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Hello everyone and welcome back! In our last section we
discussed stimulants and how they worked. In this section we are going to
discuss the other end of the continuum. That is, depressants which are
otherwise called sedative hypnotics.
So let's begin by talking about the oldest sedative hypnotic and that is
shown in slide two. Surprisingly, it is alcohol. We've talked about this
before. Alcohol has been used for thousands of years as a sedative hypnotic.
It is primarily used for self medication.
For example, if you look at slide three it is used the relieve stress. It is
used to help people to sleep; a glass of wine at bedtime. And, it is also
used to alleviate general anxiety.
In general, when we talk about the other depressants, as you see in slide
four, they have all sorts of names. They have downers, hypnotics, sedatives,
minor tranquilizers, anti anxiety medications, and on, and on, and on.
When we talk about classes of drugs as we see in slide five there are really
three major types. There is the non-barbiturate type, there are
barbiturates, and then there are the anti-anxiety medications or what we
call minor tranquilizers or called benzodiazepines.
So let's talk about the non-barbiturates first. As we can see in slide six,
most barbiturates were developed before the 1900's. There were a wide
variety of different compounds and they include such things as chloral
hydrates, paraldehyde, and sulfonal. Most of these drugs are not used today
however they are used occasionally in medicine.
Let's talk about the bromides first on slide seven. This is one of the
earliest sedative hypnotics. Basically, it looks like a chloride ion and
what it does is shut down action potentials. It is also eliminated very
slowly. Gradually what you need to do is titrate the individual for a period
of time. Ultimately, this will result in the desired affect for the long
term.
However, the bromides have a wide variety of problems. As we see in slide
eight they have lots of side effects. As you can also see, they take a long
time to administer and they also take a long time to get out of the system
after you have them in there. We still use them for some kinds of epileptic
seizures and sedations but most of the time we can use a variety of other
compounds which are much better. So, consequently they are not used much
today.
Chloral hydrate as we see in slide nine is probably the oldest sleep
inducing agent and it was first synthesized in 1832. It causes sleep in
about half an hour and therapeutically has very little effect on
respiration. However, if you get the dosage level too high it causes severe
respirtory depression and ultimately causes low blood pressure. When you
combine this drug with alcohol it results in a very potent medication. This
is what is called the classic "Mickey Finn". This was the common "knockout
drop" used in the old movies during the old spy era. It is not used much
today but chloral hydrate is still around and used as a sleep medication.
Paraldehyde, as we see on slide ten, is a polymer of acetaldehyde so it is
very similar to that. It is even occasionally used to treat /DT's. Sleep
occurs in about fifteen minutes and the drug is metabolized to acetaldehyde
by the liver and is eliminated through the lungs. Consequently it gives off
an odor. Paraldehyde, as you know from other things is also highly toxic to
the liver, stomach, and the kidneys. Consequently we do not use it much
today in medicine.
Barbital as we see in slide eleven is a derivative of barbituric acid. It
was introduced in the early 1900's and became extremely popular. In 1912 a
related compound called Phenobarbital was introduced and since then we have
had lots and lots of derivatives that have been developed. Fifty are
commercially available and about twenty are still on the market.
Barbituric acid as seen in slide twelve is the parent compound of all the
barbiturates but its basic structure lacks some particular stuff to make it
a depressant. So what you need to do is add some other compounds which we do
and that are how we get all the other types. Basically what barbiturates do
is depress the nervous system over time and it occupies the GABA receptor
which we will talk about in a little while.
When you talk about the sedative hypnotics or depressants they are usually
based on the onset and duration of action. As we can see in slide thirteen
there are a variety of classification categories that one has to examine.
These include the ultra short, short, intermediate, and the long types of
drugs.
So let's begin by looking at ultra short drugs. These drugs are primarily
used in anesthesia and as we see in slide fourteen the onset of action are
very, very rapid; ranging from seconds to about a minute. And here you have
all sorts of different drugs that are listed here. These drugs are not
usually preferred by drug users because they work so fast. However, there is
one drug in the category that is used by drug users and that is called GHB.
Let's look at GHB on slide fifteen. As we can see, GHB is a barbiturate and
is also called "Natures Quaalude". It is primarily used as a general
anesthetic but is also used for sleep disorders, alcohol and opiate abuse.
However, what makes this drug interesting is that it is a classic date rape
drug.
It is very, very potent, and as we can see in slide sixteen it produces
disinhibition, excitement, and drunken-like behavior. But in combination of
all of this it also produces amnesia, that is, the person does not recall
what they were doing while they were under the influence of the drug.
