GEMC: Basics of Toxicology: Resident Training

Project: Ghana Emergency Medicine Collaborative

Document Title: Basics of Toxicology

Author(s): Patrick Carter, MD, University of Michigan Medical School

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Basics of ToxicologyBasics of Toxicology

Medical Student Lecture Medical Student Lecture SeriesSeries

Emergency MedicineEmergency Medicine

revised 6/20093

ObjectivesObjectives

Describe the role of GI Describe the role of GI decontamination decontamination

Recognize common toxidromesRecognize common toxidromes Recognize substances for which Recognize substances for which

specific antidotes existspecific antidotes exist Initiate ED management of a Initiate ED management of a

patient with an overdosepatient with an overdose

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The undifferentiated The undifferentiated patientpatient

A patient is dropped off at the ED A patient is dropped off at the ED door. He is minimally responsive. door. He is minimally responsive. His friends say they think he took His friends say they think he took something and drive off…something and drive off…

Where do we start?Where do we start?

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Approach to Approach to (possible)(possible) Tox Tox patientpatient

Simultaneous treatment & diagnosisSimultaneous treatment & diagnosis Immediate action:Immediate action:

ABC(D) , IV / O2 / monitorABC(D) , IV / O2 / monitor Thinking:Thinking:

Is this a tox problem?Is this a tox problem? If yes, are there complicating factors?If yes, are there complicating factors?

Got drunk and fell down, now with head Got drunk and fell down, now with head injury?injury?

Resources to get a history?Resources to get a history?

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Approach to Approach to (likely)(likely) Tox Tox patientpatient

YouYou’’ve considered a differential and you ve considered a differential and you think it is a toxicologic issuethink it is a toxicologic issue

Immediate action:Immediate action: Supportive therapy (airway etc)Supportive therapy (airway etc) DecontaminationDecontamination

Thinking:Thinking: Toxidrome present?Toxidrome present? What more information do I need?What more information do I need?

Definitive ManagementDefinitive Management Is there an antidote or specific treatment?Is there an antidote or specific treatment?

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Overdose HistoryOverdose History

Time of ingestionTime of ingestion Talk to witnessesTalk to witnesses Get pill bottles & Get pill bottles &

count!count! Assume common Assume common

co-ingestantsco-ingestants AlcoholAlcohol Acetaminophen Acetaminophen AspirinAspirin

Jmh649, Wikimedia Commons

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DecontaminationDecontamination GI exposureGI exposure

Most common route (75% of toxic exposures)Most common route (75% of toxic exposures) Prevent absorptionPrevent absorption

Topical exposuresTopical exposures Remove clothingRemove clothing Wash skinWash skin

Enhance eliminationEnhance elimination Whole bowel irrigationWhole bowel irrigation SorbitolSorbitol Diuresis / ion trappingDiuresis / ion trapping HemodialysisHemodialysis

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GI DecontaminationGI Decontamination

***Activated Charcoal******Activated Charcoal*** Absorbs up to 60% of ingestantAbsorbs up to 60% of ingestant 1 gm/kg +/- Sorbitol1 gm/kg +/- Sorbitol Maximal effect if given early (<1 hr)Maximal effect if given early (<1 hr) Will not bind – metals, electrolytes, acidsWill not bind – metals, electrolytes, acids ContraindicationsContraindications

Depressed MS – Intubate to avoid aspirationDepressed MS – Intubate to avoid aspiration Bowel obstruction / perforationBowel obstruction / perforation Acid/ alkali ingestionAcid/ alkali ingestion

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GI Decontamination – GI Decontamination –

Rare interventionsRare interventions Gastric lavageGastric lavage

Early presentation of potentially lethal ODEarly presentation of potentially lethal OD– e.g. tricyclics, iron, CCBs, B-blockerse.g. tricyclics, iron, CCBs, B-blockers

High Risk – aspiration / perforation / airway High Risk – aspiration / perforation / airway compromisecompromise

Syrup of Ipecac – Rarely used nowSyrup of Ipecac – Rarely used now Induces vomiting & eliminates less than charcoalInduces vomiting & eliminates less than charcoal Cardiomyopathy risk Cardiomyopathy risk

