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TCA mechanisms of Toxicity

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TCA mechanisms of Toxicity Anti-cholinergic Na+ channel blockade K+ channel blockade Alpha 1 antagonism Serotonin reuptake inhibition GABA antagonism – PowerPoint PPT presentation

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Title: TCA mechanisms of Toxicity


1
TCA mechanisms of Toxicity
  • Anti-cholinergic
  • Na channel blockade
  • K channel blockade
  • Alpha 1 antagonism
  • Serotonin reuptake inhibition
  • GABA antagonism
  • Anticholinergic toxidrome
  • Wide QRS
  • Prolonged QT
  • Hypotension
  • Seritonin syndrome
  • Seizures

2
Anticholinergic Toxidrome
  • Agitation/altered LOC
  • Red, hot, dry skin
  • Tachycardia
  • Dilated pupils
  • No bowel sounds
  • Urinary retension
  • Mild hyperthermia
  • Mild hyperreflexia

3
Case of the day!
  • After you intubate, patient has a generalized
    seizure
  • Why?
  • Anticholinergic effect
  • Gaba antagonism
  • Hypotension
  • Why are seizures so bad?
  • Management?

4
TCA overdoses and seizures
Acidosis
Seizure
Cardiac toxicity
DEATH
Shock
5
TCA toxicity and Seizures
  • Management
  • First line benzodiazepines
  • Second line phenobarbital
  • Third line agents propofol
  • Avoid dilantin (Na channel blockade)
  • Should you give bicarb? Yes

6
Flumazenil
  • Why is flumazenil contraindicated in a patient
    with BZD TCA overdose?
  • Will precipitate seizures ----gt acidosis, cardiac
    toxicity, death, call CMPA
  • Flumazenil is generally not indicated in the
    overdose setting for this reason
  • One exception may be a pediatric ingestion of BZD
    with absolutely no suspicion of coingestant

7
Case of the day!
  • HR 120, BP 80/50
  • What is your management?
  • Why?

8
TCAs and Hypotension
  • Fluids, go early to pressors
  • Norepinephrine is the pressor of choice
  • If you are going to use dopamine, titrate up to
    alpha range (15 - 20 ug/kg/min)
  • Why is norepinephrine better than dopamine?

9
TCAs and Hypotension
  • Dopamine is a precursor to norepinephrine
  • Dopamine stimulates the release of stored
    norepinephrine
  • Dopamine stimulates adrenergic receptors

10
TCAs and Hypotension
11
TCAs and Hypotension
12
TCAs and Hypotension
  • Extreme options!
  • ECMO
  • Cardiac bypass
  • IABP

13
Case of the day!Interpretation?Will she have a
bad outcome?
14
TCA toxicity and the ECG
  • Sinus tachycardia
  • Prolonged QT
  • Wide QRS
  • Wide complex tachycardia SVT with aberrancy or
    Vtach
  • Right BBB
  • Tall R wave in aVR
  • R/S ration in aVR gt
  • Terminal 40 msec right axis

15
TCA toxicity and the ECG
  • Tall R in aVR, R/S ratio in aVR gt 0.7

16
TCA toxicity and the ECG
  • Terminal 40 msec right axis

17
TCA toxicity and the ECG
  • Terminal 40 msec right axis

18
TCA toxicity and the ECG
  • What ECG features are predictive of TCA toxicity?
  • QRS width
  • Tall R in aVR
  • R/S ratio in aVR
  • Terminal 40 msec right axis
  • Which are the most sensitive/specific for TCA
    toxicity?

19
QRS width
20
aVR tall R wave and R/S ratio
21
Terminal 40 msec right axis
22
What is the differential dx of wide QRS in the
overdose setting?
23
ECG and Toxicology
  • Wide QRS (Na channel blockade)
  • TCAs
  • Gravol, bendadryl
  • Cocaine and other sympathomimetics
  • Haldol and other neuroleptics
  • Celexa
  • Carbemezepine?
  • kdjflfjljletc
  • Prolonged QTc
  • TCA
  • Haldol etc
  • Ia
  • Ic
  • dfjkl

24
Case of the day!
  • Vtach
  • Management?

25
TCA and Sodium Bicarbonate
  • Sodium Bicarbonate is the treatment of choice for
    cardiac toxicity
  • Dose 1-2 mEq/kg iv bolus q10 min prn
  • End points no indication, pH 7.50 - 7.55
  • Monitor response with repeat ECGs

26
TCA and Sodium Bicarbonate How does it work?
  • Increases protein binding
  • TCAs are albumin bound which is pH sensitive
    minor role b/c large Vd and lipophilic thus most
    TCA is in tissue not serum
  • Alkalosis
  • the TCA to Elevated pH decreases the binding of
    the voltage gated sodium channel
  • Sodium loading
  • Na load with bicarb creates a larger gradient
    across the Na channel

27
TCA and Sodium Bicarbonate What are the
indications?
  • Hypotension
  • Wide complex tachycardia
  • Conduction blocks
  • QRS gt 100 msec (or gt 120 msec)
  • New/unexplained RBBB
  • R in aVR gt 3mm, R/S ratio gt 0.7, or terminal 40
    msec right axis
  • ? Which are goldfranks recommendations
  • ? seizures

28
TCA and Sodium Bicarbonate Bolus versus
infusion?
  • Boluses are preferred for initial indications
    Why?
  • All studies showing effect of bicarb have used a
    bolus
  • Probably better b/c big Na load with bolus
    overcomes Na blockade Na load likely more
    important than pH change
  • Repeat boluses vs infusion never directly studied
  • Bicarb infusion resonable for patient requiring
    repeat boluses

29
Could Fab fragments be the cure for the TCA
overdose??
30
Case of the day!
  • ICU resident order serum TCA level and urine TCA
    screen ------gt what do you say?

31
TCA and lab testing
  • Urine TCA screen
  • Dip stick screen, immunoassay
  • HORRIBLE specificity thus the lab doesnt even do
    it
  • Serum TCA levels
  • Do NOT correlate with toxicity
  • False ves
  • Benadryl
  • Gravol
  • Flexeril
  • dfldjf
  • fldljfkl

32
TCA overdose and disposition
  • Toxicity develops within 6 hrs
  • Monitored for 6hrs NO seizures, hypotension,
    arrythmias, no bicarb Rx
  • Can d/c home or to psych
  • ICU for seizures, hypotension, arrythmias,
    decreased LOC
  • Telemetry for prolonged QTc
  • Duration of cardiac monitoring
  • 24hrs after normalization of BP, off
    alkalinization/antidysrhythmics/pressors
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