Basically what this drug does is increases dopamine levels in the brain and
that gives us the euphoric effects.
However, it also has a wide variety of side effects and these are shown in
slide seventeen. These include respiratory depression, seizures, vomiting,
and assorted other things. So this is not a drug one wants to play with as
well. If you take too much of it and combine it with alcohol you can have a
major problem. The thing about this drug as well, is that it is odorless. It
is also tasteless and you do not know you are consuming it especially when
putting it with alcohol.
The next major category of drugs is shown in slide eighteen and these are
the short action sedative hypnotics. These are the drug preferred by the
users. You have an onset of action in about twenty to thirty minutes and the
effects usually last for three to six hours. Primarily these drugs are used
for sleep or sedation.
As we can see in slide nineteen there is a wide variety of different drugs
that are out there primarily used in the drug abusing communities. These are
Phenobarbital or what are commonly called Yellows Yellow Jackets and these
drugs are often used in veterinary anesthesia and in human anesthesia as
well. Secobarbitals which are basically referred to as "reds" are primarily
sleep medications but they have other effects as well.
Intermediate drugs as we see in slide twenty are also preferred by abusers.
Their onset of action is usually about forty to sixty minutes and, like the
short action drugs, their duration is about four to six hours. These are
primarily used for sleep or sedation.
As we can see on slide twenty-one there is a wide variety of types.
Long sedative hypnotics as seen on slide twenty-two are not really preferred
by drug abusers because they take such a long time to have an impact. These
drugs are primarily used for continuous sedation. They are also used in
epilepsy and for mild anxiety. Onset of action is about one to two hours but
the duration of action is six to twelve hours.
As we can see in slide twenty-three there are a couple of major types that
primarily work here.
Generally when one talks about the sedative hypnotics one describes where
they have the mechanism of action. As we can see in slide twenty-four the
primary site for barbiturates is on the picrotoxin binding site of the GABAa
receptor. When this occurs there is a decrease of excitability of the
tissue. Ultimately, all of the central nervous system is sensitive to
barbiturates but the RIA system that we talked about earlier is the most
sensitive.
The behavioral effects of the sedative hypnotics include things such as,
disinhibition, slurred speech, disorientation, appearing drunk, etc., with
major effects of having a weak, rapid pulse and dilated pupils.
Now there is also a wide variety of side effects from the use of
barbiturates. This primarily occurs when one is taking them over time. For
example, as we see in slide twenty-six, there is a decrease in REM sleep.
Consequently the person is not as rested as they would normally be in the
morning. There is also a high potential for abuse. Twenty-five percent of
all suicides basically occur from the barbiturates. This also causes other
enzymes to break down and it also breaks down other types of drugs as well.
These drugs also develop rapid tolerance, and as we can see in slide
twenty-seven, it causes what is called rapid down regulation which means you
need more and more of the drug to have the same effect. During withdrawal
you often have increased stimulation that results in seizures, delirium,
anxiety and a wide variety of other things.
There is another class of sedative hypnotics and these are called the non
barbiturates. The first one of these as we see in slide twenty-eight is
chloral hydrate. Chloral hydrate is both a barbiturate and a non
barbiturate. As we can see here there are a wide variety of different types.
The effects of non barbiturates, as we see in slide twenty-nine, are very
similar to the classic barbiturates. They act as sedatives and hypnotics,
and the side effects are the same as well. Further, their overdoses are much
harder to treat. Generally the non barbiturates have the same behavioral
effects as the barbiturates. And, they are very dangerous when combined with
alcohol.
As we can see in slide thirty, the behavioral effects are about the same as
the barbiturates. You get slurred speech, disorientation, and drunken
behavior without the odor of alcohol.
Now the next major category of the sedative hypnotics/depressants are what
is called the antianxiety medications or what we call the minor
tranquilizers. These are listed in two major groups on slide thirty-one.
The carbonates as we see on slide thirty-two are meprobamates which are
called Miltown and Equanil.
Its action seen in slide thirty-three is very similar to intermediate-acting
barbiturates however it is less toxic. It produces less sedation than the
classic barbiturates and other drugs but it also does not give the
respiratory suppression of barbiturates as well.
Behaviorally, as we see in slide thirty-four the action is very similar to
the traditional barbiturates. Sedation, muscle relaxation, it also reduces
anxiety and can help prevent seizures. Generally the effects are a mild
euphoria.
