بنام خداوند بخشنده مهربان

TRICYCLIC ANTIDEPRESSANT

POISONING

TRICYCLIC ANTIDEPRESSANT

POISONING

Tertiary Amines (tricyclic antidepressants)Amitriptyline Elavil™Doxepin Sinequan™Imipramine Tofranil™Trimipramine Surmontil™Amoxapine Asendin™Maprotiline Ludiomil™Clomipramine

Secondary Amines (tricyclic antidepressants)Nortriptyline (metabolite of

amitriptyline) Pamelor™Protriptyline Vivactil™Desipramine (metabolite of

imipramine) Norpramine™

Dose > 1 g : Life treatening

Toxic dose: > 5 mg / kg Child : One pill can kill

فارماكوكينتيكفارماكوكينتيكمحلول در چربي برابر غلظت آن در خون100-10غلظت آن در بافتها در 1در طی ساعات اولیه پس از خوردن کمتر از %

خون است شروع عالئم سريعشروع عالئم تهديد كننده حيات در طي ساعات اوليه 95-90باند با پروتئینی باال%متابولیسم کبدی

Overdose and ToxicityPatients presenting with a suspected

TCA overdosed may exhibit no symptomatology or minor complications.

Although the patients may appear well initially, they can rapidly and without warning develop life-threatening complications (hypotension, seizures, cardiac arrest)!!

When in-hospital deterioration occurs, it is almost always within the first few hours after arrival and frequently within the

first 60 minutes.

A.) Cardiovascular effects:

1. Hypotension is the most frequent serious cardiovascular effect that occurs secondary to:

a. Vasodilation form alpha1-adrenergic receptor blockade.

b. Direct quinidine-like myocardial depression

c. Depletion of presynaptic norepinephrine stores

• Hypotension has been strongly correlated to the subsequent development of lifethreatening-ventricular arrhythmias.

2. Sinus tachycardia lasting hours to days results from the anticholinergic toxicity.

• Supraventricular tachycardia (SVT) may occur secondary to anticholinergic toxicity.

• By itself, sinus tachycardia or SVT is usually not a serious complication in the setting of a TCA overdose.

Sinus TachycardiaSinus Tachycardia

3. Conduction delays

a. Widening of the QRS complex may result in unusual ECG patterns, and sinus tachycardia may be difficult to distinguish from ventricular tachycardia.

b. Other ECG conduction abnormalities include prolonged PR and QTc interval, right axis shift, and high degree atrioventricular block.

Wide QRSWide QRS (> 0.10 (> 0.10 s) s)

4. Arrhythmias include premature ventricular or atrial

contractions, ventricular tachycardia,ventricular fibrillation, slow idioventricular rhythm,

electromechanical dissociation, and asystole.

When asystole occurs, hypotension and bradycardia usually precede it.

Ventricular Ventricular TachycardiaTachycardia

B.) CNS effects:

Altered mental status Altered mental status (Coma) (Coma)

1. Altered Mental Status

a. Delirium, agitation, and hallucinations may occur secondary to anticholinergic toxicity.

b. Patient may have a level of consciousness ranging from mild sedation to coma.

2. Myoclonus and choreoathetosis are relatively benign muscle contractions that are sometimes

mistaken for prolonged seizures.

SeizureSeizure

3. Seizuresa. Prior mental status does not predict

the occurrence of seizuresb. Usually brief and self-limited.c. Prolonged seizures do occur, and

resulting acidosis and hypoxia may potentiate cardiotoxicity.

d. Amoxapine and maprotiline appear to have a relatively greater seizure potential.

C.) Anticholinergic effects:

Peripheral autonomic nervous system complications are common and by themselves do not cause significant morbidity. Centrally mediated anticholinergic effects are a more serious complication (see CNS effects) requiring close monitoring and supportive care.

The presence or absence of anticholinergic symptoms does not predict more serious complications.

Management of TCA Management of TCA PoisoningPoisoning

ABCD; AntidoteEmesis (Ipecac ?)Gastric Lavage Activated Charcoal: 1 g/kg, 50-100 g

Multiple Dose Activated CharcoalCathartic : Sorbitol 70%, 1-2 cc / kg

From TRIPP, CPEM

A:Airway compromise B: Breathing difficulties

C : Circulation

Blood pressureBlood pressurePulse (rate; regularity)Pulse (rate; regularity)IV line; ECGIV line; ECGManage hypotensionManage hypotensionManage Dysrhythmia Manage Dysrhythmia

Antidote: Sodium Antidote: Sodium BicarbonateBicarbonate

Severe toxicity : HypotensionComaSeizures Arrythmia

Wide QRS > 0.1 s R avR 3 mm

Dose: 1-2 mEq/kg bolus, rebolus prn to maintain a desired arterial pH of 7.5.

