Toxicology/Poisonings Flashcards
Name some one-pill killers
One dose can be life threatening
Clonidine Oil of wintergreen (methylsalicylate) Camphor Toxic alcohols (methanol, ethylene propyl) TCAs Benzocaine CCBs Sulfonylurea Propanolol Buprenorphine Chlorpromazine Chloroquine Hydroxychloroquine Lomotil Methadone (and other opioids) Quinidine Quinine
What three treatments/antidotes should be considered in all comatose patients?
Oxygen
Glucose
Naloxone
Describe the following toxidrome: SYMPATHOMIMETIC
UPPERS
Agitation, Delirium, Psychosis, Seizure Tachycardia Hypertension Fever/Hyperthermia Mydriasis (increased pupil size - reactive) Sweaty
Describe the following toxidrome: ANTICHOLINERGIC
Blind as a bat, hot as a hare, dry as a bone, red as a beet, mad as a hatter
The bowels and bladder lose their tone and the heart beats on alone
Delirium, Psychosis, Seizure, Coma/somnolence
Tachycardia
Hypertension
Fever/Hyperthermia
Mydriasis (increased pupil size - sluggish)
Decreased bowel sounds
Flushed/Dry skin
Describe the following toxidrome: CHOLINERGIC (ORGANOPHOPHATES)
Pouring with secretions
SLUDGE And the 3 killer B’s
DUMBELS
Salivation Lacrimation Urination Diarrhea GI Distress Emesis Bronchorrhea Bradycardia Bronchospasm
Diarrhea Urination Miosis Bradycardia/Bronchorrea/Bronchospasm Emesis Lacrimation Salivation
Fasiculations Seizures Can have tachycardiac (nicotinic) and bradycardia (muscarinic) Normal or hypertension Tachypnea Miosis Sweaty
Describe the following toxidrome: OPIATES (CLONIDINE)
DOWNERS
Somnolence/Coma Tachycardia Hypotension Hypothermia Bradypnea Significant MIOSIS Decreased bowel sounds
Describe the following toxidrome: SEDATIVE-HYPNOTICS (BARBITUATES)
ALSO DOWNERS
Somnolence/Coma Hypotension Hypothermia Bradypnea Bullae on skin (IV drug use)
Describe the following toxidrome: SALICYLATES
Coma/Somnolence, Seizures Normal or tachycardia Hyperthermia Tachypnea Sweaty skin
Name 3 differences between Sympathomimetics and Anticholinergics
Skin - Sweaty (SYM), Dry/flushed (ANTICHOL)
Pupils - Reactive (SYM), Sluggish (ANTICHOL)
Bowel sounds - No impact (SYM), Decreased (ANTICHOL)`
Bitter almond smell in your coffee - what toxin?
Cyanide
Name the toxins with characteristic smells
Cyanide - almonds Arsenic, thallium, organophosphates, selenic acid - garlic Chloral hydrate, paraldehyde - pears Hydrogen sulfide - rotten eggs Methyl salicylate - wintergreen
List the toxins that are poorly absorbed by activated charcoal
Heavy metals (Lithium, iron)
Alcohols
Hydrocarbons
List the possible indications for Whole Bowel Irrigation (WBI)
Body packers/stuffers Ingestion of metals, lithium Ingestion of sustained release preparations Ingestion of pharmaceutical patches Massive overdoses Concretions of pills
List the possible indications for hemodialysis
Ethylene glycol Lithium Methanol Salicylate Theophylline
List some drugs that may lead to delayed expression of clinical toxicity
Sulfonylurea (oral hypoglycemics) Acetaminophen Iron Sustained release drug formulations MAOIs Thyroid hormones Warfarin
Toxic level for acetaminophen
150 mg/kg
Pathophysiology of acetaminophen poisoning
Acetaminophen saturates the hepatic metabolism pathways
Depletes glutathione
Causes increased production of NAPQi (N-acetyl-p-benzoquinone imine) - which binds to liver hepatocytes and causes necrosis
What are the 4 stages of acetaminophen poisoning?
