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Cigarette smoking and rate of gastric emptying: Effect on alcohol absorption

Authors:

Abstract

To examine the effects of cigarette smoking on alcohol absorption and gastric emptying. Randomised crossover study. Research project in departments of medicine and nuclear medicine. Eight healthy volunteers aged 19-43 who regularly smoked 20-35 cigarettes a day and drank small amounts of alcohol on social occasions. Subjects drank 400 ml of a radiolabelled nutrient test meal containing alcohol (0.5 g/kg), then had their rates of gastric emptying measured. Test were carried out (a) with the subjects smoking four cigarettes an hour and (b) with the subjects not smoking, having abstained for seven days or more. The order of the tests was randomised and the tests were conducted two weeks apart. Peak blood alcohol concentrations, absorption of alcohol at 30 minutes, amount of test meal emptied from the stomach at 30 minutes, and times taken for 50% of the meal to leave the proximal stomach and total stomach. Smoking was associated with reductions in (a) peak blood alcohol concentrations (median values in non-smoking versus smoking periods 13.5 (range 8.7-22.6) mmol/l v 11.1 (4.3-13.5) mmol/l), (b) area under the blood alcohol concentration-time curve at 30 minutes (264 x 10(3) (0-509 x 10(3)) mmol/l/min v 140 x 10(3)) (0-217 x 10(3) mmol/l/min), and (c) amount of test meal emptied from the stomach at 30 minutes (39% (5-86%) v 23% (0-35%)). In addition, smoking slowed both the 50% gastric emptying time (37 (9-83) minutes v 56 (40-280) minutes) and the intragastric distribution of the meal. There was a close correlation between the amount of test meal emptied from the stomach at 30 minutes and the area under the blood alcohol concentration-time curve at 30 minutes (r = 0.91; p less than 0.0001). Cigarette smoking slows gastric emptying and as a consequence delays alcohol absorption.
Cigarette
smoking
and
rate
of
gastric
emptying:
effect
on
alcohol
absorption
Richard
D
ohnson,
Michael
orowitz,
Anne
F
Maddox,
Judith
MA\ishart,
David
J
C
earman
Department
of
Medicine,
Royal
Adelaide
Hospital,
North
Terrace,
Adelaide,>
South
Australian
Richard
D
Johnson,
FRACP,
senior
visiting
specialist
Michael
Horowitz,
FRACP,
associate
professor
of
medicine
Judith
M
Wishart,
BSC,
research
assistant
David
J
C
Shearman,
FRACP,
professor
of
medicine
Department
of
Nuclear
Medicine,
Royal
Adelaide
Hospital,
North
Terrace,
Adelaide,
South
Australia
Anne
F
Maddox,
MIR,
research
assistant
Correspondence
and
requests
for
reprints
to:
Dr
Johnson.
BMJ
1991;302:20-3
Abstract
Objective-To
examine
the
effects
of
cigarette
smoking
on
alcohol
absorption
and
gastric
emptying.
Design-Randomised
crossover
study.
Setting-Research
project
in
departments
of
medicine
and
nuclear
medicine.
Subjects-Eight
healthy
volunteers
aged
19-43
who
regularly
smoked
20-35
cigarettes
a
day
and
drank
small
amounts
of alcohol
on
social
occasions.
Interventions-Subjects
drank
400
ml
of
a
radio-
labelled
nutrient
test
meal
containing
alcohol
(0.5
g/kg),
then
had
their
rates
of
gastric
emptying
measured.
Test
were
carried
out
(a)
with
the
subjects
smoking
four
cigarettes
an
hour
and
(b)
with
the
subjects
not
smoking,
having
abstained
for
seven
days
or
more.
The
order
of
the
tests
was
randomised
and
the
tests
were
conducted
two
weeks
apart.
Main
outcome
measures-Peak
blood
alcohol
concentrations,
absorption
of
alcohol
at
30
minutes,
amount
of
test
meal
emptied
from
the
stomach
at
30
minutes,
and
times
taken
for
50%
of
the
meal
to
leave
the
proximal
stomach
and
total
stomach.
Results
-Smoking
was
associated
with
reductions
in
(a)
peak
blood
alcohol
concentrations
(median
values
in
non-smoking
versus
smoking
periods
13-5
(range
8.7-22.6)
mmol/l
v
11-1
(4-3-13-5)
mmol/l),
(b)
area
under
the
blood
alcohol
concentration-
time
curve
at
30
minutes
(264x
103
(0-509x
103)
mmol/lV
min
v
140x
103
(0-217x
103)
mmol/l/min),
and
(c)
amount
of
test
meal
emptied
from
the
stomach
at
30
minutes
(39%
(5-86%)
v
23%
(0-35%)).
In
addition,
smoking
slowed
both
the
50%
gastric
emptying
time
(37
(9-83)
minutes
v
56
(40-280)
minutes)
and
the
intragastric
distribution
of
the
meal.
There
was
a
close
correlation
between
the
amount
of
test
meal
emptied
from
the
stomach
at
30
minutes
and
the
area
under
the
blood
alcohol
concentration-time
curve
at
30
minutes
(r=0.91;
p<0
0001).
Conclusion-Cigarette
smoking
slows
gastric
emptying
and
as
a
consequence
delays
alcohol
absorption.
Introduction
Although
alcohol
and
tobacco
are
among
the
most
widely
used
drugs
in
the
world
and
are
often
used
together,
little
is
known
of
their
pharmacokinetic
interactions.