Whole bowel irrigationWhole bowel irrigation Sustained release preparationsSustained release preparations Body packersBody packers

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2 am Toxicology 2 am Toxicology ResourcesResources

Poison ControlPoison Control 1-800-POISON11-800-POISON1

MicromedexMicromedex General drug infoGeneral drug info

PoisindexPoisindex Overdose Overdose

managementmanagement IdentidexIdentidex

Imprint Imprint identificationidentification

Parhamr, Wikimedia Commons

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Treatment Goals with ODTreatment Goals with OD

ABCABC’’ss Identify (if possible) substancesIdentify (if possible) substances Reduce absorptionReduce absorption Enhance eliminationEnhance elimination Specific antidotes (if possible)Specific antidotes (if possible)

Relatively few but important to knowRelatively few but important to know Supportive care Supportive care

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Classic Classic ToxidromesToxidromes

Hint for exam:Hint for exam:

Know theseKnow these

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Narcotic Narcotic SympathomimeticSympathomimetic AnticholinergicAnticholinergic CholinergicCholinergic

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NarcoticsNarcotics

Natural & synthetic compounds Natural & synthetic compounds which mimic endogenous endorphinswhich mimic endogenous endorphins

Heroin, Morphine, Dilaudid, Demerol, Heroin, Morphine, Dilaudid, Demerol, Vicodin, Methadone, Fentanyl (China Vicodin, Methadone, Fentanyl (China White), OxycontinWhite), Oxycontin

Different pharmacologic parametersDifferent pharmacologic parameters Common drugs of abuseCommon drugs of abuse Street drugs – adulterated (mixed Street drugs – adulterated (mixed

OD)OD)16

Narcotics – Clinical pictureNarcotics – Clinical picture

TemTempp HRHR RRRR PupilsPupils BSBS’’ss SkinSkin

NarcoticNarcotic

SympathomimeSympathomimetictic

Anti-cholinergicAnti-cholinergic

CholinergicCholinergic

--- ---

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Narcotics - treatmentNarcotics - treatment

Support ABCsSupport ABCs Narcan 2mg IV q2min until effect Narcan 2mg IV q2min until effect

Comes in 0.4mg vials!Comes in 0.4mg vials! Can require massive dosesCan require massive doses IV / IM / SQ / ET routesIV / IM / SQ / ET routes Short acting & may require repeat Short acting & may require repeat

doses or IV dripdoses or IV drip

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SympathomimeticsSympathomimetics

Fight or flight systemFight or flight system Drug activate adrenergic nervous Drug activate adrenergic nervous

systemsystem Cross-activation of dopaminergic Cross-activation of dopaminergic

euphoria & hallucinations euphoria & hallucinations

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NarcoticNarcotic ------ ------

SympathomimeSympathomimetictic



--- --- sweaty

Sympathomimetics – Sympathomimetics – clinical pictureclinical picture

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Common Common sympathomimeticssympathomimetics

CocaineCocaine CaffeineCaffeine EphedrineEphedrine MDMA (ecstasy)MDMA (ecstasy) LSD (prominent hallucinations)LSD (prominent hallucinations) Pseudephedrine (Sudafed)Pseudephedrine (Sudafed)

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Sympathomimetics - Sympathomimetics - treatmenttreatment

ABCsABCs Supportive care / timeSupportive care / time Cocaine – avoid B-blockersCocaine – avoid B-blockers

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Anticholinergic ToxidromeAnticholinergic Toxidrome

Antagonism of the cholinergic Antagonism of the cholinergic nervous system (parasympathetic)nervous system (parasympathetic)

Sympathetic disinhibition & loss of Sympathetic disinhibition & loss of parasympathetic functionsparasympathetic functions

Common medication side-effectCommon medication side-effect Less commonly abused class of Less commonly abused class of

drugsdrugs

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Anticholinergics - clinical Anticholinergics - clinical picturepicture



SympathomimeSympathomimetictic ------ ------ sweatysweaty



--- dry

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AnticholinergicsAnticholinergics

