Tài liệu CLINICAL PHARMACOLOGY 2003 (PART 12A) pdf

10
Nonmedical
use of
drugs
SYNOPSIS
The
nonmedical
use of
drugs presents social problems
with
important
pharmacological
aspects.
Social
aspects
Rewards
for the
individual
Decriminalisation
and
legalisation
Dependence
Drugs
and
sport
Tobacco
Dependence
Nicotine
pharmacology
Effects
of

chronic smoking
Starting
and
stopping
use
Passive
smoking
Ethyl
alcohol
Pharmacology
Car
driving
and
alcohol
Chronic
consumption
Withdrawal
Pregnancy
Pharmacological
deterrence
Psychodysleptics
•
Experiences
with
psychodysleptics
•
Individual
substances,
especially
cannabis

Stimulants
•
cocaine,
•
amfetamines.
•
methylxanthines (caffeine), ginseng, khat
Social
aspects
The
enormous social importance
of
this subject
warrants discussion here.
All
the
naturally occurring sedatives, narcotics,
euphoriants,
hallucinogens
and
excitants
were
discovered
thousands
of
years ago,
before
the
dawn
of

civilisation
By the
late
Stone
Age man
was
systematically
poisoning
himself.
The
presence
of
poppy heads
in the
kitchen middens
of
the
Swiss
Lake
Dwellers shows
how
early
in his
history
man
discovered
the
techniques
of
self-

transcendence
through drugs. There were dope
addicts
long
before
there were
farmers.
1
The
drives that induce
a
person more
or
less
mentally healthy
to
resort
to
drugs
to
obtain chemical
vacations
from
intolerable selfhood will
be
briefly
considered here,
as
well
as

some account
of the
pharmacological aspects
of
drug dependence.
The
dividing-line between legitimate
use of
drugs
for
social purposes
and
their abuse
is
indistinct
for it
is
not
only
a
matter
of
which drug,
but of
amount
of
drug
and of
whether
the

effect
is
directed antisocially
or
not. 'Normal' people seem
to be
able
to use
alcohol
for
their occasional purposes without harm but,
given
the
appropriate personality
and/or
environ-
mental adversity, many
may
turn
to it for
relief
and
1
Huxley A1957 Annals
of the New
York
Academy
of
Sciences
67:

677.
165
10
NONMEDICAL
USE OF
DRUGS
become dependent
on it,
both psychologically
and
physically.
But
drug abuse
is not
primarily
a
pharmacological problem,
it is a
social problem
with important pharmacological aspects.
A
further
issue
is
whether
a
boundary
can be
drawn between
the

therapeutic
and
nontherapeutic
use of a
therapeutic drug and, some would argue,
if
it
can be
drawn,
should
it be? The
matter
has
been
highlighted
by the use of
SSRI
antidepressants, e.g.
fluoxetine
(Prozac),
not to
treat depression
but to
elevate mood
—
make
a
person
feel
'better than

well' (see nonmedical use, below).
SOMETERMSUSED
Abuse potential
of a
drug
is
related
to its
capacity
to
produce immediate
satisfaction,
which
may be a
feature
of the
drug itself (amfetamine
and
heroin
give rapid
effect
while
tricyclic
antidepressants
do
not)
and its
route
of
administration

in
descending
order: inhalation/i.v.; i.m./s.c.; oral.
Drug abuse
2
implies excessive
(in
terms
of
social
norms) nonmedical
or
social drug use.
Nonmedical drug use, i.e.
all
drug
use
that
is not on
generally
accepted medical grounds,
may be a
term
preferred
to
'abuse'.
Nonmedical
use
means
the

continuous
or
occasional
use of
drugs
by
individuals,
whether
of
their
own
'free'
choice
or
under
feelings
of
compulsion,
to
achieve their
own
wellbeing,
or
what they conceive
as
their
own
wellbeing (see
motives below).
Drugs used

for
nonmedical purposes
are
often
divided into
two
groups, hard
and
soft.
Hard drugs
are
those that
are
liable seriously
to
disable
the
individual
as a
functioning member
of
society
by
inducing severe psychological and,
in the
case
of
cerebral depressants, physical, dependence.
The
group includes heroin

and
cocaine.
Soft
drugs
are
less dependence-producing. There
2
The
World
Health Organization adopts
the
definition
of the
United
Nations Convention
on
Psychotropic Drugs (1971).
Drug
abuse means
the use of
psychotropic substances
in a
way
that would
'constitute
a
public
health
and
social

problem'.
may
be
psychological dependence,
but
there
is
little
or
no
physical dependence except with heavy doses
of
depressants
(alcohol).
The
group includes
seda-
tives
and
tranquillisers, amphetamines, cannabis,
hallucinogens, alcohol, tobacco
and
caffeine.
This
classification
fails
to
recognise individual
variation
in

drug use. Alcohol
can be
used
in
heavy
doses
that
are
gravely disabling
and
induce severe
physical
dependence with convulsions
on
sudden
withdrawal; i.e.
for the
individual
the
drug
is
'hard'.
But
there
are
many people mildly psychologically
dependent
on it who
retain their position
in

home
and
society.
Hard-use where
the
drug
is
central
in the
user's
life
and
soft-use
where
it is
merely incidental,
are
terms
of
assistance
in
making this distinction, i.e.
what
is
classified
is not the
drug
but the
effect
it has

on, or the way it is
used
by, the
individual.
Drug dependence (see
p.
168).
Addiction.
The
term 'addict'
or
'addiction'
has not
been completely abandoned
in
this book because
it
remains convenient.
It
refers
to the
most severe
forms
of
dependence where compulsive craving dominates
the
subject's daily
life.
Such cases pose problems
as

grave
as
dependence
on
tea-drinking
is
trivial.
But
the use of the
term drug dependence
is
welcome,
because
it
renders irrelevant arguments about
whether some drugs
are
addictive
or
merely habit-
forming.
Nonmedical drug
use has two
principal
forms:
•
Continuous
use,
when
there

is a
true
dependence,
e.g.
opioids, alcohol, benzodiazepines.
•
Intermittent
or
occasional
use to
obtain
a
recreational experience, e.g. 'ecstasy'
(tenamfetamine),
LSD, cocaine, cannabis,
solvents,
or to
relieve
stress,
e.g. alcohol.
Both
uses commonly
occur
in the
same
subject,
and
some drugs, e.g. alcohol,
are
used

in
both ways,
but
others, e.g. 'ecstasy', LSD, cannabis,
are
virtually
confined
to the
second use.
Drives
to
nonmedical
(or
nonprescription) drug
use
are:
•
Relief
of
anxiety, tension
and
depression; escape
from
personal psychological problems;
detachment
from
harsh reality; ease
of
social
intercourse.

166
10
•
Search
for
self-knowledge
and
for
meaning
in
life,
including religion.
The
cult
of
'experience'
including aestheticism
and
artistic creation,
sex
and
'genuine',
'sincere'
interpersonal
relationships,
to
obtain
a
sense
of

'belonging'.
•
Rebellion against
or
despair about orthodox
social
values
and the
environment. Fear
of
missing something,
and
conformity with
own
social
subgroup (the young, especially).
•
Fun,
amusement, recreation, excitement,
curiosity (the young, especially).
Rewards
for the
individual
It
is
inherently unlikely that chemicals could
be
central
to a
constructive culture

and no
convincing
support
for the
assertion
has yet
been produced.
(That
chemicals might
be
central
to a
destructive
culture
is
another matter.) Certainly, like-minded
people practising what
are
often
illegal activities
will
gather into closely knit subgroups
for
mutual
support,
and
will
feel
a
sense

of
community,
but
that
is
hardly
a
'culture'. Even when drug-using
sub-
groups
are
accepted
as
representing
a
subculture,
it
may be
doubted
if
drugs
are
sufficiently
central
to
their ideology
to
justify
using
'drug'

in the
title.
But
claims
for
value
to the
individual
and to
society
of
drug experience must surely
be
tested
by the
criterion
of
fruitfulness
for
both,
and the
judgement
of
the
individual concerned alone
is
insufficient;
it
must
be

agreed
by
others.
The
results
of
both legal
and
illegal drug
use do not
give
encouragement
to
press
for a
large-scale experiment
in
this
field.
It
is
claimed that drugs provide
mystical
experience
and
that this
has
valid religious content. Mystical
experience
may be

defined
as a
combination
of
feelings
of
unity (oneness with nature
and/or
God),
ineffability
(experience beyond
the
subject's power
to
express),
joy
(peace, sacredness), knowledge (insight
into truths
of
life
and
values, illuminations),
and
transcendence
(of
space
and
time).
When
such

states
do
occur there
remains
the
question whether they tell
us
something about
a
reality outside
the
individual
or
merely something
about
the
mind
of the
person having
the
experience.
Mystical
experience
is not a
normal dose-related
pharmacodynamic
effect
of any
drug,
its

occurrence
REWARDS
FOR THE
INDIVIDUAL
depends
on
many
factors
such
as the
subject's
personality, mood, environment, conditioning.
The
drug
facilitates
rather than induces
the
experience;
and
drugs
can
facilitate
unpleasant
as
well
as
pleasant experiences.
It is not
surprising that mystical
experience

can
occur with
a
wide range
of
drugs
that alter consciousness:
.I
seemed
at
first
in a
state
of
utter
blankness

with
a
keen vision
of
what
was
going
on in the
room
around
me, but no
sensation
of

touch.
I
thought
that
I
was
near death; when, suddenly,
my
soul
became
aware
of
God,
who was
manifestly
dealing with
me,
handling
me, so to
speak,
in an
intense personal,
present
reality
I
cannot describe
the
ecstasy
I
felt.

