Tricyclic_Antidepressants_Flashcards

Question 1

Why are tricyclic antidepressants (TCAs) used less commonly for depression now?

Answer 1

TCAs are used less commonly for depression due to their side-effects and toxicity in overdose.

Question 2

What are TCAs widely used for despite their side-effects and toxicity?

Answer 2

TCAs are widely used in the treatment of neuropathic pain, where smaller doses are typically required.

Question 3

What is the primary mechanism by which TCAs exert their antidepressant effects?

Answer 3

The primary mechanism by which TCAs exert their antidepressant effects is through the inhibition of the reuptake of neurotransmitters.

Question 4

How do TCAs affect serotonin (5-HT) levels?

Answer 4

TCAs inhibit the reuptake of serotonin (5-HT), leading to increased concentrations in the synaptic cleft and enhanced serotonergic neurotransmission.

Question 5

How do TCAs affect noradrenaline (NA) levels?

Answer 5

TCAs inhibit the reuptake of noradrenaline (NA), leading to increased concentrations in the synaptic cleft and intensified noradrenergic neurotransmission.

Question 6

What are some receptors that TCAs interact with, contributing to their side-effect profile?

Answer 6

TCAs interact with histamine, muscarinic, and adrenergic receptors, contributing to their side-effect profile.

Question 7

What are the effects of antagonism of histamine receptors by TCAs?

Answer 7

Antagonism of histamine receptors by TCAs leads to drowsiness.

Question 8

What are the effects of antagonism of muscarinic receptors by TCAs?

Answer 8

Antagonism of muscarinic receptors by TCAs leads to dry mouth, blurred vision, constipation, and urinary retention.

Question 9

What are the effects of antagonism of adrenergic receptors by TCAs?

Answer 9

Antagonism of adrenergic receptors by TCAs leads to postural hypotension and lengthening of the QT interval.

Question 10

Which TCA is commonly used in the management of neuropathic pain and the prophylaxis of headache?

Answer 10

Low-dose amitriptyline is commonly used in the management of neuropathic pain and the prophylaxis of headache (both tension and migraine).

Question 11

Which TCA has a lower incidence of toxicity in overdose?

Answer 11

Lofepramine has a lower incidence of toxicity in overdose.

Question 12

Which TCAs are considered the most dangerous in overdose?

Answer 12

Amitriptyline and dosulepin (dothiepin) are considered the most dangerous in overdose.

Question 13

Which TCAs are more sedative and which are less sedative?

Answer 13

More sedative TCAs include amitriptyline, clomipramine, dosulepin, and trazodone. Less sedative TCAs include imipramine, lofepramine, and nortriptyline.

Question 14

What is notable about trazodone in relation to tricyclic antidepressants?

Answer 14

Trazodone is technically a ‘tricyclic-related antidepressant’.

Question 15

DO THE SAME FOR TRICYCLIC ANTIDEPRESSANTS

Answer 15

Tricyclic antidepressants

Tricyclic antidepressants (TCAs) are used less commonly now for depression due to their side-effects and toxicity in overdose. They are however used widely in the treatment of neuropathic pain, where smaller doses are typically required.

The primary mechanism by which TCAs exert their antidepressant effects is through the inhibition of the reuptake of neurotransmitters
Serotonin (5-HT): This neurotransmitter has a pivotal role in mood regulation. Inhibition of its reuptake leads to increased concentrations in the synaptic cleft, enhancing serotonergic neurotransmission.
Noradrenaline (NA): Similar to 5-HT, blocking the reuptake of NA increases its synaptic cleft concentration, intensifying noradrenergic neurotransmission.

As well as 5-HT and NA, tricyclics interact with number of other receptors that contribute to their side-effect profile:
antagonism of histamine receptors
drowsiness
antagonism of muscarinic receptors
dry mouth
blurred vision
constipation
urinary retention
antagonism of adrenergic receptors
postural hypotension
lengthening of QT interval

Choice of tricyclic
low-dose amitriptyline is commonly used in the management of neuropathic pain and the prophylaxis of headache (both tension and migraine)
lofepramine has a lower incidence of toxicity in overdose
amitriptyline and dosulepin (dothiepin) are considered the most dangerous in overdose

More sedative Less sedative
Amitriptyline
Clomipramine
Dosulepin
Trazodone* Imipramine
Lofepramine
Nortriptyline

*trazodone is technically a ‘tricyclic-related antidepressant’

Question 16

During an out of hours shift, you are called to see a 78-year-old man who has developed acute urinary retention on a background of 2 years of urinary hesitancy and poor stream. He has a history of ischaemic heart disease, hypertension and he tells you that his usual GP has recently started him on a new medication for neuropathic pain.

Which of the following drugs is most likely to have precipitated the urinary retention?

Diazepam
Venlafaxine
Amitriptyline
Fluoxetine
Zopiclone

Answer 16

Amitriptyline

Tricyclic antidepressants may cause urinary retention

Amitriptyline has anticholinergic effects being associated with tachycardia, dry mouth, mydriasis and urinary retention.

These features are not typical of selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, or serotonin and norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine, with urinary retention and dry mouth rarely reported.

Diazepam, a benzodiazepine does not have anticholinergic effects.

Zopiclone is a benzodiazepine-like agent whose side effects include metallic taste and headache.