Let's move on to the tricyclic antidepressants. These are
very well known agents. TCA's inhibit the reuptake
of norepinephrine and serotonin. 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. TCA's
have a high volume of distribution and they are not dialyzable.
So these are important considerations when we are using TCA's.
TCA's also have a blocking effect on peripheral tissues.
So they do have side effects. Now think about how they work.
They will block histamine. They will block muscarinic receptors.
They will block adrenergic receptors specifically alpha
adrenergic effects. And this results in multiple side effects
and we will go through them right now. With respect to the
H1 antagonism, you can get sedation, drowsiness and weight gain.
With acetylcholine antagonism you can get blurred eyes, dry
mouth and constipation. In terms of the side effects virtually
every patient that I have ever put on a TCA complains of dry
mouth. In terms of alpha 1 antagonism you can get priapism.
And this can be quite a problem in patients who are also
taking drugs like Viagra. You can also have alpha 2 antagonism.
This results in postural hypotension where people feel light
headed when they move from a sitting position to a standing
position. They will complain of dizziness and also a reflex
tachycardia so their heart rate climbs when they stand up.
Now the older drugs have more side effects, the newer drugs
have fewer side effects. 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 1960's. And the newer
drugs like desipramine have fewer side effects. The norepinephrine
uptake inhibition can cause dry mouth, urinary retention
and tremor. The reuptake of serotonin can cause GI
disturbances and the antagonism of serotonin can cause nausea.
One of the big concerns that I always have with tricyclic
antidepressants is that your seizure threshold is reduced.
So patients are going to have an increased risk of seizure.
That is also seen in the monoamine oxidase inhibitors.
There is an additive effect with alcohol or ethanol. Depressive
patients are at high risk for ethanol abuse. So TCA's become
particularly problematic in those group of patients. The other
issue that we have to be very aware of with TCA's is that they
may antagonize methyldopa and clonidine. 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.
Now there are "three C's" of TCA toxicity. Coma, convulsions
and cardiotoxicity. So if you remember this about the TCA's
the "three C's" are very very important.