3
This experience occurred
in the
19th
century
with chloroform;
a
general anaesthetic obsolete
because
of
cardiac depression
and
hepatotoxicity.
There
is no
good evidence that drugs
can
produce experience that passes
the
test
of
results,
i.e.
fruitfulness
to the
individual
and to
society.
Plainly there
is a

risk
of the
experience becoming
an
end in
itself
rather than
a
means
of
development.
CONCLUSIONS
The
value
of
nonmedical
use of
psychotropic drugs
can
be
summed
up
thus.
• For
relaxation, recreation, protection
from
and
relief
of
stress

and
anxiety; relief
of
depression:
moderate
use of
some 'soft' drugs
may be
accepted
as
part
of our
society.
• For
spiritually valuable experience:
justification
is
extremely doubtful.
• As
basis
for a
'culture'
in the
sense that drug
experience
(a) can be, and (b)
should
be
central
to an

individually
or
socially constructive
way of
life:
a
claim without validity.
• For
acute excitement: extremely dangerous.
GENERAL
PATTERN
OF USE
Divisions
are not
rigid
and
they change with fashion.
3
Quoted
in
James
W
(1902)
Varieties
of
religious experience.
Longmans, Harlow,
and
many
subsequent

editions
of
this
classic.
See
also Leary
T
(1970).
The
politics
of
ecstasy.
MacGibbon
and
Kee, London. Other editions, USA.
167
10
NONMEDICAL
USE OF
DRUGS
• Any
age:
alcohol; tobacco; mild dependence
on
hypnotics
and
tranquillisers; occasional
use of
LSD
and

cannabis.
•
Aged
16-35
years: hard-use
drugs,
chiefly
heroin,
cocaine
and
amphetamines
(including
'ecstasy'). Surviving users tend
to
reduce
or
relinquish heavy
use as
they enter middle
age.
•
Under
16
years: volatile inhalants,
e.g.
solvents
of
glues, aerosol sprays, vaporised
(by
heat)

paints, 'solvent
or
substance' abuse,
'glue-
sniffing'.
•
Miscellaneous:
any
drug
or
combination
of
drugs reputed
to
alter consciousness
may
have
a
local
vogue, however
brief,
e.g.
drugs used
in
parkinsonism
and
metered aerosols
for
asthma.
Decriminalisation

and
legalisation
The
decision whether
any
drug
is
acceptable
in
medical
practice
is
made
after
an
evaluation
of its
safety
in
relation
to its
efficacy.
The
same principle
should
be
used
for
drugs
for

nonmedical
or
social
use.
But the
usual
scientific
criteria
for
evaluating
efficacy
are
hardly applicable.
The
reasons
why
people choose
to use
drugs
for
nonmedical purposes
are
listed above. None
of
them carries serious weight
if
the
drug
is
found

to
have serious risks
to the
individuals
4
or to
society,
with either acute
or
chronic
use.
Ordinary prudence dictates that
any
such risks
should
be
carefully
defined
before
a
decision
on
legalisation
is
made.
There
is no
doubt that many individuals think,
rightly
or

wrongly,
that
private
use of
cannabis,
if
not of
'harder'
drugs,
is
their
own
business
and
that
the law
should permit
this
freedom.
The
likelihood
that demand
can be
extinguished
by
education
or by
threats
appears
to be

zero.
The
autocratic imple-
mentation
of
laws that
are not
widely accepted
in the
community leads
to
violent
crime, corruption
in the
police,
and
alienation
of
reasonable people
who
would otherwise
be an
important stabilising
influ-
ence
in
society.
4
Hazard
to the

individual
is not a
matter
for the
individual
alone
if it
also
has
consequences
for
society.
But
though written laws
are so
often
inflexible
and
combine
what would best
be
separated,
informal
judicial
discretion under present
law may be
per-
mitting more experimentation than would recurrent
legislative
debate.

It is
recognised that
this
untidy
approach,
which
may be
best
for the time
being,
cannot
satisfy
the
extravagant advocates either
of
licence
or of
repression.
A
suggested intermediate course
for
cannabis,
and
perhaps even
for
heroin,
is
that penalties
for
possession

of
small amounts
for
personal
con-
sumption should
be
removed (decriminalisation
as
opposed
to
legalisation), whilst retaining criminal
penalties
for
suppliers. Such
an
approach
is
increasingly
and
informally
being implemented.
Nobody knows what would happen
if the
production, supply
and use of the
major
drugs,
cannabis,
heroin

and
cocaine, were
to be
legalised,
as
tobacco
and
alcohol
are
legalised (with weak selling
restrictions).
There
are
those
who,
shocked
by the
evils
of
illegal trade, consider that legalisation could
only
make matters better.
The
debate continues
about
what kinds
of
evils
affecting
the

individual
and
society
can be
tolerated
and how
they
can be
balanced
against each other.
Dependence
Drug
dependence
is a
state arising
from
repeated,
periodic
or
continuous administration
of a
drug,
that
results
in
harm
to the
individual
and
sometimes

to
society.The
subject
feels
a
desire,
need
or
compulsion
to
continue
using
the
drug
and
feels
ill if
abruptly deprived
of
it
(abstinence
or
withdrawal
syndrome).
For
discussion
of
abrupt withdrawal
of
drugs

in
general
see
page
119.
Drug dependence
is
char-
acterised
by:
•
Psychological dependence:
the
first
to
appear;
there
is
emotional distress
if the
drug
is
withdrawn.
•
Physical dependence: accompanies
psychological
dependence
in
some cases; there
is

a
physical illness
if the
drug
is
withdrawn.
•
Tolerance.
168
DEPENDENCE
10
PSYCHOLOGICAL
DEPENDENCE
This
may
occur with
any
drug that alters con-
sciousness however bizarre, e.g. muscarine (see
p.
436)
and to
some that,
in
ordinary
doses,
do
not,
e.g. non-narcotic analgesics, purgatives, diuretics;
these latter provide problems

of
psychopathology
rather
than
of
psychopharmacology.
Psychological
dependence
can
occur merely
on a
tablet
or
injection,
regardless
of its
content,
as
well
as
to
drug
substances.
Mild
dependence
does
not
require that
a
drug should have important psychic

effects;
the
subject's
beliefs
as to
what
it
does
are as
important, e.g. purgative
and
diuretic dependence
in
people obsessed with dread
of
obesity.
We are all
physically dependent
on
food,
and
some develop
a
strong emotional
dependence
and eat too
much
(or
the
reverse); sexual

activity,
with
its
unique
mix of
arousal
and
relaxation,
can for
some become
compulsive
or
addictive.
PHYSICAL
DEPENDENCE
AND
TOLERANCE
Physical
dependence
and
tolerance imply that
adaptive
changes have taken place
in
body tissues
so
that when
the
drug
is

abruptly withdrawn these
adaptive
changes
are
left
unopposed, resulting
generally
in a
rebound overactivity
The
discovery
that
the CNS
employs morphine-like substances
(endomorphins, dynorphins)
as
neurotransmitters
offers
the
explanation that exogenously admin-
istered opioid
may
suppress endogenous pro-
duction
of
endorphins
by a
feedback
mechanism.
When administration

of
opioid
is
suddenly
stopped there
is an
immediate
deficiency
of
end-
ogenous opioid, which thus causes
the
withdrawal
syndrome.
Tolerance
may
result
from
a
compensatory
biochemical
cell
response
to
continued exposure
to
opioid.
In
short, both physical dependence
and

tolerance
may
follow
the
operation
of
homeostatic
adaptation
to
continued high occupancy
of
opioid
receptors.
Changes
of
similar type
may
occur
with
GABA
transmission, involving benzodiazepines.
Tolerance
also results
from
metabolic changes
(enzyme induction)
and
physiological/behavioural
adaptation
to

drug
effects,
e.g. opioids. Physical
dependence develops
to a
substantial degree with
cerebral
depressants,
but is
minor
or
absent with
excitant
drugs.
There
is
commonly cross-tolerance between
drugs
of
similar,
and
sometimes even
of
dissimilar,
chemical
groups, e.g. alcohol
and
benzodiazepines.
There
is

danger
in
personal experimentation;
as
an
American addict
has
succinctly
put it,
'They
all
think they
can
take
just
one
joy-pop
but
it's
the
first
one
that hooks you'.
5
Unfortunately
subjects cannot decide
for
them-
selves that their
dependence

will remain mild.
TYPES
OF
DRUG
DEPENDENCE
The
World Health Organization recommends that
drug dependence
be
specified
by
'type'
when under
detailed discussion.
Morphine-type:
—
psychological dependence severe
—
physical dependence severe; develops quickly
—
tolerance marked
—
cross-tolerance with related drugs
—
naloxone induces abstinence syndrome.
Barbiturate-type:
—
psychological dependence severe
—
physical dependence very severe; develops

slowly
at
high
doses
—
tolerance less marked than with morphine
—
cross-tolerance with alcohol, chloral,
meprobamate, glutethimide, chlordiazepoxide,
diazepam, etc.
Amfetamine-type:
—
psychological dependence severe
—
physical dependence slight: psychoses
occur
during
use
—
tolerance occurs.
Cannabis-type:
—
psychological dependence
—
physical dependence dubious
(no
characteristic
abstinence syndrome)
—
tolerance

occurs.
5
Maurer
D W,
Vogel
V H
1962
Narcotics
and
narcotic
addiction.
Thomas,
Springfield.
169
10
NONMEDICAL
USE OF
DRUGS
Cocaine-type:
—
psychological dependence severe
—
physical dependence
slight
—
tolerance slight
(to
some actions).
Alcohol-type:
—

psychological dependence severe
—
physical dependence with prolonged heavy
use
—
cross-tolerance with other sedatives.
Tobacco-type:
—
psychological dependence
—
physical dependence.
Drug
mixtures:
Barbiturate-amfetamine
mixtures
induce
a
characteristic alteration
of
mood that does
not
occur
with either drug alone
—
psychological dependence strong
—
physical dependence occurs
—
tolerance occurs.
Heroin-cocaine

