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Project: Ghana Emergency Medicine Collaborative
Document Title: Basics of Toxicology
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2
Basics of ToxicologyBasics of Toxicology
Medical Student LectureMedical Student Lecture
SeriesSeries
Emergency MedicineEmergency Medicine
revised 6/2009
3
ObjectivesObjectives
 Describe the role of GI decontaminationDescribe the role of GI decontamination
 Recognize common toxidromesRecognize common toxidromes
 Recognize substances for whichRecognize substances for which
specific antidotes existspecific antidotes exist
 Initiate ED management of a patientInitiate ED management of a patient
with an overdosewith an overdose
4
The undifferentiated patientThe undifferentiated patient
 A patient is dropped off at the ED door.A patient is dropped off at the ED door.
He is minimally responsive. His friendsHe is minimally responsive. His friends
say they think he took something andsay they think he took something and
drive off…drive off…
 Where do we start?Where do we start?
5
Approach toApproach to (possible)(possible) Tox patientTox patient
 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 injury?Got drunk and fell down, now with head injury?
 Resources to get a history?Resources to get a history?
6
Approach toApproach to (likely)(likely) Tox patientTox patient
 YouYou’ve considered a differential and you think’ve considered a differential and you think
it is a toxicologic issueit 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?
7
Overdose HistoryOverdose History
 Time of ingestionTime of ingestion
 Talk to witnessesTalk to witnesses
 Get pill bottles &Get pill bottles &
count!count!
 Assume commonAssume common
co-ingestantsco-ingestants
 AlcoholAlcohol
 AcetaminophenAcetaminophen
 AspirinAspirin
Jmh649, Wikimedia Commons
8
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
9
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
10
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 compromiseHigh Risk – aspiration / perforation / airway compromise
 Syrup of Ipecac – Rarely used nowSyrup of Ipecac – Rarely used now
 Induces vomiting & eliminates less than charcoalInduces vomiting & eliminates less than charcoal
 Cardiomyopathy riskCardiomyopathy risk
 Whole bowel irrigationWhole bowel irrigation
 Sustained release preparationsSustained release preparations
 Body packersBody packers
11
2 am Toxicology Resources2 am Toxicology Resources
 Poison ControlPoison Control
 1-800-POISON11-800-POISON1
 MicromedexMicromedex
 General drug infoGeneral drug info
 PoisindexPoisindex
 OverdoseOverdose
managementmanagement
 IdentidexIdentidex
 Imprint identificationImprint identification
Parhamr, Wikimedia Commons
12
Treatment Goals with ODTreatment Goals with OD
 ABCABC’s’s
 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 careSupportive care
13
ClassicClassic
ToxidromesToxidromes
Hint for exam:Hint for exam:
Know theseKnow these
14
 NarcoticNarcotic
 SympathomimeticSympathomimetic
 AnticholinergicAnticholinergic
 CholinergicCholinergic
15
NarcoticsNarcotics
 Natural & synthetic compounds whichNatural & synthetic compounds which
mimic endogenous endorphinsmimic endogenous endorphins
 Heroin, Morphine, Dilaudid, Demerol,Heroin, Morphine, Dilaudid, Demerol,
Vicodin, Methadone, Fentanyl (ChinaVicodin, Methadone, Fentanyl (China
White), OxycontinWhite), Oxycontin
 Different pharmacologic parametersDifferent pharmacologic parameters
 Common drugs of abuseCommon drugs of abuse
 Street drugs – adulterated (mixed OD)Street drugs – adulterated (mixed OD)
16
Narcotics – Clinical pictureNarcotics – Clinical picture
TempTemp HRHR RRRR PupilsPupils BSBS’s’s SkinSkin
NarcoticNarcotic
SympathomimeticSympathomimetic
Anti-cholinergicAnti-cholinergic
CholinergicCholinergic
--- ↓ ↓↓ ↓↓ ↓↓ ---
17
Narcotics - treatmentNarcotics - treatment
 Support ABCsSupport ABCs
 Narcan 2mg IV q2min until effectNarcan 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 repeatShort acting & may require repeat
doses or IV dripdoses or IV drip