Blind as a bat (mydriasis)Blind as a bat (mydriasis) Hot as hare (flushed & warm)Hot as hare (flushed & warm) Mad as a hatter (delirium)Mad as a hatter (delirium) Dry as a bone (membranes & axillae)Dry as a bone (membranes & axillae)

““CanCan’’t see, cant see, can’’t pee, cant pee, can’’t s—t, cant s—t, can’’t t spitspit””

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Common anticholinergicsCommon anticholinergics

AtropineAtropine Antihistamines Antihistamines

(Benadryl)(Benadryl) Phenothiazines Phenothiazines

(antiemetics)(antiemetics) Tricyclic Tricyclic

antidepressantsantidepressants Jimsonweed Jimsonweed

(Datura)(Datura) Denniss, Wikimedia Commons

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Anticholinergics - Anticholinergics - TreatmentTreatment

ABCsABCs DecontaminationDecontamination Supportive / timeSupportive / time Urinary drainageUrinary drainage

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Cholinergic ToxidromeCholinergic Toxidrome

Increased acetylcholine activityIncreased acetylcholine activity Nicotinic NS: increased nerve Nicotinic NS: increased nerve

transmission and muscle activationtransmission and muscle activation Muscarinic NS: liquid managementMuscarinic NS: liquid management Rarely abusedRarely abused Occupational exposures - Occupational exposures -

insecticidesinsecticides

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Cholinergics – clinical Cholinergics – clinical picturepicture

Nicotinic effectsNicotinic effects Tachycardia, muscle fasciculations, weakness Tachycardia, muscle fasciculations, weakness

(nerve transmissions can(nerve transmissions can’’t get through), t get through), respiratory depression, paralysis,miosisrespiratory depression, paralysis,miosis

Muscarinic effects - SLUDGEMuscarinic effects - SLUDGE SalivationSalivation LacrimationLacrimation UrinationUrination DefecationDefecation GI upsetGI upset EmesisEmesis

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Cholinergics – clinical Cholinergics – clinical picturepicture



SympathomimeSympathomimetictic ------ ------ sweatysweaty

Anti-cholinergicAnti-cholinergic ------ drydry

CholinergicCholinergic --- --- sweaty

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Common CholinergicsCommon Cholinergics

Organophosphate Organophosphate insecticidesinsecticides

Nerve gas (i.e. Sarin, Nerve gas (i.e. Sarin, VX)VX)

Myasthenia Gravis Myasthenia Gravis medsmeds

““Green tobacco Green tobacco sicknesssickness”” Nicotine poisoning Nicotine poisoning

during harvestduring harvest

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Cholinergics - TreatmentCholinergics - Treatment

ABCsABCs DecontaminationDecontamination Atropine 2 mg q 5 minutes until Atropine 2 mg q 5 minutes until

secretions dry (massive doses)secretions dry (massive doses) Pralidoxime (2PAM) if Pralidoxime (2PAM) if

organophosphatesorganophosphates Supportive care / timeSupportive care / time

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Case 1Case 1

2 yo M got into older sister2 yo M got into older sister’’s s medication. Mother brings to ED stating medication. Mother brings to ED stating hehe’’s had an allergic reactions had an allergic reaction

P145 R25 T100.1 Skin flushed but no P145 R25 T100.1 Skin flushed but no urticaria or rash. Seems to be picking urticaria or rash. Seems to be picking at the air. Pupils dilated. Dry diaper.at the air. Pupils dilated. Dry diaper.

Nurses requesting Benadryl for his Nurses requesting Benadryl for his allergic reaction.allergic reaction.

Is this a good idea? WhatIs this a good idea? What’’s going on?s going on?

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Case 1 contCase 1 cont

Anticholinergic toxidromeAnticholinergic toxidrome SisterSister’’s medication s medication Detrol Detrol

AnticholinergicAnticholinergic Benadryl also anticholinergic!Benadryl also anticholinergic!

Treatment?Treatment?

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Case 2Case 2

15 people from a local government 15 people from a local government building with vomiting and building with vomiting and weakness.weakness.

2 patients with respiratory distress 2 patients with respiratory distress require intubation. Copious oral require intubation. Copious oral secretions are noted.secretions are noted.

