See also [[Sodium channel blocker]], [[Anticholinergic toxicity]] [goldfrank TCA overdose](x-devonthink-item://2F041FBD-FF1C-4E21-9CD5-5550C288F006?page=1070), [Austin - Tricyclic Guideline Oct 2022](x-devonthink-item://E8F2E0BE-3BC1-49D9-94DD-D84EAA4B446A), [Murray’s TCA](x-devonthink-item://DA1896AC-D57C-4A67-B2C7-65B1D27BB53E?page=391) Interesting case: [TCA OD and HCO3 OD](https://www5.austlii.edu.au/au/cases/act/ACTCD/2025/1.html) > [!key points] > - **risk_dose**:: *>10 mg/kg* life threatening, >20mg/kg ↓ GCS > - **Antidote**:: [[HCO3 therapy|NaHCO3]], intubation, hyperventilation > - **key_points**:: [[Sodium channel blocker]], [[Anticholinergic toxicity]] Tricyclic antidepressants: - amitriptyline - Endep - dothiepin - doxepin - nortriptyline - clomipramine # mechanism *See* [goldfrank TCA overdose](x-devonthink-item://2F041FBD-FF1C-4E21-9CD5-5550C288F006?page=1071&istart=4173&ilength=14&search=PATHOPHYSIOLOGY) - has [[Sodium channel blocker|Na channel blocking]] and alpha blocking effects - noradrenaline and serotonin reuptake inhibitor - this is the basis of their therapeutic activity - GABA receptor blocker - **myocardial toxicity** due to ==blockade of fast sodium channels== - blockade at **muscarinic** , **histamine**, and post-synaptic alpha-1 receptors - cause reversible inhibition of potassium channels and direct myocardial depression unrelated conduction abnormalities - **Agitation**, delirium, and depressed sensorium are primarily caused by central ==anticholinergic and antihistaminic== effects. Details regarding the exact mechanism of CA-induced seizures remain elusive. - **seizures** may result from a combination of an increased concentration of monoamines (particularly norepinephrine), muscarinic antagonism, neuronal sodium channel alteration, and GABA inhibition > **Major toxicity in overdose relates to CNS and CVS** # Toxicological effects **cardiac** - conduction disturbances - block fast sodium channels (class 1a) - prolonged QRS - VT, VF, asystole - myocardial depression **peripheral anticholinergic effects** - sinus tachycardiac (common) - blurred vision - [[Mydriasis]] - urinary retention - gut illeus - reduced salvation - hyperthermia - dry, warm, flushed skin **central anticholinergic effects** - drowsiness, confusion - myoclonic jerks - [[Seizures]] (often after myoclonic jerks) - coma can develop rapidly after seizures **anti-alpha1 effects** - vasodilation and hypotension [[Serotonin Syndrome]] - when used in combination with SSRI drugs # ECG - **prolongation of QRS interval** \> 100ms predictive of seizures (Austin says >120 ms) \> 160ms (4 small squares) predictive of ventricular arrhythmia - large **terminal R wave** in aVR >3mm - increased **R/S ratio** >0.7 in aVR - sinus tachycardia (2/2 anticholinergic effects) - QT prolongation is also noted secondary to potassium channel blockade, but TdP NOT generally seen in TCA ![[Pasted image 20250131071833.png]] ![[Pasted image 20250131073340.png]] # Risk assessment | dose | effect | | ------------ | ----------------------------------------------------------------------------------------------------- | | < 5mg/kg | minimal sx | | 5 - 10 mg/kg | drowsiness and mild anticholinergic effects, unlikely major tox | | > 10mg/kg | potetial for all major effects (coma, hypotension, seizures, dysrhythmias within 2-4 hrs of ingestion | | > 30mg/kg | severe toxicity, pH dependent cardiotoxiicity, coma expected >24 hours | # management - needs early intubation (manage ventilation, ) - can arrest if not ventilated - ==Indications for [[HCO3 therapy#TCA overdose|HCO3]]==: [[Seizures]], arrhythmias, QRS >120ms, on induction immediately prior to intubation - use 8.4% 1mL/kg bolus. repeat Q1-5 min target pH 7.5-7.55 until restoration of perfusing rhythm, improvement in QRS, PH established - ==Maximum total dose is 6 mL/kg== (6 mmol/kg). Urgently seek advice from a clinical toxicologist if there is inadequate response to the maximum total dose. - ==QRS may not return to <100 ms, but this is not a mandate for ongoing sodium bicarb if pt stable and pH maintained by hyperventilation== - avoid hyper-CO2 - worsening acidosis → use [[HCO3 therapy#TCA overdose|HCO3]] - need to blow off CO2 from NaHCO3 - need to take control of ventilation - ==aim pCO2 30-35== - *seizures*: NaHCO3 as above. further benzodiazepam if seizure continues, prepare for [[Airway#Rapid Sequence intubation (RSI)|RSI]] with [[Peri-intubation collapse#metabolic acidosis|modifications for acidosis]] - *hypotension*: IV crystaloid. use give metaraminol or ==noradrenaline== + correct acidosis if fluid resistant hypotension - consider adding inotrope if bedside ECHO suggests poor contractility - broad complex dysrhythmias: HCO3 as per above. if refractive/unstable can consider lidocaine 1-1.5mg/kg IV after pH is established - decontamination: activated charcoal only after airway is secured / - no roll for enhanced elimination # disposition - if clinically well and normal ECG, can discharge 6 hours post exposure (pending mental health assessment) # notes - MAOI + TCA can cause hyperpyretic reactions and death -