Toxicology
TOXIDROMES
Sympathomemetic
(hyperadrenergic state)
Representative  Cocaine (↓ reuptake of DA,
Agent NE, 5-HT)
 Amphetamine (↑ monoamine
neurotransmitters release –
dopamine, serotonin & NE)
 Usually M > F
 Highest prevalence: Age 35 –
49
 Western > Eastern US
 Meth users likely to have
comorbid psychiatric disorder
Clinical Pathophysiology:
Features Methamphetamine
incorporated into cytoplasmic
vesicles in presynaptic
adrenergic neurons where it
displaces epinephrine, norepi,
dopamine, & serotonin, which
are subsequently released into
the synapse
Post–synaptic receptor →
excess adrenergic (alpha–1,
beta–1) + dopaminergic
stimulation!
Sympathetic hyperactivity –
Tachycardia, HTN, mydriasis
Psychosis, Diaphoresis
Hyperthermia
 Psychomotor agitation /
psychosis (i.e. delusions and
tactile hallucinations)
 Ventricular Arrhythmia
 Cocaine:
o Atrophic nasal mucosa with
erythema; septum
perforation in severe cases
(vasoconstriction)
 Epistaxis, rhinitis
(intranasal use)
o Chest pain (due to coronary
Opioid
 Heroin
 Morphine
 Oxycodone
Mu, Kappa, and delta-opioid
receptor agonists
 CNS depression,  Muscarinic effects
somnolence, altered mental
status
 Miosis (pinpoint pupils) –
may be normal / enlarged if
co–ingestions (e.g.
methamphetamine)
 Respiratory depression –
bradypnea, shallow
breathing
o ↓ RR & Tidal Volume (↓
minute ventilation) → CO2
retention  Nicotinic effects (muscle
 Hypothermia (or
normothermia)
 Bradycardia
 Constipation, ↓ bowel  Bradycardia,
sounds
 Euphoria
 Slowed reflexes
 Decreased gag reflex
 Impaired coordination
 Risk factors
o Substance abuse
o Chronic opioid use
o Hospitalized patients
(especially postoperative)
o Hepatic or renal
insufficiency
Cholinergic
 Organophosphate
insecticides (e.g. pesticides, antagonist
nerve agents [sarin, soman]
– colourless, tasteless gas
often with fruity odor)
 Carbamate insecticides
 Anticholinesterase
inhibitors (Physostigmine,
Donepezil)
 Pilocarpine (AChR agonist)
“DUMBBBELS”
o Diaphoresis
o Urination
o Miosis
o Bronchospasms,
Bronchorrhea,
Bradycardia
o Emesis (Nausea &
vomiting)
o Lacrimation
o Salivation
fasciculations, paralysis &
weakness) → respiratory
depression and death
miosis/mydriasis, excessive
secretions (e.g. diaphoresis,
rhonchi, drooling), seizures,
respiratory failure, paralysis
Anticholinergic Salicylates toxicity Sedative–Hypnotic Hallucinogenic
 ACh receptor (AChR)  Aspirin  Barbiturates  Phencyclidine (PCP)
 Oil of wintergreen  BZDs  Lysergic acid diethylamide (LSD)
(Scopolamine, (Benzodiazepines)  Psilocybin
Atropine, ipratropium) GABA Modulators:  Mescaline
 Low potency BZDs increase
antipsychotics, FREQUENCY of Chloride
oxybutynin channel opening;
 Dimenhydrinate Barbiturates increase
(Gravol) DURATION of Chloride
 Jimson weed (Datura channel opening
stramonium) –
anticholinergic,  Cardiopulmonary  Depressed level of  PCP acts on:
atropine-containing o Tachycardia, consciousness, o N-methyl-D-aspartate (NMDA)
plant which is abused arrhythmia somnolence receptor antagonist,
for its hallucinatory o Primary respiratory  slurred speech particularly in hippocampus
properties alkalosis (due to  ataxia and limbic system (causing
medullary respiratory  mild respiratory excitatory & psychotic effects)
centre activation) → depression o Dopamine, norepinephrine,
tachypnea, Hyperpnea  most patients with and serotonin receptors
(with consequent low BZD toxicity are (causing adrenergic and
PaCO2) arousable with normal dopaminergic effects)
o Pulmonary edema vital signs o Sigma receptor complex
 Systemic – Subsequent  N.B. If signs of (causing psychotic and
AG metabolic acidosis bradycardia, anticholinergic receptors)
o uncoupling of oxidative respiratory  Hallucinations, Dysphoria,
phosphorylation in the depression, Anxiety
mitochondria leading to hypotension, and  Specific to PCP – rapid onset of
anaerobic metabolism hyperreflexia are action, duration of action < 8
(with resultant low present, consider co- hours
HCO3– from acid ingestion of other o Psychotic & Violent behavior,
buildup) sedative–hypnotic delusions of enhanced