Like
most
other
drugs,
alcohol
is
absorbed
predominantly
from
the
small
intestine
by
virtue
of
its
enormous
surface
area
as
compared
with
the
stomach.
Because
the
rate
of
alcohol
absorption
is
dependent
on
gastric
emptying'2
factors
which
modify
gastric
emptying
will
also
modulate
the
rate
of
alcohol
absorption.2"
For
example,
the
rate
of
alcohol
absorption
is
slower
when
a
beverage
containing
alcohol
is
consumed
with
or
after
a
meal
rather
than
on
an
empty
stomach,2
faster
after
administration
of
metoclopramide
and
various
forms
of
gastric
surgery,
and
slower
after
administration
of
propantheline.4s
The
effect
of
tobacco
smoking
and
nicotine
on
gastric
emptying
is
controversial,
studies
finding
increased,6
decreased,7'0
or
unchanged61'
12
rates
of
gastric
emptying.
To
our
knowledge
the
effect
of
tobacco
smoking
on
alcohol
absorption
has
not
been
studied.
This
study
examines
the
effects
of
cigarette
smoking
on
alcohol
absorption
and
gastric
emptying.
Subjects
and
methods
The
studies
were
performed
in
eight
normal
volun-
teers
(seven
men,
one
woman)
aged
19-43
years
(median
25)
who
smoked
cigarettes
regularly
(20-35
a
day).
The
subjects'
body
weights
ranged
from-65
to
98
kg
(median
85
kg).
None
was
receiving
any
medicines
and
none
had
evidence
of
gastrointestinal
disease.
All
drank
small
quantities
of
alcohol
on
social
occasions,
but
alcohol
was
avoided
for
48
hours
before
each
measurement
of
gastric
emptying.
Written,
informed
consent
was
obtained
in
all
cases
and
the
study
was
approved
by
the
human
ethics
committee
of
the
Royal
Adelaide
Hospital.
Protocol-Each
volunteer
had
measurements
of
gastric
emptying
performed
in
a
crossover
study
(a)
while
smoking
four
cigarettes
an
hour,
beginning
15
minutes
before
the
study,
and
(b)
while
not
smoking,
having
abstained
from
cigarettes
for
at
least
seven
days.
The
order
of
the
tests
was
randomised
and
they
were
conducted
two
weeks
apart.
Each
study
began
at
roughly
1600,
the
subject
having
fasted
since
eating
a
standardised
breakfast
between
0700
and
0800.'3
All
the
cigarettes
were
filtered,
and
their
median
nicotine
and
tar
yields
were
0
9
(range
0
6-1
1)
mg
and
10
(6-12)
mg
per
cigarette
respectively.
The
liquid
test
meal
(400
ml)
consisted
of
orange
juice
diluted
in
water,
0
5
g
absolute
alcohol
per
kg
body
weight,
and
28-37
MBq
indium-113m
labelled
diethylenetriaminepenta-acetic
acid.2
The
energy
content
of
the
orange
juice
(total
carbohydrate
212
g,
sugar
16-4
g,
protein
1-6
g,
fat
0-2
g)
was
402
kJ,
and
for
a
70
kg
subject
an
additional
1026
kJ
was
contained
in
the
alcohol.
The
energy
content
for
the
meal
for
a
70
kg
subject
was
therefore
approximately
3-55
kJ/ml.
The
temperature
of
the
meal
ranged
from
190
to
21°C
and
its
pH
ranged
from
3-9
to
4-0.
Measurement
of
gastric
emptying-Details
of
the
isotope
test
have
been
reported.'3
Each
study
was
performed
with
the
subject
seated
in
front
of
a
scintillation
camera.
The
test
meal
was
consumed
within
two
minutes
and
the
point
of
completion
of
the
meal
taken
as
time
zero.
Data
were
corrected
for
movement
of
the
subject,
radionuclide
decay,
and
y
ray
(tissue)
attenuation.
13
From
the
curves
of
gastric
emptying
(expressed
as
a
percentage
of
the
total
meal
remaining
within
the
stomach
over
time)
we
derived
(a)
the
duration
of
the
lag
phase
before
any
of
the
meal
emptied
into
the
stomach,
(b)
the
amount
of
the
meal
that
had
emptied
from
the
stomach
at
10,
30,
and
60
minutes,
and
(c)
the
time
to
50%
emptying
of
the
total
stomach.
The
total
stomach
was
divided
into
proximal
and
distal
regions
of
interest
by
using
a
line
drawn
half
way
along
and
at
90
degrees
to
the
long
axis.
The
time
taken
for
50%
of
the
meal
to
leave
the
proximal
gastric
region
was
measured.
Measurement
of
blood
alcohol
concentrations
-In
each
study
blood
samples
for
measurement
of
alcohol
concentrations
were
taken
from
a
catheter
situated
in
BMJ
VOLUME
302
5
JANUARY
1991
20
a
forearm
vein
five
minutes
before
and
five,
10,
15,
20,
30,
45,
60,
75,
90,
105, 120,
135,
150,
165,
180,
and
210
minutes
after
the
test
meal
had
been
taken.
To
avoid
possible
contamination
the
skin
was
previously
cleaned
with
a
non-alcoholic
antibacterial
solution.
Samples
of
blood
were
stored
at
4°C
and
assayed
for
alcohol
within
72
hours
by
gas-liquid
chromatography.'4
The
areas
under
the
venous
blood
alcohol
concentration-
time
curves
between
zero
and
30
minutes,
zero
and
60
minutes,
and
zero
and
210
minutes
were
calculated.'
