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- Identification
of drugs that
interact with
herbs in drug
development: Drug Discovery
Today, Vol.
12, No. 15-16.
(August 2007),
pp. 664-673.To
date, several
clinically
important
drugs have
been
identified
that interact
with commonly
used herbs.
These drugs
include (among
others)
warfarin,
midazolam,
digoxin,
amitriptyline,
indinavir,
cyclosporine,
tacrolimus and
irinotecan.
Importantly,
many of these
drugs have
very narrow
therapeutic
indices. Most
of them are
substrates for
cytochrome
P450s (CYPs)
and/or
P-glycoprotein
(P-gp).
Because
drug-herb
interactions
can
significantly
affect
circulating
levels of drug
and, hence,
alter the
clinical
outcome, the
identification
of drugs that
interact with
commonly used
herbal
medicines has
important
implications
in drug
development.
In silico, in
vitro, animal
and human
studies are
often used to
identify drug
interactions
with herbs. We
propose that
drug-herb and
herb-CYP
interaction
studies should
be
incorporated
into drug
development.
Source: Drug Discovery Today, Vol. 12, No. 15-16. (August 2007), pp. 664-673. - Characteristic
s and motives
of college
students who
engage in
nonmedical use
of
methylphenidat
e.: The American
journal on
addictions /
American
Academy of
Psychiatrists
in Alcoholism
and
Addictions,
Vol. 17, No.
3. (n 2008),
pp.
167-171.Methyl
phenidate
(MPH) has a
long history
of being an
effective
medication for
attention
deficit/hypera
ctivity
disorder
(ADHD).
Recently, the
nonmedical use
of MPH has
increased,
particularly
among college
students. To
investigate
this, we
surveyed 2,087
students
regarding MPH
misuse. Of
2,087
respondents,
110 (5.3%)
used MPH
nonmedically
at least once.
Most obtained
MPH free from
a friend,
acquaintance,
or family
member. Misuse
of Ritalin(R)
occurred four
times more
frequently
than
Concerta.(R)
Among Ritalin
abusers,
Intranasal use
was reported
more often
than oral.
Students
reported using
MPH
nonmedically
for
recreational
reasons as
well as to
improve
academic
performance.
Source: The American journal on addictions / American Academy of Psychiatrists in Alcoholism and Addictions, Vol. 17, No. 3. (n 2008), pp. 167-171. - Age of
Methylphenidat
e Treatment
Initiation in
Children With
ADHD and Later
Substance
Abuse:
Prospective
Follow-Up Into
Adulthood.: The American
journal of
psychiatry (1
April
2008)Objective
Animal studies
have shown
that age at
stimulant
exposure is
positively
related to
later drug
sensitivity.
The purpose of
this study was
to examine
whether age at
initiation of
stimulant
treatment in
children with
attention
deficit
hyperactivity
disorder
(ADHD) is
related to the
subsequent
development of
substance use
disorders.
Method The
authors
conducted a
prospective
longitudinal
study of 176
methylphenidat
e-treated
Caucasian male
children (ages
6 to 12) with
ADHD but
without
conduct
disorder. The
participants
were followed
up at late
adolescence
(mean age=18.4
years;
retention
rate=94%) and
adulthood
(mean
age=25.3;
retention
rate=85%). One
hundred
seventy-eight
comparison
subjects also
were included.
All subjects
were diagnosed
by blinded
clinicians.
The Cox
proportional
hazards model
included the
following
childhood
predictor
variables: age
at initiation
of
methylphenidat
e treatment,
total
cumulative
dose of
methylphenidat
e, treatment
duration, IQ,
severity of
hyperactivity,
socioeconomic
status, and
lifetime
parental
psychopatholog
y. Separate
models tested
for the
following four
lifetime
outcomes: any
substance use
disorder,
alcohol use
disorder,
non-alcohol
substance use
disorder, and
stimulant use
disorder.
Other outcomes
included
antisocial
personality,
mood, and
anxiety
disorders.
Results There
was a
significant
positive
relationship
between age at
treatment
initiation and
non-alcohol
substance use
disorder. None
of the
predictor
variables
accounted for
this
association.
Post hoc
analyses
showed that
the
development of
antisocial
personality
disorder
explained the
relationship
between age at
first
methylphenidat
e treatment
and later
substance use
disorder. Even
when
controlling
for substance
use disorder,
age at
stimulant
treatment
initiation was
significantly
and positively
related to the
later
development of
antisocial
personality
disorder. Age
at first
methylphenidat
e treatment
was unrelated
to mood and
anxiety
disorders.
Conclusions
Early age at
initiation of
methylphenidat
e treatment in
children with
ADHD does not
increase the
risk for
negative
outcomes and
may have
beneficial
long-term
effects.
Source: The American journal of psychiatry (1 April 2008) - The impact of
prescribed
psychotropics
on youth: Clinical
Practice and
Epidemiology
in Mental
Health, Vol. 3
(20 October
2007), 21.
Source: Clinical Practice and Epidemiology in Mental Health, Vol. 3 (20 October 2007), 21. - Expression of
constitutive
androstane
receptor,
hepatic
nuclear factor
4 alpha, and
P450
oxidoreductase
genes
determines
interindividua
l variability
in basal
expression and
activity of a
broad scope of
xenobiotic
metabolism
genes in the
human liver.: Drug Metab
Dispos, Vol.
35, No. 9.
(September
2007), pp.
1700-1710.Iden
tification of
genetic
variation
predictive of
clearance rate
of a wide
variety of
prescription
drugs could
lead to
cost-effective
personalized
medicine. Here
we identify
regulatory
genes whose
variable
expression
level among
individuals
may have
widespread
effects upon
clearance rate
of a variety
of drugs.
Twenty liver
samples with
variable CYP3A
activity were
profiled for
expression
level and
activity of
xenobiotic
metabolism
genes as well
as genes
involved in
the regulation
thereof.
Regulatory
genes whose
expression
level
accounted for
the highest
degree of
collinearity
among
expression
levels of
xenobiotic
metabolism
genes were
identified as
possible
master
regulators of
drug clearance
rate.
Significant
linear
correlations
(p < 0.05)
were
identified
among mRNA
levels of
CYP2A6,
CYP2B6,
CYP2C8,
CYP2C9,
CYP2C19, MRP2,
OATP2, P450
oxidoreductase
(POR), and
UDP-glucuronos
yltranferase
1A1,
suggesting
that these
xenobiotic
metabolism
genes are
coregulated at
the
transcriptiona
l level. Using
partial
regression
analysis,
constitutive
androstane
receptor (CAR)
and hepatic
nuclear factor
4 alpha (HNF4
alpha) were
identified as
the nuclear
receptors
whose
expression
levels are
most strongly
associated
with
expression of
coregulated
xenobiotic
metabolism
genes. POR
expression
level, which
is also
associated
with CAR and
HNF4 alpha
expression
level, was
found to be
strongly
associated
with the
activity of
many
cytochromes
P450. Thus,
interindividua
l variation in
the expression
level of CAR,
HNF4 alpha,
and POR
probably
determines
variation in
expression and
activity of a
broad scope of
xenobiotic
metabolism
genes and,
accordingly,
clearance rate
of a variety
of
xenobiotics.
Identification
of
polymorphisms
in these
candidate
master
regulator
genes that
account for
their variable
expression
among
individuals
may yield
readily
detectable
biomarkers
that could
serve as
predictors of
xenobiotic
clearance
rate.
Source: Drug Metab Dispos, Vol. 35, No. 9. (September 2007), pp. 1700-1710.
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