o Fever (low grade), (most commonly strength
Diaphoresis alcohol) o Dissociative feelings
 Head o Hallucinations
o Tinnitus (cochlear  Benzodiazepine o Ataxia
neurotoxicity; early withdrawal – o Amnesia
symptom) tremulousness, o Multi–directional Nystagmus
o Dizziness anxiety, (horizontal, vertical, &/or
o Altered Mental Status hallucinations, & rotatory “torsional”)
 Altered mental status,
o Cerebral edema elevated vital signs o Diminished pain perception
confusion,
(e.g. HTN,
 vasoconstriction), MI Opioid withdrawal hallucinations (“Mad o Seizure tachycardia), seizures o Severe HTN
o ↑ energy (alertness & o Lacrimation as a hatter”)  Gastrointestinal (may occur later) o Seizures, rigidity and life–
arousal), decreased o Pupillary dilation  Non–reactive o Nausea, vomiting o Usually psychiatric threatening hyperthermia at
appetite, & ↓ need for sleep o Yawning Mydriasis (“blind as a (stimulation of hx consistent w/ Rx higher doses
o Personality & mood changes o Diaphoresis bat”) chemoreceptor trigger BZD (e.g. anxiety, o Withdrawal – insomnia, mood
o Mydriasis, Tonic–Clonic o GI symptoms (N/V/D)  dry flushed skin (“red zone) insomnia) disturbance
Seizures, Rhabdomyolysis o Goose flesh as beet”) o Hepatitis o BZD modulates  Specific to LSD, & Psilocybin
o Euphoria, irritability  Maternal opioid abuse in  Anhidrosis (“dry as  Ketonuria inhibitory effect on o Visual Hallucinations &
o Unexplained weight loss, pregnancy → neonatal bone”) GABA receptors; illusions
anxiety, panic attacks, abstinence syndrome  Urinary retention sudden withdrawal o Euphoria (or dysphoria)
grandiosity, (neonatal opioid  absent / decreased → excitatory state o Tachycardia, HTN
o May have rapid withdrawal) bowel sounds (similar to alcohol) o Depersonalization
improvement without o Irritability  hyperthermia (“hot as o Dysphoria / Panic at higher
treatment and history of o Tremors a hare”) doses
acute, short–lived o Vomiting  Dry mucous o No nystagmus, no combative
depression following a binge o Diarrhea membranes agitation
(“cocaine crash”) o Excessive salivation  Seizures,
o Associations – cocaine dysrhythmias,
induced cardiomyopathy, rhabdomyolysis
Paranoia, Drug-induced
depression, Renal Tubular
Necrosis, Rhabdomyolysis
 Methamphetamine –
duration up to 20 hours:
o Violent behaviour
o Anxiety, Agitation
o Psychosis, diaphoresis
o Tachycardia/HTN
o Choreiform movements
o Tooth decay (“Meth
mouth”)
 Cocaine / Amphetamine
Withdrawal – dysphoria,
difficulty concentrating,
hypersomnia, hunger,
depression & possible
suicidality, anergia, miosis,
anhedonia
o Most symptoms resolved by
7 – 10 days, but up to 3
weeks
Complications  Acute myocardial ischemia Death – respiratory arrest, Death – respiratory arrest Death –hyperthermia & Death – acute lung injury, Stupor to coma, Hyperthermia, mydriasis, nausea
 Aortic Dissection (rare) acute lung injury from paralysis, dysrhythmias cerebral edema depressed Sympathomimetic symptom
 Intracranial hemorrhage Associations bronchorrhea, or seizures respirations, apnea,
 Pulmonary infarction o Hepatitis bradycardia
(pleuritic chest pain, o Abscesses
 dyspnea, hypoxemia) o Right sided endocarditis
 Bowel ischemia, placental o HIV/AIDs
abruption o Overdose
Workup  ABG – Respiratory Acidosis RBC acetylcholinesterase  ABG  
GMR – hypoglycemia activity o Low PaCO2
Evaluate for presence of other Atropine (diagnostic & o Low HCO3–
drugs (e.g. acetaminophen) therapeutic) – absence of o Near normal arterial pH
ECG for prolonged QTc with cholinergic signs (e.g. (2 primary acid base
methadone overdose erythema, tachycardia, disorders shift pH in
mydriasis) after small (1mg) opposite directions)
dose supports diagnosis o N.B. over time,
uncompensated
metabolic acidosis is
the primary finding
Management  Cooling, hydration Ventilation, airway  Initial stabilization – ABCs  Physostigmine (if  Multidose activated  Ventilatory support  Generally supportive
Management of chest pain management (Airway protection & appropriate), charcoal (if presentation  Parenteral BZDs (e.g. lorazepam,