Statistical
analysis
-
Data
were
analysed
with
the
Wilcoxon
matched
pairs
signed
ranks
test
and
Pearson's
product
moment
correlation.
95%
Confidence
intervals
were
calculated
and
p
values
<0
05 taken
as
significant
in
all
analyses.
Results
Blood
alcohol
concentrations-The
areas
under
the
venous
blood
alcohol
concentration-time
curves
between
zero
and
30
minutes
and
zero
and
60
minutes
and
the
peak
blood
alcohol
concentrations
were
significantly
less
during
the
smoking
period
compared
with
values
during
the
non-smoking
period
(fig
1,
table
I).
Most
of
the
subjects
had
detectable
but
low
blood
alcohol
concentrations
at
210
minutes,
and
there
was
a
non-significant
reduction
in
the
area
under
the
blood
alcohol
concentration-time
curve
between
zero
and
210
minutes
in
the
smoking
period
compared
with
the
non-smoking
period
(p=0062).
Gastric
emptying-Gastric
emptying
was
significantly
slower
during
the
smoking
period
than
when
not
smoking
(table
II,
fig
2).
In
all
subjects
the
emptying
curve
was
non-linear,
and
in
the
non-smoking
periods
it
usually
approximated
a
monoexponential
pattern.
In
all
studies
performed
during
smoking
there
was
a
lag
phase
(minimum
duration
four
minutes)
before
any
of
the
meal
emptied
from
the
stomach
(table
II).
The
50%
emptying
time
from
the
proximal
gastric
region
was
significantly
greater
during
smoking
(fig
2).
There
were
significant
correlations
between
the
50%
emptying
times
from
the
proximal
stomach
and
total
stomach
140
I
120-
co
401
FIG
1-Mean
blood
alcohol
concentrations
after
consumption
of
test
meal
during
smoking
and
non-smoking
periods.
Bars
are
SEM
Time
(min)
300-i
E
0
In
-
0
co
cu
E
0
4-
E
0
0L
200-
100-
0-
150-
.-I
E
0
-C
0
E
0
(0
'a
100-
50-
p=0
014
Non-smoking
Smoking
p=0
01
4
0~~~~j
~~~I-
Non-smoking
Smoking
FIG
2-Individual
50%
emptying
times
(T50)
from
total
stomach
and
proximal
stomach
during
smoking
and
non-smoking
periods
300-
E
q
200-
c
E
la
100-
Cu
0
0
0
Non-smoking
r.0-83
(0-30
to
0-97);
p<0.01
0
0
Smoking
r-
0-95
(0-74
to
0-99);
p<0001
O
L,
.
.g
.
I
0
20
40
6
80
d
100
120
140
TABLE
I
-Median
blood
alcohol
concentrations
(ranges)
during
smoking
and
non-smoking
periods
Variable
Non-smoking
Smoking
p
Value
Peak
blood
alcohol
(mmol/l)
13-5
(87-226)
11
1(43-135)
0-008
Area
under
curve
at
30
minutes
(mmoWllmin)
(x
103)
264
(0-509)
140
(0-217)
0
014
Area
under
curve
at
60
minutes
(mmol/1/min)
(x
10')
647
(80-909)
469
(62-562)
0
013
Area
under
curve
at
210
minutes
(mmollUmin)
(x
10')
1609
(913-2132)
1429
(498-1827)
0
062
TABLE
II
-Median
gastric
emptying
values
(ranges)
during
smoking
and
non-smoking
periods
Variable
Non-smoking
Smoking
p
Value
Lag
(min)
2
(1-23)
13
(4-86)
0
010
Amount
emptied
at
10
minutes
(%)
11
(0-52)
0
(0-8)
0o010
Amount
emptied
at
30
minutes
(%)
39
(5-86)
23
(0-35)
0-014
Amount
emptied
at
60
minutes
(/)
72
(28-95)
56
(0-83)
0-013
50%
Emptying
time
from
total
stomach
(min)
37
(9-83)
56
(40-280)
0-012
50%
Emptying
time
from
proximal
stomach
(min)
14
(4-45)
24
(8-130)
0-014
Proximal
stomach
T50
(min)
FIG
3-Relations
between
50%
emptying
times
(T5o)
from
proximal
stomach
and
total
stomach
during
smoking
and
non-smoking
periods.
(r
Values
expressed
with
95%
confidence
intervals
in parentheses)
(fig
3)
in
both
the
non-smoking
(r=0-83
(95%
con-
fidence
interval
0
30
to
0
97);
p<0
01)
and
smoking
(r=0-95
(0-74
to
0-99);
p<0
001)
periods.
Relation
between
alcohol
absorption
and
gastric
emptying-The
areas
under
the
venous
blood
alcohol
concentration-time
curve
between
zero
and
30
minutes
and
zero
and
60
minutes
correlated
significantly
with
the
amount
of
the
meal
emptied
from
the
stomach
at
30
minutes
and
60
minutes
respectively
(fig
4).
In
the
non-
smoking
periods
the
correlations
were
r=0
95
(95%
confidence
interval
0
74
to
0
99;
p<0001)
and
r=0
90
(0
53
to
0-98;
p<0001)
respectively,
whereas
in
the
smoking
periods
the
correlations
were
r=0-78
(0-17
to
BMJ
VOLUME
302
5
JANUARY
1991
tS
n
21
FIG
4-Areas
under
venous
blood
alcohol
concentration-time
curve
plotted
against
percentage
of
liquid
meal
emptiedfrom
stomach
at
30
minutes
and
60
minutes
during
smoking
and
non-smoking
periods.
