00:01
Let's move on to a different class.
00:03
These are called SNRIs,
the Serotonin and Norepinephrine
Reuptake Inhibitor.
00:09
Now, in classical pharmacology,
we would classify this under
the heterocyclic antidepressants.
00:15
But we've separated these agents
out from a clinical point of view.
00:18
And so now in pharmacology,
we separate them out too.
00:21
The SNRIs are very
similar to the TCAs,
but they have more specific
reuptake actions.
00:29
So you can see here our diagram
shows you what we're talking about.
00:32
The SNRIs do not have a blocking
effect on the peripheral tissues,
so we believe that they're going
to have fewer side effects.
00:40
Cymbalta is the most commonly
used in this particular class.
00:45
It is used in depressive disorders,
sometimes used in
neuropathic pain disorders.
00:49
And it's also used more
recently in diabetic neuropathy.
00:52
So we are seeing it in my
diabetes clinic for example.
00:56
Venlafaxine or Effexor XR
is a heavily prescribed drug,
because it has relatively
few side effects,
and it has less affinity
for norepinephrine transporters
than duloxetine.
01:08
In terms of the
side effect profile,
you can get an increased
blood pressure with this agent
and the side effects are
very similar to the SSRIs.
01:18
The withdrawal symptoms are a
particular concern with venlafaxine.
01:22
And incidentally,
this is a good exam question.
01:24
Even if you miss
one dose of this drug,
you can have withdrawal symptoms.
01:28
So it's very important number one
to learn this for your exams.
01:32
And number two,
when you're out in practice,
make sure you prescribe
enough Effexor,
enough venlafaxine to ensure that
these patients don't run out.
01:42
And I think that some of
the new laws coming out
allowing pharmacists
to prescribe are good.
01:48
In the event that they
can't get to their doctor,
the pharmacist can prescribe
an emergency supply of Effexor
so that you don't get
those withdrawal symptoms.
01:57
These SNRIs have relatively
targeted activity
against the serotonin receptor.
02:05
Now, remember that the
serotonin receptor is a
G-protein-mediated receptor.
It's located in the neocortex.
02:15
It's important to know
that for the future
because we're going to have
new drugs that are coming out
that will target this mechanism.
02:22
Bottom line, it's a more
specific type of activity
than the previous class of drugs
that I discussed.
02:27
The activity of these
classes of drugs
on the receptor and on reuptake
results in antianxiety
and antidepressant activity.
02:40
Let's move on to
another class of drugs
called the serotonin antagonists.
So, this is a little bit different.
02:47
It's not acting on reuptake
its actually acting right
on the receptor.
02:50
Now, more specifically, it's acting
on the serotonin type 2A receptor.
02:55
It is again a
G-protein-coupled receptors
located in the neocortex.
03:02
It is a short acting
agent and maybe prescribed
between two or four times a day.
It's a multidose regimen drug,
and you have several
agents out there.
03:14
In addition,
these medications weekly inhibit
serotonin reuptake
by presynaptic neurons.
03:18
Now, we don't use some of them
because of intense
cytochrome interaction
and we have others
that are better used.
03:26
Now, the most common in this drug
class is something called Trazodone.
03:31
Trazodone is commonly
used as a sleep aid.
03:34
It is a relatively
short acting drug.
03:36
And we like it for that reason,
because if we give it at night
to help people go to sleep,
it wears off halfway
through the evening.
03:44
so that when they wake up,
they shouldn't feel tired.
03:47
Additionally, there are a couple
other notable serotonin modulators
used in the treatment
of depression.
03:54
Both inhibit presynaptic reuptake
and they also have additional
serotonin receptor activity.
04:00
Vilazodone is a partial agonist
of postsynaptic 5-HT1A receptors.
04:07
Vortioxetine acts on
multiple 5-HT receptors,
either as an antagonist or agonist.
04:15
An interesting aspect
of Vortioxetine is that
is may have a benefit for patients
with cognitive dysfunction.
04:22
Let's move on to the SSRIs.