WhatWhat’’s going on?s going on?35

Case 2 contCase 2 cont

Cholinergic toxidromeCholinergic toxidrome SLUDGESLUDGE

Nerve gas / deliberate exposureNerve gas / deliberate exposure 1995 – Sarin in Tokyo subway1995 – Sarin in Tokyo subway

Treatment?Treatment?

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ClassicClassicIngestionsIngestions

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AcetaminophenAcetaminophen

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Common Common ““cry for helpcry for help”” UbiquitousUbiquitous

Accidental ODAccidental OD’’s – s – ““multi-symptom cold medmulti-symptom cold medss””

Common co-ingestant Common co-ingestant Initially asymptomatic or mild GI upsetInitially asymptomatic or mild GI upset Quiescent period of a few days after Quiescent period of a few days after

intoxication (LFTs may be elevated)intoxication (LFTs may be elevated) Delayed & sometimes fatal liver toxicityDelayed & sometimes fatal liver toxicity

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Metabolite toxic to hepatocytes Metabolite toxic to hepatocytes causing hepatic necrosiscausing hepatic necrosis

At therapeutic doses, glutathione At therapeutic doses, glutathione neutralizes metabolite and neutralizes metabolite and prevents toxicityprevents toxicity

At high doses glutathione depleted At high doses glutathione depleted and toxicity results and toxicity results

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Rumack-Rumack-Matthews Matthews NomogramNomogram

Predicts hepatic Predicts hepatic toxicity based on toxicity based on level and time of level and time of overdoseoverdose

Toxic theshold Toxic theshold 140 mcg/ml140 mcg/ml

Melrin Cyrstal, Wikimedia Commons

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Specific intoxications: Specific intoxications: TylenolTylenol

The rule of 140The rule of 140 Toxic dose is 140 mg/kgToxic dose is 140 mg/kg Toxic level at 4 hours is 140 mcg/mlToxic level at 4 hours is 140 mcg/ml First dose of NAC is 140 mg/kg po First dose of NAC is 140 mg/kg po

(subsequent 17 doses are 70mg/kg)(subsequent 17 doses are 70mg/kg)

If 15 kg child, how many ES Tylenol If 15 kg child, how many ES Tylenol pills (500 mg each) for toxic level?pills (500 mg each) for toxic level?

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Treatment: N-acetylcysteine Treatment: N-acetylcysteine Replenishes glutathione in the liverReplenishes glutathione in the liver Tastes AWFULTastes AWFUL

May require NGT administrationMay require NGT administration Newer IV form (Acetadote – 2004)Newer IV form (Acetadote – 2004)

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SalicylatesSalicylates

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ASA, Peptobismol, ASA, Peptobismol, Oil of wintergreen Oil of wintergreen

1 tsp = 7gm salicylate (peds lethal dose)1 tsp = 7gm salicylate (peds lethal dose) Symptoms onset within 1 hour Symptoms onset within 1 hour Enteric-coated delays absorptionEnteric-coated delays absorption Gastric bezoars also delay absorptionGastric bezoars also delay absorption Renal clearanceRenal clearance

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SymptomsSymptoms Vomiting, tinnitus, hyperpnea, fever Vomiting, tinnitus, hyperpnea, fever

(mild)(mild) Acidosis, AMS, seizures and shock Acidosis, AMS, seizures and shock

(severe)(severe) **Metabolic acidosis w/ respiratory **Metabolic acidosis w/ respiratory

alkalosisalkalosis Toxicity begins at 50mg/kg (acute)Toxicity begins at 50mg/kg (acute)

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Specific intoxications: Specific intoxications: SalicylatesSalicylates

General guidelines for severityGeneral guidelines for severity Mild <300 mg /kg ingestedMild <300 mg /kg ingested Moderate 300-500 mg/kgModerate 300-500 mg/kg Severe / potentially lethal > 500 mg/kgSevere / potentially lethal > 500 mg/kg

Serum level > 30 mg/dl at 6 hrs - toxicSerum level > 30 mg/dl at 6 hrs - toxic Done nomogramDone nomogram

Historical interest onlyHistorical interest only Serum level not predictive of degree of Serum level not predictive of degree of

toxicity toxicity

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Salicylates - TreatmentSalicylates - Treatment

