FRCA Notes

Tricyclic Antidepressants

  • Tricyclic anti-depressants (TCAs) are so-called beacuse of their three-ring structure, although have largely replaced by second-generation agents with better side-effect profiles
  • Although no longer recommended as first line treatment of depression, they may be used in the treatment of neuropathic/chronic pain and for nocturnal enuresis
  • Overdose of TCAs leads to a characteristic toxidrome, the details of which are covered in the page on tricyclic antidepressant overdose
  • Examples include:
    • Amitriptylline
    • Nortriptyline
    • Imipramine
    • Dothiepin
  • Act by competitive inhibition of both the SERT (serotonin) and NET (noradrenaline) re-uptake channels on the pre-synaptic membrane of neuronal cells
  • Also act as sodium channel antagonists (i.e. act like class I anti-arrhythmics)

  • Other effects include antagonism at:
    • 5-HT receptors
    • ɑ1-adrenoreceptors
    • NMDA receptors
    • H1 and H2 histamine receptors
    • mACh receptors
    • L-type calcium channels

Absorption

  • Highly lipid soluble and therefore well absorbed from the gut

Distribution

  • Highly protein bound
  • High volume of distribution

Metabolism

  • High inter-patient variation with respect to drug metabolism
  • Undergo hepatic metabolism to active metabolites e.g. imipramine is metabolised to desipramine and nortriptyline


Drug Anti-cholinergic effect Sedative properties Postural hypotension
Amitriptylline ++++ ++++ ++
Nortriptyline ++ ++ +++
Imipramine ++ ++ +
Desipramine + + +

Cardiovascular

  • Postural hypotension
  • Tachycardia and arrhythmias

Neurological

  • Sedation
  • Confusion
  • Muscle twitches

Genitourinary

  • Sexual dysfunction

Gastrointestinal

  • Nausea and vomiting
  • Altered appetite
  • Weight gain

Anti-cholinergic effects

  • Dry mouth
  • Blurred vision
  • Constipation
  • Urinary retention
  • Increased body temperature