|
2. BZD's in
Action
In spite of the
intense interest the benzodiazepines have generated over the
past few decades, no one's really sure exactly how the drugs
go about the business of turning down nervousness and jitters.
But we do know what they do, and where they do it.
Most researchers
today believe the drugs act in the brain's thalamus, hypothalamus,
and limbic system, the ring of structures beneath the cerebral
cortex that forms the so-called "emotional center"
of the brain.
Here, the BZD's
function as pharmacological "keys" that turn the locks
of the body's own internal relaxation system.
What that system
is, exactly, is still unknown, but researchers think it involves
the new class of brain chemicals (known as neuropeptides) that
regulate the body's response to pain and stress.
By interacting
with these built-in electrochemical relaxation circuits, BZD's
do the job of triggering emotional tranquilization -- and the
physical release of muscular tension -- about as well as the
job can be done.
So far, so good.
But in getting
that job done, they do a lot of other little jobs on body systems
that don't really need to be done -- like producing drowsiness,
fatigue, and impaired cognition, for example -- and it's here
that the first of a range of BZD-inspired problems begin to show
up.
Effects, Intended
& Otherwise
In fact, a complete
list of unwelcome side effects reported with benzodiazepines
reads like a shopping list of characteristics nobody really wants:
uncoordination, lethargy, decreased motivation, weight gain,
fatigue, sleepiness, impaired cognitive functioning and memory,
emotional blunting (even depression or hostility), vertigo, blurred
or double vision, decreased sex drive, nausea, constipation,
and dry mouth.
And if you think
nervousness is a problem, wait till you have the side effects
of tranquilization in your life -- that's when you really begin
to have something to worry about.
And while not
everyone reports all -- or necessarily even most of -- the side
effects listed above, a majority report some of them, especially
tiredness and fatigue.
Other, less-frequently-reported
effects of the benzodiazepines should also be mentioned. Occasional
side effects include sleep disturbances and nightmares, even
occasional cardiovascular irregularities -- increased heart rate,
decreased blood pressure, flushing, and headache -- that nobody
wants, either, and which can become (or contribute to) major
health problems.
Why do the BZD's
cause such a wide range of side effects?
No one really
knows the answer to that question, either.
But it is known
that certain of the effects of benzodiazepines are dose-related,
which means that smaller doses tend to produce fewer side effects
while heavier doses (and longer-term dosing) produce more.
Another problem with long-term use is tolerance, the need to
take increasing amounts of a drug to produce the same effects.
What tolerance
means to a BZD user is that the dose that makes you less nervous
during week I is not necessarily going to be the same dose that
makes you less nervous in week 17. You simply become used to
the effects.
And while this
can be a good thing (like when users become immune to certain
depressant effects of the drugs -- drowsiness or lethargy, for
example), it can be a bad thing, too -- especially when tolerant
users increase their dose (sometimes to dangerous levels) to
achieve the same effects.
And tolerance
doesn't stop there. Among regular users, another form of tolerance,
called cross-tolerance, also develops, which means that a BZD
user automatically becomes tolerant to the effects of other CNS
depressant drugs. In other words, a person strung out on Valium
may need to take dangerously high doses of other depressant drugs
to produce their intended effects.
On top of all
the other drawbacks we've mentioned, the benzodiazepines seem
to simply hit certain people harder than others.
Older people,
particularly, are more likely to experience side effects, even
be judged "senile" as a result of benzodiazepine therapy.
Children, too, sometimes experience a disproportionate number
of adverse reactions to BZD's, and for this reason (among others),
benzodiazepines are not recommended for use with very young people.
Classifications,
Indications & Et Ceterations
According to
most investigators (including the British Committee on the Review
of Medicines) there are no important differences among the benzodiazepines,
in spite of the fact that BZD's are sometimes prescribed for
different purposes. All BZD's are classified medically as anxiolytic
(or anxiety-reducing) drugs, except for Dalmane and Restoril,
which are usually prescribed for their sedative-hypnotic (or
sleep-producing) properties.
Even though there
are no important differences in their effects, the BZD's are
often lumped pharmacologically into one of two classes, depending
on how long they produce their effects in the body.
Long-acting BZD's
(examples include Valium, Centrax, Dalmane, and Tranxene) produce
their effects over a longer period of time than do the short-acting
benzodiazepines (like Ativan, Serax, and Restoril). But that
doesn't mean the long-acting drugs go to work slowly -- far from
it. In fact, just the opposite is true.
That's because
the drugs are absorbed at different rates, depending on the precise
configuration of their chemical structure. Valium is among the
fastest BZD's (achieving peak blood levels in about an hour),
while Serax is the slowest, needing about three hours to produce
maximum blood concentrations -- and maximum effects.
Benzodiazepines
also vary widely in the length of time they remain in the body
-- and continue to produce effects.
Some, like Valium,
have a long half-life and produce breakdown products (called
metabolites) that are themselves psychoactive, and which can
remain active for several days. (One of Valium's metabolites,
desmethyldiazepam, remains active for up to five days, while
another, oxazepam, is so effective all by itself that it's marketed,
under the trade name Serax, by another manufacturer.)
The short --
acting BZD's -- Serax, for example have a much shorter half-life,
generally produce no psychoactive metabolites, and are eliminated
from the body in as little as one day.
What the longer
half-lives of the long-acting BZD's may mean is still mostly
unknown. It's difficult to track all the effects of metabolites
in the body, for one thing. For another, the longer-range effects
of the metabolites often happen on top of (and are modified by)
the actions of the latest daily dose of the drug. What it all
adds up to is a symphony of largely uncharted effects in the
body and mind -- with a chemical as the main conductor.
Selling Points
So with all this
going against them, what (you may find yourself wondering about
this time) has made benzodiazepines so attractive for quite so
long?
Well, surprisingly,
the drugs do have a lot going for them, especially when you stack
them up against meprobamate and the barbiturates.
For one thing,
BZD's usually have little effect, at therapeutic doses, on respiration
and heart rate, which represents a very significant benefit,
at least for overdose victims. Since the drugs are often prescribed
to tense (or otherwise unhappy) people, and since suicide tends
to be tried most often by the emotionally-troubled, the benzodiazepines'
wide margin of safety has been a main selling point since they
were introduced.
In addition,
the drugs are effective at low dosage levels for a variety of
applications, as anti-convulsants and muscle relaxants as well
as anxiety-stoppers, and this hasn't really escaped anyone's
attention, either -- especially given the milder side effects
(and fewer side effects) associated with the drugs and contrasted
with meprobamate and the barbiturates.
Finally, there's
this matter of addiction. The benzodiazepines can produce a true
addiction, one having both physical and psychological components,
but the severity of the addiction tends to be less than that
produced by Miltown or the barbiturates.
This doesn't
mean kicking a Valium or Ativan habit is easy (it isn't), but
getting straight following a long-term BZD habit tends to be
a good deal less life-threatening (if not any less emotionally-traumatic)
than does withdrawal from Miltown or most other depressants.
But no matter
how you slice it, it's also not fun.
|
.