STAGE 1 (30 min - 24 hours) Asymptomatic, occasionally N/V, diaphoresis, pallor
STAGE 2 (24 - 48 hours) N/V, RUQ abdo pain, elevates liver enzymes
STAGE 3 ( 72 - 96 hours)
Fulminant hepatic failure with jaundice, thrombocytopenia, increased INR, hypoglycemia, hepatic encephalopathy
Renal failure and cardiomyopathy may occur
STAGE 4
If patient survives - resolution of Sx
When do you draw an acetaminophen level?
at 4 - 24 hours post ingestion
Plot on the Rumack-Matthew nomogram to determine if antidote is required
What is the antidote for acetaminophen toxicity? How does it work
NAC N-acetyl-cysteine Replenishes glutathione in the liver Detoxifies the toxic metabolite - NAPQi Alleviates existing hepatotoxicity through antioxidant and pro-circulatory properties
Effective when initiated within 8 hours of ingestion
Given IV over 21 hours (can be given PO - old regimen)
SE - anaphylactic reaction, reaction with pts with asthma
Describe the treatment for salicylate poisoning?
ABCDEF
Activated charcoal - in < 1-2 h post ingestion
IVF
Urine alkalinization - if peak level > 35 mg/dL (350 mg/L)
- reduces salicylate access to the brain
Hemodialysis - if patient meets these criteria: unremitting metabolic acidosis, pulmonary edema, severe renal impairment, coma, seizures, liver impairment, salicylate level > 70 mg/dL (700 mg/L)
What hazard is associated with intubation of salicylate poisoned patients?
Tend to have profound respiratory alkalosis
Abrupt reversal with a sedative and paralytic - causes significant acidemia which may increase salicylate entry to the brain and cause seizures
How does iron produce toxicity?
Iron acts on the GI mucosa
Inhibits oxidative phosphorylation in the mitochondria
Body has no mode of excretion of excess iron
What are the toxic levels of iron?
Ingestion levels: Mild: 20 - 60 mg/kg Moderate: 60 - 100 Serious: 100-200 Lethal : > 200
Serum levels roughly correlate with toxicity:
< 350 mcg/dL – minimal
350-500 mcg/dL – mild
>500 mcg/dL – serious
Check serum iron levels 4-6 hours post ingestion
AXR - can sometimes show iron pills that have not been absorbed yet
What are the stages of Iron toxicity?
STAGE 1 (up to 6 hours)
GI Symptoms, N/V, GI bleed
If severe - shock due to volume loss, coma
STAGE 2 (6 - 24 hours)
GI Symptoms resolve, patient looks relatively well
Transient phase
STAGE 3 (>24 hours) Metabolic acidosis, hepatocellular injury, elevated transaminases, jaundice, intractable shock, seizures, coma
STAGE 4 (4-6 weeks) Resolution of symptoms, patients who survive can get gastric scarring and cause pyloric stenosis
What is the antidote for iron poisoning?
Deferoxamine
An iron chelator
Dose: 5-15 mg/kg/hour (up to 6g/day) IV
Stop it for 6 h q24h - to prevent ARDS or pulmonary fibrosis
Causes vin-rose urine
What reasons would you stop deferoxamine?
Clinical improvement:
Urine runs clear
Metabolic acidosis resolves
Iron level returns to normal
Adverse effects: Anaphylactic reaction ARDS Pulmonary fibrosis Cramps Neuropathy
What gastrointestinal decontamination is helpful and what is not helpful in iron toxicity?
Helpful - WBI - if undissolved tabs on AXR, or massive overdose
Not- helpful - activated charcoal
List the major toxicities of TCAs
Na channel blockade - in the cardiac conduction system - dysrhythmias Seizures alpha blockade - hypotension Inhibition of NE reuptake Anticholinergic toxicity
What ECG findings correlate with TCA toxicity?
