tricyclic overdose and toxicology, jordan barnett md
DESCRIPTION
2007 Lecture regarding Tricyclic overdose toxicology and poison management in the Emergency Department, Jordan Barnett MDTRANSCRIPT
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Cyclic Antidepressant Overdose
Dr. Jordan B. Barnett, MD FACEP
Interim Chairman, Department of Emergency Medicine at Episcopal
Hospital
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Overview
• Widely used therapy for major depression
• Third most common cause of drug related death in US throughout 1980s
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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
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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
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Metabolism
• Demethylation
• hydroxlation
• Glucuronidization
• increased metabolism via enhancement of barbiturates, tobacco, etoh.
• Excreted in bile and enter enterohepatic cycle
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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
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TCA Pharmacology Cont.
• alpha adrenergic blocking
• anticholinergic
• membrane stabilizing effects similar to quinidine and local anesthetics
• calcium channel blocking effects
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Cardiac Complications
• CA block fast sodium channel (responsible for depolarization of conduction tissue
• CAs slow repolarization (QT prolonged)
• Depressed Automaticity
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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%)
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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
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Signs and Symptoms
• CNS depression
• Anticholinergic toxicity
• Depression of cardiac conduction and contractility
• Disorientation
• Coma, Myoclonus, clonus, seizures
• tachycardia, mydriasis
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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
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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
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Sequence of ECG changes
• IV conduction block
• Arrhythmias
• Cardiac condtractility depressed
• bradycardia
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Those who die….
• Hypotension
• Conduction blocks
• SVT
• Death usually not due to ventricular arrhythmias!
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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
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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
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Cathartics
• Recommended
• Yet no effect until patient begins to awaken (Remember- anticholinergic effects!)
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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
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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%
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Other studies needed...
• Sodium (antagonizes CA)
• Potassium (increases toxic effects)
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Drug removal
• Peritoneal dialysis or forced diuresis not effective
• Hemoperfusion removes only small quantities
• Fluid loading, alkalinization, pressors are mainstay
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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
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Treatment of specific complications
• Seizures
• Cardiac depression (hypotension and conduction blocks)
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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.
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Status Epilepticus
• Often complicated by hyperthermia
• Amoxapine, maprotiline, Despiramine often implicated
• Often requires general anesthesia or paralysis.
• Don’t use succinylcholine since vagal effects - vecuronium safer!
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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
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How to Alkalinize
• Hyperventilation
• Administration of 1-5 meq/kg of bicarbinate. This, can, however, increase myocardial ischemia
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Why is sodium Bicarbinate Effective?
• Sodium reverses blocked membrane channel
• In some studies hypertonic saline as effective as bicarbonate
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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
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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
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IF P R E S E N T:A B G , C X R , V en tila te to p h 7 .5 , E va lu a te E lec tro lytes ,
A d m it
D isch arg eP sych ia tric C on su lt
C lin ica l C on d it ion im p rovin g ?R eassess a t 6 h ou rs
N o M a jo r s ig n sN o B ow e l S ig n s
M a jo r s ig n s o f P o ison in gD ec reased L O C
R esp ira to ry D ep ress ionH yp o ten s ion , a rrh yth m ias , con d u c tion b lock , se izu res
L avag eA c tiva ted C h arcoa l
C a th art ic
E s tab lish IVC ard iac M on ito rin g
E C GIm m ed ia te an d C on tin u ou s O b serva tion
H is to ry o r su sp ic ion o f in g es tion