(r
Values
expressed
with
95%
confidence
intervals
in
parentheses)
FIG
5-Relations
between
peak
blood
alcohol
concentrations
and
50%
total
gastric
emptying
time
during
smoking
and
non-smoking
periods.
(r
Values
expressed
with
95%
confidence
interval
in
parentheses)
600-
500-
o
%
400-
300-
°o
E
6
0
Non-smo6king
_
200-
*
r=
0
95
(0-74
to
0-99);
p<O-001
0
Smioking
100-
r.
0
78
(0-17
to
0
96);
p<0-05
E
2
0
20
40
60
80
100
%
Liquid
emptied
from
stomach
at
30
minutes
8
co
1100-
,
1000-
8
900-
o
800-
o
700
c
i
600-
e
~500
*
<
400-
Non-smoking
300-
r.
0-90
(0-53
to
0-98);
p<0-001
2001
Smoking
100
*
°
r-
0-89(050
to
098);
p<001
0
2o
40
6o
8o
100
%
Liquid
emptied
from
stomach
at
60
minutes
25-0
250-
0
Non-smnoking
r=0-86
(0-39
to
0-97)
p<0
01
g
20
0-
O
0
Smoking
E
0
r=
0-83
(0-30
to
097);
p<0-01
15
0-
10
0-
*
.0
0~~~~~~~~~
0
100
260-
300
Total
stomach
T50
(min)
0-96;
p<0
05)
and r=0-89
(0
50
to
0-98;
p<001).
In
both
the
non-smoking
and
smoking
periods
there
was
a
significant
inverse
relation
between
the
peak
blood
alcohol
concentrations
and
the
50%
gastric
emptying
time
(non-smoking
period:
r=0-86
(95%
confidence
interval
0
39
to
0-97),
p<0-01;
smoking
period:
r=0-83
(0
30
to
0
97),
p<001)
(fig
5).
Discussion
After
ingestion
of
an
equivalent,
weight
adjusted
dose
of
alcohol
there
is
considerable
interindividual
and
intraindividual
variation
in
the
rate
of
absorption
and
peak
blood
alcohol
concentrations.'
Our
findings
confirm
that
these
differences
are
largely
attributable
to
variations
in
the
rate
of
gastric
emptying.'
2
We
studied
only
eight
subjects.
Nevertheless,
a
crossover
design
was
used,
which
in
seven
of
the
eight
subjects
showed
that
the
rate
of
total
gastric
emptying
was
slower
during
smoking.
In
the
remaining
subject
the
rate
was
unchanged
(fig
2).
Thus
in
this
series
cigarette
smoking
significantly
reduced
peak
blood
alcohol
concentrations
and
delayed
alcohol
absorption,
presumably
by
slowing
gastric
emptying.
These
observations
have
considerable
social
and
medicolegal
relevance.
It
is
legally
permissible
to
back
calculate
to
the
time
of
a
motor
vehicle
accident
the
blood
alcohol
concentration
in
motorists
suspected
of
drink-driving
offences.
The
variability
in
peak
blood
alcohol
concentrations
in
this
study
points
to
the
limitations
of
back
calculation
of
blood
alcohol
concentrations.
'S
Moreover,
smoking
and
nicotine
intake
should
be
controlled
for
in
studies
of
alcohol
absorption,
unlike
in
previous
stucies.16-19
The
effect
of
smoking
and
nicotine
on
gastric
emptying
has
been
the
subject
of
several
studies."'2
In
all
but
one
study6
smoking
was
found
to
delay
gastric
emptying
of
a
digestible
solid
meal.7
10
Miller
et
al
and
Petring
et
al
found
that
smoking
did
not
affect
the
rate
of
emptying
of
a
liquid
meal."'0
Petring
et
al
used
the
rate
of
paracetamol
absorption
as
an
indirect
measure
of
liquid
gastric
emptying,
and
this
technique
is
known
to
be
fairly
insensitive.20
Miller
et
al
studied
gastric
emptying
of
water,
and
their
observations
may
be
accounted
for
by
the
absence
of
nutrients
in
the
liquid
meal.
We
have
shown
that
smoking
significantly
slows
gastric
emptying
of
a
liquid
meal
containing
nutrients
and
that
this
delay
reflects,
at
least
in
part,
slowing
of
the
intragastric
distribution
of
the
meal.
The
contribution
of
nicotine
to
the
delay
in
gastric
emptying
produced
by
cigarette
smoking
remains
controversial.
Gritz
et
al
found
that
gastric
emptying
of
a
solid
meal
was
slightly
but
significantly
delayed
after
smoking
high
versus
low
nicotine
cigarettes.9
They
did
not,
however,
include
a
"non-smoking"
test.
In
other
studies
ingestion
of
nicotine
gum
had
no
effect
on
gastric
emptying.
'o
12
There
is
little
information
about
the
motor
mechanisms
by
which
cigarette
smoking
slows
gastric
emptying.
McDonnell
and
Owyang
have
recently
shown
that
smoking
inhibits
antral
contractions,2'
which
may
account
for
slowed
gastric
emptying
of
digestible
solid
meals.