18
SympathomimeticsSympathomimetics
 Fight or flight systemFight or flight system
 Drug activate adrenergic nervousDrug activate adrenergic nervous
systemsystem
 Cross-activation of dopaminergicCross-activation of dopaminergic 
euphoria & hallucinationseuphoria & hallucinations
19
TempTemp HRHR RRRR PupilsPupils BSBS’s’s SkinSkin
NarcoticNarcotic ------ ↓↓ ↓↓↓↓ ↓↓↓↓ ↓↓↓↓ ------
SympathomimeticSympathomimetic
Anti-cholinergicAnti-cholinergic
CholinergicCholinergic
↑ ↑↑ --- --- sweaty↑
Sympathomimetics – clinicalSympathomimetics – clinical
picturepicture
20
Common sympathomimeticsCommon sympathomimetics
 CocaineCocaine
 CaffeineCaffeine
 EphedrineEphedrine
 MDMA (ecstasy)MDMA (ecstasy)
 LSD (prominent hallucinations)LSD (prominent hallucinations)
 Pseudephedrine (Sudafed)Pseudephedrine (Sudafed)
21
Sympathomimetics - treatmentSympathomimetics - treatment
 ABCsABCs
 Supportive care / timeSupportive care / time
 Cocaine – avoid B-blockersCocaine – avoid B-blockers
22
Anticholinergic ToxidromeAnticholinergic Toxidrome
 Antagonism of the cholinergic nervousAntagonism of the cholinergic nervous
system (parasympathetic)system (parasympathetic)
 Sympathetic disinhibition & loss ofSympathetic disinhibition & loss of
parasympathetic functionsparasympathetic functions
 Common medication side-effectCommon medication side-effect
 Less commonly abused class of drugsLess commonly abused class of drugs
23
Anticholinergics - clinicalAnticholinergics - clinical
picturepicture
TempTemp HRHR RRRR PupilsPupils BSBS’s’s SkinSkin
NarcoticNarcotic ------ ↓↓ ↓↓↓↓ ↓↓↓↓ ↓↓↓↓ ------
SympathomimeticSympathomimetic ↑↑ ↑↑↑↑ ------ ↑↑ ------ sweatysweaty
Anti-cholinergicAnti-cholinergic
CholinergicCholinergic
↑ ↑ --- ↓↓↓↓ dry↑
24
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)
 ““Can’t see, can’t pee, can’t s—t, can’tCan’t see, can’t pee, can’t s—t, can’t
spit”spit”
25
Common anticholinergicsCommon anticholinergics
 AtropineAtropine
 AntihistaminesAntihistamines
(Benadryl)(Benadryl)
 PhenothiazinesPhenothiazines
(antiemetics)(antiemetics)
 TricyclicTricyclic
antidepressantsantidepressants
 JimsonweedJimsonweed
(Datura)(Datura)
Denniss, Wikimedia Commons
26
Anticholinergics - TreatmentAnticholinergics - Treatment
 ABCsABCs
 DecontaminationDecontamination
 Supportive / timeSupportive / time
 Urinary drainageUrinary drainage
27
Cholinergic ToxidromeCholinergic Toxidrome
 Increased acetylcholine activityIncreased acetylcholine activity
 Nicotinic NS: increased nerveNicotinic NS: increased nerve
transmission and muscle activationtransmission and muscle activation
 Muscarinic NS: liquid managementMuscarinic NS: liquid management
 Rarely abusedRarely abused
 Occupational exposures - insecticidesOccupational exposures - insecticides
28
Cholinergics – clinical pictureCholinergics – clinical picture
 Nicotinic effectsNicotinic effects
 Tachycardia, muscle fasciculations, weaknessTachycardia, 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
29
Cholinergics – clinical pictureCholinergics – clinical picture
TempTemp HRHR RRRR PupilsPupils BSBS’s’s SkinSkin
NarcoticNarcotic ------ ↓↓ ↓↓↓↓ ↓↓↓↓ ↓↓↓↓ ------
SympathomimeticSympathomimetic ↑↑ ↑↑↑↑ ------ ↑↑ ------ sweatysweaty
Anti-cholinergicAnti-cholinergic ↑↑ ↑↑ ------ ↑↑ ↓↓ drydry
CholinergicCholinergic --- ↓↓ --- ↑↑ sweaty↓↓
30
Common CholinergicsCommon Cholinergics
 OrganophosphateOrganophosphate
insecticidesinsecticides
 Nerve gas (i.e. Sarin,Nerve gas (i.e. Sarin,
VX)VX)
 Myasthenia GravisMyasthenia Gravis
medsmeds
 ““Green tobaccoGreen tobacco
sickness”sickness”
 Nicotine poisoning duringNicotine poisoning during
harvestharvest
31
Cholinergics - TreatmentCholinergics - Treatment
 ABCsABCs
 DecontaminationDecontamination
 Atropine 2 mg q 5 minutes untilAtropine 2 mg q 5 minutes until
secretions dry (massive doses)secretions dry (massive doses)
 Pralidoxime (2PAM) ifPralidoxime (2PAM) if
organophosphatesorganophosphates
 Supportive care / timeSupportive care / time
32
Case 1Case 1
 2 yo M got into older sister2 yo M got into older sister’s medication.’s medication.