 IV BZDs (lorazepam) – Naloxone (may need ventilation)  BZDs – sedation is within 2 hours of diazepam) to treat severe PCP–
decreases BP & anxiety / repeated doses) – titrated to  Decontamination –  Cooling, supportive ingestion) associated psychomotor
psychomotor agitation achieve RR ≥ 12/min, but not Remove patients clothes, management  Urine alkalinization with agitation
 Aspirin (C/I if high suspicion to achieve normal mental irrigate skin and/or eyes to potassium repletion
of aortic dissection) should status prevent cutaneous o Infusion of IV sodium
be given early; N.B. Add Exclude other AMS causes absorption bicarbonate
Clopidogrel if evidence of (e.g. hypoglycemia)  Atropine reverses  Hemodialysis (if
ACS (ischemic changes on Consider continuous cardiac muscarinic effects pulmonary edema or
ECG, cardiac biomarkers) ± monitoring (if QTc > 500 (competitive inhibition of fluid overload, AMS,
PCI if indicated – reduce msec) acetylcholine at NM) renal failure, cerebral
acute thrombus formation  Pralidoxime edema, severe acidosis,
 Nitroglycerin & CCB (cholinesterase– very high salicylate level)
(verapamil) for pain – reactivating agent) –  IV PPIs
coronary vasodilation reverses nicotinic  Supplemental glucose
 IV Phentolamine (alpha receptor antagonist) – used in (neuromuscular) and (typically given dextrose
patients with cocaine–related chest pain whose HTN fails to muscarinic symptoms 5% water with
respond to BZDs and nitroglycerin o administer after atropine bicarbonate solution)
 Beta blockers are CONTRAINDICATED in acute cocaine as it may cause transient
ingestion cholinesterase inhibition  N.B. A common mistake
o Theoretical risk of unopposed cocaine–induced alpha–1 and worsen symptoms to fail to recognize a
adrenergic receptor mediated arterial vasoconstriction momentarily mixed acid–base
(including worsening coronary vasoconstriction) disorder due to a normal
 Fibrinolytics– not preferred due to increased risk of pH. Over time, as
intracranial hemorrhage metabolic acidosis
 Immediate cardiac catheterization with reperfusion when worsens, patient will be
indicated unable to ventilate
quickly enough to
compensate

 IV buprenorphine can be used to treat symptoms of opioid withdrawal, which is usually characterized by flulike symptoms (e.g. myalgia, rhinorrhea, diarrhea)
 Thiamine deficiency can lead to Wernicke-Korsakoff syndrome. The disease presents as ataxia, ophthalmoplegia, and confusion (Wernicke’s) in addition to confabulation
and amnesia (Korsakoff’s).
o Particularly common in alcoholics
 Benzodiazepines (BZDs)
o Indications
 Anxiety
 Insomnia (short – term)
 Agitation
 Alcohol & sedative – hypnotic withdrawal
 Preoperative sedation
 Seizures
o ADRs (Adverse Effects)
 Daytime sedation
 Confusion / impaired attention
 Memory impairment (anterograde amnesia)
 Ataxia
 Slowed psychomotor performance
 Increased risk of falls, motor vehicle accidents & hip fractures in the elderly
 Respiratory depression (uncommon unless combined with alcohol)
o Withdrawal – typically peak after several days if intermediate– to long–acting BZDs; within 24 hours if short–acting BZDs
 Autonomic instability – Tachycardia, increased blood pressure, hyperpyrexia
 Restlessness, anxiety, panic attacks, irritability
 Insomnia
 Delirium
 Tremor
 Psychosis
 Seizures, death (rare)
o Tx of Withdrawal – IV BZDs (e.g. lorazepam, diazepam) with subsequent tapering once withdrawal symptoms are controlled
 Methylenedioxymethamphetamine (MDMA, Ecstasy) intoxication – ↓ reuptake of DA and 5-HT
o Euphoria
o Increased energy
o ± Bruxism and hyperthermia
o Altered sense of time, altered sensation
o Association – Serotonin Syndrome, Hyponatremia / Thirst / Seizures, SIADH, Hallucinogen Persisting Perception Disorder
o Withdrawal – anxiety, concentration difficulties, depression
 Marijuana (THC, Cannabis) Intoxication – a cannabinoid which stimulates endocannabinoid CB1 and CB2 receptors
o Physiologic Effects
 Dry mouth
  Conjunctival injection
 Tachycardia
 Increased appetite (“munchies”)
 Increased respiratory rate
o Cognitive Effects
 Euphoria, calmness