Nicotine
reportedly
inhibits
antral
contractions
in
dogs.22
Valenzuela
et
al
reported
that
smoking
decreased
basal
pyloric
pressure,23
but
in
the
light
of
current
knowledge24
the
methodology
used
in
their
study
must
be
considered
to
be
technically
inadequate
and
the
results
viewed
with
scepticism.
The
slowing
of
the
intragastric
distribution
suggests
that
cigarette
smoking
decreases
proximal
gastric
tone,
which
may
account
for
the
slowed
emptying
of
a
nutrient
liquid
meal.25
In
view
of
the
probable
crucial
role
of
the
pylorus
in
the
regulation
of
nutrient
liquid
emptying,
however,26
27
the
effect
of
smoking
on
pyloric
motility
warrants
further
study
with
improved
methodology.
Muller-Lissner
reported
that
duodeno-
gastric
reflux
is
increased
by
smoking.8
The
retardation
of
gastric
motility
produced
by
smoking
may
be
important
in
the
pathogenesis
of
gastroesophageal
reflux20
and
the
reported
effects
of
cigarette
smoking
on
satiety.29
The
area
under
the
blood
alcohol
concentration-time
curve
at
30
minutes
was
taken
as
the
index
of
the
rate
of
alcohol
absorption
in
this
and
other
studies'
2
on
the
basis
that
the
rate
of
absorption
at
30
minutes
was
much
greater
than
the
rate
of
hepatic
metabolism.
We
now
know,
however,
that
the
stomach
metabolises
alcohol
by
virtue
of
the
presence
of
alcohol
de-
hydrogenase
in
gastric
mucosa,6'9
and
at
low
doses
of
alcohol
(0
15
g/kg)
consumed
in
the
fed
state
this
"first
pass"
effect
is
significant.
The
magnitude
of
this
effect
is
likely
to
be
greater
if
there
is
more
prolonged
contact
of
alcohol
with
the
gastric
mucosa
because
of
slowed
gastric
emptying.
Therefore,
although
much
higher
doses
of
alcohol
(0
5
g/kg)
were
used
in
our
study
and
the
subjects
were
fasting,
possibly
gastric
metabolism
of
alcohol
contributed
to
the
significant
reduction
in
the
area
under
the
blood
alcohol
concentration-time
curve
at
30
and
60
minutes
and
the
trend
for
a
significant
reduction
at
210
minutes
in
the
smoking
period
as
well
as
slower
gastric
emptying.
We
could
not
assess
total
alcohol
absorption
because
the
blood
alcohol
concentrations
did
not
reach
zero
in
all
subjects.
The
computer
program
used
to
divide
the
stomach
into
proximal
and
distal
regions
was
developed
by
Mr
P
Collins.
The
study
was
funded
by
the
Australian
Associated
Brewers.
1
Holt
S.
Observations
on
the
relation
between
alcohol
absorption
and
the
rate
of
gastric
emptying.
Can
Med
AssocJ7
1981;124:267-77.
22
BMJ
VOLUME
302
5
JANUARY
1991
2
Horowitz
M,
Maddox
A,
Bochner
M,
et
al.
Relationships
between
gastric
emptying
of
solid
and
caloric
liquid
meals
and
alcohol
absorption.
Amj
Physiol
1989;257:G291-8.
3
McFarlane
A,
Pooley
L,
Welch
I
McL,
Rumsey
RDE,
Read
NW.
How
does
dietary
lipid
lower
blood
alcohol
concentrations?
Gut
1986;27:15-8.
4
Finch
JE,
Kendall
MJ,
Mitchard
M.
An
assessment
of
gastric
emptying
by
breathalyser.
Brj
Clin
Pharmacol
1974;1:223-6.
5
Cotton
PB,
Walker
G.
Ethanol
absorption
after
gastric
operations
and
in
the
coetiac
syndrome.
Postgrad
Medj
1973;49:27-8.
6
Grimes
DS,
Goddard
J.
Effect
of
cigarette
smoking
on
gastric
emptying.
BMJ
1978;ii:460-1.
7
Nowak
A,
Jonderko
K,
Kaczor
R,
Nowak
S,
Skrzypek
D.
Cigarette
smoking
delays
gastric
emptying
of
a
radiolabelled
solid
food
in
healthy
smokers.
Scandj
Gastroenterol
1987;22:54-8.
8
Muller-Lissner
SA.
Bile
reflux
is
increased
in
cigarette
smokers.
Gastroenterology
1986;90:
1205-9.
9
Gritz
ER,
Ippoliti
A,
Jarvik
ME,
et
al.
The
effect
of
nicotine
on
the
delay
of
gastric
emptying.
Alimentation,
Pharmnacology
and
Therapy
1988;2:173-8.
10
Miller
G,
Palmer
KR,
Smith
B,
Ferrington
C,
Merrick
MV.
Smoking
delays
gastric
emptying
of
solids.
Gut
1989;30:50-3.
11
Petring
OU,
Adelhoj
B,
Ibsen
M,
Brynnum
J,
Poulsen
HE.
Abstaining
from
cigarette
smoking
has
no
major
effect
on
gastric
emptying
in
habitual
smokers.
Brj
Anaesth
1985;57:
1104-6.
12
Chaudhuri
TK,
Fink
S.
Effect
of
nicotine
gum
on
gastric
emptying.
Chest
1988;94:
1122.
13
Collins
PJ,
Horowitz
M,
Cook
DJ,
Harding
PE,
Shearman
DJC.
Gastric
emptying
in
normal
subjects:
a
reproducible
technique
using
a
single
scintillation
camera
and
computer
system.