04:24
There are two ways to
come up with this acronym.
04:28
The proper way are Selective
serotonin reuptake inhibitors,
but some people say that
the SSRI stands for
Serotonin specific
reuptake inhibitor
regardless of which one you use,
SSRI is the most common class of
antidepressant drugs on the market.
04:46
I think personally that
these are the best class
because they have the
fewest side effects.
04:50
Now, these act through inhibition of
the serotonin reuptake transporter,
there is minimal effects
on norepinephrine uptake.
04:59
There are minimal side effects
to these medications
although they are present.
05:03
And initiation of medications
in the SSRI class
results in very good
anti-anxiety activity
and very good
antidepressant activity.
05:14
There are so many
that I don't even know
where to start in terms
of listing the drugs.
05:20
There are over 120 SSRIs
out on the market.
05:26
So the list is very long.
05:29
It has the same effectiveness in
terms of antidepressant activity,
as the tricyclic antidepressants.
And I say that as a compliment.
05:36
And on top of that, they have fewer
almost negligible side effects.
05:41
They do have side effects,
but they're relatively rare.
05:44
SSRIs and SNRIs can both cause
sexual dysfunction
and decreased libido.
05:49
It is important to ask patients
about this possible side effect.
05:52
This is very clinically
relevant and testable.
05:55
In terms of toxicity and overdose,
one must be aware that
you can get headache nausea,
an increase in anxiety paradoxically
and an increase in agitation.
06:06
You can get the jitters. So patients
are very jittery and tremulous.
06:10
And you can use a low dose
benzodiazepine
to treat the jitters
when they have overdose.
06:15
Extrapyramidal side
effects can occur as well.
06:18
These include
akathisia and dyskinesias
and some dystonic reactions.
06:26
In terms of drug interactions
with this class of drugs,
remember that one of them
called fluoxetine or Prozac
inhibits the CYP450 2D6
and 3A4 moieties
So any drugs that go through that
system can affect the drug levels.
06:42
You can also have
increased plasma levels
due to dextromethorphan,
propranolol, tamoxifen
and the tricyclic antidepressants.
06:51
Luvox can inhibit
cytochrome P450 1A2
and other agents like Celexa
can have effect other drugs
with that go through the
cytochrome P450 system.
07:06
However, in terms of
those drug interactions,
this particular drugs to citalopram
affects fewer drugs than the others.
07:15
There is something that
I want to talk about
called serotonin syndrome.
07:19
It was first described
as a reaction
between Mono Amine
Oxidase Inhibitors
and the Selective serotonin
reuptake inhibitors.
07:27
Serotonin syndrome
is not something to ignore.
07:31
It can be a life threatening
problem or syndrome.
07:34
First of all,
it has several components.
07:37
The CNS stimulation
component can include
severe muscle rigidity,
myoclonus, and hyperreflexia.
07:44
You can also get
hyperthermia suspected to be
due to increased muscle activity,
and you can also get
seizures and mydriasis.
07:52
Cardiovascular symptoms
associated with this syndrome
include tachycardia and unstable
meaning high blood pressures.
08:01
And GI issues can include
increased bowel sounds,
and you can actually
have diarrhea as well.
08:09
Now, there's a mnemonic
that you can use
to remember the various
symptoms in serotonin syndrome.
08:16
And the mnemonic is MADAM'S TIPS.
08:19
I apologize for the sexist nature
of this mnemonic,
but it works very well.
Please accept my apologies.
08:28
There's M-A-D-A-M-S T-I-P-S.
08:31
So, each have the start
with that letter.
08:35
Let's start with M,
Mental status changes.
08:38
You can get Agitation,
you can get Diarrhea.
08:41
A can be for Ataxia.
08:44
You can get Myoclonus
and Shivering.
08:48
T stands for Tachycardia.
You can get Increased reflexes.
08:52
You can get Pyrexia
or what we call fever,
And you can also get
a lot of Sweating.
08:58
So there you have the
mnemonic MADAM'S TIPS.
09:00
That will help you remember
the serotonin syndrome.