• Sodium bicarbonate infusion is usually required to maintain a desired pH of 7.45-7.55.

Dose: 100-150 mEq NaHCO3 per liter in D5W 1/2 NS at 150-200 cc/hr (rates should be adjusted per patient)

Antidote: Sodium Antidote: Sodium BicarbonateBicarbonate

Not Severe toxicity

Infusion (50-150 mEq / L D5W)

C.) Hypotension 1. Trendelenburg position, IV fluids, and sodium

bicarbonate. 2. Norepinephrine is the drug of first choice as it is a

potent selective alpha-adrenergic receptor agonist. TCAs are selective alpha-adrenergic blockers. ( requires IV placement of central line)

Dose: 0.1-0.2 mcg/kg/min initially and then titrate to effect.

3. Dobutamine may be used if the hypotension is due to a loss of inotropy where the cardiac output is low and the pulmonary artery wedge pressure is > 18 mm Hg.

Dose: 2.5 mcg/kg/min initially titrated up to 15 mcg/kg/min

4. Dopamine use in managing the TCA poisoned patient is falling out of favor. Dopamine needs to be converted to norepinephrine for in order to achieve positive alpha-adrenergic stimulation in vivo. Overdoses involving TCAs as well as cocaine and amphetamines cause catecholamine depletion making dopamine less effective when managing hypotension in these cases.

Ventricular Ventricular Tachycardia Tachycardia Unstable VT: Basic + ACLSStable VT: NaHCO3: 1-2 mEq / kg, IVLidocaine: 1.5 mg / kg, Total: 3 mg /kg Infusion: 2-4 mg/min

Mg SO4 : 1-2 g IV slowOverdrive Pacing

ConvulsionsConvulsionsOxygen, airway, IV Line; NaHCO3Diazepam: Adult: 5-10 mg IV ( Total

30 mg) Child: 0.1-0.3 mg / kgConsider ventilation ( intubation,

ABG)Phenytoine (-)Phenobarbital: 10 mg / kg IVSodium Thiopental: 3- 5 (15 mg /

kg), infusion 1-5mg / kg/ h (Hypotension, Res. Depression)

Midazolam : 0.1-0.3 mg/kg boluse , Infusion

ContraindicationContraindication

PhenytoinAntiarrhythmic Drugs: Type 1a , 1c (Procainamide,…)PropranololFlumazenil

SummarySummary

Intubation; Oxygen; (Glucose, Naloxone)IV line; ECG; ABG; Urine cathetherSodium bicarbonate 1-2 mEq/kg boluseSerum (1/3 2/3) 1L / 8h+ 50 mEq NaHCO3

باتشكرازحوصلهشما

دكتر فرزاد قشالقيدكتر فرزاد قشالقيمتخصص طب قانوني و مسموميتهامتخصص طب قانوني و مسموميتها

دانشیار دانشکده پزشکیدانشیار دانشکده پزشکیE. mail:gheshlaghi@med.mui.ac.irE. mail:gheshlaghi@med.mui.ac.ir

Management of TCA Management of TCA PoisoningPoisoning

1- A B C D

(Antidote)

داروهاي ضد افسردگي سه داروهاي ضد افسردگي سه حلقه ايحلقه اي

آ مي تريپتيلين نورتريپتيلين ا يمپرا مين كلومپيرا مين تريميپيرا مين دوكسيپين ما پروتيلين ; آموكساپين

عالئم مسموميتعالئم مسموميت عالئم آنتي كلينرژيكسيستم عصبي مركزي قلبي عروقي اسیدوز متابولیک

MidriasisMidriasis

Sinus TachycardiaSinus Tachycardia

HypertermiaDry skin and mucous

membranesUrinary RetentionIleus

Sinus TachycardiaSinus Tachycardia

Hypotension

DeliriumHallocination

HypotensionHypotension

Fluids : N.S, Lactated Ringer Adult: 500-1000 cc

Children: 10-20 cc / kgSodium Bicarbonate : 1-2 meq/kgNorepinephrine : 0.1-0.5 µg/kg/min Dopamine : 10-20 µg / kg / min

Tricyclic Tricyclic AntidepressantsAntidepressants

SymptomsSymptoms1- Midriasis ; Tachycardia 2- Coma 3- Delirium 4- Seizures 5- Hypotension QRS > 0.1s ; R avR >= 3 mm ; Right Axis

deviation ; Arrhythmias (VT); First A-V block