Gut
1983;24:117-25.
14
Cooper
JDH.
Determination
of
blood
ethanol
by
gas
chromatography.
Clin
Chim
Acta
1971;33:483-5.
15
Lewis
KO.
Back
calculation
of
blood
alcohol
concentration.
BMJ
1987;295:
800-1.
16
DiPadova
C,
Worner
TM,
Julkunen
RJK,
Leiber
CS.
Effects
of
fasting
and
chronic
alcohol
consumption
on
the
first-pass
metabolism
of
ethanol.
Gastroenterology
1987;92:1169-73.
17
Caballeria
J,
Baraona
E,
Rodamilans
M,
Leiber
CS.
Effects
of
cimetidine
on
gastric
alcohol
dehydrogenase
activity
and
blood
ethanol
levels.
Gastroenterologe
1989;%:388-92.
18
Caballeria
J,
Frezza
M,
Hernandez-Munoz
R,
et
al.
Gastric
origin
of
the
first-pass
metabolism
of
ethanol
in
humans:
effect
of
gastrectomy.
Gastroenteroloy
1989;97:1205-9.
19
Frezza
M,
DiPadova
C,
Pozzato
G,
Terpin
M,
Baraona
E,
Lieber
CS.
High
blood
alcohol
levels
in
women;
the
role
of
decreased
gastric
alcohol
dehydrogenase
activity
and
first-pass
metabolism.
N
Engl
Med
1990;322:
95-9.
20
Horowitz
M,
Collins
PJ,
Shearman
DJC.
Disorders
of
gastric
emptying
and
the
application
of
radionuclide
methods.
Arch
Intern
Med
1985;145:1467-75.
21
McDonnell
WM,
Owyang
C.
Smoking
markedly
inh4bits
gastric
motility
in
smokers
and
nonsmokers
[Abstract].
Gastroenterology
1989;%:A332.
22
Carlson
GM,
Rudden
RW,
Hug
CC,
Schmiege
SK,
Bass
P.
Analysis
of
the
site
of
nicotine
action
on
gastric
antral
and
duodenal
contractile
activity.
J
Pharmacol
Exp
Ther
1970;172:377-83.
23
Valenzuela
JE,
Defilippi
C,
Csendes
A.
Manometric
studies
on
the
human
pyloric
sphincter:
effect
of
cigarette
smoking,
metoclopramide,
and
atropine
Gastroenterology
1976;70:481-3.
24
Heddle
R,
Dent
J,
Toouli
J,
Read
NW.
Topography
and
measurement
of
pyloric
pressure
waves
and
tone
in
humans.
AmJ7
Physiol
1989;255:G491-7.
25
Azpiroz
F,
Malagelada
JR.
Intestinal
control
of
gastric
tone.
Am
J
Pkvsiol
1985;249:G501-9.
26
Heddle
R,
Fone
D,
Dent
J,
Horowitz
M.
Stimulation
of
pyloric
motility
by
intraduodenal
dextrose
in
normal
subjects.
Gut
1988;29:1349-57.
27
Houghton
LA,
Read
NW,
Heddle
R,
et
al.
Relationship
of
the
motor
activity
of
the
antrum,
pylorus
and
duodenum
to
gastric
emptying
of
a
solid-liquid
mixed
meal.
Gastroenteroloy
1988;94:1285-91.
28
McCallum
RW,
Mensch
R,
Lange
R.
Definition
of
the
gastric
emptying
abnormality
present
in
gastroesophageal
reflux
patients
[Abstract].
Gastroenterolgy
1981;80:A1226.
29
Grunberg
NE.
Nicotine
as a
psychoactive
drug:
appetite
regulation.
PsychopharmacolBull
1986;22:875-8
1.
(Accepted
18
September
1990)
Infectious
Diseases
Unit,
Department
of
Medicine,
Royal
Postgraduate
Medical
School,
London
W12
OHS
Rachanee
Cheingsong-
Popov,
PHD,
senior
research
officer
Christina
Panagiotidi,
MSC,
technician
Jonathan
Weber,
MRCP,
senior
lecturer
Department
of
Haematology,
Royal
Postgraduate
Medical
School,
London
W12
OHS
Stella
Bowcock,
MRCP,
senior
registrar
Treloar
Haemophilia
Centre,
Lord
Mayor
Treloar
College,
Hampshire
Anthony
Aronstam,
FRCPATH,
consultant
haematologist
Academic
Department
of
Public
Health,
St
Mary's
Hospital
Medical
School,
London
W2
1PG
Jane
Wadsworth,
PHD,
senior
lecturer
Correspondence
to:
Dr
J
Weber,
Jefferiss
Wing,
St
Mary's
Hospital
Medical
School,
LondonW2
INY.
BMJ7
1991;302:23-6
Relation
between
humoral
responses
to
HIV
gag
and
env
proteins
at
seroconversion
and
clinical
outcome
of
HIV
infection
Rachanee
Cheingsong-Popov,
Christina
Panagiotidi,
Stella
Bowcock,
Anthony
Aronstam,
Jane
Wadsworth,
Jonathan
Weber
Abstract
Objective-To
study
the
contribution
of
the
humoral
response
to
HIV-I
at
seroconversion
to
disease
outcome
after
84
months.
Design-A
retrospective
longitudinal
study.
Setting-Two
haemophilia
centres
in
the
United
Kingdom.