Mother brings to ED stating he’s had anMother brings to ED stating he’s had an
allergic reactionallergic reaction
 P145 R25 T100.1 Skin flushed but noP145 R25 T100.1 Skin flushed but no
urticaria or rash. Seems to be picking at theurticaria or rash. Seems to be picking at the
air. Pupils dilated. Dry diaper.air. Pupils dilated. Dry diaper.
 Nurses requesting Benadryl for his allergicNurses requesting Benadryl for his allergic
reaction.reaction.
 Is this a good idea? WhatIs this a good idea? What’s going on?’s going on?
33
Case 1 contCase 1 cont
 Anticholinergic toxidromeAnticholinergic toxidrome
 SisterSister’s medication’s medication  DetrolDetrol
 AnticholinergicAnticholinergic
 Benadryl also anticholinergic!Benadryl also anticholinergic!
 Treatment?Treatment?
34
Case 2Case 2
 15 people from a local government15 people from a local government
building with vomiting and weakness.building with vomiting and weakness.
 2 patients with respiratory distress2 patients with respiratory distress
require intubation. Copious oralrequire 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?
36
ClassicClassic
IngestionsIngestions
37
AcetaminophenAcetaminophen
38
AcetaminophenAcetaminophen
 CommonCommon “cry for help”“cry for help”
 UbiquitousUbiquitous
 Accidental ODAccidental OD’s – “multi-symptom cold meds”’s – “multi-symptom cold meds”
 Common co-ingestantCommon co-ingestant
 Initially asymptomatic or mild GI upsetInitially asymptomatic or mild GI upset
 Quiescent period of a few days afterQuiescent 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
39
AcetaminophenAcetaminophen
 Metabolite toxic to hepatocytes causingMetabolite toxic to hepatocytes causing
hepatic necrosishepatic necrosis
 At therapeutic doses, glutathioneAt therapeutic doses, glutathione
neutralizes metabolite and preventsneutralizes metabolite and prevents
toxicitytoxicity
 At high doses glutathione depleted andAt high doses glutathione depleted and
toxicity resultstoxicity results
40
AcetaminophenAcetaminophen
 Rumack-MatthewsRumack-Matthews
NomogramNomogram
 Predicts hepaticPredicts hepatic
toxicity based ontoxicity based on
level and time oflevel and time of
overdoseoverdose
 Toxic thesholdToxic theshold
140 mcg/ml140 mcg/ml
Melrin Cyrstal, Wikimedia Commons
41
Specific intoxications: TylenolSpecific intoxications: Tylenol
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 poFirst 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 TylenolIf 15 kg child, how many ES Tylenol
pills (500 mg each) for toxic level?pills (500 mg each) for toxic level?
