TCA overdose Flashcards
What are TCA’s?
Tricyclic antidepressants
Developed initially for severe depression
Now used commonly for neuropathic pain and migraine propyhlaxis
What are examples of TCA’s?
amitriptyline, nortriptyline and dosulepin.
What is the MOA of TCA’s?
Act on multiple neurotransmitter pathways to enhance the effects of certain hormones while inhibiting others.
Two main MOA’s:
- Reuptake inhibition:
- Prevents the neurotransmitter from being transported back into the pre-synaptic neurone once released into the synaptic cleft.
- Subsequently, the neurotransmitter remains in the synaptic cleft and continues to activate the postsynaptic receptor, increasing its effect.
- Pathways affected: Serotonin (5-HT receptors), Noradrenaline (NA receptors) - Postsynaptic receptor antagonism:
- Prevents the neurotransmitter from activating the postsynaptic receptor, overall reducing its effect.
- Pathways affected: Histamine (H1 receptors), A-1 Adrenoreceptors, Acetylcholine receptors
Which TCA’s are especially dangerous?
Amitriptyline and dosulepin (dothiepin)
What is the key mechanism by which TCAs achieve their antidepressant effects?
Inhibiting the reuptake of serotonin and noradrenaline.
However, the lack of specificity and effects on other pathways results in an extensive side effect profile and contributes to their toxicity in overdose.
What are the clinical manifestations of the different pathways?
Serotonin: nausea, gastrointestinal upset, sexual dysfunction
Noradrenaline: tachycardia, tremors
Antihistamine: sedation, weight gain
Anticholinergic: dry mouth, blurred vision, confusion, constipation, tachycardia, urinary retention
Alpha-1 adrenergic: postural hypotension, drowsiness, dizziness
what is the relation between TCAs and sodium?
TCAs act on the fast sodium channels in myocardial cells, resulting in sodium channel blockade and risk of cardiac arrhythmias, convulsions, and coma in overdose.
What are RFs for a TCA overdose?
Intentional OD
- Suicide attempt
- Self harm
Unintentional or Accidental OD
- Less common
- Risk in elderly with cognitive impairment who take more than prescribed dose
- Risk with child who may ingest meds when unattended
Are TCA’s toxic and what are their more severe effects?
Highly toxic
Most severe effects: cardiovascular and neurological instability
Narrow therapeutic window - so toxicity can be seen at low levels
When do the sx of OD become apparent?
Within 6 hrs
What are the key clinical features of TCA toxicity?
Signs of anticholinergic activity and result of sodium channel blockade
Severe effects: arrhythmia, cardiovascular collapse, convulsions and coma.
Typical sx:
- Dry mouth
- Hot, dry skin
- Confusion and hallucinations
- Palpitations
What are features of severe poisoning?
arrhythmias
seizures
metabolic acidosis
coma
What should you cover in a hx for TCA OD?
History of ingestion:
- How much ingested
- Calculation of mg/kg ingestion helpful prognostically.
- Mixed OD taken? Manage each substance individually
- PMHx
- Past psychiatric history
Collateral Hx
- If pt has reduced level of consciousness
- From family or paramedics
- Paramedics often bring empty medication boxes
What are ABCDE clinical signs of TCA OD?
Airway
- Airway compromise (snoring, secretions, low RR)
Breathing
- Respiratory depression
Circulation
- Hypotension and arrhythmia (due to myocardial sedum channel blockade)
- Tachycardia and vasodilation (due to serotonergic activity)
- ECG findings
Disability
- AVPU or GCS
- Can have seizure or coma
- Pts may present actively seizing or in postictal state
- Check glucose!!
Exposure
- Hyperthermic - due to serotonergic effects
- Anticholinergic signs - dry skin, eyes and mouth, urinary retention and ileum
What increases the risk of serotonin syndrome?
Co-ingestion with other medications which up-regulate serotonin
What is serotonin syndrome?
- Potentially life-threatening presentation
- Due to over activation of central and peripheral serotonin receptors
- Causes by serotonergic drugs
What are features of serotonin syndrome?
- Altered mental state
- Neuomuscular hyperactivity
- Autonomic hyperactivity
- HTN
- Tachycardia
- Diaphoresis
- Myoclonus
- Hyperreflexia
- Severe: Hyperthermia, muscle rigidity
How is serotonin syndrome managed?
Supportive
Benzodiazepines are often used for sedation
What investigations are done in TCA OD? Why may they be done? What may they show?
- Obs - tachycardia, hypotension, hyperthermia
- ECG
- Glucose - exclude hypoglycemia
- Blood gas - mixed acidosis (requires bicarbonate as tx)
- FBC - to establish baseline
- U & E - hypokalaemia
- Mg and bone profile - electrolyte disturbances can worsen arrhythmia
- LFTs - if concerned re co-ingestion of other meds, esp paracetamol
- Paracetamol and salicylate levels: typically checked in all patients
- CXR - airway compromise, risk of aspiration pneumonia
- CT head - pt has significantly reduced GCS, or seizures.
What ECG changes may be seen?
What may they be a/w?
sinus tachycardia
widening of QRS
prolongation of QT interval
Widening of QRS > 100ms a/w increased risk of seizures
QRS > 160ms a/w ventricular arrhythmias
These rhythms predispose to VTach and VFib
How may TCA OD be diagnosed?
Hx of ingestion and collateral hx
How Is TCA OD managed?
- No specific antidote
- Activated charcoal if conscious and presenting within 1 hr of ingestion
- Sodium bicarbonate in arrhythmia and acidosis to prevent ventricular arrhythmias
- Resus and ABCDE
1st line : IV Bicarbonate
- Other drugs for arrhythmias
- IV lipid emulsion increasing used to bind free drug and reduce toxicity
IV bicarbonate as a tx?
1st line for hypotension or arrhythmias
Indications:
- Widening of the QRS interval >100 msec
- Ventricular arrhythmia
What drugs are contraindicated in tx and why?
- Class 1a (e.g. quinidine) and class Ic antiarrhythmics (e.g. Flecainide)
- They prolong depolarisation
- Class III drugs such as amiodarone 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 the management of tricyclic-induced arrhythmias
