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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TemTempp HRHR RRRR PupilsPupils BSBS’’ss SkinSkin
NarcoticNarcotic ------ ------
SympathomimeSympathomimetictic
Anti-cholinergicAnti-cholinergic
CholinergicCholinergic
--- --- 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
TemTempp HRHR RRRR PupilsPupils BSBS’’ss SkinSkin
NarcoticNarcotic ------ ------
SympathomimeSympathomimetictic ------ ------ sweatysweaty
Anti-cholinergicAnti-cholinergic
CholinergicCholinergic
--- 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
TemTempp HRHR RRRR PupilsPupils BSBS’’ss SkinSkin
NarcoticNarcotic ------ ------
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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AcetaminophenAcetaminophen
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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AcetaminophenAcetaminophen
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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AcetaminophenAcetaminophen
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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AcetaminophenAcetaminophen
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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SalicylatesSalicylates
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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SalicylatesSalicylates
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
47
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
50
Tricyclic antidepressantsTricyclic antidepressants
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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Tricyclic antidepressantsTricyclic antidepressants
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
53
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?
57
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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