Patients-88
Haemophiliac
patients
infected
with
HIV-I
for
whom
sera
were
available
from
before
seroconversion
and
in
whom
clinical
foliow
up
data
were
available.
Results-Kaplan-Meier
survival
analysis
showed
a
significant
difference
between
a
high
titre
(>1600)
p24
antibody
response
at
seroconversion
and
pro-
longed
time
before
the
development
of
HIV
related
disease
(p=00008).
In
contrast,
higher
titres
of
antibody
to
gpl20
at
seroconversion
(>25
600)
cor-
related
with
more
rapid
clinical
deterioration
(p=0025).
Conclusions-The
first
humoral
response
to
HIV
proteins
at
seroconversion
is
associated
with
clinical
outcome;
patients
with
an
initial
low
titre
antibody
response
to
the
gagp24
protein
have
a
significantly
faster
rate
of
progression
to
CDC
stage
IV
disease.
Patients
with
a
high
titre
p24
antibody
response
progress
to
AIDS
more
slowly,
and
these
data
provide
an
explanation
why
p24
antigenaemia
is
not
universally
detected
in
patients
with
AIDS.
It
is
unclear
whether
the
association
between
a
strong
initial
p24
antibody
response
and
slower
progression
of
HIV
disease
is
causal
and
if
so
whether
it
is
due
to
viral
or
host
factors.
Introduction
After
infection
with
HIV-I
there
is
a
vigorous
humoral
response
to
structural
and
regulatory
viral
antigens.
8
Antibodies
to
the
env
gene
products
gpl6O/gpl2O
and
gp4l
are
produced
early
followed
shortly
by
antibodies
to
the
gag
gene
product
p24.9
By
studying
sequential
serum
samples
from
infected
patients
we
and
other
investigators
have
found
that
there
is
an
apparent
lowering
of
titre
of
p24
(gag)
antibodies
in
patients
with
more
rapid
progression
to
HIV
related
disease
(AIDS
related
complex
and
AIDS)"'-17
whereas
no
such
change
is
seen
with
gp4l
(env)
antibodies.
Subsequently,
it
has
been
repeatedly
shown
that
50-70%
of
patients
with
AIDS
have
detectable
titres
of
serum
p24
antigen
whereas
only
rarely
is
p24
antigen
detectable
in
asymptomatic
patients'82';
detection
of
p24
antigen
before
symptomatic
disease
correlated
significantly
with
prognosis
over
27
months.'9
The
loss
of
antibody
precedes
p24
antigenaemia
by
12-18
months,22
and
this
has
been
interpreted
as
being
due
to
the
formation
of
immune
complexes
of
p24
antibodies
with
rising
concentrations
of
p24
antigen.2324
We
have
recently
shown,
however,
that
undetectable
titres
of
p24
antibodies
in
antigenaemic
patients
do
not
rise
after
the
reduction
of
p24
antigen
titre
with
zidovudine
treatment25;
this
suggests
that
the
mechanism
for
the
decline
in
titre
of
p24
antibody
is
unlikely
to
be
the
simple formation
of
immune
complexes.
Cohort
data
have
shown
that
over
time
increasing
numbers
of
patients
with
preserved
high
titres
of
p24
antibody
and
without
detectable
titres
of
p24
antigen
develop
AIDS,
and
the
association
of
loss
of
p24
antibodies
with
prognosis
becomes
less
significant
(unpublished
data).25
No
explanation
has
yet
been
offered
for
these
findings
or
for
the
failure
to
detect
viral
antigens
in
30-50%
of
patients
with
AIDS,
even
when
plasma
viraemia
can
be
readily
detected.2627
As
the
presence
of
p24
antigen
has
been
used
as
a
surrogate
marker
of
virus
replication
these
data
require
elucidation.
We
thus
studied
the
role
of
the
first
humoral
response
to
HIV
gag,
env
proteins
at
seroconversion
BMJ
VOLUME
302
5
JANUARY
1991
23
... 9,19,21 Males have been reported as the most frequent perpetrators of harmful alcohol use. 5,22,23 Alcohol use is perceived to be more socially acceptable among males than females and this might be the underlying factor for the higher rate recorded among the male participants. However, evidence indicates a convergence in the prevalence of alcohol use among the two genders, as the gap has been documented to be closing in recent years. ...
... 40 Also, nicotine has been shown to reduce the intoxicating effects of alcohol, which could prompt individuals seeking the intoxicating effect to drink more. 22,41 Since both behaviours are complementary and the major focus of primary health physicians is often on smoking, there is an urgent need to integrate screening and behavioural counselling interventions for both lifestyle habits at the primary health care facilities in the region. Likewise, prevention programmes should take cognisance of both behaviours, and there should be a reconsideration of the long-separated public health policies relating to tobacco and alcohol use. ...
... Nicotine is believed to reduce the intoxicating effects of alcohol, which will likely prompt individuals seeking this effect to drink more. 22,41 Finally, middle-aged individuals are likely to have more disposable income, which improves their purchasing power and enables them to increase their intensity of binge drinking. ...
