Opioid Overdose: Limitations in Naloxone Reversal of Respiratory Depression and Prevention of Cardiac Arrest
Anesthesiology,
Год журнала:
2023,
Номер
139(3), С. 342 - 353
Опубликована: Июль 4, 2023
Opioids
are
effective
analgesics,
but
they
can
have
harmful
adverse
effects,
such
as
addiction
and
potentially
fatal
respiratory
depression.
Naloxone
is
currently
the
only
available
treatment
for
reversing
negative
effects
of
opioids,
including
However,
effectiveness
naloxone,
particularly
after
an
opioid
overdose,
varies
depending
on
pharmacokinetics
pharmacodynamics
that
was
overdosed.
Long-acting
those
with
a
high
affinity
at
µ-opioid
receptor
and/or
slow
dissociation
kinetics,
resistant
to
naloxone.
In
this
review,
authors
examine
pharmacology
naloxone
its
safety
limitations
in
opioid-induced
depression
under
different
circumstances,
ability
prevent
cardiac
arrest.
Язык: Английский
Nanotherapeutics for Alleviating Anesthesia‐Associated Complications
Advanced Science,
Год журнала:
2024,
Номер
11(15)
Опубликована: Фев. 11, 2024
Abstract
Current
management
of
anesthesia‐associated
complications
falls
short
in
terms
both
efficacy
and
safety.
Nanomaterials
with
versatile
properties
unique
nano‐bio
interactions
hold
substantial
promise
as
therapeutics
for
addressing
these
complications.
This
review
conducts
a
thorough
examination
the
existing
nanotherapeutics
highlights
strategies
developing
prospective
nanomedicines
to
mitigate
anesthetics‐related
toxicity.
Initially,
general,
regional,
local
anesthesia
along
commonly
used
anesthetics
related
prevalent
side
effects
are
introduced.
Furthermore,
employing
nanotechnology
prevent
alleviate
is
systematically
demonstrated
from
three
aspects,
that
is,
1)
safe
nano‐formulization
anesthetics;
2)
nano‐antidotes
sequester
overdosed
alter
their
pharmacokinetics;
3)
pharmacodynamic
activities
treat
Finally,
prospects
challenges
facing
clinical
translation
anesthesia‐related
discussed.
work
provides
comprehensive
roadmap
effective
toxicity,
which
can
potentially
revolutionize
Язык: Английский
Investigation of monoclonal antibody CSX-1004 for fentanyl overdose
Nature Communications,
Год журнала:
2023,
Номер
14(1)
Опубликована: Дек. 5, 2023
Abstract
The
opioid
crisis
in
the
United
States
is
primarily
driven
by
highly
potent
synthetic
fentanyl
leading
to
>70,000
overdose
deaths
annually;
thus,
new
therapies
for
are
urgently
needed.
Here,
we
present
first
clinic-ready,
fully
human
monoclonal
antibody
CSX-1004
with
picomolar
affinity
and
related
analogs.
In
mice
reverses
antinociception
intractable
respiratory
depression
caused
ultrapotent
carfentanil.
Moreover,
toxicokinetic
evaluation
a
repeat-dose
rat
study
tissue
cross-reactivity
reveals
favorable
pharmacokinetic
profile
of
no
safety-related
issues.
Using
translational
non-human
primate
(NHP)
model
depression,
demonstrate
CSX-1004-mediated
protection
from
repeated
challenges
3-4
weeks.
Furthermore,
treatment
produces
up
15-fold
potency
reduction
NHP
respiration,
operant
responding
assays
without
affecting
non-fentanyl
opioids
like
oxycodone.
Taken
together,
our
data
establish
feasibility
as
promising
candidate
medication
preventing
reversing
fentanyl-induced
overdose.
Язык: Английский
An Engineered Human-Antibody Fragment with Fentanyl Pan-Specificity That Reverses Carfentanil-Induced Respiratory Depression
ACS Chemical Neuroscience,
Год журнала:
2023,
Номер
14(16), С. 2849 - 2856
Опубликована: Авг. 3, 2023
The
opioid
overdose
crisis
primarily
driven
by
potent
synthetic
opioids
resulted
in
more
than
500,000
deaths
the
US
over
last
20
years.
