Overdoses Flashcards
What are tricyclic antidepressants (TCAs)?
A class of medications developed initially for severe depression.
Now more used to manage neuropathic pain and for migraine prophylaxis.
Give 3 examples of TCAs
1) amitriptyline
2) nortriptyline
3) dosulepin
What are the 2 most common drugs most commonly taken in fatal overdose?
1) analgesic drugs (most common)
2) TCAs: highly toxic in overdose.
What are the 2 main mechanisms of action of TCAs?
1) Reuptake inhibition (more neurotransmitter remains in synaptic cleft) i.e. INCREASED effect
2) Postsynaptic receptor antagonism: prevents the neurotransmitter from activating the postsynaptic receptor, overall reducing its effect i.e. DECREASED effect
What 2 neurotransmitters do TCAs have an INCREASED effect on (i.e. via reuptake inhibition)?
1) serotonin (5-HT receptors)
2) Noradrenaline (NA receptors)
What 2 neurotransmitters do TCAs have a DECREASED effect on (i.e. via postsynaptic receptor antagonism)?
1) histamine (H1 receptors)
2) A-1 adrenoreceptors
3) Acetylcholine receptors
What is the key mechanism by which TCAs achieve their antidepressant effect?
Inhibiting the reuptake of serotonin and noradrenaline.
What causes increased side effects and toxicity in overdose of TCAs?
The lack of specificity and effects on other pathways results in an extensive side effect profile
List of side effects of TCAs due to each pathway:
Serotonin: nausea, GI upset, sexual dysfunction
Noradrenaline: tachycardia, tremors
Histamine: sedation, weight gain
Anticholinergic: dry mouth, blurred vision, confusion, constipation, tachycardia, urinary retention
Alpha-1 adrenergic: postural hypotension, drowsiness, dizziness
TCAs also act on the fast sodium channels in myocardial cells, resulting in sodium channel blockade and risk of cardiac arrhythmias, convulsions, and coma in overdose.
When do the clinical manifestations of TCA overdose typically appear?
within 6 hours of ingestion
Which 2 TCAs are particularly dangerous in overdose?
1) amitriptyline
2) dosulepin (dothiepin)
What are the key clinical features of TCA overdose?
Signs of anticholinergic toxicity:
- dry mouth
- dilated pupils
- tachycardia
- blurred vision
- agitation
Signs of sodium channel blockade:
- arrhythmias
- CVS collapse
- convulsions
- metabolic acidosis
- coma
What ECG changes may be seen in TCA overdose?
1) sinus tachycardia
2) widening of QRS
3) prolongation of QT interval
What are the complications of widening of QRS?
1) Widening of QRS > 100ms: associated with an increased risk of seizures
2) Widening of QRS > 160ms: associated with ventricular arrhythmias
How may TCA overdose affect breathing?
In patients presenting with severe toxicity, respiratory depression may occur resulting in reduced respiratory rate and reduced SpO2.
How may TCA overdose affect circulation?
1) TCAs cause myocardial sodium channel blockade: hypotension & arrhythmia
2) Serotonergic activity: tachycardia and peripheral vasodilation may occur
3) ECG findings: widened QRS, prolonged QTc (predispose to ventricular tachycardia and ventricular fibrillation)
What is serotonin syndrome?
A potentially life-threatening presentation precipitated by the overactivation of both central and peripheral serotonin receptors.
Caused by using serotonergic drugs e.g. TCAs, SSRIs, opioids, MAOIs.
What are the 3 hallmark features of serotonin syndrome?
1) altered mental state
2) neuromuscular hyperactivity
3) autonomic hyperactivity
This results in:
- HTN
- tachycardia
- sweating
- myoclonus
- hyperreflexia
- severe: hyperthermia, muscle rigidity
Bedside investigations in TCA overdose?
1) Vital signs (as part of ABCDE): tachycardia, hypotension, hyperthermia
2) ECG: widened QRS, prolonged QTc
3) Blood glucose: exclude hypoglycaemia
4) Blood gas: mixed acidosis
Lab investigations in TCA overdose?
1) FBC: baseline
2) U&Es:
- hypokalaemia common
- patients with renal impairment more at risk as TCAs renally excreted
3) Magnesium & bone profile: electrolyte disturbances can worsen arrhythmia and require correction
4) LFTs
5) Paracetamol & salicylate levels: typically checked in all patients presenting with overdose, particularly where the history is unclear
How is potassium level affected by TCA overdose?
Hypokalaemia: risk of seizures or cardiac arrhythmias
How are TCAs excreted?
Renally
What imaging may be relevant in TCA overdose?
1) CXR: useful in the assessment of patients who are presenting with reduced conscious level and airway compromise, where there is a risk of aspiration pneumonia
2) CT head: considered in patients with significantly reduced GCS to rule out concurrent intracranial pathology.
Acute management of TCA overdose?
There is no specific antidote to TCAs, therefore management is supportive.
1) ABCDE
2) Can give activated charcoal to conscious patient –> prevent absorption if they present within one hour of ingestion
3) Sodium bicarb: given in arrhythmia and acidosis to prevent progression to ventricular arrhythmias.