42
AcetaminophenAcetaminophen
 Treatment: N-acetylcysteineTreatment: 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)
43
SalicylatesSalicylates
44
SalicylatesSalicylates
 ASA, Peptobismol,ASA, Peptobismol,
 Oil of wintergreenOil of wintergreen
 1 tsp = 7gm salicylate (peds lethal dose)1 tsp = 7gm salicylate (peds lethal dose)
 Symptoms onset within 1 hourSymptoms onset within 1 hour
 Enteric-coated delays absorptionEnteric-coated delays absorption
 Gastric bezoars also delay absorptionGastric bezoars also delay absorption
 Renal clearanceRenal clearance
45
SalicylatesSalicylates
 SymptomsSymptoms
 Vomiting, tinnitus, hyperpnea, fever (mild)Vomiting, tinnitus, hyperpnea, fever (mild)
 Acidosis, AMS, seizures and shockAcidosis, 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)
46
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 toxicitySerum level not predictive of degree of toxicity
47
Salicylates - TreatmentSalicylates - Treatment
 Increased elimination in urineIncreased 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, seizureComa, seizure
 Renal, hepatic, or pulmonary failureRenal, hepatic, or pulmonary failure
 Pulmonary edemaPulmonary edema
 Severe acid-base imbalanceSevere acid-base imbalance
 Deterioration in conditionDeterioration in condition
48
TricyclicTricyclic
AntidepressantsAntidepressants
49
Tricyclic antidepressantsTricyclic antidepressants
 Depression, sleep, & pain disordersDepression, sleep, & pain disorders
 Less common due to SSRI prevalenceLess common due to SSRI prevalence
 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 channelsQuinidine-like (Ia) effects on Na channels
 Sinus tach, Vfib, VtachSinus tach, Vfib, Vtach
 SeizuresSeizures
51
Tricyclic antidepressantsTricyclic antidepressants
Screening EKGScreening EKG
 Widened QRSWidened QRS
 > 100ms – sz & dysrhythmia risk> 100ms – sz & dysrhythmia risk
 R wave in aVR and S waves in I, aVLR wave in aVR and S waves in I, aVL
 Prolonged QTcProlonged QTc
52
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 - TxTricyclic antidepressants - Tx
 ABCsABCs
 Bicarbonate dripBicarbonate drip
 Reduces cardiac effectsReduces cardiac effects
 Control seizuresControl seizures
 BenzodiazepinesBenzodiazepines
 PhenobarbitalPhenobarbital
 Avoid phenytoin – risk of dysrhythmiasAvoid phenytoin – risk of dysrhythmias
54
Case 3:Case 3:
 27 yo F brought in by family. Confused27 yo F brought in by family. Confused
and vomiting.and vomiting. “She took some Tylenol“She took some Tylenol
this morning” (about 4 hours ago)this morning” (about 4 hours ago)
 P125 BP135/65 T99.4 Warm, dry skin.P125 BP135/65 T99.4 Warm, dry skin.
Oriented x 2. Sometimes nonsensicalOriented 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?
55
Case 3Case 3
Gary Seidman, Flickr
56
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?
58
Case 4Case 4
 32 yo M brought in because of violent32 yo M brought in because of violent
behaviorbehavior
 Agitated and combativeAgitated and combative
 P125 BP 160/95 T99.4P125 BP 160/95 T99.4
 Warm & sweaty. Dilated pupils. ExamWarm & sweaty. Dilated pupils. Exam
otherwise non-focalotherwise non-focal
 Differential?Differential?
59
Case 4Case 4
 UDS – cocaine positiveUDS – cocaine positive
 Treatment?Treatment?