Wide QRS > 100 ms
Prolonged QT
R wave height greater than 3 mm in lead aVR
How does bicarb improve the QRS interval in TCA toxicity?
Na Bicarb competitively inhibits the Na blockade by increasing available serum sodium
Also the serum alkalinization promotes improved conduction that narrows the QRS and causes cessation of the ventricular tachycardia
What drugs cause bradyarrhythmias?
What are helpful antidotes?
Beta blockers
CCB
Digoxin-containing compounds
Not amenable to atropine, epinephrine and pacing
Beta blockers: Glucagon, lipid emulsions
CCB: Calcium, insulin/glucose, lipid emulsions
Digoxin: Digi-Fab
What is flumazenil an antidote for and what are the concerns for using it?
Benzos
Benzo-receptor antagonist
May precipitate benzo withdrawal
May precipitate seizures and their complications
Short duration of action compared with duration of benzo toxicity
How do you treat seizures from an overdose/toxic exposure?
Benzos
Barbituates
Pyridoxine - isoniazid overdose
Don’t use:
Phenytoin - Na channel issue - can complicate TCA toxicity
Signs and Sx of isolated benzo overdose
Sedation
Ataxia
Respiratory depression
Apnea
Deep coma
Cardiovascular instability
THINK COINGESTANTS - ethanol, barbituates, other sedative-hypnotics
Toxidrome for opioid toxicity
FAME
Flaccid coma
Apnea
Miosis
Extraocular paralysis
Causes global depression of central and autonomic nervous systems
Antidote for opioid toxicity?
Naloxone
May need higher doses for - methadone, LAAM, dextromethorhan, pentazocine, fentanyl
OR
Smaller doses for - people habituated to opioid use
What drug mimics opioid toxicity but does not respond to naloxone?
Clonidine
Alpha-adrenergic agonist
Acts centrally to reduce sympathetic outflow
Signs and Sx of clonidine poisoning
Miosis Coma Apnea Bradycardia Hypotension Transient arousal with stimulation
As little as 0.1 mg (1 tablet)
Which drugs can cause hallucinations or psychosis?
Anticholinergics (antihistamines, Jimson weed)
Dissociatives (phenycyclidine, ketamine, dextromethrophan)
Hallucinogens (LSD, psilocybin, mescaline)
Sympathomimetics (amphetamines, cocaine, MDMA-ecstasy, bath salts, synthetic cannabinoids - spice, K2)
Withdrawal from ethanol or sedative-hypnotics
Why don’t we use haloperidol for sedation?
May lower the seizure threshold
May add to the cardiotoxicity of some drugs
May limit the patient’s ability to dissipate heat
Signs and Sx of cocaine toxicity
Initial rush of euphoria and increased energy Agitation Tachycardia Hypertension Hyperthermia Mydriasis Tremor Seizures Intracranial hemorrhage Myocardial ischemia Rhabdomyolysis Pneumothorax Psychosis Death
What treatments are effective in cocaine toxicity?
