Hi, welcome to the pharmacology lectures by Lecturio. My name
is Dr. PJ Shukle and today's lecture is going to be about
the sedative and hypnotic drugs that we use in everyday
clinical practice. Here is an overview of the medications
that we are going to be covering in this section of the
lectures. We have benzodiazepines which are probably the most
commonly used of the sedative drugs out there. We also have
barbiturates which are commonly more used in anaesthesia.
And we have atypical drugs that can be used in various forms
and in various clinical scenarios. Benzodiazepines are often
converted to active metabolites in the liver. Examples include
diazepam and flurazepam. The important medications that you
should know is really diazepam for your medication, but
flurazepam is used a lot in clinical practice. One of the
problems of these medications is that they can actually
accumulate over several days. So one has to be very careful
with these medications in using them on a day to day basis.
Some of these benzodiazepines are conjugated outside the liver.
An example is lorazepam or oxazepam. Once again lorazepam is
something that you should know for your exams. Oxazepam is
something that we see more clinically. Now these particular
drugs do not form active metabolites. Barbiturates are
extensively metabolized in the liver. An example or a
prototypical drug is the short acting secobarbital. Phenobarbital
can be excreted in the urine unchanged. Phenobarbital is a
longer acting version and it's often used in patients who have
epilepsy. The unclassified drugs have rapid metabolism by
liver enzymes and they have a shorter duration of action.
Most of the times we are using these drugs as sleep aids
because they wear off by the morning. Here is a dose response
curve for all of the medications in one graph. When you look
at this graph you can see that at low dose, we just talked
about sedation, disinhibition and anxiolysis which is the
removal of the feeling of anxiety. At higher doses, we start
to see hypnosis where we see loss of consciousness and
reduction of awareness. Once we get into the anaesthesia range
the benzodiazepines are used less and less. You can see that
they sort of peak out at the anesthesia, hypnosis range.
Barbiturates however are fairly toxic. So they keep going up
in the toxicity spectrum. So you can actually get medullary
depression and coma. And many times we will use barbiturates
to induce a coma in certain situations. Let's start off with
sedation, disinhibition and anxiolysis. So obviously at this
lower dose of the spectrum, anxiolysis and sedation is going
to be mostly with the benzodiazepines. These are at low doses
of both sets of drugs. Benzodiazepines are used far more
frequently for anxiolysis than any other category. And the
newer unclassified drugs are starting to come into play
with this particular type of therapy. And you are starting
to notice that the newer drugs, and the more new
the flatter the curve, have a flatter curve which means that
they peak out in the anxiolysis spectrum. Going back to our
curve, let's talk a little bit more about antiseizure activity.
Now antiseizure activity is present with both your benzodiazepines
and your barbiturates. It's present at very low levels of
barbiturates like phenobarbital as I mentioned before.
And it's present at higher doses of the benzodiazepines like
lorazepam and midazolam. When we move into the hypnosis part of
the spectrum, we start to see the benzodiazepines tailing off.
Benzodiazepines can induce sleep. And rapid eye movement is
often reduced, so people will get fewer dreams when they are
on benzodiazepines. Now when you stop taking benzodiazepines
there is a rebound effect with respect to your REM sleep,
rapid eye movement sleep, and people will become hyper-REM,
they will have more REM sleep. And they will have very vivid
dreams and sometimes they will actually have nightmares.
As you get into the newer agents, we are starting to see fewer
and fewer side effects. So a good example of that kind of a drug
is zopiclone. We use it for insomnia, it has a very rapid onset
of action and it has minimal daytime cognitive impairment.
This is a very good drug for use in insomnia and it's
essentially replacing the older Ativan, which is lorazepam
or Versed. It's replacing all of those old medications with
these new medications because of their efficacy and lack of
symptoms. Let's move on to the anaesthesia spectrum of our
sedative hypnotic drug. You can see that the curve is flattening
out with the benzodiazepines. Those benzodiazepines are great
for certain types of anesthesia induction but for long term
anaesthesia induction, we're using more barbiturates as time
goes on. Anesthesia refers to a complete loss of cortical function.
You have amnesia, you have suppressed reflexes, you can have
anterograde amnesia and you can actually have it with some of the
benzodiazepines. Now we are going to talk about something called
date rape or rape drug under toxicology, so keep that in mind
with the benzodiazepines. Now, in the operating room we are using
a lot of barbiturates. In the intensive care unit we use
a lot of benzodiazepines. In the operating room, one of the
most common benzodiazepines used is thiopental. Now short term
sedation with benzodiazepines is excellant. So when I was
working in the intensive care unit, I would often
use IV Ativan or IV Lorazepam to sedate my patients for rapid
sequence induction and intubation. Many other anaesthetist
seem to prefer intraveneous diazepam, I preferred lorazepam.
Whatever you choose, it doesn't really matter. Just recognise
that these are the two main agents that we use intraveneously
for short term sedation. Let's move on to the top of the spectrum.
We are now talking about medullary depression and coma. And
you can see that this is starting to become the sole province
of the barbiturate class of medications. So medullary suppression
and coma means that these patients often will have a respiratory arrest.
They will develop low blood pressure because they have lost
a lot of that sympathetic tone. There can be cardiovascular
collapse if you are not administering the
medications properly and it can also result in death.