60
Slides & content for this lecture developed by
Stacey Noel, MD
With revisions by
Colin Greineder, MD & Laura Hopson, MD
61

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GEMC: Basics of Toxicology: Resident Training

  • 1. Project: Ghana Emergency Medicine Collaborative Document Title: Basics of Toxicology Author(s): Patrick Carter, MD, University of Michigan Medical School License: Unless otherwise noted, this material is made available under the terms of the Creative Commons Attribution Share Alike-3.0 License: http://creativecommons.org/licenses/by-sa/3.0/ We have reviewed this material in accordance with U.S. Copyright Law and have tried to maximize your ability to use, share, and adapt it. These lectures have been modified in the process of making a publicly shareable version. The citation key on the following slide provides information about how you may share and adapt this material. Copyright holders of content included in this material should contact open.michigan@umich.edu with any questions, corrections, or clarification regarding the use of content. For more information about how to cite these materials visit http://open.umich.edu/privacy-and-terms-use. Any medical information in this material is intended to inform and educate and is not a tool for self-diagnosis or a replacement for medical evaluation, advice, diagnosis or treatment by a healthcare professional. Please speak to your physician if you have questions about your medical condition. Viewer discretion is advised: Some medical content is graphic and may not be suitable for all viewers. 1
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  • 3. Basics of ToxicologyBasics of Toxicology Medical Student LectureMedical Student Lecture SeriesSeries Emergency MedicineEmergency Medicine revised 6/2009 3
  • 4. ObjectivesObjectives  Describe the role of GI decontaminationDescribe the role of GI decontamination  Recognize common toxidromesRecognize common toxidromes  Recognize substances for whichRecognize substances for which specific antidotes existspecific antidotes exist  Initiate ED management of a patientInitiate ED management of a patient with an overdosewith an overdose 4
  • 5. The undifferentiated patientThe undifferentiated patient  A patient is dropped off at the ED door.A patient is dropped off at the ED door. He is minimally responsive. His friendsHe is minimally responsive. His friends say they think he took something andsay they think he took something and drive off…drive off…  Where do we start?Where do we start? 5
  • 6. Approach toApproach to (possible)(possible) Tox patientTox patient  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 injury?Got drunk and fell down, now with head injury?  Resources to get a history?Resources to get a history? 6
  • 7. Approach toApproach to (likely)(likely) Tox patientTox patient  YouYou’ve considered a differential and you think’ve considered a differential and you think it is a toxicologic issueit 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? 7
  • 8. Overdose HistoryOverdose History  Time of ingestionTime of ingestion  Talk to witnessesTalk to witnesses  Get pill bottles &Get pill bottles & count!count!  Assume commonAssume common co-ingestantsco-ingestants  AlcoholAlcohol  AcetaminophenAcetaminophen  AspirinAspirin Jmh649, Wikimedia Commons 8
  • 9. 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 9
  • 10. 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 10
  • 11. 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 compromiseHigh Risk – aspiration / perforation / airway compromise  Syrup of Ipecac – Rarely used nowSyrup of Ipecac – Rarely used now  Induces vomiting & eliminates less than charcoalInduces vomiting & eliminates less than charcoal  Cardiomyopathy riskCardiomyopathy risk  Whole bowel irrigationWhole bowel irrigation  Sustained release preparationsSustained release preparations  Body packersBody packers 11