mixtures: similar characteristics.
ROUTE
OF
ADMINISTRATION
AND
EFFECT
With
the
i.v. route
or
inhalation much higher peak
plasma concentrations
can be
reached than with
oral
administration. This accounts
for the
'kick'
or
'flash'
that abusers report
and
which many seek,
likening
it to
sexual orgasm
or
better.
As an
addict

said 'The ultimate high
is
death'
and it has
been
reported that when hearing
of
someone dying
of an
overdose, some addicts will seek
out the
vendor since
it
is
evident
he is
selling 'really good
stuff'.
6
Addicts
who
rely
on
illegal sources
are
inevitably exposed
to
being supplied diluted
or
even inert preparations

at
high prices. North American addicts
who
have come
to
the UK
believing themselves
to be
accustomed
to
high doses
of
heroin have
suffered
acute poisoning
when given, probably
for the
first
time, pure heroin
at
an
official
UK
drug dependence clinic.
SUPPLY
OF
DRUGSTO
ADDICTS
In the UK,
supply

of
officially
listed drugs
(a
range
of
opioids
and
cocaine)
for the
purpose
of
sustaining
6
Bourne
P
1976
Acute
drug abuse emergencies. Academic
Press,
New
York.
addiction
is
permitted under strict legal limitations.
Addicts
must
be
notified
by the

physician
to the
Home
Office
and in the
case
of
some opioids
and
cocaine,
the
physician requires
a
special licence.
By
such
procedure
it is
hoped
to
limit
the
expansion
of
the
illicit
market,
and its
accompanying crime
and

dangers
to
health, e.g.
from
infected
needles
and
syringes.
The
object
is to
sustain young
(usually)
addicts,
who
cannot
be
weaned
from
drug use,
in
reasonable health until they relinquish their
dependence
(often
over about
10
years).
When
injectable
drugs

are
prescribed there
is
currently
no way of
assessing
the
truth
of an
addict's
statement that
he/she
needs
x mg of
heroin
(or
other
drug),
and the
dose
has to be
assessed intuitively
by
the
doctor. This
has
resulted
in
addicts obtaining
more

than they need
and
selling
it,
sometimes
to
initiate
new
users.
The use of
oral methadone
or
other opioid
for
maintenance
by
prescription
is
devised
to
mitigate this problem.
TREATMENT
OF
DEPENDENCE
Withdrawal
of the
drug.
Whilst obviously impor-
tant, this
is

only
a
step
on
what
can be a
long
and
often
disappointing journey
to
psychological
and
social
rehabilitation, e.g.
in
'therapeutic commu-
nities'.
A
heroin addict
may be
given methadone
as
part
of a
gradual withdrawal programme (see
p.
337)
for
this drug

has a
long duration
of
action
and
blocks
access
of
injected
opioid
to the
opioid receptor
so
that
if, in a
moment
of
weakness,
the
subject
takes
heroin,
the
'kick'
is
blocked.
More
acutely,
the
physical

features
associated with discontinuing high
alcohol
use may be
alleviated
by
chlordiazepoxide
given
in
decreasing doses
for 4-6
days. Sympathetic
autonomic overactivity
can be
treated with
a (3-
adrenoceptor blocker
(or
clonidine) (see Abrupt
withdrawal
of
drugs).
Maintenance
and
relapse.
Relapsed addicts
who
live
a
fairly

normal
life
are
sometimes best treated
by
supplying drugs under supervision. There
is no
legal
objection
to
doing this
in the UK
(see above)
but
naturally this course, which abandons hope
of
cure,
should
not be
adopted until
it is
certain that
cure
is
virtually impossible.
A
less
harmful
drug
by a

less
harmful
route
may be
substituted, e.g. oral
170
10
methadone
for
i.v. heroin. Addicts
are
often
par-
ticularly
reluctant
to
abandon
the
i.v. route, which
provides
the
'immediate
high'
that they find,
or
originally found,
so
desirable.
Severe
pain

in an
opioid addict
presents
a
special
problem.
High-efficacy
opioid
may be
ineffective
(tolerance)
or
overdose
may
result;
low-efficacy
opioids will
not
only
be
ineffective
but may
induce
withdrawal symptoms, especially
if
they have some
antagonist
effect,
e.g. pentazocine. This leaves
as

drugs
of
choice nonsteroidal anti-inflammatory
drugs (NSAIDs), e.g. indometacin,
and
nefopam
(which
is
neither opioid
nor
NSAID).
Mortality
Young
illicit users
by
i.v. injection (heroin, benzo-
diazepines, amphetamine) have
a
high
mortality.
Either
death follows overdose,
or
septicaemia, endo-
carditis,
hepatitis,
AIDS,
gas
gangrene, tetanus
and

pulmonary embolism ensue
from
the
contaminated
materials
used without aseptic precautions (schemes
to
provide clean equipment mitigate this). Smugglers
of
illicit cocaine
or
heroin sometimes carry
the
drug
in
plastic bags concealed
by
swallowing
or in the
rectum
('body packing'). Leakage
of the
packages,
not
surprisingly,
may
have
a
fatal
result.

7
Escalation
A
variable proportion
of
subjects
who
start with
cannabis eventually take heroin. This
disposition
to
progress
from
occasional
to
frequent
soft
use of
drugs through
to
hard drug use,
when
it
occurs,
is
less
likely
to be due to
pharmacological actions, than
7

A
49-year-old
man
became
ill
after
an
international
flight.
An
abdominal radiograph showed
a
large number
of
spherical
packages
in his
gastrointestinal tract,
and
body-
packing
was
suspected.
As he had not
defaecated,
he was
given
liquid
paraffin.
He

developed ventricular
fibrillation
and
died. Post mortem examination showed that
he had
ingested more than
150
latex
packets, each containing
5 g of
cocaine,
making
a
total
of
almost
1 kg
(lethal oral dose
1-3 g).
The
liquid
paraffin
may
have contributed
to his
death
as the
mineral
oil
dissolves latex. Sorbitol

or
lactulose with
activated
charcoal should
be
used
to
remove ingested
packages,
or
surgery
if
there
are
signs
of
intoxication.
(Visser
L
et al
1998
Do not
give liquid
paraffin
to
packers.
Lancet
352:
1352)
DEPENDENCE

to
psychosocial
factors,
although increased sug-
gestibility induced
by
cannabis
may
contribute.
De-escalation
also occurs
as
users become disil-
lusioned with drugs over about
10
years.
'Designer
drugs'
This unhappily chosen term means molecular mod-
ifications
produced
in
secret
for
profit
by
skilled
and
criminally minded chemists. Manipulation
of

fentanyl
has
resulted
in
compounds
of
extraordinary
potency.
In
1976
a
too-clever 23-year-old addict seeking
to
manufacture
his own
pethidine 'took
a
synthetic
shortcut
and
injected himself with what
was
later
with
his
help proved
to be two
closely related
byproducts;
one was

MPTP (methylphenyltetra-
hydropyridine).
8,9
Three days later
he
developed
a
severe parkinsonian syndrome that responded
to
levodopa. MPTP selectively destroys melanin-
containing cells
in the
substantia nigra. Further such
cases
have occurred
from
use of
supposed
synthetic
heroin.
MPTP
has
since been used
in
experimental
research
on
parkinsonism. What
the
future

holds
for
individuals
and for
society
in
this area
can
only
be
imagined.
Volatile
substance abuse
Seekers
of the
'self-gratifying
high'
also inhale
any
volatile
substance that
may
affect
the
central nervous
system. These include: adhesives ('glue-sniffing'),
lacquer-paint solvents,
petrol,
nail varnish,
any

pressurised aerosol
and
butane liquid
gas
(which
latter
especially
may
'freeze'
the
larynx, allowing
fatal
inhalation
of
food,
drink, gastric contents,
or
even
the
liquid
itself
to
flood
the
lungs). Even
solids, e.g. paint scrapings, solid shoe polish,
may
be
volatilised over
a

fire.
These substances
are
particularly abused
by the
very young (school-
children),
no
doubt largely because they
are
accessible
at
home
and in
ordinary
shops
and
they
cannot easily
buy
alcohol
or
'street'
drugs (although
this latter
may be
changing
as
dealers target
the

youngest).
CNS
effects
include confusion
and
8
Williams A1984 British Medical Journal 289:
1401-1402.
9
Davis
G C et al
1979 Psychiatry Research
1:
249.
171
10
NONMEDICAL
USE OF
DRUGS
hallucinations, ataxia, dysarthria, coma, convul-
sions, respiratory
failure.
Liver, kidney,
lung
and
heart damage occur. Sudden cardiac death
may be
due to
sensitisation
of the

heart
to
endogenous
catecholamines.
If the
substance
is put in a
plastic
bag
from
which
the
user takes deep inhalations,
or
is
sprayed
in a
confined space,
e.g.
cupboard, there
is
particularly high risk.
A
17-year-old
boy was
offered
the use of a
plastic
bag and a can of
hair spray

at a
beach
party.
The
hair
spray
was
released into
the
plastic
bag and the
teenager
put his
mouth
to the
open
end of the bag
and
inhaled
he
exclaimed, 'God,
this
stuff
hits
ya
fast!'
He got up, ran 100
yards;
and
died.