 Slowed reflexes, impaired time perception
 Incoordination
 Impaired short–term memory, and poor concentration
 When exposed to higher doses → Dysphoria / panic, social withdrawal, anxiety, paranoia
o Psychomotor impairment lasts beyond the timeframe of euphoria and can persists for up to a day, altering ability to operate automobiles and increasing the risk
of motor vehicle collisions
o Patients with cannabis intoxication are managed supportively
o Associations – Psychosis, Paranoia, Cannabinoid Hyperemesis Syndrome (relieved emesis in response to heat / ‘hot showers’, poorly understood mechanism)
 Synthetic cathinones (“bath salt”) – consist of large family of synthetic amphetamine analogs
o May increase the release, or inhibits the reuptake, of norepinephrine, dopamine, and serotonin
o Symptoms of intoxication
 Severe agitation
 Combativeness
 Psychosis, delirium, myoclonus, and rarely, seizures
 Tachycardia and increased BP
 Prolonged duration of effect (e.g. delirium and psychosis may last up to a week)
o Routine urine toxicology screens cannot detect synthetic cathinones
 Opioid withdrawal
o Etiology: sudden reduction or termination of opioid intake in physiologically dependent individuals
o Clinical features
 Withdrawal symptoms develop within 6 – 12 hours of last dose of a short-acting opioid, with a peak 24 – 48 hours after symptom onset
 Flu-like symptoms: rhinorrhea, lacrimation, chills, piloerection, myalgia, arthralgia, leg cramps
 Gastrointestinal complaints: nausea, vomiting, abdominal pain / cramping, diarrhea, hyperactive bowel sounds
 Features of sympathetic hyperactivity: mydriasis, tachycardia, hypertension, hyperreflexia, diaphoresis / sweating
 Features of CNS stimulation / Psychological: insomnia, yawning, irritability, anxiety, agitation, aggression, dysphoric mood
 Goose flesh
o Treatment: supportive care
 Opioid agonist – buprenorphine/naloxone or low-dose methadone (preferred)
 Non–opioid: alpha-2-adrenergic agonists (clonidine for anxiety, restlessness, hypertension) or adjunctive medications (antiemetics, antidiarrheals -
loperamide, benzodiazepine)
 Ibuprofen for myalgias, baclofen (muscle cramps)
 Common withdrawal Syndromes
 o Alcohol withdrawal
 Pathophysiology – Alcohol is a GABA agonist, and glutamate antagonist
 alcohol intoxication leads to increased GABA levels (major inhibitory neurotransmitter) and decrease Glutamate (major excitatory
neurotransmitter)
 Compensatory upregulation of glutamate receptors in patients with alcoholism → sympathetic overdrive with alcohol withdrawal
 Symptoms develop within 6 – 24 hours after last drink
 0 – 36 hours
 GI Upset, Tremors or tremulousness, agitation, insomnia
 12 – 48 hours
 Alcoholic Halluconosis – visual hallucinations in presence of intact orientation, anxiety, delirium, psychosis, diaphoresis,
 6 – 48 hours
 Withdrawal seizures
 48+ hours
 Life-threatening Delirium Tremens 2 – 4 days after the last drink
 Cardiovascular compromise due to sympathetic overdrive
 Examination findings – withdrawal seizures, tachycardia, palpitations, elevated BP
o Benzodiazepine (BZD) withdrawal
 Similar symptoms to alcohol withdrawal, but with less predictability in time of onset and duration of symptoms
 Tremors, anxiety, perceptual disturbances, psychosis, insomnia
 Examination findings – seizures, tachycardia, palpitations
 Long–acting BZDs (e.g. clonazepam) are likely to have later onset and a longer course of withdrawal symptoms
o Heroin withdrawal / Opioid withdrawal
 Symptom onset within 6 – 12 hours, can peak within 36 – 72 hours, and may persist for several days
 Nausea, vomiting, abdominal cramping, diarrhea, muscle aches (myalgias, arthralgias)
 Examination findings – Dilated pupils (mydriasis), yawning, piloerection, lacrimation, sweating, rhinorrhea, hyperactive bowel sounds
 Patients appear restless and irritable with elevated heart rate and blood pressure (although usually not as elevated as in alcohol withdrawal)
 Symptoms can be very distressing but are not life-threatening
o Stimulant withdrawal (e.g. cocaine, amphetamines)