  • 12. 2 am Toxicology Resources2 am Toxicology Resources  Poison ControlPoison Control  1-800-POISON11-800-POISON1  MicromedexMicromedex  General drug infoGeneral drug info  PoisindexPoisindex  OverdoseOverdose managementmanagement  IdentidexIdentidex  Imprint identificationImprint identification Parhamr, Wikimedia Commons 12
  • 13. Treatment Goals with ODTreatment Goals with OD  ABCABC’s’s  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 careSupportive care 13
  • 14. ClassicClassic ToxidromesToxidromes Hint for exam:Hint for exam: Know theseKnow these 14
  • 15.  NarcoticNarcotic  SympathomimeticSympathomimetic  AnticholinergicAnticholinergic  CholinergicCholinergic 15
  • 16. NarcoticsNarcotics  Natural & synthetic compounds whichNatural & synthetic compounds which mimic endogenous endorphinsmimic endogenous endorphins  Heroin, Morphine, Dilaudid, Demerol,Heroin, Morphine, Dilaudid, Demerol, Vicodin, Methadone, Fentanyl (ChinaVicodin, Methadone, Fentanyl (China White), OxycontinWhite), Oxycontin  Different pharmacologic parametersDifferent pharmacologic parameters  Common drugs of abuseCommon drugs of abuse  Street drugs – adulterated (mixed OD)Street drugs – adulterated (mixed OD) 16
  • 17. Narcotics – Clinical pictureNarcotics – Clinical picture TempTemp HRHR RRRR PupilsPupils BSBS’s’s SkinSkin NarcoticNarcotic SympathomimeticSympathomimetic Anti-cholinergicAnti-cholinergic CholinergicCholinergic --- ↓ ↓↓ ↓↓ ↓↓ --- 17
  • 18. Narcotics - treatmentNarcotics - treatment  Support ABCsSupport ABCs  Narcan 2mg IV q2min until effectNarcan 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 repeatShort acting & may require repeat doses or IV dripdoses or IV drip 18
  • 19. SympathomimeticsSympathomimetics  Fight or flight systemFight or flight system  Drug activate adrenergic nervousDrug activate adrenergic nervous systemsystem  Cross-activation of dopaminergicCross-activation of dopaminergic  euphoria & hallucinationseuphoria & hallucinations 19
  • 20. TempTemp HRHR RRRR PupilsPupils BSBS’s’s SkinSkin NarcoticNarcotic ------ ↓↓ ↓↓↓↓ ↓↓↓↓ ↓↓↓↓ ------ SympathomimeticSympathomimetic Anti-cholinergicAnti-cholinergic CholinergicCholinergic ↑ ↑↑ --- --- sweaty↑ Sympathomimetics – clinicalSympathomimetics – clinical picturepicture 20
  • 21. Common sympathomimeticsCommon sympathomimetics  CocaineCocaine  CaffeineCaffeine  EphedrineEphedrine  MDMA (ecstasy)MDMA (ecstasy)  LSD (prominent hallucinations)LSD (prominent hallucinations)  Pseudephedrine (Sudafed)Pseudephedrine (Sudafed) 21
  • 22. Sympathomimetics - treatmentSympathomimetics - treatment  ABCsABCs  Supportive care / timeSupportive care / time  Cocaine – avoid B-blockersCocaine – avoid B-blockers 22
  • 23. Anticholinergic ToxidromeAnticholinergic Toxidrome  Antagonism of the cholinergic nervousAntagonism of the cholinergic nervous system (parasympathetic)system (parasympathetic)  Sympathetic disinhibition & loss ofSympathetic disinhibition & loss of parasympathetic functionsparasympathetic functions  Common medication side-effectCommon medication side-effect  Less commonly abused class of drugsLess commonly abused class of drugs 23
  • 24. Anticholinergics - clinicalAnticholinergics - clinical picturepicture TempTemp HRHR RRRR PupilsPupils BSBS’s’s SkinSkin NarcoticNarcotic ------ ↓↓ ↓↓↓↓ ↓↓↓↓ ↓↓↓↓ ------ SympathomimeticSympathomimetic ↑↑ ↑↑↑↑ ------ ↑↑ ------ sweatysweaty Anti-cholinergicAnti-cholinergic CholinergicCholinergic ↑ ↑ --- ↓↓↓↓ dry↑ 24
  • 25. 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)  ““Can’t see, can’t pee, can’t s—t, can’tCan’t see, can’t pee, can’t s—t, can’t spit”spit” 25
  • 26. Common anticholinergicsCommon anticholinergics  AtropineAtropine  AntihistaminesAntihistamines (Benadryl)(Benadryl)  PhenothiazinesPhenothiazines (antiemetics)(antiemetics)  TricyclicTricyclic antidepressantsantidepressants  JimsonweedJimsonweed (Datura)(Datura) Denniss, Wikimedia Commons 26
  • 27. Anticholinergics - TreatmentAnticholinergics - Treatment  ABCsABCs  DecontaminationDecontamination  Supportive / timeSupportive / time  Urinary drainageUrinary drainage 27
