Toxicology Flashcards
What to consider in kids pulled from a housefire??
What signs and symptoms would you see?
carbon monoxide, cyanide poisoning
CO: altered mental status +/- cyanosis despite normal pulse ox +/- flu like symptoms if chronic exposure
measure with co-oximeter, treat with 100% non-rebreather, hyperbaric O2
cyanide: headache, dizziness, fast heart rate, shortness of breath, and vomiting. Followed by seizures, slow heart rate, low blood pressure, loss of consciousness, and cardiac arrest
Which medications are potentially life threatening to a 10kg toddler following the ingestion of a single dose?
Sulfonylureas Propranolol Clonidine Calcium channel blockers Quinidine (class 1a anti-arrhythmic) Disopyramide (antiarrhythmic, Na-channel blocker) Flecainide (class 1c anti-arrhythmic) Chlorpromazine (antipsychotic) Clozapine (atypical antipsychotic) Cyclic antidepressants Hydroxychloroquine (antimalarial) Chloroquine (antimalarial) Buprenorphine (opioid) Methadone Diphenoxylate/atropine (lomotil) Methyl salicylate (wintergreen essential oil) Camphor (evergreen oil) Benzocaine (orogel)
What three antidotal drugs should be considered in the resuscitation of the comatose child?
oxygen
glucose
naloxone
What basic 5 elements go into the assessment of a toxidrome?
Mental status Vital signs pupil size and reactivity skin color and moisture bowel sounds
How can you distinguish an anticholinergic toxidrome from a sympathomimetic toxidrome?
Both have delirium, psychosis, seizures, increased HR, BP, temperature and pupil size.
In anticholinergic poisoning, the pt has sluggishly reactive pupils, absent bowel sounds and flushed but DRY skin.
Sympathomimetic patients are more likely to be agitated.
What common drugs or intoxicants are poorly absorbed by activated charcoal?
ineffective: alcohol, iron, lithium
poorly effective: hydroxycarbons, metals
What are indications for activated charcoal?
- substance known to bind well
- intact or protected airway (intubated)
- within 60 minutes of ingestion
List possible indications for whole-bowel irrigation
ingestion of metals, lithium ingestion of sustained release medications ingestion of patches massive overdoses concretions of pills body packers or stuffers
Lipid emulsions should be considered (in consultation with a toxicologist) after what ingestions?
bupivacaine verapamil beta-blockers some TCAs chlorpromazine
What factors predict adequate removal of a poison by hemodialysis?
name 5 examples
- small volume of distribution
- little protein binding
- water soluble
- low molecular weight
- low endogenous clearance
- single compartment kinetics
ie: ethylene glycol, lithium, methanol, salicylate, theophylline
Describe the rationale behind urinary alkalinization, what are potential pitfalls?
adminitering sodium bicarb or acetate to raise the urine pH to 8 so that renally excreted toxicants, weak acids, are converted to their ionized form within the proximal tubules and not reabsorbed distally (ion trapping). Used in cases like salicylate, phenobarb poisoning, rhabdomyolysis
pitfalls: inhibited in the presence of hypokalemia, associated with pulmonary and cerebral edema, fluid administration to be monitored carefully
Describe the pathophysiology of acetaminophen poisoning
After acute overdoses of >150mg/kg/day, the typical metabolism expends all glutathione and results in p450 cytochrome oxidase metabolism and N-acetyl-p-benzoquine. The latter metabolite is toxic to hepatocytes and causes centrilobular liver necrosis.
What are the 4 stages of acetaminophen poisoning?
1 (30 minutes-24hrs) often asymptomatic, occasionally nausea, vomiting, diaphoresis, pallor
2 (24-48hrs) nausea, vomiting, RUQ pain, enzymitis
3 (72-96 hrs) fulminant hepatic failure with jaundice, thrombocytopenia, prolonged PTT, hepatic encephalopathy, renal failure, cardiomyopathy
4 resolution
What is the antidote for acetaminophen overdose and how does it work?
