Week 2_ Discussion NURS 6630
ligiarivera
Replie1Instructions-Week2.docxInstructions:
Respond to your colleague in one of the following ways:
· If your colleagues’ posts influenced your understanding of these concepts, be sure to share how and why. Include additional insights you gained.
· If you think your colleagues might have misunderstood these concepts, offer your alternative perspective and be sure to provide an explanation for them. Include resources to support your perspective.
**minimum of three (3) scholarly references are required for each reply cited within the body of the reply & at the end**
Reply # 1
Sheila Shafer
Initial Post
Top of Form
Constitutive receptor activity/inverse agonism and functional selectivity/biased agonism are two concepts in contemporary pharmacology possessing significant indications for drug use in medicine and research and new drug development processes since a drug can be simultaneously an agonist, an antagonist, and an inverse agonist acting at the same receptor (Berg & Clarke, 2018). Agonists are drugs with affinity (bind to the target receptor) and intrinsic efficacy (change receptor activity to produce a response). Antagonists have affinity but zero intrinsic efficacy; therefore, they bind to the target receptor but do not produce a response. Occupying a fraction of the receptor population (defined by the affinity of the antagonist), an antagonist reduces the probability of occupancy by an agonist. Thus, the presence of an antagonist will reduce receptor occupancy by an agonist with a corresponding reduction in response. Dopamine receptor antagonism is a compelling molecular target for treating various psychiatric disorders, including substance use disorders (Wager et al., 2017).
G-protein-coupled receptors (GPCRs) or seven transmembrane receptors (7-TM receptors) are the most prominent family of human cell surface receptors, a large protein group positioned on the cell membrane which binds to extracellular elements (Rehman & Dimri, 2021). GPCRs then transmit signals from extracellular substances to the G protein in the intracellular space. Ion gated channels control access in and out of neurons. The voltage-gated ion channels (VGIC) permit only one type of ion to permeate; ligand-gated ion channels (LGIC) are less selective, enabling two or more types of ions to pass through the channel pore (Clar & Maani, 2021). The agonist spectrum is a comparison that relates to both ion channels and G-protein-linked receptors. Both g couple proteins and ion gated channels are protein receptors embedded in cell membranes that bind to a molecule.
Epigenetics refers to the genetic information directed at defining the role of the entire genome. It studies heritable and stable changes in gene expression occurring through modifications in the chromosome rather than in the DNA sequence. Epigenetic mechanisms regulate gene expression through chemical changes of DNA bases and alterations to the chromosomal superstructure (Al Aboud et al., 2021). Pharmacology has been the most promising way to treat illnesses through epigenetic regulation. The role of epigenetics in providing pharmacologic action is to alter the drug's metabolic and pharmacokinetic response as in how microRNAs regulate virus and host in the pathogenesis of the disease (Rastgoo et al., 2017). Drugs get designed and experimented with restoring gene activity in illnesses induced or exacerbated by epigenetic mechanisms like stress-related dysfunctions, cancer, and inflammation. Kaliman P. (2019). The FDA has approved drugs that target epigenetic regulators to treat various cancers (Cheng et al., 2019).
A psychiatric mental health nurse practitioner (PMHNP) must understand pharmacologic actions and how prescriptions affect the central nervous system (CNS). An illustration is the effect of stimulants on patients with attention deficit hyperactivity disorder (ADHD) prescribed methylphenidate, which binds to the dopamine and norepinephrine transporters and blocks reuptake, raising the extracellular levels of these neurotransmitters (Chang et al., 2021). It is paramount for the PMHNP to grasp the medication's mechanism, metabolism, adverse effects, and half-life to deter undesired dilemmas or get the coveted clinical conclusion when managing multiple medicines. This information determines when to wean or discontinue administering the drugs to avoid withdrawal symptoms. Plus, info on phamarcoepigenetics and drug antagonism/agonism are vital in identifying drugs' short-term and long-term efficacy.
References
Al Aboud, N. M., Tupper, C., & Jialal, I. (2021). Genetics, Epigenetic Mechanism. In StatPearls. StatPearls Publishing.