Though
naloxone,
a
short-acting
medication,
remains
primary
treatment
option
for
temporarily
reversing
effects,
alternative
countermeasures
are
needed.
Monoclonal
antibodies
present
versatile
therapeutic
opportunity
that
can
be
tailored
to
and
help
prevent
post-treatment
renarcotization.
ultrapotent
analog
carfentanil
is
especially
concerning
due
its
unique
pharmacological
properties.
With
this
mind,
we
generated
fully
human
antibody
through
drug-specific
B
cell
sorting
strategy
with
combination
of
fentanyl
probes.
resulting
pan-specific
was
further
optimized
scFv
phage
display,
producing
C10-S66K.
This
monoclonal
displays
high
affinity
carfentanil,
fentanyl,
other
analogs
reversed
carfentanil-induced
respiratory
depression.
Additionally,
X-ray
crystal
structures
bound
provided
structural
insight
into
key
drug:antibody
interactions.
Язык: Английский
Antibody Immunotherapies for Personalized Opioid Addiction Treatment
Journal of Pharmacology and Experimental Therapeutics,
Год журнала:
2025,
Номер
392(4), С. 103522 - 103522
Опубликована: Фев. 25, 2025
Approved
therapies
for
managing
opioid
addiction
involve
intensive
treatment
regimens
which
remain
both
costly
and
ineffective.
As
pharmaceutical
interventions
have
achieved
variable
success
treating
substance
use
disorders
(SUD),
alternative
therapeutics
must
be
considered.
Antidrug
antibodies
induced
by
vaccination
or
introduced
as
monoclonal
antibody
formulations
can
neutralize
destroy
opioids
in
circulation
before
they
reach
their
central
nervous
system
targets
act
enzymes
to
deactivate
receptors,
preventing
the
physiologic
psychoactive
effects
of
substance.
A
lack
"reward"
those
suffering
from
SUD
has
been
shown
result
cessation
promote
long-term
abstinence.
Decreased
production
costs
advent
novel
gene
that
stimulate
vivo
renewed
interest
this
strategy.
Furthermore,
advances
understanding
immunopathogenesis
revealed
distinct
mechanisms
neuroimmune
dysregulation
underlying
disorder.
Beyond
assisting
with
drug
use,
could
treat
reverse
pathophysiologic
hallmarks
contribute
cause
chronic
cognitive
defects
resulting
use.
In
review,
we
synthesize
key
current
literature
regarding
efficacy
immunotherapies
SUD.
We
will
explore
neuropharmacology
these
treatments
relating
evidence
studies
on
counteract
various
behaviors
drawing
parallels
similar
immunopathology
observed
neurodegenerative
disorders.
Finally,
discuss
implications
immunization
technologies
application
computational
methods
developing
personalized
treatments.
SIGNIFICANCE
STATEMENT:
Significant
new
contributing
our
recently
emerged
leading
a
paradigm
shift
concerning
role
immunology
neuropathogenesis
Concurrently,
immunotherapeutic
such
advanced
capabilities
applications
take
advantage
principles.
This
article
reviews
antibody-based
being
studied
highlights
directions
further
research
may
management
Язык: Английский
In vitro biophysical and pharmacological profiling predicts in vivo efficacy of anti-carfentanil monoclonal antibodies in mice
Biochemical and Biophysical Research Communications,
Год журнала:
2025,
Номер
770, С. 151995 - 151995
Опубликована: Май 10, 2025
Язык: Английский
An Engineered Human-Antibody Fragment with Fentanyl Pan-Specificity that Reverses Carfentanil-Induced Respiratory Depression
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Июль 4, 2023
The
opioid
overdose
crisis
primarily
driven
by
potent
synthetic
opioids
resulted
in
more
than
500,000
deaths
the
US
over
last
20
years.
Though
naloxone,
a
short
acting
medication,
remains
primary
treatment
option
for
temporarily
reversing
effects,
alternative
countermeasures
are
needed.