10
Signs
of
frequent
volatile substance abuse
include perioral eczema
and
inflammation
of the
upper respiratory tract.
Drugs
and
sport
The
rewards
of
competitive sport, both financial
and in
personal
and
national prestige,
are the
cause
of
determination
to win at
(almost)
any
cost.
Drugs

are
used
to
enhance performance though
efficacy
is
largely undocumented. Detection
can be
difficult
when
the
drugs
or
metabolites
are
closely
related
to or
identical with endogenous
sub-
stances,
and
when
the
drug
can be
stopped well
before
the
event without apparent loss

of
efficacy,
e.g. anabolic steroids
(but
suppression
of
endogenous trophic hormones
can be
measured,
and can
assist).
PERFORMANCE
ENHANCEMENT
There
follow
illustrations
of the
mechanisms
by
which drugs
can
enhance performance
in
various
sports; naturally, these
are
proscribed
by the
authorities (International Olympic Committee (IOC)
Medical

Commission,
and the
governing bodies
of
individual sports).
10
Bass
M
1970 Sudden
sniffing
death. Journal
of the
American
Medical Association 212: 2075.
For
'strength sports'
in
which body weight
and
brute
strength
are the
principal determinants
(weight
lifting, rowing, wrestling): anabolic agents,
e.g. clenbuterol (B-adrenoceptor agonist), andro-
stenedione, methandienone, nandrolone, stanozolol,
testosterone. Taken together with
a
high-protein diet

and
exercise, these increase lean body weight
(muscle)
but not
necessarily strength.
It is
claimed
they allow more intensive training regimens
(limiting
cell
injury
in
muscles).
Rarely,
there
may
be
episodes
of
violent behaviour, known amongst
athletes
as
'roid
[steroid] rage'.
High doses
are
used,
with risk
of
liver damage

(cholestatic,
tumours) especially
if the
drug
is
taken
long-term, which
is
certainly
insufficient
to
deter
'sportsmen'.
They
may be
more inclined
to
take
more seriously
the
fact
that anabolic steroids
suppress pituitary gonadotrophin,
and so
testos-
terone production.
Growth
hormone
(somatrem, somatropin)
and

corticotrophin
use may be
combined with that
of
anabolic
steroids.
Chorionic
gonadotrophin
may be
taken
to
stimulate testosterone production
(and
prevent testicular atrophy). Similarly,
tamoxifen
(antioestrogen)
may be
used
to
attenuate some
of
the
effects
of
anabolic steroids.
For
events
in
which output
of

energy
is
explosive
(100
m
sprint): stimulants,
e.g.
amphetamine,
bro-
mantan, carphendon, cocaine, ephedrine
and
caffeine
(>
12
mg/1
in
urine). Death
has
probably occured
in
bicycle
racing (continuous hard exercise with short
periods
of
sprint)
due to
hyperthermia
and
cardiac
arrhythmia

in
metabolically stimulated
and
vaso-
constricted
subjects exercising maximally under
a
hot
sun.
For
endurance sports
to
enhance
the
oxygen
carrying
capacity
of the
blood (bicycling,
mar-
athon running):
erythropoietin,
'blood
doping'
(the
athlete
has
blood withdrawn
and
stored, then

transfused
once
the
deficit
had
been made
up
naturally,
so
raising
the
plasma haemoglobin
above
normal).
For
events
in
which steadiness
of
hand
is
essential
(pistol,
rifle
shooting):
B-adrenoceptor
blockers. Tremor
is
reduced
by the

B
2
-adrenoceptor blocking
effect,
as are
somatic symptoms
of
anxiety.
For
events
in
which body pliancy
is a
major
factor
(gymnastics):
delaying puberty
in
child gymnasts
by
endocrine techniques.
172
TOBACCO
10
For
weight reduction,
e.g.
boxers, jockeys:
diuretics.
These

are
also
used
to flush out
other
drugs
in the
hope
of
escaping detection; severe
volume depletion
can
cause venous thrombosis
and
pulmonary embolism.
Generally,
owing
to
recognition
of
natural
bio-
logical
differences
most competitive events
are sex
segregated.
In
many events
men

have
a
natural
physical biological advantage
and the
(inevit-
able)
consequence
has
been that women have
been deliberately virilised
(by
administration
of
androgens)
so
that they
may
outperform their
sisters.
It
seems
safe
to
assume that
anything
that
can be
thought
up to

gain advantage will
be
tried
by
competitors eager
for
immediate
fame.
Reliable
data
are
difficult
to
obtain
in
these areas.
No
doubt placebo
effects
are
important,
i.e.
beliefs
as
to
what
has
been taken
and
what

effects
ought
to
follow.
The
dividing line between what
is and
what
is
not
acceptable practice
is
hard
to
draw.
Caffeine
can
improve physical performance
and
illustrates
the
difficulty
of
deciding what
is
'permissible'
or
'impermissible'.
A cup of
coffee

is
part
of a
normal
diet,
but
some consider taking
the
same amount
of
caffeine
in a
tablet, injection
or
suppository
to be
'doping'.
For
any
minor
injuries
sustained during athletic
training NSAIDs
and
corticosteroids (topical, intra-
articular)
suppress
symptoms
and
allow

the
training
to
proceed maximally. Their
use is
allowed
subject
to
restrictions about route
of
administration,
but
strong
opioids
are
disallowed. Similarly,
the IOC
Medical
Code defines acceptable
and
unacceptable treatments
for
relief
of
cough,
hay
fever,
diarrhoea, vomiting,
pain
and

asthma. Doctors should remember that
they
may get
their athlete patients into trouble with
sports
authorities
by
inadvertent prescribing
of
banned substances.
11
Some
of the
isssues
seem
to be
ethical rather than
medical
as
witness
the
reported competition
success
of a
swimmer
who,
it is
alleged,
had
been

persuaded
under
hypnosis into
the
belief
that
he
was
being pursued
by a
shark.
Tobacco
Tobacco
was
introduced
to
Europe
from
South
America
in the
16th
century. Although
its
potential
for
harm
was
early recognised
its use was

taken
up
avidly
in
every society that
met it.
Current estimates
are
that there
are 1.1
billion smokers worldwide.
In
1990
there were
3
million smoking-related deaths
per
year, projected
to
rise
to 8
million
by
2020
(representing
12% of all
deaths).
12
COMPOSITION
The

principal components
are tar and
nicotine,
the
amounts
of
which
can
vary greatly depending
on
the
country
in
which cigarettes
are
sold. Regulation
and
voluntary agreement
by
manufacturers aspires
to
achieve
a
'global cigarette' containing
at
most
12
mg of tar and 1 mg of
nicotine.
The

composition
of
tobacco smoke
is
complex
(about
500
compounds have been
identified)
and
varies with
the
type
of
tobacco
and the way it is
smoked.
The
chief
pharmacologically active ingre-
dients
are
nicotine (acute
effects)
and
tars (chronic
effects).
Smoke
of
cigars

and
pipes
is
alkaline
(pH
8.5)
and
nicotine
is
relatively un-ionised
and
lipid-soluble
so
that
it is
readily absorbed
in the
mouth. Cigar
and
pipe smokers thus obtain nicotine without inhaling
(they
also have
a
lower death rate
from
lung cancer;
which
is
caused
by

non-nicotine constituents).
Smoke
of
cigarettes
is
acidic
(pH
5.3)
and
nicotine
is
relatively
ionised
and
insoluble
in
lipids. Desired
amounts
are
absorbed only
if
nicotine
is
taken into
the
lungs, where
the
enormous
surface
area

for
absorption compensates
for the
lower lipid solubility.
Cigarette smokers
therefore
inhale
(and
have
a
high
rate
of
death
from
tar-induced lung
cancer).
The
amount
of
nicotine absorbed
from
tobacco smoke
varies
from
90% in
those
who
inhale
to 10% in

those
who do
not.
Tobacco
smoke contains
1-5%
carbon monoxide
and
habitual smokers have
3-7%
(heavy smokers
as
much
as
15%)
of
their haemoglobin
as
carboxy-
11
UK
prescribers
can
find
general advice
in the
British
National
Formulary.
12

Editorial
1999
Tobacco
money
and
medical research.
Nature Medicine 5:125
173
10
NONMEDICAL
USE OF
DRUGS
haemoglobin, which cannot carry oxygen. This
is
sufficient
to
reduce exercise capacity
in
patients with
angina pectoris. Chronic carboxyhaemoglobinaemia
causes
polycythaemia (which increases
the
viscosity
of
the
blood).
Substances
carcinogenic
to

animals (polycyclic
hydrocarbons
and
nicotine-derived N-nitrosamines)
have been identified
in
tobacco smoke condensates
from
cigarettes, cigars
and
pipes. Polycyclic hydro-
carbons
are
responsible
for the
hepatic enzyme
induction that occurs
in
smokers.
Tobacco dependence
Psychoanalysts have made
a
characteristic con-
tribution
to the
problem. 'Getting something orally',
one
asserted ,
'is the
first

great libidinous
experience
in
life';
first
the
breast, then
the
bottle, then
the
comforter,
then
food
and
finally
the
cigarette.
13
Sigmund Freud, inventor
of
psychoanalysis,
was
a
lifelong
tobacco addict.
He
suggested that some
children
may be
victims

of a
'constitutional
intensification
of the
erotogenic significance
of the
labial
region', which,
if it
persists, will provide
a
powerful
motive
for
smoking.
14
While
psychological dependence
is
strong
and
accounts
for
part
of the
difficulty
of
stopping
smoking,
nicotine

possesses
all the
characteristics
of
a
drug
of
dependence
and
there
is
powerful reason
to
regard nicotine addiction
as a
disease.
A
report
on
the
subject concludes that most smokers
do not
do so
from
choice
but
because they
are
addicted
to

nicotine.
15
The
immediate satisfaction
of
smoking
is
due to
nicotine
and
also
to
tars, which provide
flavour.
Initially
the
factors
are
psychosocial; pharma-
codynamic
effects
are
unpleasant.
But
under
the
psychosocial
pressures
the
subject continues, learns

to
limit
and
adjust
nicotine intake,
so
that
the
pleasant pharmacological
effects
of
nicotine develop
13
Scott
R B
1957 British Medical Journal
1: 67 1.
14
Quoted
in
Royal Collage
of
Physicians 1977 Smoking
or
health. Pitman, London.
In
1929 Freud
posed
for a
photograph holding