Berg, K. A., & Clarke, W. P. (2018). Making Sense of Pharmacology: Inverse Agonism and Functional Selectivity. The international journal of neuropsychopharmacology, 21(10),
962–977. https://doi.org/10.1093/ijnp/pyy071
Chang, J.-C., Lin, H.-Y., Lv, J., Tseng, W.-Y. I., & Gau, S. S.-F. (2021). Regional brain volume predicts response to methylphenidate treatment in individuals with ADHD. BMC
Psychiatry, 21(1), 26. https://bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-021-03040-5
Cheng, Y., He, C., Wang, M., Ma, X., Mo, F., Yang, S., Han, J., & Wei, X. (2019). Targeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials. Signal transduction and
targeted therapy, 4, 62. https://doi.org/10.1038/s41392-019-0095-0
Clar, D.T. & Maani, C.V. (2021). Physiology, Ligand Gated Chloride Channel. [Updated 2021 Aug 9]. In: StatPearls [Internet]. StatPearls Publishing;
https://www.ncbi.nlm.nih.gov/books/NBK540983/
Kaliman, P. (2019). Epigenetics and meditation. Current opinion in psychology, 28, 76–80.https://doi.org/10.1016/j.copsyc.2018.11.010
Rastgoo, N., Abdi, J., & Hou, J. (2017). Role of epigenetics-microRNA axis in drug resistance of multiple myeloma. Journal of hematology & oncology 10(121).
https://doi.org/10.1186/s13045-017-0492-1
Rehman, S., & Dimri, M. (2021). Biochemistry, G Protein Coupled Receptors. In StatPearls. StatPearls Publishing.
Wager, T. T., Chappie, T., Horton, D., Chandrasekaran, R. Y., Samas, B., Dunn-Sims, E. R., Hsu, C., Nawreen, N., Vanase-Frawley, M. A., O'Connor, R. E., Schmidt, C. J., Dlugolenski, K., Stratman, N.
C., Majchrzak, M. J., Kormos, B. L., Nguyen, D. P., Sawant-Basak, A., & Mead, A. N. (2017). Dopamine D3/D2 Receptor Antagonist PF-4363467 Attenuates Opioid Drug-Seeking Behavior
without Concomitant D2 Side Effects. ACS chemical neuroscience, 8(1), 165–177. https://doi.org/10.1021/acschemneuro.6b00297
Bottom of Form
Instructions:
Respond
to your
colleague
in one of the following ways:
·
If your colleagues’ posts influenced your understanding of these concepts, be sure to share
how and why. Include additional insights you gained.
·
If y
ou think your colleagues might have misunderstood these concepts, offer your alternative
perspective and be sure to provide an explanation for them. Include resources to support your
perspective.
**minimum of three
(3)
scholarly references are required for each
reply
cited
within the body of the reply & at the end
**
Reply
#
1
Sheila
Shafer
Initial
Post
Constitutive
receptor
activity/inverse
agonism
and
functional
selectivity/biased
agonism
are
two
concepts
in
contemporary
pharmacology
possessing
significant
indications
for
drug
use
in
medicine
and
research
and
new
drug
development
processes
since
a
drug
can
be
simultaneously
an
agonist,
an
antagonist,
and
an
inverse
agonist
acting
at
the
same
receptor
(Berg
&
Clarke,
2018).
Agonists
are
drugs
with
affinity
(bind
to
the
target
receptor)
and
intrinsic
efficacy
(change
receptor
activity
to
produce
a
response).
Antagonists
have
affinity
but
zero
intrinsic
efficacy;
therefore,
they
bind
to
the
target
receptor
but
do
not
produce
a
response.
Occupying
a
fraction
of
the
receptor
population
(defined
by
the
affinity
of
the
antagonist),
an
antagonist
reduces
the
probability
of
occupancy
by
an
agonist.
Thus,
the
presence
of
an
antagonist
will
reduce
receptor
occupancy
by
an
agonist
with
a
corresponding
reduction
in
response.
Dopamine
receptor
antagonism
is
a
compelling
molecular
target
for
treating
various
psychiatric
disorders,
including
substance
use
disorders
(Wager
et
al.,
2017).
G
-
protein
-
coupled
receptors
(GPCRs)
or
seve
n
transmembrane
receptors
(7
-
TM
receptors)
are
the
most
prominent
family
of
human
cell
surface
receptors,
a
large
protein
group
positioned
on
the
cell
membrane
which
binds
to
extracellular
elements
(Rehman
&
Dimri,
2021).
GPCRs
then
transmit
signals
from
e
xtracellular
substances
to
the
G
protein
in
the
intracellular
space.
Ion
gated
channels
control
access
in
and
out
of
neurons.
The
voltage
-
gated
ion
channels
(VGIC)
permit
only
one
type
of
ion
to
permeate;
ligand
-
gated
ion
channels
(LGIC)
are
less
selective
,
enabling
two
or
more
types
of
ions
to
pass
through
the
channel
pore
(Clar
&
Maani,
2021).
The
agonist
spectrum
is
a
comparison
that
relates
to
both
ion
channels
and
G
-
protein
-
linked
receptors.
Both
g
couple
proteins
and
ion
gated
channels
are
protein
rec
eptors
embedded
in
cell
membranes
that
bind
to
a
molecule.
Epigenetics
refers
to
the
genetic
information
directed
at
defining
the
role
of
the
entire
genome.
