TRICYCLIC ANTIDEPRESSANTS Flashcards
What is the mechanism of action of tricyclic antidepressants in the treatment of depression?
Non-specific blockers of presynaptic monoamine uptake - mostly serotonin (5-HT) and noradrenaline
As well as serotonin, what neurotransmitters are affected by tricyclic antidepressants?
Muscarinic blockers
α-adrenergic blockers
Histamine blockers
What is the most common indication for tricyclic antidepressants nowadays?
Neuropathic pain.
TCAs are now less commonly used 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.
Which patients with depression might we choose to give tricyclic antidepressants to instead of SSRIs?
Those in whom sedation would be beneficial, eg those experiencing insomnia or psychotic depression patients. SSRIs can make insomnia worse.
What are the side effects of tricyclic antidepressants as a result of its anti-muscarinic properties?
Dry mouth
Constipation
Urinary retention
Blurred vision
What are the side effects of tricyclic antidepressants as a result of its anti-histaminergic properties?
Weight gain
Sedation
What are the side effects of tricyclic antidepressants as a result of its anti-α-adrenergic properties?
Postural hypotension
What are the cardiotoxic side effects of tricyclic antidepressants?
QT interval prolongation
ST segment elevation
Heart block arrhythmias - due to noradrenaline uptake blocking in the heart
Tricyclic antidepressants can be divided into those that are more or less sedative. What are the more sedative TCAs?
Amitriptyline
Clomipramine
Dosulepin
Tricyclic antidepressants can be divided into those that are more or less sedative. What are the less sedative TCAs?
Imipramine
Lofepramine
Nortriptyline
Which tricyclic antidepressant has the lowest incidence of toxicity in overdose?
Lofepramine
Which two tricyclic antidepressants are particularly dangerous in overdose?
Amitriptyline
Dosulepin (dothiepin)
What are the early features of tricyclic antidepressant overdose?
Relate mostly to anticholinergic properties:
Dry mouth
Dilated pupils
Agitation
Sinus tachycardia
Blurred vision
What are the more severe features of tricyclic antidepressant overdose?
Arrhythmias
Seizures
Metabolic acidosis
Coma
What are the non-neurotransmitter and non-cardiac complications and side effects of tricyclic antidepressants?
Peripheral neuropathy
Gynaecomastia
SIADH
What are the ECG changes associated with tricyclic antidepressant overdose?
Sinus tachycardia
Widening of QRS: (more than 100ms is associated with an increased risk of seizures whilst QRS more than 160ms is associated with ventricular arrhythmias)
Prolongation of QT interval
How do we manage someone who has taken an overdose of amitriptyline?
IV bicarbonate reduces risk of seizures and arrhythmias in severe toxicity
IV lipid emulsion is increasingly used to bind free drug and reduce toxicity
What are the anti-arrhythmics that are contraindicated in the management of TCA overdose?
Class 1a (e.g. Quinidine) and class Ic antiarrhythmics (e.g. Flecainide) are contraindicated as they prolong depolarisation.
Class III drugs such as amiodarone and sotalol should also be avoided as they prolong the QT interval.
Response to lignocaine is variable and it should be emphasized that correction of acidosis is the first line in management of tricyclic induced arrhythmias
What is the rare arrhythmia associated with prolonged QT interval?
Torsades de pointes
Why is torsades de pointes arrhythmia particularly dangerous?
Deteriorates into VF and hence leads to sudden death
How do we treat someone whose rhythm is found to be torsades de pointes on ECG?
IV magnesium sulphate
