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Tricyclic Antidepressants (TCAs) – Antidepressants

by Pravin Shukle, MD
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    00:01 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.

    00:23 So these are important considerations when we are using TCA's. TCA's also have a blocking effect on peripheral tissues.

    00:31 So they do have side effects. Now think about how they work. They will block histamine. They will block muscarinic receptors.

    00:42 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.

    00:59 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.

    01:16 And this can be quite a problem in patients who are also taking drugs like Viagra. You can also have alpha 2 antagonism.

    01:24 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.

    01:39 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.

    02:15 One of the big concerns that I always have with tricyclic antidepressants is that your seizure threshold is reduced.

    02:22 So patients are going to have an increased risk of seizure. That is also seen in the monoamine oxidase inhibitors.

    02:29 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.

    03:01 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.


    About the Lecture

    The lecture Tricyclic Antidepressants (TCAs) – Antidepressants by Pravin Shukle, MD is from the course CNS - Pharmacology.


    Included Quiz Questions

    1. Lowers seizure threshold
    2. Second pass metabolism
    3. Low volume of distribution
    4. Few and minor side effects
    5. Dialyzable
    1. alpha-1 antagonist: postural hypotension, dizziness, reflex tachycardia
    2. histamine antagonism: sedation, drowsiness, weight gain
    3. Serotonin antagonist: nausea
    4. alpha-2 antagonist: postural hypotension, dizziness, reflex tachycardia
    5. Acetylcholine antagonist: blurred vision, dry mouth, constipation

    Author of lecture Tricyclic Antidepressants (TCAs) – Antidepressants

     Pravin Shukle, MD

    Pravin Shukle, MD


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