It
studies
heritable
and
stable
changes
in
gene
expression
occurring
through
modificati
ons
in
the
chromosome
rather
than
in
the
DNA
sequence.
Epigenetic
mechanisms
regulate
gene
expression
through
chemical
changes
of
DNA
bases
and
alterations
to
the
chromosomal
superstructure
(Al
Aboud
et
al.,
2021).
Pharmacology
has
been
the
most
promising
way
to
treat
illnesses
through
epigenetic
regulation.
The
role
of
epigenetics
in
providing
pharmacologic
action
is
to
alter
the
drug's
metabolic
and
pharmacokinetic
response
as
in
how
microRNAs
regulate
virus
and
host
in
the
pathogenesis
of
the
disease
(Ra
stgoo
et
al.,
2017).
Drugs
get
designed
and
experimented
with
restoring
gene
activity
in
illnesses
induced
or
exacerbated
by
epigenetic
mechanisms
like
stress
-
related
dysfunctions,
cancer,
and
inflammation.
Kaliman
P.
(2019).
The
FDA
has
approved
drugs
tha
t
target
epigenetic
regulators
to
treat
various
cancers
(Cheng
et
al.,
2019).
A
psychiatric
mental
health
nurse
practitioner
(PMHNP)
must
understand
pharmacologic
actions
and
how
prescriptions
affect
the
central
nervous
system
(CNS).
An
illustr
ation
is
the
effect
of
stimulants
on
patients
Instructions:
Respond to your colleague in one of the following ways:
If your colleagues’ posts influenced your understanding of these concepts, be sure to share
how and why. Include additional insights you gained.
If you think your colleagues might have misunderstood these concepts, offer your alternative
perspective and be sure to provide an explanation for them. Include resources to support your
perspective.
**minimum of three (3) scholarly references are required for each reply cited
within the body of the reply & at the end**
Reply # 1
Sheila Shafer
Initial Post
Constitutive receptor activity/inverse agonism and functional selectivity/biased agonism are two
concepts in contemporary pharmacology possessing significant indications for drug use in medicine and
research and new drug development processes since a drug can be simultaneously an agonist, an antagonist, and
an inverse agonist acting at the same receptor (Berg & Clarke, 2018). Agonists are drugs with affinity (bind to
the target receptor) and intrinsic efficacy (change receptor activity to produce a response). Antagonists have
affinity but zero intrinsic efficacy; therefore, they bind to the target receptor but do not produce a response.
Occupying a fraction of the receptor population (defined by the affinity of the antagonist), an antagonist reduces
the probability of occupancy by an agonist. Thus, the presence of an antagonist will reduce receptor occupancy
by an agonist with a corresponding reduction in response. Dopamine receptor antagonism is a compelling
molecular target for treating various psychiatric disorders, including substance use disorders (Wager et al.,
2017).
G-protein-coupled receptors (GPCRs) or seven transmembrane receptors (7-TM receptors) are the most
prominent family of human cell surface receptors, a large protein group positioned on the cell membrane which
binds to extracellular elements (Rehman & Dimri, 2021). GPCRs then transmit signals from extracellular
substances to the G protein in the intracellular space. Ion gated channels control access in and out of neurons.
The voltage-gated ion channels (VGIC) permit only one type of ion to permeate; ligand-gated ion channels
(LGIC) are less selective, enabling two or more types of ions to pass through the channel pore (Clar & Maani,
2021). The agonist spectrum is a comparison that relates to both ion channels and G-protein-linked receptors.
Both g couple proteins and ion gated channels are protein receptors embedded in cell membranes that bind to a
molecule.
Epigenetics refers to the genetic information directed at defining the role of the entire genome. It studies
heritable and stable changes in gene expression occurring through modifications in the chromosome rather than
in the DNA sequence. Epigenetic mechanisms regulate gene expression through chemical changes of DNA
bases and alterations to the chromosomal superstructure (Al Aboud et al., 2021). Pharmacology has been the
most promising way to treat illnesses through epigenetic regulation. The role of epigenetics in providing
pharmacologic action is to alter the drug's metabolic and pharmacokinetic response as in how microRNAs
regulate virus and host in the pathogenesis of the disease (Rastgoo et al., 2017). Drugs get designed and
experimented with restoring gene activity in illnesses induced or exacerbated by epigenetic mechanisms like
stress-related dysfunctions, cancer, and inflammation. Kaliman P. (2019). The FDA has approved drugs that
target epigenetic regulators to treat various cancers (Cheng et al., 2019).
A psychiatric mental health nurse practitioner (PMHNP) must understand pharmacologic actions and
how prescriptions affect the central nervous system (CNS). An illustration is the effect of stimulants on patients
