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Tricyclic Overdose and Toxicology, Jordan Barnett MD
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Cyclic Antidepressant Overdose Dr. Jordan B. Barnett, MD FACEP Interim Chairman, Department of Emergency Medicine at Episcopal Hospital Overview Widely used therapy for major depression Third most common cause of…
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Content Preview
- Cyclic Antidepressant Overdose Dr. Jordan B. Barnett, MD FACEP Interim Chairman, Department of Emergency Medicine at Episcopal Hospital
- Overview
- Widely used therapy for major depression
- Third most common cause of drug related death in US throughout 1980s
- 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
- 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
- Metabolism
- Demethylation
- hydroxlation
- Glucuronidization
- increased metabolism via enhancement of barbiturates, tobacco, etoh.
- Excreted in bile and enter enterohepatic cycle
- 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
- TCA Pharmacology Cont.
- alpha adrenergic blocking
- anticholinergic
- membrane stabilizing effects similar to quinidine and local anesthetics
- calcium channel blocking effects
- Cardiac Complications
- CA block fast sodium channel (responsible for depolarization of conduction tissue
- CAs slow repolarization (QT prolonged)
- Depressed Automaticity
- 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%)
- 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
- Signs and Symptoms
- CNS depression
- Anticholinergic toxicity
- Depression of cardiac conduction and contractility
- Disorientation
- Coma, Myoclonus, clonus, seizures
- tachycardia, mydriasis
- 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
- 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
- Sequence of ECG changes
- IV conduction block
- Arrhythmias
- Cardiac condtractility depressed
- bradycardia
- Those who die….
- Hypotension
- Conduction blocks
- SVT
- Death usually not due to ventricular arrhythmias!
- 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
- 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
- Cathartics
- Recommended
- Yet no effect until patient begins to awaken (Remember- anticholinergic effects!)
- 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
- 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%
- Other studies needed...
- Sodium (antagonizes CA)
- Potassium (increases toxic effects)
- Drug removal
- Peritoneal dialysis or forced diuresis not effective
- Hemoperfusion removes only small quantities
- Fluid loading, alkalinization, pressors are mainstay
- 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
- Treatment of specific complications
- Seizures
- Cardiac depression (hypotension and conduction blocks)
- 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.
- 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!
- 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
- How to Alkalinize
- Hyperventilation
- Administration of 1-5 meq/kg of bicarbinate. This, can, however, increase myocardial ischemia
- Why is sodium Bicarbinate Effective?
- Sodium reverses blocked membrane channel
- In some studies hypertonic saline as effective as bicarbonate
- 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
- 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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