Now there are some interesting points about the carbonates. As we can see on
slide thirty-five, they were primarily used up until the 1950's and we still
use them today. You generally overdose on about twenty to thirty pills and
when you do overdose you get a great big ball of pills in the stomach. This
requires that you pump the stomach to get them all out. The reason they have
decreased in use today is because of another drug classification group that
came out and these are the benzodiazepines. Benzodiazepines do a better job
and are safer.
Let's look at these on slide thirty-six. Benzodiazepines are the newest
class of drug. They are also some of the most widely prescribed medications
used in the world. They are also frequently abused. Like carbonates they
produce all sorts of effects. Primarily they are used to reduce anxiety,
muscle relaxation, prevent seizures, and another effect they are used for is
sedation and sleep.
There are three major groups of benzodiazepines; short-acting, intermediate
acting, and long acting.
Short-acting drugs as we see in slide thirty-eight have a very rapid onset
and a short duration. These drugs are used primarily to treat insomnia.
As we can see in slide thirty-nine there is a wide variety of types.
Intermediate acting have a little longer duration and a little longer time
for onset. As we see in slide forty there are some types listed here as
well.
Long term is a little bit different. As we see in slide forty-one, they are
used primarily to treat general anxiety. They are also used for muscle
relaxation. For example, when you throw out your back. They are also used as
an adjunct to anesthesia to relax muscle groups.
As we can see in slide forty-two there is a wide variety of types here as
well.
There are other uses as well for these drugs. As we can see in slide
forty-three they can be used as a short-acting anesthetic and they are also
used for seizure disorders.
The site of action for benzodiazepines as we can see in slide forty-four is
also the GABAa receptor. What it can do is completely block or partially
block the benzodiazepine binding site. Most of these drugs block this
binding site and that is what gives you the behavioral effects.
For anxiety, as we see in slide forty-five, basically what we do is shutdown
a few structures that are associated with the fear responses. These include
the amygdala, insula, and other structures.
For muscle relaxation, as we see in slide forty-six, the drugs shutdown
structures in the spinal cord, in the cerebellum, and in the brain stem.
With the Antiepileptic drugs as we see in slide forty-seven, what the
benzodiazepines do is shut down the cerebellum and the hippocampus.
For pleasure, these drugs also shutdown the nucleus acumbens and the ventral
tegnentum in the Thalamus.
Now, there is another major group of benzodiazepines and these are called
the partial agonists. These only block one particular type of receptor. The
result is that they reduce anxiety, but does not give you the high and this
is where the new research is going.
The classic drug that you have commonly heard of is shown on slide fifty and
is Rohypnol. It is technically a benzodiazepine and is marketed outside the
United States. It is used for reducing anxiety, causing sedation and
amnesia. However, when combining it with alcohol like GHB it acts like
chloral hydrate and it knocks the person out and causes amnesia. So it is a
classic date-rape drug that a lot of people use. The side effects of
Rohypnol are very similar to the barbiturates. As we see in slide fifty-two
it causes sedation, it causes impairment in the motor system, drowsiness,
mental confusion, and of course amnesia especially when taken with alcohol.
Generally the effects are dose related.
Rohypnol as we can also see in slide fifty-three causes other issues. It can
decrease cognitive performance especially memory, it also decreases academic
performance and psychomotor functioning as well. These effects can occur for
long periods of time even after the drugs are not used however the
impairments usually decrease over time.
In general, the benzodiazepines are not as dangerous as the barbiturates.
They can increase the effects of barbiturates when you put them with them;
they cause a synergistic effect just as alcohol does. Generally the
benzodiazepines usually do not give as great a sedation effect as the
barbiturates. They work on different binding sites and since they work on
the binding site that alcohol binds on it can be used with alcohol
withdrawal. You also do not see as great of tolerance effects and that is
also occurring over time as well.
So, in general when you talk about the sedatives hypnotics, benzodiazepines
and barbiturates and on and on with all the different drugs, basically what
they all do as we see in slide fifty-five, is slow the system down. They all
work on the GABAa receptor and they also work on other receptors as well.
When used correctly they are very effective for what they do. But all these
drugs develop tolerance and all of these drugs have withdrawal effects that
are the opposite of their effects so they are going to cause stimulation,
nervousness, anxiety, etc.
Well that concludes this section on the sedative hypnotics/depressants. In
our next section we are going to begin looking at the opiates so until then
we hope you are enjoying your day and we look forward to talking with you
soon.
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