 Increased appetite, irritable, drowsy, hypersomnia, fatigued, intense psychomotor retardation, severe depression (‘crash’)
 No significant examination findings / physical symptoms
o Nicotine withdrawal
 Dysphoria, irritability, anxiety, increased appetite
 No significant examination findings
o Cannabis withdrawal (Marijuana withdrawal)
 Irritability, anxiety, depressed mood, insomnia, decreased appetite
 No significant examination findings
 Acetaminophen Intoxication
o Pathophysiology – Depletion of intrahepatic glutathione → accumulation of NAPQI (toxic metabolite of acetaminophen)
 o Clinical Features
 Can be asymptomatic within 1st 24 hours or may have non–specific symptoms (nausea, vomiting, anorexia, fatigue)
 24 – 72 hr
 After 24 hours, patients may develop severe liver injury (↑ AST, ALT)
 72 – 96 hr
 AST / ALT levels peak (sometimes > 10,000 U/L)
 Severe cases: ↑ PT/PTT (hepatic synthetic dysfunction), hypoglycemia, lactic acidosis, ↑ bilirubin, acute kidney injury
 4 – 14 days: Recovery
o Diagnosis
 Serum acetaminophen level (4 – 24 hrs)
 LFTs, BUN/Creatinine, Electrolytes
o Management
 If Single dose ≥ 7.5 g (pediatric ≥ 150mg/kg) →
 No → if Chronic ingestion → check acetaminophen levels (and continue down decision / algorithm tree)
 Yes → ≤ 4 hours since ingestion → administer activated charcoal (gastric decontamination) → check acetaminophen levels 4 hours post ingestion,
or immediately if presentation is 4 – 24 hours after ingestion (N.B. not reliable when measured < 4 hours after ingestion because levels are
unreliable and poor predictors of toxicity)
o Monitor for liver injury if:
 If Levels above treatment line in Rumack–Matthew nomogram (provides likelihood for hepatotoxic effects), or
 If > 10 mcg/ml with timing of ingestion unclear, or
 If evidence of liver injury
o Administer N–acetylcysteine empirically while awaiting results of Rumack–Matthew normogram
 Increases intrahepatic glutathione, facilitating removal of N – acetyl benzoquinone imine, a primary toxic metabolite of
acetaminophen
 Continue N–acetylcysteine administration if acetaminophen levels are above the Rumack–Matthew normogram treatment line
 Because treatment is most effective when given promptly, delayed hospital presentation is associated with worse outcomes
 Psychiatric consultation
 Lead Poisoning in Adults
o Risk Factors
 Occupational exposure (e.g., lead paint, batteries, ammunition, construction)
o Clinical Features
 Gastrointestinal (abdominal pain, constipation, anorexia)
 Neurologic (cognitive deficits, peripheral sensorimotor neuropathy, headaches, ataxia, short-term memory loss)
 Hematologic (anemia)
 Hypertension and possible nephrotoxicity (e.g. elevated creatinine)
o Laboratory findings
 Microcytic Anemia
 Inhibition of enzymes responsible for heme and RNA synthesis in both bone marrow and mature erythrocytes
 Elevated venous lead level
  Elevated serum zinc protoporphyrin level
 Basophilic stippling on peripheral smear
 Hyperuricemia
 Impaired purine metabolism
o Management
 Removal of lead source
 Chelation therapy
 Acute Radiation Syndrome
o Tachycardia, Nausea, Vomiting, and diarrhea
o Progresses to include anemia, and encephalopathy
o Measure exposure with Geiger-Muller Counter

Standard Urine Drug Screen

Drugs Duration of positive test Duration of positive test False positives
(short–term use) (long–term use)
Amphetamine ≤ 2 days ≤ 4 days  Atenolol, proponalol
 Buproprion
 Nasal decongestants
Cocaine ≤ 2 days ≤ 7 days  High specificity
Cannabis ≤ 3 days 1 – 2 months  Hemp–containing foods
Opioids* ≤ 3 days ≤ 3 days  Poppy seeds
Phencyclidine ≤ 7 days ≤ 7 days  Dextrometrophan
 Diphenhydramine, doxylamine
 Ketamine
 Tramadol
 Venlafaxine
 * Standard urine drug screens do not detect semi–synthetic (e.g. hydrocodone, hydromorphone, oxycodone)
or synthetic (e.g. fentanyl, meperidine, methadone, tramadol) opioids
Toxic Alcohols
Toxicity Clinical Features Laboratory results Management
Alcoholic  Binge drinking Associations  High osmolar gap  Glucose + Saline (D5NS)
ketoacidosis with heavy  Cirrhosis –  Glucose often mildly elevated with low  Thiamine & potassium repletion