a
large cigar prominently.
'He was
always
a
heavy smoker—twenty cigars
a day
were
his
usual
allowance
and he
tolerated abstinence
from
it
with
the
greatest
difficulty'.
Jones
E
1953 Sigmund Freud:
life
and
work. Hogarth Press, London.
and
tolerance
to the
adverse
effects

occurs. Thus
to
the
psychosocial pressure
is now
added pharma-
cological
pleasure.
Tolerance
and
some physical dependence occur.
Transient
withdrawal
effects
include
EEG and
sleep
changes, impaired performance
in
some psycho-
motor
tests,
disturbance
of
mood,
and
increased
appetite (with weight gain), though
it is
difficult

to
disentangle psychological
from
physical
effects
in
these last.
ACUTE
EFFECTS
OF
SMOKING
TOBACCO
•
Increased
airways
resistance
occurs
due to the
nonspecific
effects
of
submicronic particles, e.g.
carbon
particles less than
1 um
across.
The
effect
is
reflex;

even inert particles
of
this size cause
bronchial narrowing
sufficient
to
double airways
resistance;
this
is
insufficient
to
cause dyspnoea,
though
it
might
affect
athletic performance. Pure
nicotine inhalations
of
concentration comparable
to
that reached
in
smoking
do not
increase
airways resistance.
•
Ciliary

activity,
after
transient stimulation,
is
depressed,
and
particles
are
removed
from
the
lungs more slowly.
•
Carbon
monoxide
absorption
may be
clinically
important
in the
presence
of
coronary heart
disease (see above) although
it is
physiologically
insignificant
in
healthy young adults.
Nicotine

pharmacology
Pharmacokinetics
Nicotine
is
absorbed through mucous membranes
in a
highly pH-dependent fashion.
The
t
1
/
2
is 2 h. It is
largely
metabolised
to
inert
substances,
e.g.
cotinine, though some
is
excreted unchanged
in the
urine
(pH
dependent,
it is
un-ionised
at
acid pH).

Cotinine
is
used
as a
marker
for
nicotine intake
in
smoking surveys because
of its
convenient
t
1
/
2
(20 h).
15
Tobacco Advisory Group, Royal College
of
Physicians
2000
Nicotine addiction
in
Britain. London RCP.
174
10
Pharmacodynamics
Large
doses.
16

Nicotine
is an
agonist
to
receptors
at
the
ends
of
peripheral cholinergic nerves
whose
cell
bodies
lie in the
central nervous system,
i.e.
it
acts
at
autonomic
ganglia
and at the
voluntary neuro-
muscular
junction
(see Fig.
21.1). This
is
what
is

meant
by the
term 'nicotine-like'
or
'nicotinic'
effect.
Higher doses paralyse
at the
same
points.
The
central
nervous
system
is
stimulated,
including
the
vomiting centre, both directly
and via
chemore-
ceptors
in the
carotid body; tremors
and
convulsions
may
occur.
As
with

the
peripheral actions, depression
follows
stimulation.
Doses from/with smoking. Nicotine causes release
of
catecholamines
in the
CNS,
also serotonin,
and
antidiuretic hormone, corticotrophin
and
growth
hormone.
The
effects
of
nicotine
on
viscera
are
probably
largely
reflex,
from
stimulation
of
sensory receptors (chemoreceptors)
in the

carotid
and
aortic bodies, pulmonary circulation
and
left
ventricle.
Some
of the
results
are
mutually
antagonistic.
The
following account tells what generally
happens
after
one
cigarette,
from
which about
1 mg
nicotine
is
absorbed, although much
depends
on
the
amount
and
depth

of
inhalation
and on the
duration
of
end-inspiratory breath-holding.
On the
cardiovascular
system
the
effects
are
those
of
sympathetic autonomic stimulation. There
is
vasoconstriction
in the
skin
and
vasodilatation
in
16
Fatal
nicotine
poisoning
has
been reported
from
smoking,

from
swallowing tobacco,
from
tobacco
enemas,
from
topical
application
to the
skin
and
from
accidental
drinking
of
nicotine
insecticide
preparations.
In
1932
a
florist
sat
down
on a
chair,
on the
seat
of
which

a 40%
free
nicotine insecticide solution
had
been spilled.
Fifteen
minutes
later
he
felt
ill
(vomiting,
sweating,
faintness,
and
respiratory
difficulty,
followed
by
loss
of
consciousness
and
cardiac
irregularity).
He
recovered
in
hospital
over

about
24 h. On the
fourth
day he was
deemed
well enough
to
leave
hospital
and was
given
his
clothes
which
had
been kept
in a
paper bag.
He
noticed
the
trousers
were still damp. Within
one
hour
of
leaving hospital
he had to be
readmitted
suffering

again
from
poisoning
due
to
nicotine
absorbed
transdermally
from
his
still
contaminated
trousers.
He
recovered
over
three weeks,
apart
from
persistent
ventricular
extrasystoles
[Faulkner
J M
1933
1AM
A100:
1663].
NICOTINE
PHARMACOLOGY

the
muscles, tachycardia
and a
rise
in
blood
pressure
of
about
15
mmHg systolic
and 10
mmHg
diastolic,
and
increased plasma noradrenaline
(norepinephrine). Ventricular extrasystoles
may
occur.
Cardiac output, work
and
oxygen consump-
tion rise. Increased demand
for
blood
flow
that
is not
met
because coronary vessels

are
narrowed
by
atherosclerosis
may be a
mechanism
of
tobacco-
induced angina pectoris. Nicotine increases platelet
adhesiveness,
an
effect
that
may be
clinically
significant
in
atheroma
and
thrombosis.
Metabolic
rate.
Nicotine increases
the
metabolic
rate,
only slightly
at
rest,
17

but
approximately doubles
it
during light exercise (occupational tasks, house-
work).
This
may be due to
increase
in
autonomic
sympathetic activity.
The
effect
declines
over
24 h
on
stopping
smoking
and
accounts
for the
char-
acteristic
weight gain that
is so
disliked
and
which
is

sometimes given
as a
reason
for
continuing
or
resuming smoking. Smokers weigh
2-4 kg
less
than nonsmokers
(not
enough
to be a
health
issue).
Tolerance
develops
to
some
of the
effects
of
nicotine, taken repeatedly over
a few
hours;
a
first
experience
commonly causes nausea
and

vomiting, which quickly ceases with repetition
of
smoking. Tolerance
is
usually rapidly lost;
the
first
cigarette
of the day has a
greater
effect
on
the
cardiovascular system than
do
subsequent
cigarettes.
Conclusion:
the
pleasurable
effects
of
smoking
are
derived
from
a
complex mixture
of
multiple phar-

macological
and
nonpharmacological
factors.
In
this account nicotine
is
represented
as
being
the
major
(but
not the
sole) determinant
of
tobacco
dependence
after
the
smoker
has
adapted
to the
usual
initial
unpleasant
effects.
But
there

remains
some uncertainty
as to its
role,
e.g.
nicotine
i.v.
fails
adequately
to
substitute
the
effects
of
smoking.
An
understanding
of the
full
function
of
nicotine
is
important
if
less
harmful
alternatives
to
smoking, such

as
nicotine chewing
gum,
are to
be
exploited.
17
The
metabolic
rate
at
rest accounts
for
about
70% of
daily
energy
expenditure.
175
10
NONMEDICAL
USE OF
DRUGS
Effects
of
chronic smoking
SMOKING
AND
CANCER
Bronchogenic

carcinoma
Between
1920
and
1950
an
epidemic
of
bronchogenic
carcinoma
occurred
(rate
in men
increased
20-fold)
which
can be
attributed
to
cigarette
smoking;
lesser
causes include exposure
to a
variety
of
industrial
chemicals
and
atmospheric pollution.

The
risk
of
death
from
lung cancer
is
related
to the
number
of
cigarettes
smoked
and the age of
starting. Giving
up
smoking reduces
the
risk
of
death progressively
from
the
time
of
cessation.
18
Other
cancers
The

risk
of
smokers developing cancer
of the
mouth, throat
and
oesophagus
is
5-10
times greater
than that
of
nonsmokers.
It is as
great
for
pipe
and
cigar
smokers
as it is for
cigarette smokers. Cancer
of
the
pancreas, kidney
and
urinary tract
is
also
commoner

in
smokers.
DISEASES
OF THE
HEART
AND
BLOOD
VESSELS
Coronary
heart disease (CHD)
is now the
leading
cause
of
death
in
many developed countries.
In the
UK
about
30% of
these deaths
can be
attributed
to
smoking.
Under
the age of 65
years
smokers

are
about
twice
as
likely
to die of
ischaemic
heart
disease
as are
nonsmokers,
and
heavy
smokers
about
3.5
times
as
likely.
Sudden death
may be the
first
manifestation
of
CHD
and,
especially
in
young
men,

is
related
to
cigarette
smoking. Smoking
is
especially dangerous
for
people
in
whom other risk
factors
(increased
blood cholesterol, high blood pressure)
are
present.
18
Peto
R et al
2000
Smoking, smoking cessation,
and
lung
cancer
in the UK
since 1950: combination
of
national
statistics
with

two
case-control studies.
British
Medical
Journal
321: 323-329.
Atherosclerotic
narrowing
of the
smallest coronary
arteries
is
enormously increased
in
heavy
and
even
in
moderate smokers;
the
increased platelet adhe-
siveness caused
by
smoking increases
the
readiness
with which thrombi
form.
Stopping smoking reduces
the

excess risk
of
CHD
in
people
under
the age of 65, and
after
about
4
years
of
abstinence
the
risk approximates
to
that
of
nonsmokers.
Pipe
and
cigar smokers
run
little
or no
excess
risk
of CHD
provided they
are not