  • 28. Cholinergic ToxidromeCholinergic Toxidrome  Increased acetylcholine activityIncreased acetylcholine activity  Nicotinic NS: increased nerveNicotinic NS: increased nerve transmission and muscle activationtransmission and muscle activation  Muscarinic NS: liquid managementMuscarinic NS: liquid management  Rarely abusedRarely abused  Occupational exposures - insecticidesOccupational exposures - insecticides 28
  • 29. Cholinergics – clinical pictureCholinergics – clinical picture  Nicotinic effectsNicotinic effects  Tachycardia, muscle fasciculations, weaknessTachycardia, 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 29
  • 30. Cholinergics – clinical pictureCholinergics – clinical picture TempTemp HRHR RRRR PupilsPupils BSBS’s’s SkinSkin NarcoticNarcotic ------ ↓↓ ↓↓↓↓ ↓↓↓↓ ↓↓↓↓ ------ SympathomimeticSympathomimetic ↑↑ ↑↑↑↑ ------ ↑↑ ------ sweatysweaty Anti-cholinergicAnti-cholinergic ↑↑ ↑↑ ------ ↑↑ ↓↓ drydry CholinergicCholinergic --- ↓↓ --- ↑↑ sweaty↓↓ 30
  • 31. Common CholinergicsCommon Cholinergics  OrganophosphateOrganophosphate insecticidesinsecticides  Nerve gas (i.e. Sarin,Nerve gas (i.e. Sarin, VX)VX)  Myasthenia GravisMyasthenia Gravis medsmeds  ““Green tobaccoGreen tobacco sickness”sickness”  Nicotine poisoning duringNicotine poisoning during harvestharvest 31
  • 32. Cholinergics - TreatmentCholinergics - Treatment  ABCsABCs  DecontaminationDecontamination  Atropine 2 mg q 5 minutes untilAtropine 2 mg q 5 minutes until secretions dry (massive doses)secretions dry (massive doses)  Pralidoxime (2PAM) ifPralidoxime (2PAM) if organophosphatesorganophosphates  Supportive care / timeSupportive care / time 32
  • 33. Case 1Case 1  2 yo M got into older sister2 yo M got into older sister’s medication.’s medication. Mother brings to ED stating he’s had anMother brings to ED stating he’s had an allergic reactionallergic reaction  P145 R25 T100.1 Skin flushed but noP145 R25 T100.1 Skin flushed but no urticaria or rash. Seems to be picking at theurticaria or rash. Seems to be picking at the air. Pupils dilated. Dry diaper.air. Pupils dilated. Dry diaper.  Nurses requesting Benadryl for his allergicNurses requesting Benadryl for his allergic reaction.reaction.  Is this a good idea? WhatIs this a good idea? What’s going on?’s going on? 33
  • 34. Case 1 contCase 1 cont  Anticholinergic toxidromeAnticholinergic toxidrome  SisterSister’s medication’s medication  DetrolDetrol  AnticholinergicAnticholinergic  Benadryl also anticholinergic!Benadryl also anticholinergic!  Treatment?Treatment? 34
  • 35. Case 2Case 2  15 people from a local government15 people from a local government building with vomiting and weakness.building with vomiting and weakness.  2 patients with respiratory distress2 patients with respiratory distress require intubation. Copious oralrequire intubation. Copious oral secretions are noted.secretions are noted.  WhatWhat’s going on?’s going on? 35
  • 36. 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? 36
  • 39. AcetaminophenAcetaminophen  CommonCommon “cry for help”“cry for help”  UbiquitousUbiquitous  Accidental ODAccidental OD’s – “multi-symptom cold meds”’s – “multi-symptom cold meds”  Common co-ingestantCommon co-ingestant  Initially asymptomatic or mild GI upsetInitially asymptomatic or mild GI upset  Quiescent period of a few days afterQuiescent 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 39
  • 40. AcetaminophenAcetaminophen  Metabolite toxic to hepatocytes causingMetabolite toxic to hepatocytes causing hepatic necrosishepatic necrosis  At therapeutic doses, glutathioneAt therapeutic doses, glutathione neutralizes metabolite and preventsneutralizes metabolite and prevents toxicitytoxicity  At high doses glutathione depleted andAt high doses glutathione depleted and toxicity resultstoxicity results 40
  • 41. AcetaminophenAcetaminophen  Rumack-MatthewsRumack-Matthews NomogramNomogram  Predicts hepaticPredicts hepatic toxicity based ontoxicity based on level and time oflevel and time of overdoseoverdose  Toxic thesholdToxic theshold 140 mcg/ml140 mcg/ml Melrin Cyrstal, Wikimedia Commons 41