alcohol o Portal HTN, bleeding, jaundice, asterixis, spider angiomata, palmar erythema bicarbonate and High anion gap  Ondansetron (Nausea & vomiting)
consumption o LFTs, GGT, thrombocytopenia, clotting factors metabolic acidosis (ketosis)
and decreased  Wernicke Korsakoff Syndrome  N.B. Urinary ketones may be weakly
food intake for o Encephalopathy, ophthalmoplegia, ataxia, amnesia, confabulation positive
several days o Thiamine, mammillary bodies o Major and earliest ketone produced by
(starvation  Pancreatitis fat metabolism is beta-
ketoacidosis) o Epigastric ABD pain, N/V, flank ecchymosis, periumbilical ecchymosis hydroxybutyrate, but lab-measured
 Ethanol o Hypocalcemia, amylase, lipase ketone is acetoacetate; thus may be
metabolism  Beri-Beri falsely negative
inhibits o Symmetrical peripheral neuropathy (“Dry”)  Alcohol levels usually low or negative
gluconeogensis o High – output Heart Failure (“Wet”)
 Slurred speech o Thiamine, Volume Overload (Wet), non-inflammatory demyelination (Dry)
 Unsteady gait,  Dilated Cardiomyopathy
Ataxia o Systolic Heart Failure, systolic murmur, S3
 Altered o Dilated Ventricles, heart ballooning, BBB
mentation,
 Peripheral Neuropathy
disorientation
 Testicular Atrophy
 Emotional
 Cerebellar Degeneration
Lability
o Vertigo, Ataxia, dysarthria, dysmetria
 Disinhibition
o Dysdiadochokinesia, FNT, Stewart-Holmes sign (rebound elbows), cerebellar
 Abdominal pain,
drift
nausea,
 Gastritis
vomiting,
o Hematemesis, upper abdominal pain, indigestion, early satiety
dehydration
o Endoscopy, H. Pylori (stool antigen or urease breath tests)
 Marchiafava-Bignami Disease
o Neuropsychiatric symptoms (personality change, dementia, subthreshold
psychotic symptoms)
o Corpus Callosum degeneration, Vitamin B levels
Methanol  Visual blurring, central scotoma  High osmolar gap  Hemodialysis, in addition to
ingestion  Optic disc hyperemia (formate metabolite → retinal damage)  Increased anion gap metabolic acidosis fomepizole indicated for toxic
(antifreeze)  Afferent pupillary defect  Hypokalemia – suggestive of alcoholism alcohol ingestion (e.g. methanol,
 Altered mentation & vomiting ethylene glycol)
 Within 24 hours – Headache, nausea, vomiting, & epigastric pain
Ethylene glycol  Inebriation & sedation, similar to ethylene glycol  High osmolar gap
ingestion  Cranial nerve palsies – slurred speech  Increased anion gap metabolic acidosis
(antifreeze)  Tetany (hypocalcemia) o Low HCO3, compensatory ↓ pCO2
 Rapid and deep breathing (Kussmaul’s respiration) – 2 O to AG metabolic acidosis  Hypocalcemia & Calcium oxalate
  Nausea, vomiting, ataxia, nystagmus, lethargy crystals in urine
 Further toxicity o Metabolism via alcohol and alcohol
o Tachypnea, agitation, confusion dehydrongenase produces:
o Flank pain  Glycolic acid, which is subsequently
o Acute Kidney Injury (haematuria, oliguria), Renal Failure converted to oxalic acid.
o Pulmonary edema Oxalic acid binds to calcium
o Changes in mental status, eventual progression to coma Glycolic acid (glycolate) injures
 Antidote – fomepizole (competitive inhibition of alcohol dehydrogenase; antidote of choice in renal tubular cells & obstruction of
ethylene glycol & methanol intoxication) or ethanol (2nd line; can be used in treatment of methanol tubules by calcium oxalate crystals
or ethylene glycol intoxication)  Glycoxylic acid
o Fomepizole inhibits alcohol dehydrogenase more potently than ethanol, and is therefore the
antidote of choice
 Prevents further break down of ethylene glycol into its toxic metabolites and causes a
dramatic improvement in acidemia, and prevents renal failure
o Fomepizole also prolongs the half – life of ethanol, thus simultaneous use with ethanol is not
recommended
o Sodium bicarbonate may alleviate metabolic acidosis; Hemodialysis may be required
Isopropyl  CNS depression  High osmolar gap 
alcohol  Disconjugate gaze  Normal anion gap
ingestion  Absent ciliary reflex  No metabolic acidosis
 Cyanide Toxicity
 Combustion of carbon– & nitrogen–
containing synthetic polymers (e.g.