heavy smokers
and do not
inhale. Heavy cigarette smokers
who
change over
to
pipe
or
cigar smoking
often
continue
to
inhale
and
thereby
fail
to
reduce their risk.
SMOKING
AND
CHRONIC
LUNG
DISEASE
The
adverse
effects
of
cigarette smoke
on the
lungs

may
be
separated
into
two
distinct
conditions.
•
Chronic
mucus
hyper
secretion,
which causes
persistent cough with sputum
and
fits
with
the
original definition
of
simple
chronic
bronchitis.
This condition arises
chiefly
in the
large airways,
usually clears
up
when

the
subject
stops
smoking
and
does
not on its own
carry
any
substantial risk
of
death.
•
Chronic
obstructive
lung
disease,
which causes
difficulty
in
breathing
due to
narrowing
of the
air
passages
in the
lungs. This condition
originates
chiefly

in the
small airways, includes
a
variable
element
of
destruction
of
peripheral
lung
units
(emphysema),
is
progressive
and
largely
irreversible
and may
ultimately lead
to
disability
and
death.
Both
conditions
can
coexist
in one
person
and

they
predispose
to
recurrent acute
infective
illnesses.
The
obstructive
syndrome
is as
specifically
related
to
smoking
as is
lung cancer. Despite
this,
in
discussing
the
health
effects
of
tobacco, there
has
generally been
far
more emphasis
on
lung cancer than

on
this more
disabling,
but
equally
fatal
disorder.
INTERACTIONS
WITH
DRUG
THERAPY
Induction
of
hepatic drug metabolising enzymes
by
non-nicotine constituents
of
smoke causes increased
176
10
metabolism
of a
range
of
drugs,
including
oestrogens,
theophylline,
warfarin.
WOMEN

AND
SMOKING
Fertility. Women
who
smoke
are
more likely
to be
infertile
or
take longer
to
conceive than women
who
do not
smoke.
In
addition, smokers
are
more liable
to
have
an
earlier menopause than
are
nonsmokers.
Increased
metabolism
of
oestrogens

may not be the
whole explanation.
Complications
of
pregnancy.
The
risks
of
sponta-
neous abortion, stillbirth,
and
neonatal death
are
approximately
doubled. There
are
various placental
abnormalities.
The
placenta
is
heavier
in
smoking
than nonsmoking women
and its
diameter larger.
The
enlarged placenta
and

placental abnormalities
may
represent adaptations
to
lack
of
oxygen
due to
smoking, secondary
to
raised concentrations
of
circulating
carboxyhaemoglobin.
The
child.
The
babies
of
women
who
smoke
are
approximately
200 g
lighter
than
those
of
women

who do not
smoke. They have
an
increased risk
of
death
in the
perinatal
period
which
is
independent
of
other variables such
as
social class, level
of
education,
age of
mother, race
or
extent
of
antenatal
care.
The
increased risk rises
two-fold
or
more

in
heavy smokers
and
appears
to be
entirely accounted
for
by the
placental abnormalities
and the
conse-
quences
of low
birthweight. Ex-smokers
and
women
who
give
up
smoking
in the
first
20
weeks
of
pregnancy have
offspring
whose
birthweight
is

similar
to
that
of the
children
of
women
who
have
never smoked.
Starting
and
stopping
use
Contrary
to
popular
belief
it is not
generally
difficult
to
stop, only
14%
finding
it
Very
difficult'.
But ex-
smoker

status
is
unstable
and the
long-term success
rate
of a
smoking withdrawal clinic
is
rarely above
30%.
The
situation
is
summed
up by the
witticism,
'Giving
up
smoking
is
easy,
I've
done
it
many
times'.
STARTING
AND
STOPPING

USE
Though they
are as
aware
of the
risks
of
smoking
as
men,
women
find
it
harder
to
stop; they
con-
sistently
have lower success rates. This trend crosses
every
age
group
and
occupation. Women particularly
dislike
the
weight gain.
Aids
to
giving

up. The
addictive
effects
of
tobacco
smoking
are
substantially
due to
nicotine,
and it is
logical
to
substitute nicotine
for
tobacco smoke
as a
pharmacological
aid to
quitting. Nicotine
is
available
in a
number
of
formulations, including chewing
gum, transdermal patch, oral
and
nasal spray. When
used casually without special attention

to
technique,
nicotine formulations have proved
no
better than
other aids
but,
if
used
carefully
and
withdrawn
as
recommended,
the
accumulated results
are
almost
two
times better than
in
smokers
who try to
stop
without
this
assistance.
19
Restlessness during
terminal illness

may be due to
nicotine withdrawal
and go
unrecognised;
a
nicotine patch
may
benefit
a
(deprived) heavy smoker. Nicotine transdermal
patches
may
cause nightmares
and
abnormal
dreaming,
and
skin reactions (rash, pruritus
and
'burning'
at the
application site).
Amfebutamone/bupropion
may
provide
an
alter-
native,
or
addition,

to
nicotine. When
the
drug
was
being investigated
as an
antidepressant,
researchers
noticed that patients gave
up
smoking,
and it was
developed
as an aid to
smoking cesation.
Amfe-
butamone selectively inhibits neuronal uptake
of
noradrenaline (norepinephrine)
and
dopamine
and
may
reduce nicotine craving
by an
action
on the
mesolimbic system. Evidence
from

a
small number
of
clinical
trials suggests that amfebutamone
may be at
least
as
effective
as the
nicotine patch with which
it
may
usefully
be
combined.
It may
cause
dry
mouth
and
insomnia,
and is
contraindicated
in
those with
a
history
of
epilepsy.

If
the
patient
is
heavily tobacco-dependent
and
severe
anxiety, irritability, headache, insomnia
and
weight
gain (about
3 kg) and
tension
are
concomi-
tants
of
attempts
to
stop smoking,
an
anxiolytic
sedative
(or
B-adrenoceptor
blocker)
may be
useful
for
a

short time,
but it is
important
to
avoid
substituting
one
drug-dependence
for
another.
19
Lancaster
T et al
2000
Effectiveness
of
interventions
to
help
people
to
stop smoking:
findings
from
the
Cochrane
Library.
British
Medical Journal 321:
355-358.

177
10
NONMEDICAL
USE OF
DRUGS
There
is
ample evidence
to
warrant strong advice
against starting
to
smoke
but
over-hasty
and un-
reasonable prohibitions
on
patients' longstanding
pleasures
(or
vices)
do no
good.
The
pliable patient
is
made wretched,
but
most

are
merely alienated.
My
doctor's issued
his
decree
That
too
much wine
is
killing
me,
And
furthermore
his ban he
hurls
Against
my
touching naked
girls.
How
then?
Must
I no
longer share
Good
wine
or
beauties, dark
and

fair?
Doctor,
goodbye,
my
sail's
unfurled,
I'm
off
to try the
other world.
D
G
Rossetti,
poet (1828-82)
Passive
(involuntary)
smoking
Many
nonsmokers
are
exposed
to
tobacco smoke,
and
environmental tobacco smoke
has
been classified
as a
known human carcinogen
in the USA

since
1992.
20
Although
the
risks are, naturally, smaller,
the
number
of
people
affected
is
large.
One
study
estimated that breathing other people's smoke
increases
a
person's
risk
of
ischaemic heart disease
by a
quarter.
21
Smoke
drawn through
the
tobacco
and

taken
in
by the
smoker
is
known
as
mainstream
smoke.
Smoke
which arises
from
smouldering tobacco
and
passes directly into
the
surrounding air, whence
it
may
be
inhaled
by
smokers
and
nonsmokers alike,
is
known
as
sidestream
smoke. Mainstream

and
sidestream smoke
differ
in
composition, partly
because
of the
different
temperatures
at
which they
are
produced. Substances found
in
greater con-
centrations
in
undiluted sidestream smoke than
in
undiluted mainstream smoke include: nicotine
(x
2.7), carbon monoxide
(x
2.5), ammonia
(x
73),
20
Environmental
Protection
Agency (EPA 1992

A/600/6-
90/006F).
21
Law M R,
Morris
J K,
Wald
N J
1997
Environmental
tobacco
smoke
exposure
and
ischaemic
heart
disease:
an
evaluation
of the
evidence.
British
Medical
Journal 315:
973-988.
and
some carcinogens (e.g. benzo-a-pyrene
x
3.4).
Sidestream smoke constitutes about

85% of
smoke
generated
in an
average room during cigarette
smoking.
Ethyl alcohol
(Ethanol)
The
services rendered
by
intoxicating
substances
in
the
struggle
for
happiness
and in
warding
off
misery
rank
so
highly
as a
benefit
that both
individuals
and

races have
given
them
an
established
position within their
libido-economy.
It
is
not
merely
the
immediate gain
in
pleasure which
one
owes
to
them,
but
also
a
measure
of
that
independence
of the
outer world which
is so
sorely

craved
We are
aware that
it is
just this property
which
constitutes
the
danger
and
injuriousness
of
intoxicating
substances
.
22
Alcohol
is
chiefly
important
in
medicine because
of
the
consequences
of its
misuse/abuse. Alcohol
misuse
is a
social problem with pharmacological

aspects, which latter
are
discussed here.
The
history
of
alcohol
is
part
of the
history
of
civilisation 'ever
since Noah made
his
epoch-making discovery'.
23
Pharmacokinetics
Absorption
of
alcohol taken orally
is
rapid,
for it is
highly lipid-soluble
and
diffusible
from
the
stomach

and the
small intestine. Solutions above
20% are
absorbed more slowly because high concentrations
of
alcohol
inhibit gastric peristalsis, thus delaying
the
arrival
of the
alcohol
in the
small intestine which
is
the
major
site
of
absorption.
Absorption
is
delayed
by
food,
especially milk,
the
effect
of
which
is

probably
due to the fat it
contains.
Carbohydrate also delays absorption
of
alcohol.
Distribution
of
alcohol
is
rapid
and
throughout
the
body water (dist. vol.
0.7
1/kg men:
0.6
1/kg
women);
it is not
selectively stored
in any
tissue.
22
Freud
S
1939
Civilisation,
war and

death,
Psycho-analytic
epitomes,
No. 4.
Hogarth
Press,
London.
23
Genesis;
9: 21;
Huxley
A1957
Annals
of the New
York
Academy
of
Sciences
67:
675.
178
ETHYL ALCOHOL (ETHANOL)
10
Fig. 10.1 Approximate blood concentrations after three
doses
of
alcohol.
Maximum
blood concentrations
after

oral
alcohol
therefore
depend
on
numerous
factors
including
the
total
dose, sex,
the
strength
of the
solution,
the
time
over
which
it is
taken,
the
presence
or
absence
of
food,
the
time relations
of

taking
food
and
alcohol
and the
kind
of
food
eaten,
as
well
as on the
speed
of
metabolism
and
excretion.
A
single dose
of
alcohol,
say 60 ml (48 g)
(equivalent
to 145 ml of
whisky,
5-6
measures,
or
units;
see