  • 42. Specific intoxications: TylenolSpecific intoxications: Tylenol 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 poFirst 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 TylenolIf 15 kg child, how many ES Tylenol pills (500 mg each) for toxic level?pills (500 mg each) for toxic level? 42
  • 43. AcetaminophenAcetaminophen  Treatment: N-acetylcysteineTreatment: 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) 43
  • 45. SalicylatesSalicylates  ASA, Peptobismol,ASA, Peptobismol,  Oil of wintergreenOil of wintergreen  1 tsp = 7gm salicylate (peds lethal dose)1 tsp = 7gm salicylate (peds lethal dose)  Symptoms onset within 1 hourSymptoms onset within 1 hour  Enteric-coated delays absorptionEnteric-coated delays absorption  Gastric bezoars also delay absorptionGastric bezoars also delay absorption  Renal clearanceRenal clearance 45
  • 46. SalicylatesSalicylates  SymptomsSymptoms  Vomiting, tinnitus, hyperpnea, fever (mild)Vomiting, tinnitus, hyperpnea, fever (mild)  Acidosis, AMS, seizures and shockAcidosis, 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) 46
  • 47. 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 toxicitySerum level not predictive of degree of toxicity 47
  • 48. Salicylates - TreatmentSalicylates - Treatment  Increased elimination in urineIncreased 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, seizureComa, seizure  Renal, hepatic, or pulmonary failureRenal, hepatic, or pulmonary failure  Pulmonary edemaPulmonary edema  Severe acid-base imbalanceSevere acid-base imbalance  Deterioration in conditionDeterioration in condition 48
  • 50. Tricyclic antidepressantsTricyclic antidepressants  Depression, sleep, & pain disordersDepression, sleep, & pain disorders  Less common due to SSRI prevalenceLess common due to SSRI prevalence  High toxicity in overdoseHigh toxicity in overdose 50
  • 51. Tricyclic antidepressantsTricyclic antidepressants  Anticholinergic toxidrome plusAnticholinergic toxidrome plus  Cardiac DysrhythmiasCardiac Dysrhythmias  Quinidine-like (Ia) effects on Na channelsQuinidine-like (Ia) effects on Na channels  Sinus tach, Vfib, VtachSinus tach, Vfib, Vtach  SeizuresSeizures 51
  • 52. Tricyclic antidepressantsTricyclic antidepressants Screening EKGScreening EKG  Widened QRSWidened QRS  > 100ms – sz & dysrhythmia risk> 100ms – sz & dysrhythmia risk  R wave in aVR and S waves in I, aVLR wave in aVR and S waves in I, aVL  Prolonged QTcProlonged QTc 52
  • 53. 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
  • 54. Tricyclic antidepressants - TxTricyclic antidepressants - Tx  ABCsABCs  Bicarbonate dripBicarbonate drip  Reduces cardiac effectsReduces cardiac effects  Control seizuresControl seizures  BenzodiazepinesBenzodiazepines  PhenobarbitalPhenobarbital  Avoid phenytoin – risk of dysrhythmiasAvoid phenytoin – risk of dysrhythmias 54
  • 55. Case 3:Case 3:  27 yo F brought in by family. Confused27 yo F brought in by family. Confused and vomiting.and vomiting. “She took some Tylenol“She took some Tylenol this morning” (about 4 hours ago)this morning” (about 4 hours ago)  P125 BP135/65 T99.4 Warm, dry skin.P125 BP135/65 T99.4 Warm, dry skin. Oriented x 2. Sometimes nonsensicalOriented 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? 55
  • 56. Case 3Case 3 Gary Seidman, Flickr 56
  • 57. 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
  • 58. Case 3Case 3  Acetaminophen level – 375 mg/dlAcetaminophen level – 375 mg/dl  What next?What next? 58
  • 59. Case 4Case 4  32 yo M brought in because of violent32 yo M brought in because of violent behaviorbehavior  Agitated and combativeAgitated and combative  P125 BP 160/95 T99.4P125 BP 160/95 T99.4  Warm & sweaty. Dilated pupils. ExamWarm & sweaty. Dilated pupils. Exam otherwise non-focalotherwise non-focal  Differential?Differential? 59
  • 60. Case 4Case 4  UDS – cocaine positiveUDS – cocaine positive  Treatment?Treatment? 60
  • 61. Slides & content for this lecture developed by Stacey Noel, MD With revisions by Colin Greineder, MD & Laura Hopson, MD 61