Benzos for agitation, seizures, tachycardia
Environmental cooling for hyperthermia
Mechanical ventilation, paralysis, and bicarb for rhabdomyolysis to reduce chance of renal failure
Nitroprusside infusion for hypertension
Reserve sympatholytics
Do not use Beta blockers
Name 7 hyperthermic syndromes in toxicology
Anticholinergics Sympathomimetics Neuroleptic Malignant Syndrome Malignant hyperthermia Serotonin syndrome Salicylate poisoning (due to the uncoupling of oxidative phosphorylation) Acute withdrawal syndrome
Signs and Sx of Serotonin syndrome
Autonomic hyperactivity
Increased neuromuscular tone
Hyperreflexia
CNS depression
Methods of abusing inhalants
Sniffing
Huffing
Bagging
Inhaled hydrocarbons - cause ventricular dysrhythmias - especially if agitated - due to increased catecholamine cardiac activity
In resusc of these patients - use Beta blockers rather than epi
Signs and Sx of synthetic cannabinoids
Aggressive behaviour Paranoia Dystonia Prolonged psychosis Seizures AKI MI
Signs and Sx of bath salt intoxication
Synthetic cathinones
Like amphetamines
Prolonged agitation Aggressive and violent behaviour Hallucinations Paranoia Seizures
DDX of increased anion gap metabolic acidosis
MUDPILES
Methanol, metformin Uremia DKA - Diabetic, alcohol and starvation ketoacidosis Paraldehyde Isoniazid, Iron, Inborn errors of metabolism Lactic acidosis Ethylene glycol Salicylate
Lactic acid can be caused by sepsis, shock, seizures, anoxia, ischemia, trauma, toxins (CO, cyanide, sodium azide, hydrogen sulfide, ibuprofen, adrenergic agents, isoniazid, etc.)
Osmolar gap calculation, normal range, and DDx of large osmolar gas
Osmolar gap = Measured Osm - Calculated Osm
Calculated Osm = 2Na + Glu + BUN
Normal -7 to 10 mOSM
DDx: Acetone Ethanol Gylcols Isopropanol Magnesium Mannitol Methanol Renal failure Severe ketoacidemia Severe lactic acidosis
Why do kids have such severe hypoglycemia from ethanol intoxication?
Ethanol breakdown inhibits gluconeogenesis
Kids have poor glycogen stores
No glucose produce, all glucose used = hypoglycemia
Ethanol is metabolized by the enzymes alcohol dehydrogenase and acetaldehyde dehydrogenase – produces NADH (from NAD)
Higher ratio of NADH>NAD - inhibits gluconeogenesis
Rate of ethanol metabolism
15 mg/dL/hour
How do you treat toxic alcohol poisoning
Ethanol
Fomepizole
Aim is to inhibit alcohol dehydrogenase - so it doesn’t breakdown the toxic alcohol (methanol, or ethylene glycol) - which produces formic acid (toxic to retina) and oxalic and glycolic acids (toxic to kidneys)
Supplements: Folic acid (promotes breakdown of formic acid) Pyridoxine and thiamine (speeds breakdown of glycolic acid - into nontoxic metabolites)
What characteristics of a caustic agent are most predictive of injury
pH Concentration Volume ingested Viscosity of product Manner of exposure Duration of exposure
Complications of caustic agent ingestion
ACUTE: Upper airway obstruction Aspiration pneumonitis GI bleeding or perforation Systemic acidosis or DIC Sepsis
CHRONIC: Esophageal stricture Impaired GI function Pyloric obstruction Esophageal carcinoma - 1000 fold increased risk
Indications to scope after caustic ingestion
Ingestion of a concentrated strong acid or base
Suicidal ingestion
Large volume
Patients with vomiting or >2 signs of injury
Indications for surgical exploration following caustic ingestion
Evidence of perforation
Abdominal tenderness after acid ingestion
Inability to evaluate injuries endoscopically
Significant CNS depression
Progressive metabolic acidosis
Hypotension with tachycardia
Hydrocarbon characteristics that make them prone to aspiration
Low viscosity
Low surface tension
High volatility
Describe the time course for developing aspiration injury after hydrocarbon ingestion
Pneumonitis - 6 hours
98% by 24 hours
Signs and symptoms of severe systemic toxicity from hydrocarbon ingestin
CNS depression Seizures Hepatotoxicity Nephrotoxicity Bone marrow toxicity
Hydrocarbons noted for systemic toxicity
CHAMP
Camphor
Halogenated hydrocarbons
(carbon tetrachloride, trichloroethane)
Aromatic hydrocarbons (benzene, toluene)
Metal-containing hydrocarbons
Pesticide containing hydrocarbons
How do you manage a child who ingests anticoagulant rodenticide
Activated charcoal
Do INR 2-3 days later
If severe coagulatopathy - large amount or chronic ingestion
Give Vit K
FFP
If superwarfarin - needs monitoring for 5 days
Signs and Sx of CO poisoning
Malaise
Nausea
Lightheadedness
Headache
More severe can lead to: Confusion Coma Syncope Seizure Death
Survivors:
Cognitive defects
Personality changes
Movement disorders
Who is most affected by CO poisoning?