Fig.
10.1), taken over
a
few
minutes
on an
empty stomach will probably
produce maximal blood concentration
at
30-90
min
and
will
not all be
disposed
of for 6-8 h or
even
more.
There
are
very great individual variations.
Metabolism.
About
95% of
absorbed alcohol
is
metabolised,
the
remainder being excreted
in the

breath, urine
and
sweat; convenient methods
of
estimation
of
alcohol
in all
these
are
available.
Alcohol
in the
systemic circulation
is
oxidised
in
the
liver; principally
(90%)
by
alcohol dehydrogenase
to
acetaldehyde
and
then
by
aldehyde dehydro-
genase
to

products that enter
the
citric
acid cycle
or
are
utilised
in
various anabolic reactions. Other
alcohol-metabolising enzymes
are
microsomal
cyto-
chrome
P450
2E1
(which
is
also induced
by
alcohol)
and
catalase.
Alcohol
metabolism
by
alcohol dehydrogenase
follows
first-order
kinetics

after
the
smallest
doses. Once
the
blood concentration exceeds
about
10
mg/100
ml the
enzymatic processes
are
saturated
and
elimination rate
no
longer increases
with increasing concentration
but
becomes steady
at
10-15
ml per
hour
in
occasional drinkers. Thus
alcohol
is
subject
to

dose-dependent
kinetics,
i.e.
saturation
or
zero-order kinetics, with potentially
major
consequences
for the
individual.
Induction
of
hepatic
drug
metabolising
enzymes
occurs
with repeated exposure
to
alcohol
and
this
contributes
to
tolerance
in
habitual users,
and to
toxicity.
Increased formation

of
metabolites causes
organ
damage
in
chronic over-consumption
(acetaldehyde
in the
liver
and
probably
fatty
ethyl
esters
in
other organs)
and
increases susceptibility
to
liver
injury
when heavy drinkers
are
exposed
to
anaesthetics, industrial solvents
and to
drugs.
But
chronic

use of
large amounts reduces hepatic
metabolic
capacity
by
causing cellular damage.
An
acute
substantial dose
of
alcohol (binge drinking)
inhibits hepatic drug metabolism.
Inter-ethnic
variation
is
recognised
in the
ability
to
metabolise alcohol (see
p.
184).
Blood
concentration
of
alcohol (Fig. 10.1)
has
great
medicolegal importance. Alcohol
in

alveolar
air is in
equilibrium with that
in
pulmonary capillary blood
and
reliable, easily handled measurement devices
(breathalyser)
are
used
by
police
at the
roadside
on
both drivers
and
pedestrians.
24
Pharmacodynamics
Alcohol
acts
on the
central nervous system
in a
manner broadly similar
to
volatile anaesthetics,
exerting
on

cells
a
generally depressant
effect
that
is
probably
mediated through particular membrane
ion
channels
and
receptors. Alcohol enhances (inhibitory)
GABA-stimulated
flux
of
chloride through receptor-
gated membrane
ion
channels,
a
receptor subtype
24
An
arrested
man was
told,
in a
police station,
by a
doctor,

that
he was
drunk.
The man
asked, 'Doctor, could
a
drunk
man
stand
up in the
middle
of
this room, jump into
the
air,
turn
a
complete somersault,
and
land down
on his
feet?'
The
doctor
was
injudicious enough
to
say, "Certainly not"—and
was
then

and
there proved wrong. (Worthing
C L
1957
British
Medical Journal
1:
643.)
The
introduction
of the
breathalyser, which
has a
statutory role only
in
road
traffic
situations,
has
largely eliminated such professional
humiliations.
179
10
NONMEDICAL
USE OF
DRUGS
effect
that
may be
involved

in the
motor impairment
caused
by
alcohol. Other possible modes
of
action
include inhibition
of
calcium entry
via
voltage-gated
(L
type) calcium channels,
and
inhibition
of the
(excitatory)
NMDA (N-methyl-D-aspartate) receptor.
(See
page
184 for
chronic
effects
of
alcohol
on the
brain.)
It
is not a

stimulant; hyperactivity, when
it
occurs,
is due to
removal
of
inhibitory
effects.
Alcohol
in
ordinary doses
may act
chiefly
on the
arousal
mechanisms
of the
brainstem reticular formation,
inhibiting polysynaptic
function
and
enhancing
presynaptic inhibition. Direct cortical depression
probably only occurs with high doses. With
increasing
doses
the
subject passes through
all the
stages

of
general anaesthesia
and may die of
respiratory depression.
25
Psychic
effects
are the
most important socially
(Fig.
10.2),
and it is to
obtain these that
the
drug
is
habitually used
in so
many societies,
to
make social
intercourse
not
merely easy
but
even pleasant. They
have been admirably described
by
Sollmann:
The

first
functions
to be
lost
are the
finer
grades
of
judgement,
reflection,
observation
and
attention—
the
faculties
largely
acquired through education,
which
constitute
the
elements
of the
restraint
and
prudence
that
man
usually imposes
on his
actions.

The
orator allows
himself
to be
carried
by the
impulse
of the
moment, without
reflecting
on
ultimate
consequences,
and as his
expressions
become
freer,
they
acquire
an
appearance
of
warmth,
of
feeling,
of
inspiration.
Not a
little
of

this inspiration
is
contributed
by the
audience
if
they
are in a
similar condition
of
increased
appreciation

Another
characteristic
feature,
evidently
resulting
from
paralysis
of the
higher
functions,
is the
loss
of
power
to
control
moods.

26
Environment, personality, mood
and
dose
of
alcohol
are all
relevant
to the
final
effect
on the
individual. These
and
other
effects
that
are
characteristic
of
alcohol, have been celebrated
in the
following
couplets:
27
25
Loss
of
consciousness
occurs

at
blood concentrations
around
300
mg/100
ml;
death
at
about
400
mg/100
ml. But
the
usual cause
of
death
in
acute alcohol poisoning
is
inhalation
of
vomit.
26
Sollmann
T
1957
Manual
of
pharmacology,
8th

edn.
Saunders,
Philadelphia.
Ho! Ho!
Yes!
Yes!
It's very
all
well,
You
may
drunk
I am
think,
but I
tell
you I'm
not,
I'm as
sound
as a
fiddle
and fit as a
bell,
And
stable quite
ill to see
what's
what
And

I've swallowed,
I
grant,
a
beer
of lot —
But
I'm not so
think
as you
drunk
I
am
I
shall
stralk quite weight
and not
yutter
an
ell,
My
feech
will
not
spalter
the
least
little
jot:
If

you
knownly
had
own!—well,
I
gave
him a
dot,
And
I
said
to
him,'Sergeant, I'll come like
a
lamb
—
The floor it
seems
like
a
storm
in a
yacht,
But
I'm not so
think
as you
drunk
I am.
I'm

sorry,
I
just chair over
a
fell
—
A
trifle—this
chap,
on a
very
day hot —
If
I
hadn't
consumed
that
last
whisky
of
tot!
As
I
said
now, this fellow,
called
Abraham
—
Ah?
One

more?
Since
it's you! just
a do me
will
spot
—
But I'm not so
think
as you
drunk
I am.
Innumerable tests
of
physical
and
mental per-
formance
have been used
to
demonstrate
the
effects
of
alcohol. Results show that alcohol reduces visual
acuity
and
delays recovery
from
visual dazzle;

it
impairs taste, smell
and
hearing, muscular
co-
ordination
and
steadiness
and
prolongs reaction
time.
It
also causes nystagmus
and
vertigo.
At the
same time
the
subjects commonly have
an
increased
confidence
in
their ability
to
perform well
when tested
and
underestimate their errors, even
after

quite
low
doses. Attentiveness
and
ability
to
assimilate, sort
and
quickly take decisions
on
con-
Fig. 10.2
Four
standard
units
of
drink
(in
which
social
consumption
is
measured).
A
unit
contains
approx.
10 ml (8 g) of
alcohol.
Knowledge

of
blood
alcohol
concentration
does
not
allow
a
reliable
estimate
of how
much
has
been
consumed.
27
By Sir J C
Squire
(1884-1958). Quoted,
by
permission,
R H
A
Squire.
180
10
tinuously changing information input, decline. This
results particularly
in
inattentiveness

to the
periphery
of
the
visual
field,
which
is
important
in
motoring.
All
these
are
evidently highly undesirable
effects
when
a
person
is in a
position where
failure
to
perform
well
may be
dangerous.
Car
driving
and