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Background: Binge drinking (BD) is a significant risk factor for several acute and chronic illnesses, including injuries. This study examines the rate, frequency and intensity of BD in Buffalo City Metropolitan Municipality (BCMM), South Africa.Methods: This was a cross-sectional survey of 998 adults attending the three largest outpatient clinics in BCMM. Rate, frequency and intensity of BD were assessed using the WHO STEPwise questionnaire. Descriptive and inferential statistics were carried out to determine the rate and determinants of binge drinking.Results: The overall rate of BD was 15.0%. Frequency and intensity of BD were 5.4 episodes per month and 13.4 drinks on one occasion, respectively. The study data showed that BD was commoner in males than females (24.0% vs. 10.8%). Smokers engagemore in BD than non-smokers (44.0% vs. 9.9%). In the analysis of socio-demographic variables, BD was commonest among students, age group 18–25 years, those never married and those on incomes between 2001 and 5000 Rand per month. In themultivariate logistic regression, after adjusting for confounders, only age less than 25 years (p 0.001) and male gender (p 0.001) were significant predictors of binge drinking. Also, male gender (p = 0.002) was significantly associated with frequency of BD. There was no significant gender variation in the intensity of BD. Only age and smoking were significantly associated with the intensity of BD.Conclusion: The rate of binge drinking was high among the study participants, and those who binge drink tend to do so frequently and at a high intensity. Women who binge drink also do so at a high intensity. There is a need for sensitisation campaigns and health advocacy talks on the dangers associated with binge drinking among young adults in this setting.
... 9,19,21 Males have been reported as the most frequent perpetrators of harmful alcohol use. 5,22,23 Alcohol use is perceived to be more socially acceptable among males than females and this might be the underlying factor for the higher rate recorded among the male participants. However, evidence indicates a convergence in the prevalence of alcohol use among the two genders, as the gap has been documented to be closing in recent years. ...
... 40 Also, nicotine has been shown to reduce the intoxicating effects of alcohol, which could prompt individuals seeking the intoxicating effect to drink more. 22,41 Since both behaviours are complementary and the major focus of primary health physicians is often on smoking, there is an urgent need to integrate screening and behavioural counselling interventions for both lifestyle habits at the primary health care facilities in the region. Likewise, prevention programmes should take cognisance of both behaviours, and there should be a reconsideration of the long-separated public health policies relating to tobacco and alcohol use. ...
... Nicotine is believed to reduce the intoxicating effects of alcohol, which will likely prompt individuals seeking this effect to drink more. 22,41 Finally, middle-aged individuals are likely to have more disposable income, which improves their purchasing power and enables them to increase their intensity of binge drinking. ...
Full-text available
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Background: Binge drinking (BD) is a significant risk factor for several acute and chronic illnesses, including injuries. This study examines the rate, frequency and intensity of BD in Buffalo City Metropolitan Municipality (BCMM), South Africa. Methods: This was a cross-sectional survey of 998 adults attending the three largest outpatient clinics in BCMM. Rate, frequency and intensity of BD were assessed using the WHO STEPwise questionnaire. Descriptive and inferential statistics were carried out to determine the rate and determinants of binge drinking. Results: The overall rate of BD was 15.0%. Frequency and intensity of BD were 5.4 episodes per month and 13.4 drinks on one occasion, respectively. The study data showed that BD was commoner in males than females (24.0% vs. 10.8%). Smokers engage more in BD than non-smokers (44.0% vs. 9.9%). In the analysis of socio-demographic variables, BD was commonest among students, age group 18–25 years, those never married and those on incomes between 2001 and 5000 Rand per month. In the multivariate logistic regression, after adjusting for confounders, only age less than 25 years (p < 0.001) and male gender (p < 0.001) were significant predictors of binge drinking. Also, male gender (p = 0.002) was significantly associated with frequency of BD. There was no significant gender variation in the intensity of BD. Only age and smoking were significantly associated with the intensity of BD. Conclusion: The rate of binge drinking was high among the study participants, and those who binge drink tend to do so frequently and at a high intensity. Women who binge drink also do so at a high intensity. There is a need for sensitisation campaigns and health advocacy talks on the dangers associated with binge drinking among young adults in this setting.
... 'leaky-gut') and decreased barrier function(228). Cigarette smoking has been demonstrated to affect drug absorption by slowing down gastric emptying, tightening gastric mucosa and impairing some active drug transporters(229)(230)(231). A recent study suggested that intestinal permeability and tight junction function is under circadian control through changes in the expression of tight junctions proteins and in P-gp functional activity(232)(233)(234).New regulatory guidelines on children's medicines have emphasized the need to consider paediatric populations during drug development(235). ...
Chapter
This chapter focuses on factors influencing regional epithelial permeation of drugs related especially to transporters. It highlights the important key messages as regard to modified‐release formulations. Drug absorption for ionizable drugs is determined by the pH in the region of intended release. Uptake and efflux transporters expressed in the gastrointestinal tract modulate the absorption of several drugs. Uptake transporters are more likely to act in synergy with other enzymes whose regional distribution is similar to CYP3A4, such as glucuronosyltransferases, sulfotransferases, and glutathione‐S‐transferases. The impact of the interplay between drug transport and metabolism on regional absorption can also be studied with perfusion techniques using cannulated in situ or isolated ex vivo intestinal regions in the rat. Drug–drug interactions can lead to changed systemic exposure, resulting in variations in drug response of the coadministered drug/s as well as safety concerns especially for low therapeutic index drugs.
... Pharmacologically, ethanol and nicotine have counteracting effects which partially titrate each other. Lě et al., (2000) said that repeated administrations of nicotine stimulate alcohol consumption whereas Johnson et al., (1991) and Chen et al., (2001) proposed that nicotine reduces the intoxicating effects of alcohol. As the desired effect of alcohol is significantly diminished by nicotine, cigarette smoking appears to promote the consumption of alcohol. ...