Monoclonal
antibodies
present
versatile
therapeutic
opportunity
that
can
be
tailored
and
help
prevent
post-treatment
renarcotization.
ultrapotent
analog
carfentanil,
is
especially
concerning
due
to
its
unique
pharmacological
properties.
With
this
mind,
we
generated
fully
human
antibody
through
drug-specific
B
cell
sorting
strategy
with
combination
of
carfentanil
fentanyl
probes.
resulting
pan-specific
was
further
optimized
scFv
phage
display.
This
antibody,
C10-S66K,
displays
high
affinity
fentanyl,
other
analogs,
reversed
carfentanil-induced
respiratory
depression.
Additionally,
x-ray
crystal
structures
bound
provided
structural
insight
into
key
drug:antibody
interactions.
Язык: Английский
Metabolic management of accidental intoxication
Current Opinion in Clinical Nutrition & Metabolic Care,
Год журнала:
2024,
Номер
27(2), С. 147 - 154
Опубликована: Янв. 17, 2024
Purpose
of
review
Unintentional
intoxication
comprises
a
major
chunk
all
intoxications.
Most
patients
are
in
the
pediatric
age
group
with
another
set
being
elderly.
Substances
found
to
cause
accidental
vary
from
country
and
even
within
different
regions
country.
Frequent
reviews
current
literature
needed
be
abreast
trends.
Recent
findings
Prescription
drugs
household
chemicals
culprits
when
it
comes
intoxication.
Acetaminophen,
digoxin
metformin
some
prominent
prescription
frequently
associated
unintentional
Increasingly
alcohol
based
hand
sanitizers
becoming
an
important
etiology
these
events,
following
their
increased
usage
during
COVID-19
pandemic.
Pattern
recognition
identify
class
intoxicant
supportive
care
including
prevention
further
absorption
excretion
cornerstones
therapy.
Antidote
available
should
used
promptly.
Summary
Knowledge
about
epidemiology
intoxications,
toxidrome
pattern
appropriate
antidote
beside
adequate
timely
help
successful
management
unfortunate
victim
Язык: Английский
Análisis toxicológico y mortalidad asociada al Carfentanilo
Revista Biociencias,
Год журнала:
2023,
Номер
unknown
Опубликована: Июнь 15, 2023
Introducción:
la
detección
del
Carfentanilo,
un
opioide
peligroso,
es
crítica
debido
a
su
aparición
en
otras
drogas
y
alta
potencia.
Su
consumo
conlleva
una
serie
de
efectos
negativos
como
depresión
respiratoria,
hipotensión,
bradicardia
disminución
motilidad
intestinal.
Objetivos:
el
propósito
esta
revisión
sistemática
examinar
o
evaluar
resumir
los
principales
métodos
toxicológica
relacionados
con
las
muertes
causadas
por
carfentanilo,
centrándose
estudio
adversos
químicos
que
produce
humanos.
Metodología:
investigación
recopiló
información
relevante
campo
toxicología
forense.
La
cual
se
enfocó
carfentanilo
cómo
afecta
personas.
Se
siguieron
pautas
PRISMA
utilizó
estrategia
PICO
definiendo
enfoque
estudio.
Resultados:
han
encontrado
diferentes
detección,
análisis
sangre,
orina,
saliva,
hígado,
líquido
pericárdico
humor
vítreo.
Estos
involucran
extracción
muestras
biológicas
posterior
mediante
técnicas
avanzadas
cromatografía
espectrometría
masas.
Incluso
desarrollado
masas
portátil
para
identificar
rápidamente
presencia
drogas.
Sin
embargo,
disponibilidad
estos
entornos
atención
médica
sigue
siendo
limitada.
Conclusiones:
crucial
entender
deterioro
daños
causados
al
organismo
atender
crisis
sobre
comercialización
sustancia
altamente
peligrosa.
Esto
resalta
necesidad
urgente
abordar
este
problema
proteger
sociedad
riesgos
asociados
carfentanilo.