alcohol
The
effects
of
alcohol
and
psychotropic drugs
on
motor driving
(Fig. 10.3)
have been
the
subject
of
well-deserved attention,
and
many countries have
made laws designed
to
prevent motor accidents
caused
by
alcohol.
The
problem
has
nowhere been
solved.
In
general

it can be
said that
the
weight
of
evidence points
to a
steady deterioration
of
driving
skill
and an
increased liability
to
accidents beginning
with
the
entry
of
alcohol into
the
blood
and
steadily
increasing with blood concentration.
Alcohol plays
a
huge
part
in

causing
motor
accidents, being
a
factor
in as
many
as
50%.
For
this
reason,
the
compulsory
use of a
roadside breath test
is
acknowledged
to be in the
public interest.
In the
UK
a
blood concentration exceeding
80 mg
alcohol/
100
ml
blood (17.4 mmol/1)
28

whilst
in
charge
of a car
is
a
statutory
offence.
At
this
concentration,
the
liability
to
accident
is
about twice normal. Other
countries
set
lower limits,
e.g.
Nordic countries,
29
some states
of
USA, Australia, Greece.
So
clearly
is it in the
public interest that drunken

driving
be
reduced that
the
privileges normally
attaching
to
freedom
of
conscience
as
well
as to
personal eccentricity must take second place.
In one
instance,
an
ingenious driver, having provided
a
positive
breath
test,
offered
a
blood
sample
on the
condition
it
should

be
taken
from
his
penis;
the
physician
refused
to
take
it; the
police demanded
a
28
Approximately equivalent
to 35
micrograms alcohol
in
100
ml
expired
air (or 107 mg in 100 ml
urine).
In
practice,
prosecutions
are
undertaken only when
the
concentration

is
significantly
higher
to
avoid arguments about biological
variability
and
instrumental error. Urine concentrations
are
little
used since
the
urine
is
accumulated over time
and
does
not
provide
the
immediacy
of
blood
and
breath.
29
In
1990 Sweden lowered
the
limit

to 20
mg/100
ml,
which
has
been approached
by
ingestion
of
glucose which becomes
fermented
by gut
flora—the
'autobrewery' syndrome.
CAR
DRIVING
AND
ALCOHOL
urine sample;
the
subject
refused
on the
ground
that
he had
offered
blood
and
that

his
offer
had
been
refused.
He was
acquitted,
but a
Court
has
since
decided that
the
choice
of
site
for
blood-taking
is for the
physician,
not for the
subject,
and
that
such transparent attempts
to
evade justice should
be
treated
as

unreasonable
refusal
to
supply
a
specimen under
the
law.
The
subject
is
then treated
as
though
he had
provided
a
specimen that
was
above
the
statutory limit.
Yet
another
trick
is to
take
a
dose
of

spirits
after
the
accident
and
before
the
police
arrive.
The
police
are
told
it was
taken
as a
remedy
for
nervous shock. This
is
known
is the
'hip-flask'
defence.
Where
blood
or
breath analysis
is not
immediately

available
after
an
accident
it may be
measured hours
later
and
'back calculated'
to
what
it
would have been
at
the time of the
accident.
It is
usual
to
assume that
the
blood concentration
falls
at
about
15
mg/100
ml/h. Naturally,
the
validity

of
such calculations
leads
to
acrimonious disputes
in the
courts
of
law.
Prescribed medicines
and
driving
Ability
to
drive
can be
impaired
by
many prescribed
drugs.
In
road
traffic
accident
fatalities
7.4%
of
persons
had
taken

a
drug 'likely'
to
affect
the CNS
(chiefly
older
subjects).
In
addition, cannabis
was
found
in
2.6%.
Unfortunately,
accurate control
figures
are not
available except
in the
case
of
epilepsy:
1.3%
of
fatalities
had
taken
an
antiepileptic drug

and
the
incidence
of the
disease
in the
general
population
is
0.4%.
30
Driving
may
also
be
influenced
by
antihistamines (drowsiness,
but
less commonly
with newer nonsedative agents), mydriatics
and
antimicrobials
for
topical ocular
use
(blurred vision),
antihypertensives
(hypotension)
and

insulins
and
oral
antidiabetic agents (hypoglycaemia).
FURTHER
EFFECTS
OF
ALCOHOL
CONSUMPTION
Peripheral
vasodilatation.
Alcohol
depresses
the
vasomotor
centre
and
this
accounts
for the
feeling
30
Advice
to
patients
on
prescribed medicines
is
contained
in

Medical
Commission
on
Accident Prevention 1995 Medical
Aspects
of
Fitness
to
Drive; HMSO, London.
181
10
NONMEDICAL
USE OF
DRUGS
Fig. 10.3 Alcohol
and
driving.
of
warmth that
follows
taking
the
drug.
Body
heat
loss
is
increased
so
that

it is
undesirable
to
take
alcohol
before
going
out
into severe cold
for any
length
of
time,
but it may be
harmlessly employed
on
coming into
a
warm environment
from
the
cold
to
provide quickly
a
pleasant
feeling
of
warmth.
Blood

pressure.
An
acute dose
of 4-5
units raises
the
blood pressure which parallels
the
blood
concentration.
The
mechanism appears
to
involve
centrally
mediated sympathetic stimulation.
Diuretic
effect.
Alcohol acts
by
inhibiting secretion
of
antidiuretic hormone
by the
posterior pituitary
182
10
gland.
The
reason

it is
useless
as a
diuretic
in
heart
failure
is
that
the
diuresis
is of
water,
not of
salt.
Gastric mucosa.
Injury
occurs because alcohol
allows back
diffusion
of
acid
from
the
gastric lumen
into
the
mucosa.
After
an

acute binge
the
mucosa
shows erosions
and
also petechial haemorrhages
(recovery
may
take
3
weeks)
and up to 60% of
chronic
alcoholics show chronic gastritis.
Vomiting. This common accompaniment
of
acute
alcoholism seems
to be
partly
a
central
effect,
for the
incidence
of
vomiting
at
equivalent blood alcohol
concentrations

is
similar following oral
or
i.v. admin-
istration. This
is not to
deny that very strong solutions
and
dietary indiscretions accompanying acute
and
chronic alcoholism
can
cause vomiting
by
local
gastric
effects.
That
said,
when
death
occurs,
it is
commonly
due to
suffocation
from
inhaled
vomit.
Glucose tolerance. Alcohol initially increases

the
blood glucose,
due to
reduced uptake
by the
tissues. This leads
to
increased glucose metabolism.
But
alcohol also inhibits
gluconeogenesis
and a
person whose hepatic glycogen
is
already low, e.g.
a
person
who is
getting most
of his
calories
from
alcohol
or who has not
eaten adequately
for 3
days,
can
experience hypoglycaemia that
can be

severe
enough
to
cause irreversible brain damage. Hypo-
glycaemia
can be
difficult
to
recognise clinically
in
a
person
who has
been drunk,
and
this
adds
to
the
risk.
Hyperuricaemia occurs (with precipitation
of
gout)
due to
accelerated degradation
of
adenine
nucleotides resulting
in
increased production

of
uric
acid
and its
precursors. Only
at
high
alcohol
concentrations does alcohol-induced high blood
lactate
compete
for
renal tubular elimination
and so
diminish
excretion
of
urate.
Effects
on
sexual function. Nothing really
new has
been said since William Shakespeare wrote that
alcohol 'provokes
the
desire,
but it
takes away
the
performance'.

Performance
in
other
forms
of
athletics
is
also impaired. Prolonged substantial consumption
lowers plasma testosterone concentration
at
least
partly
as a
result
of
hepatic enzyme induction;
CAR
DRIVING
AND
ALCOHOL
feminisation
may be
seen
and men
have been
threatened with genital shrinkage.
Source
of
energy. Alcohol
may be

useful
as an
energy source (rather than
a
food)
in
debilitated
patients.
It is
rapidly absorbed
from
the
alimentary
tract
without requiring digestion
and it
supplies
7
calories
31
per
gram
as
compared with
9
from
fat and
4
from
carbohydrate

and
protein. Heavy doses
cause hyperlipidaemia
in
some people.
Tolerance
to
alcohol
can be
acquired
and the
point
has
been made that
it
costs
the
regular heavy
drinker
2.5
times
as
much
to get
visibly drunk
as it
would cost
the
average abstainer. This
is

probably
due
both
to
enzyme induction
and to
adaptation
of
the
central nervous system.
Intolerance. Inter-ethnic variation
in
tolerance
to
alcohol
is
well recognised,
for
Asian persons,
particularly Japanese, develop flushing, headache
and
nausea
after
what
are,
by
Caucasian standards,
small
amounts
of the

substance. Genetic
deficiency
of
aldehyde dehydrogenase with slow metab-
olism
of
(toxic)
acetaldehyde
may
explain
these
features.
Acute
alcohol
poisoning
is a
sufficiently
familiar
condition
not to
require detailed description.
It is
notorious that
the
characteristic behaviour changes,
excitement, mental
confusion
(including 'blackouts'),
incoordination
and

even coma,
can be due to
numerous other conditions
and
diagnosis
can be
extremely
difficult
if a
sick
or
injured
patient happens
to
have taken alcohol
as
well. Alcohol
can
cause
severe hypoglycaemia
(see
above). Measurement
of
blood alcohol
may
clarify
the
situation.
If
sedation

is
essential, diazepam
in low
dose
is
least hazardous. Alcohol dialyses well,
but
dialysis
will only
be
used
in
extreme cases.
Acute
hepatitis,
which
may be
extremely severe,
can
occur with extraordinarily heavy acute drinking
bouts.
The
serum transaminase rises
after
alcohol
in
alcoholics
but not in
others.
The

single case-report
that
after
a
binge
the
cerebrospinal
fluid
tasted
of
gin
remains unconfirmed.
31
1
calorie
= 4.2
joules.
183