wool, silk, foam, cotton, paint)
 Industrial exposure (e.g. metal
extraction in mining)
 Drugs (e.g. sodium nitroprusside –
prolonged infusion > 24hrs @ high
rates, 5 – 10 μg/kg/min, especially in
CKD / renal failure pts) – thus
recommend low infusion rates (< 2 μ
g/kg/min), short–term usage, and
close monitoring
Etiology &  Cyanide binds to cytochrome C
Pathophys oxidase and inhibits oxidative
phosphorylation
 Functional hypoxia
 Smoke injury from house fire may result in glottic edema from heat and airway
irritation due to particulate matter in smoke; may have concomitant cyanide and
carbon monoxide poisoning
Clinical  Both can lead to pink or cherry red skin (usually postmortem finding), seizures, and
Features coma
 Bitter almond breath
 Skin – Diaphoresis, flushing (cherry
red colour), cyanosis (late)
 CNS – Headache, vertigo, dizziness,
dilated pupil, altered mental status,
seizures, coma, hyperreflexia due to  Severe
thiocyanate accumulation
 CVS – tachycardia, arrhythmias, CVS
collapse
o Initially ↑ HR & BP
o Then bradycardia, hypotension
 Respiratory – tachypnea/
hyperventilation followed by
respiratory depression, pulmonary
edema
Carbon Monoxide Poisoning
 Displaces O2 from Hb → left–shift of oxygen–  Hb contains ferric (Fe3+) form of iron
hemoglobin curve → ↓ O2 delivery to tissues  Oxidized form of Hb has high affinity for cyanide
 Binds to cytochrome C oxidase → disrupts
electron transport chain
 ↑ lipid peroxidation in CNS
 Risk Factors
o Charcoal, gas, or petroleum
o Wood–burning heaters
o Cooking / gas motors operating in poorly
ventilated areas
o Defective heating systems during winter
o Building fires, smoke inhalation
o Motor vehicle exhaust
o Methylene chloride exposure (paint
thinners)
 Metabolized into CO
 Delayed CO poisoning
 Mild–to–Moderate
o Cerebral Hypoxia: Headache, confusion,
drowsiness
o Malaise, dizziness
o Nausea, Vomiting
o Cerebral hypoxia: Seizure, syncope, coma
o Myocardial injury: Myocardial ischemia
(33%; associated with increased mortality;  Complications
ECG changes, hypertroponinemia even
without obstructive coronary lesions),
Ventricular arrhythmias, Pulmonary edema Symptom severity correlates closely to MetHb level and severity of impaired O2
(cardiac dysfunction or CO–induced alveolar
damage)
Methemoglobinemia
o Oxidized iron sites / haem subunit on MetHb does not bind readily to oxygen
o Remaining available haem binding sites has increased affinity for oxygen →
leftward shift in oxygen dissociation curve
o Consequent tissue hypoxia & functional anemia
NADH MetHb reductase typically keeps oxidative stress in check by reducing MetHb
to Fe2+ state; Methemoglobinemia occurs when either
o Deficiency of reducing enzyme (NADH MetHb reductase)
o Increased oxidative stress that cannot be handled by the body
Presence of MetHb renders pulse-oximetry readings inaccurate
Risk factors / Common Causative Agents
o Drugs (oxidizing substances)
 Nitrates, nitrites –
 Nitrofurantoin
 Nitroprusside
 Phenazopyridine
 Sodium Nitrite
 Amyl nitrite
 Nitroglycerin
 Isobutyl Nitrite (“poppers”)
 Topical / local anesthetics – Lidocaine, benzocaine, bupivacaine, etc.