Infants/small children
Higher O2 consumption
Higher basal metabolic rate
How long does it take the body to eliminate Carboxyhemoglobin?
Depends on inspired oxygen concentration
RA 4-6 hours
100% O2 40-90 minutes
Hyperbaric O2 (3 atm) 15-30 mins
Criteria for hyperbaric oxygen
Syncope
Confusion
CNS depression
Very high carboxyhemoglobin levels
Cyanosis that is unresponsive to supplemental oxygen with a normal partial pressure of oxygen on arterial blood gas
Methemoglobinemia
When the iron is Ferric (3+) rather than Ferrous (2+) - can’t transport oxygen
DDx for methemoglobinemia
CONGENITAL
Hemoglobin M
NADH
Cytochrome b5 reductase deficiency
ACQUIRED
Transient, illness-associated methemoglobinemia of infancy
Toxicant induced
Transient illness associated in infants - due to diarrheahl dehydration, metabolic acidosis, UTI and other illnesses - anything causing oxidative stress
Toxins - benzocaine, dapsone, environmental nitrates (well water), nitrites (amyl nitrite), and phenazopyridine
Treatment for methemoglobinemia
Supplemental oxygen
Eliminate or treat oxidative stress
Methylene blue (1-2 mg/kg of 1% solution) - except in G6PD
What feature distinguishes toxic from GI irritant mushrooms
Time course of vomiting
Delayed vomiting - >6 hours post ingestion - is BAD
Name toxic mushroom classes and their target toxicity
SEVERE (Vomiting > 6h post ingestion)
Gyromitra - inhibits pyridoxine phosphokinase
Orellanine - nephrotoxic
Amanita + Galerina + Lepiota - hepatotoxic
SEVERE (Vomiting <6h)
Amanita smithiana - nephrotoxic
MILD (Vomiting or Sx begin < 6h) Psilocybe - magic mushroom - serotonin Ibotenic acid (Amanita muscaria) - GABA, glutamatergic Coprine (inky cap) - Disulfiram-like Emetogenic mushrooms - gastric irritants Muscarinic - cholinergic Mytotoxic - rhabdomyolysis
Name some toxic plants by symptoms class, plants, potential treatment
SYMPTOM CLASS : Plants - (Tx)
GI irritants: Pokeweed, horse chestnut, english ivy
(Supportive care)
Toxalbumin: castor bean, rosary pea, autumn crocus (colchicine containing)
(Supportive care for multisystem organ failure)
Digitalis-like toxin: Foxglove, oleander, lily of the valley
(Digoxin Fab fragments - Digifab)
Cardiac effects: Mistletoe, monkshood, false hellebore, mountain laurel
(Supportive care, standard treatment of dysrhythmias)
Nicotinic effects: Wild tobacco, tobacco, poison hemlock
(Atropine, supportive care for weakness, paralysis)
Anticholinergic effects: Jimson weed, Angel’s trumpet, Matrimony vine, henbane, belladonna
(Physostigmine for seizures, malignant hyperthermia
Benzos for delirium)
Seizures: Water hemlock (Anticonvulsants)
Hallucinations: Morning glory, nutmeg, peyote (Sedation)
Cyanogenic: Chokecherry, pits (cherry, plum, peach), seeds (apple, pear), cassava, elderberry (leaves/shoots), black locust
(Cyanide antidote - rarely needed)
