tricyclic overdose and toxicology, jordan barnett md

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2007 Lecture regarding Tricyclic overdose toxicology and poison management in the Emergency Department, Jordan Barnett MD

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  • 1. Cyclic Antidepressant Overdose Dr. Jordan B. Barnett, MDFACEP Interim Chairman, Department of Emergency Medicine at Episcopal Hospital

2. Overview

  • Widely used therapy for major depression
  • Third most common cause of drug related death in US throughout 1980s

3. Pharmacology

  • Anticholinger and amine pump blocking properties similar to phenothiazines
  • Adrenergic Stimulating affects via blocking uptake of norepinephrine at synapse
  • Block sodium channels
  • new agents are unicyclic, bicyclic, and tetracyclic

4. Bioavailability

  • slowly absorbed secondary to ionization in the stomach and slowing of peristalsis
  • Can remain in gut for 12 hours or more
  • Dissolve slowly
  • 85-98% plasma bound
  • Tissue entry is dependent on lipid solubility and their ionic dissociation at various pH levels

5. Metabolism

  • Demethylation
  • hydroxlation
  • Glucuronidization
  • increased metabolism via enhancement of barbiturates, tobacco, etoh.
  • Excreted in bile and enter enterohepatic cycle

6. Activities of TCAs

  • neuronal amine pump in cns blocked, stopping reuptake of norepinephrine and serotonin
  • Also block norepinephrine reuptake at the adrenergic synapse outside of cns, leading to adrenergic blockade of cardiovascular system

7. TCA Pharmacology Cont.

  • alpha adrenergic blocking
  • anticholinergic
  • membrane stabilizing effects similar to quinidine and local anesthetics
  • calcium channel blocking effects

8. Cardiac Complications

  • CA block fast sodium channel (responsible for depolarization of conduction tissue
  • CAs slow repolarization (QT prolonged)
  • Depressed Automaticity

9. Newer Tricyclics Safer?

  • Maprotiline (Ludiomil) is a tetracyclic with more seizures in overdose
  • Amoxapine (Asendin) is a metabolite of loxapine with few Cardiovascular effects but a higher incidence of seizures (36%) and Death (15%)

10. Newer Compounds Safer?

  • Trazadone (Desyrel) - unrelated to TCAs and equally effective yet no CNS or Cardiac effects in OD
  • Fluoxetine (Prozac) - pure serotonin blocker with little adrenergic activity - rare for CNS or cardiac effects

11. Signs and Symptoms

  • CNS depression
  • Anticholinergic toxicity
  • Depression of cardiac conduction and contractility
  • Disorientation
  • Coma, Myoclonus, clonus, seizures
  • tachycardia, mydriasis

12. Toxicity

  • Tachycardia, slurred speach, and lethargy are earliest signs
  • Coma 35%
  • Twitching and myoclonic movements in 40% confused often with seizures and do not respond to dilantin
  • Grand mal seizures in 10-20 percent

13. ECG

  • ST and T wave changes
  • Prolonged QT and QRS interval
  • Righward deviation of the QRS axis
  • Bundle branch blocks, AV Conduction blocks
  • Aberrant conduction
  • Ventricular arrhythmias, EMD, Idioventricular rhythms

14. Sequence of ECG changes

  • IV conduction block
  • Arrhythmias
  • Cardiac condtractility depressed
  • bradycardia

15. Those who die.

  • Hypotension
  • Conduction blocks
  • SVT
  • Death usually not due to ventricular arrhythmias!

16. Treatment

  • Prehospital - little can be done
  • 25% of cases, patients were alert and awake at first prehospital contact
  • All need monitoring, iV line, O2,, constant observation
  • NO IPECAC (CNS depression can be rapid)
  • Activated charcoal

17. Mandatory Preventive Care

  • Fatal cases can present with only trivial signs of poisoning and develop major toxicity and life threatening complications very quickly
  • Gastric Lavage paramount
  • Charcoal
  • Charcoal every 2 hours to reduce half life from 36 hours to 4 hours

18. Cathartics

  • Recommended
  • Yet no effect until patient begins to awaken (Remember- anticholinergic effects!)

19. Acid-Base Status

  • Cardiovascular complications are pH dependent
  • Any TCA OD with decreased CNS needs ABGs and Chest xray secondary to pulmonary edema or aspiration pneumonitis
  • Maintain pH above 7.4 and a high paO2

20. ECG AS SOON AS POSSIBLE!

  • Evaluate QRS duration, axis, rrhythm and rate
  • QRS > 100 ms has a sensitivity for major complications of only 59% and a specificity of 76%
  • Looks ofr a negative deflection in lead I and a positive deflection in aVr.This has a positive predictive value of 49% and a negative predictive value of 90%

21. Other studies needed...

  • Sodium (antagonizes CA)
  • Potassium (increases toxic effects)

22. Drug removal

  • Peritoneal dialysis or forced diuresis not effective
  • Hemoperfusion removes only small quantities
  • Fluid loading, alkalinization, pressors are mainstay

23. Prognosis

  • GCS of less than 8 predicts serious complications with a sensitivity of 86% and specificity of 89%.
  • A high GCS does not rule out significant ingestion

24. Treatment of specific complications

  • Seizures
  • Cardiac depression (hypotension and conduction blocks)

25. Seizures

  • 10% of all cases
  • Mortality of 10%Most seizures are brief and benign
  • Diazepam
  • Phenytoin can cause hypotension and bradycardia and can worsen arrhythmias.Ineffective in 188 human cases.Still widely used, however.

26. Status Epilepticus

  • Often complicated by hyperthermia
  • Amoxapine, maprotiline, Despiramine often implicated
  • Often requires general anesthesia or paralysis.
  • Dont use succinylcholine since vagal effects - vecuronium safer!

27. Cardiac Complications

  • Avoid physostigimine (Can cause seizures, cholinergic crisis - narrow therapeutic/toxic ratio)
  • Alkalinization of blood to ph 7.5.This often abolishes arrhythmias within minutes

28. How to Alkalinize

  • Hyperventilation
  • Administration of 1-5 meq/kg of bicarbinate.This, can, however, increase myocardial ischemia

29. Why is sodium Bicarbinate Effective?

  • Sodium reverses blocked membrane channel
  • In some studies hypertonic saline as effective as bicarbonate

30. Cardiac Arrest 2%

  • Prolonged CPR and cardiopulmonary bypass has been sucessful in healthy younger patients
  • isoproterenol can worsen hypotension and cardiac irritability due to unopposed beta adrenergic effects
  • Never use Dobutamine - a Beta adrenergic drug

31. Disposition and Admission Criteria

  • Observe at least 6 hrs
  • If any signs or symptoms, admission to monitored bed
  • If after 6 hrs only minor signs, such as tachycardia less than 120 or slurred speech with bowel sounds, with signs decreasing, can discharge

32.