00:01
Let's move on to the tricyclic antidepressants.
00:04
These are very well-known agents.
00:06
TCAs inhibit the reuptake of
norepinephrine and serotonin.
00:11
Now, they undergo first pass metabolism, so a lot
of the drug ends up getting dumped in the bowel
before it even reaches the target organ.
00:19
TCAs have a high volume of distribution
and they are not dialyzable,
so these are important
considerations when we're using TCAs.
00:27
TCAs also have a blocking effect on peripheral
tissues, so they do have side effects.
00:34
Now, think about how they work.
00:36
They will block histamine, they
will block muscarinic receptors.
00:42
They will block adrenergic receptors,
specifically alpha-adrenergic effects.
00:47
And this results in multiple side effects
and we'll go through them right now.
00:53
With respect to the H1 antagonism, you can
get sedation, drowsiness, and weight gain.
00:59
With acetylcholine antagonism, you can get
blurred eyes, dry mouth, and constipation.
01:05
In terms of the side effects, virtually
every patient I've ever put on a TCA
complains of dry mouth.
01:12
In terms of alpha-1 antagonism,
this results in postural hypotension
where people feel lightheaded when they move
from a sitting position to a standing position.
01:23
You can also have alpha-2 antagonism.
01:26
They will complain of dizziness and also a reflex
tachycardia,
so their heart rate climbs when they stand up.
01:32
Now, the older drugs have more side effects
than newer drugs have fewer side effects.
01:37
So, when you take a look at the
drugs on this spectrum here,
you can see that amitriptyline
is the oldest of the drugs,
first used in the 1960s, and the newer drugs
like desipramine have fewer side effects.
01:50
The norepinephrine uptake inhibition can cause
dry mouth, urinary retention, and tremor.
01:58
The reuptake of serotonin
can cause GI disturbances,
and the antagonism of serotonin can cause nausea.
02:09
One of the big concerns that I always
have with tricyclic antidepressants
is that your seizure threshold is reduced.
02:16
So, patients are going to have
an increased risk of seizure
that is also seen in the
monoamine oxidase inhibitors.
02:23
There is an additive effect
with alcohol or ethanol.
02:27
Depressive patients are at
high risk for ethanol abuse,
so TCAs become particularly
problematic in those group of patients.
02:35
The other issue that we have
to be very aware of with TCA
is that they may antagonize
methyldopa and clonidine.
02:41
So, patients who are taking these
drugs, methyldopa or clonidine,
whether it's for blood pressure
or for post-menopausal symptoms,
can have a significant interaction
between the two sets of drugs.
02:55
Now, there are three C's of TCA toxicity.
02:59
Coma, convulsions, and cardiotoxicity.
03:03
So, if you remember this about the TCAs,
the three C's are very, very important.