 Dapsone
 Contaminated well water
 Phenazopyridine
 Headache, Lightheadedness
 Fatigue, Lethargy
 Dyspnea, respiratory depression
 Seizures or coma (extremely high levels)
 Altered mental status
 Pulse oximetry shows < 90% O2 saturation (usually ~85%) without response to
100% supplemental FiO2
 Tachycardia, chest pain
 Cyanosis (Saturation-cyanosis gap = cyanosis with SpO2 in 80s)
 Dark–chocolate / dusky colored skin
o End organ failure (i.e. AMS, seizures)
o ARDS
delivery
o MetHb: < 15% -
  GI – ABD pain, N/V
 Renal – Lactic acidosis, Renal Failure
 Hypoxia not responsive to supp. O2
 Toxicity should be suspected in all
patients on nitroprusside infusion
who have unexplained metabolic
acidosis and altered mental status
 Normal co–oximetry
 ABG – Lactic acidosis, ↓ PaCO2
 VBG – ↑ ↑ PvO2
 lactate typically > 10 mEq/L
Treatment overview of suspected
Cyanide
Decontamination:
 Dermal exposure
o Removal of clothing
o Skin decontamination
Investigations
 Ingestion – activated charcoal
 All exposures – see antidote below
Respiratory support:
 NO mouth–to–mouth resuscitation
 Supplementary oxygen
 Airway protection (intubation)
Cardiovascular support:
 IV fluids for hypotension
 Multiple individuals may be involved (e.g.,  May be asymptomatic
family with similar symptoms in winter).  Low pulse oximeter reading
 Cutaneous bullae o MetHb: 15-20% -
 Cherry red mucous membranes (late finding)  Cyanosis (peripheral and central)
 Fatigue
 Chocolate brown colored blood
o MetHb: 20-50%
 Dyspnea
 Headache
 Exercise intolerance
 Dizziness
 Syncope
 Weakness
o MetHb: 50-70%
 Tachypnea
 Metabolic acidosis
 Dysrhythmias
 Seizures
 CNS depression, Coma
o MetHb > 70% – Severe hypoxemia & Death
Symptoms will be worse for any MetHb level in patients with baseline impairment
of O2 delivery (i.e. CHF, pneumonia, COPD, anemia)
 Normal O2 saturation on Pulse Oximetry Methemoglobinemia > 3% – measured on co-oximetry device
 Secondary Polycythemia (chronic CO toxicity) ABG – Normal PaO2 (only detects unbound arterial oxygen, as opposed to
 Co–oximetry of ABG: ↑ carboxyhemoglobin Haemoglobin–bound O2)
levels on spectrophotometry Saturation gap > 5% difference between oxygen saturation on pulse oximetry &
o must be assessed prior to supp. O2 ABG; thus falsely elevated oxygen saturation level)
 ABG, VBG Low PaCO2 (hyperventilation from tachypnea)
 Lactic Acidosis G6PD screening – N.B. methylene blue contraindicated in G6PD
 ↑ ↑ PvO2 “Chocolate brown” or blue blood
 portable CO–oximetry devices (not Enzyme assay (NADPH–dependent cytochrome B5 Methemoglobin reductase)
regular pulse oximetry)
o Carboxyhemoglobin > 3% for nonsmokers
o Carboxyhemoglobin > 10% for smokers
 Anion Gap Metabolic Acidosis due to lactic
acidosis from peripheral tissue hypoxia
(impaired oxygen utilization – disrupted
mitochondrial oxidative phopshorylation)
 ECG ± cardiac enzymes (↑ troponin) – CO
poisoning may cause myocardial injury due to
relative hypoxemia
 Classically associated with bilateral globus
pallidus lesions on MRI, although rarely seen
with cyanide toxicity as well.
  Antidote  High–flow 100% oxygen by non–rebreather  100% oxygen + methylene blue 1 – 2 mg/kg IV over 5 minutes (acts as an
o Sodium Thiosulfate (alternate) facemask electron acceptor for NADPH, and is reduced to leucomethylene blue, which in
 Cyanide → thiocyanide o Increased blood O2 level and enhances CO turn reduces methemoglobin to haemoglobin, ferrous form [Fe2+])
(renally excreted) removal via the lungs  High–dose Vitamin C when methylene blue contraindicated (e.g. G6PD)
o Hydroxocobalamin (preferred)  Intubation / Hyperbaric O2 (severe)  Source identification, removal (if possible) and decontamination
 Binds with cyanide →
cyanocobalamin (renally
excreted)
Management
 If antidote not available, Nitrites
(induces methemoglobinemia)
o Oxidizes hemoglobin →
methemoglobin, which will bind
to cyanide
(cyanomethemoglobin; less
toxicity)
o Contraindicated in CO poisoning
 FIGURE 1: TOXICOLOGIC ASSESSMENT OF CYANOSIS

 Arsenic poisoning
o Mechanism
 Binds to sulfhydryl groups
 Disrupts cellular respiration & gluconeogenesis
o Sources
 Pesticides / insecticides
 Contaminated water (often from wells)
 Antique Pressure–treated wood
o Manifestations
  Acute
 Garlic breath
 Vomiting
 Watery diarrhea
 QTc prolongation
 Chronic
 Hypo/Hyperpigmentation
 Hyperkeratosis & scaling to the palms and soles
 Stocking–glove neuropathy
 Pancytopenia
 Mild transaminase elevation → hepatitis
 Urine arsenic levels
o Treatment - chelation
 Dimercaprol (British anti-Lewisite)
 DMSA (meso-2,3-dimercaptosuccinic, succimer)