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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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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 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 Tissue entry is dependent on lipid solubility and their ionic dissociation at various pH levels Metabolism 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 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) 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 Depression of cardiac conduction and contractility Coma, Myoclonus, clonus, seizures Toxicity Tachycardia, slurred speach, and lethargy are earliest signs Twitching and myoclonic movements in 40% confused often with seizures and do not respond to dilantin Grand mal seizures in 10-20 percent ECG Prolonged QT and QRS interval Righward deviation of the QRS axis Bundle branch blocks, AV Conduction blocks Ventricular arrhythmias, EMD, Idioventricular rhythms Sequence of ECG changes Cardiac condtractility depressed Those who die…. 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) Mandatory Preventive Care Fatal cases can present with only trivial signs of poisoning and develop major toxicity and life threatening complications very quickly Charcoal every 2 hours to reduce half life from 36 hours to 4 hours Cathartics 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... 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 Cardiac depression (hypotension and conduction blocks) Seizures Mortality of 10%Most seizures are brief and benign 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 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 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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