Increased elimination in urine Increased elimination in urine Urine alkalinizationUrine alkalinization

3 amps of bicarb in 1 L of D5W3 amps of bicarb in 1 L of D5W Hemodialysis indicated ifHemodialysis indicated if

Coma, seizure Coma, seizure Renal, hepatic, or pulmonary failure Renal, hepatic, or pulmonary failure Pulmonary edema Pulmonary edema Severe acid-base imbalance Severe acid-base imbalance Deterioration in condition Deterioration in condition

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Tricyclic Tricyclic AntidepressantsAntidepressants

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Tricyclic antidepressantsTricyclic antidepressants

Depression, sleep, & pain disordersDepression, sleep, & pain disorders Less common due to SSRI Less common due to SSRI

prevalenceprevalence High toxicity in overdoseHigh toxicity in overdose

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Anticholinergic toxidrome plusAnticholinergic toxidrome plus Cardiac DysrhythmiasCardiac Dysrhythmias

Quinidine-like (Ia) effects on Na Quinidine-like (Ia) effects on Na channelschannels

Sinus tach, Vfib, VtachSinus tach, Vfib, Vtach SeizuresSeizures

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Screening EKGScreening EKG Widened QRS Widened QRS

> 100ms – sz & dysrhythmia risk> 100ms – sz & dysrhythmia risk R wave in aVR and S waves in I, R wave in aVR and S waves in I,

aVLaVL Prolonged QTcProlonged QTc

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Electrocardiographic changes associated with tricyclic antidepressant overdose. The QRS complex is prolonged with delayed right ventricular activation and intraventricular conduction delay, which results in rightward shift in the terminal 40 msec frontal plane QRS vector. In qualitative terms, this shift manifests as a deep, slurred S wave in leads I and AVL, and an R wave in lead AVR (blue arrows).

Source Undetermined

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Tricyclic antidepressants - Tricyclic antidepressants - TxTx

ABCsABCs Bicarbonate dripBicarbonate drip

Reduces cardiac effectsReduces cardiac effects Control seizuresControl seizures

BenzodiazepinesBenzodiazepines PhenobarbitalPhenobarbital Avoid phenytoin – risk of Avoid phenytoin – risk of

dysrhythmiasdysrhythmias54

Case 3:Case 3:

27 yo F brought in by family. Confused 27 yo F brought in by family. Confused and vomiting. and vomiting. ““She took some Tylenol She took some Tylenol this morningthis morning”” (about 4 hours ago) (about 4 hours ago)

P125 BP135/65 T99.4 Warm, dry skin. P125 BP135/65 T99.4 Warm, dry skin. Oriented x 2. Sometimes nonsensical Oriented x 2. Sometimes nonsensical answers. +gag reflex. Dilated pupils.answers. +gag reflex. Dilated pupils.

What do you need to know?What do you need to know? Does this fit with a Tylenol OD?Does this fit with a Tylenol OD?

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Case 3Case 3

Gary Seidman, Flickr

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Case 3Case 3

What are your initial orders?What are your initial orders? Hint: ABC, IV, O2, monitorHint: ABC, IV, O2, monitor What labs / tests do you want?What labs / tests do you want? Medications?Medications?

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Case 3Case 3

Acetaminophen level – 375 mg/dlAcetaminophen level – 375 mg/dl What next?What next?

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Case 4Case 4

32 yo M brought in because of 32 yo M brought in because of violent behaviorviolent behavior

Agitated and combativeAgitated and combative P125 BP 160/95 T99.4P125 BP 160/95 T99.4 Warm & sweaty. Dilated pupils. Warm & sweaty. Dilated pupils.

Exam otherwise non-focalExam otherwise non-focal Differential?Differential?

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Case 4Case 4

UDS – cocaine positiveUDS – cocaine positive Treatment?Treatment?

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Slides & content for this lecture developed byStacey Noel, MD

With revisions by Colin Greineder, MD & Laura Hopson, MD

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GEMC: Basics of Toxicology: Resident Training

Education

Transcript of GEMC: Basics of Toxicology: Resident Training