt for PCN allergic pts w/ strep infxns (URI)
-----------------------
NOT good for staph & strep SSTIs b/c 7% staph susceptible
NOT for pedi otitis media
***DOC: atypical CAP
b/c excellent intracellular [ ] azith> clarith= eryth Gold standard: Legionella
Excellent for intracellular bugs, e.g.
- Mycobact. avium
- (NOT TB)
-
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r (typical) drug [ ]
Therapeutic Uses Adverse Effects/Toxicity
NEVER use cipro for G(+)!!!!
(incl strep pneumo)
*Cipro most effectv FQ for outpatient
UTI (E. coli) tho some strains resist FQ
still suscept to amox
*Rx: UTI
*Diarrhea: shigella, E. Coli, salmonella &
campylobacter
*MDR TB
of FQ
azo
Ciprofloxacin_______
Many CYP450 drug interactions (incl i
metab)
Phototoxicity
Gemifloxacin_______
50% pt develop rash after 7 days
Damage growing cartilage (tho short t
Tendon rupture
Q-T elongation:
- pt w/ congenital prolonged Q-T
- pt on other drugs that Q-T (sotal
Slow K+-medtd repolzn prolong Q-T
tachy (torsade de pointes)
*Also Rx M. avium (MAC)
-
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Therapeutic Uses Adverse Eff
DR strep pneumo
pt RxCAP
e: Rx inpt CAP Alt Rx: ceph (ceftriaxone, cefotaxime) + ML
e: outpt complicated UTIs
tract w/ func & struct abnorm, (e.g. calculi or catheter)
, children & hospitlzd pts
rinary tract affected (pyelonephritis)
- pt w/ congenital prolonged
- pt on other drugs that Q-
re likely resist
: shigella, E. Coli, salmonella & campylobacter
Slows K+
-medtd repolzn proltachy (torsade de pointes)
Levo & moxilow risk unless fac
imbalance)
Damage to growing cartilag
Tendon rupture
Q-T elongation:
actvy vs TB
DR strep pneumo
pt RxCAP
e: Rx inpt CAP Alt Rx: ceph (ceftriaxone, cefotaxime) + ML
infxns: Salmonella (some resist b/c Rx chickens)
shigella, E. Coli, salmonella & campylobacter
UTI b/c p.o. only sm drug amt in urine
-
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Pharmacological Effects Therapeutic Uses
m (incl enteric bact) & rapidly
in combo w/ an inhibitor of cell wall
class (e.g. gent -lactam)
!!!
ell wall synth inhbtr
inhb cell wall synth easier for AG to
S/E when *AG+p 5 d
Renal dysfunction ri
Furosemide(Rx: uri
*Can avoid nephroto
* Neuromuscular blo
blocking agents in O
Poss Very Toxic!
time & [ ] dep!
Longer CP> some cri
*Nephrotoxicity: (re
Damage to proximal tu
[creatinine]plasmaCo-Rx w/ other nephro
nephrotox
*Ototoxicity: (reversi
Vestibular ataxia, v
1 against extracellular bacilli
*TB (see TB drugs)
Ace in the hole for bact
resistant to gent& tobra
Given p.o. prior to surgery
decontaminate gut
Soley renalelim: dose in pt
w/ renal failure
Widely used in antibacterial
ear drops, eye drops &
ointments
Esp for Pseudo.
Add low dose -lactam or Vanc
(staph, strep or enterococcus)
-
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Mechanism of
Resistance
(same as PCN)
1. PBP site!
2.
Bugs begin tomake cephalo-
sporinases
cts/Toxicity
) poss esp w/ i.v. push
r spectrum cephs
rgy
s
-
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of clot factors 2, 7, 9, 10)
, assocd w/ cefotetan)
uctase
Adverse Effects/ToxicityMechanism of
Resistance
helate cations prevent drub absorb fr GI tract
---------------------------
1.Mut protects
binding site
2.Pump efflux
(tho Doxymay still
work)
blems (common)
e p.o. with:
Mg++
it - Al++
Fe++
-
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Widespread use in
livestock food
resistance of
Enterococci
nfections: b/c suppress fecal coliforms (C. diff & Candida grow)d GI func
al, vaginal candidiasis
seudomembranous colitis (Rx: metronidazole)
yclines bind to Ca++
rming teeth discoloration
rming bone deformity
sensitization: sunburn esp in fair people
otoxic (large do