N-acetylcysteine (NAC)
it replenishes and substitutes for depleted glutathione stores
best benefit if given within 8 hrs of ingestion, IV over 21 hrs
risk of anaphylaxis
What is the approach to acute salicylate poisoning?
When to start advanced care?
Activated charcoal IV fluids Urinary alkalization (mild alkalemia will reduce access to the brain)
Avoid intubation or at least mimic resp alkalosis (resp acidemia increases transit to brain)
Hemodialysis if metabolic acidosis, pulmonary edema, severe renal impairment, coma or seizures, liver impairment, level >70mg/dL
How does iron produce toxicity? What does it manifest as?
GI stage: vomiting, diarrhea, hypotension (mucosal irritant)
Quiescent stage: stop vomiting and labs worsen
Multiorgan failure with GI hemorrhage and shock (inhibitor of oxidative phosphorylation in the mitochondria)
occasionally 4-6 weeks later gastric scarring with pyloric obstruction
deferoxamine treatment if symptomatic or levels 350-500 can induce hypotension and vin rose pee
no mode of iron excretion (aside from bleeding)
How much iron is toxic? What are the ranges and expected toxicity?
dose ingested: toxicity 20-60mg/kg : mild gastrointestinal symptoms 60-100mg/kg : moderate toxicity 100-200mg/kg : serious toxicity >200mg/kg : possibly lethal
How much iron is present in the following commonly available preparations? ferrous sulphate ferrous gluconate ferrous fumarate Feosol elixir chewable vitamins infant liquid vitamins
ferrous fumarate: 105mg (32% 325mg tab) ferrous sulphate: 65mg (20% 325mg tab) ferrous gluconate: 40mg (12% 325mg tab) Feosol elixir: 44mg/5mL chewable vitamins: 4-18mg infant liquid vitamins: 10mg/mL
What is the antidote for iron poisoning?
Risks?
Deferoxamine, an iron chelator
5-15mg/kg/hr
associated with pulmonary fibrosis and ARDS
List the major toxicities of cyclic antidepressants
- dysrhythmia (sodium channel blockers in cardiac conduction system)
- seizures
- alpha-1 adrenergic blockade
- inhibition of norepinephrine reuptake
- anticholinergic toxicity
What electrocardiographic findings correlate wtih potential toxicity from cyclic antidepressants?
QRS complex > 0.1 seconds
prolonged QTc for age
R wave height greater than 3 mm for age
What treatment to consider for ventricular dysrhythmia with prolonged QRS interval?
consider drug-induced dysrhythmias and give sodium bicarbonate! it has been shown to narrow the QRS and improve function
many agents that cause v-tach in overdose block the fast sodium channels
What ingestions can cause a brady-dysrhythmia and how to treat?
beta blockers
calcium channel blockers
digitalis-containing compounds
clonidine
treat as per PALS: atropine, ephinephrine, pacing
beta blockers -> glucagon, calcium, insulin, lipid emulsions
calcium channel blockers -> calcium, insulin/glucose, lipids
digitalis-containing compounds -> digoxin-specific Fab
How do you treat poison-induced seizures?
Name two special considerations in specific poisoning of cyclic antidepressants and isoniazid
Benzodiazepines 1st line
Barbituates (phenobarbital) 2nd line
in cyclic antidepressant overdose DO NOT give IV phenytoin as cardiovascular effects may be complicated
in isoniazid overdose, they need PYRIDOXINE
Describe the findings in a clonidine overdose
miosis coma apnea bradycardia hypotension ... can mimic opioid ingestion, however clonidine kids often transiently respond to stimulation
Hallucinations or psychosis are prominent in which drugs of abuse?
- anticholinergics (antihistamines, Jimsonweed)
- dissociatives (PCP, ketamine, dextromethorphan)
- hallucinogens (LSD, psilocybin, mescaline)
- sympathomimetics (amphetamines, cocaine, MDMA, bath salts, synthetic cannabinoids)
- withdrawal from ethanol or sedative-hypnotics
Why should neuroleptics be cautiously used in drug-induced agitation?
they lower the seizure threshold, may compound cardiovascular toxicity, may limit ability to dissipate heat
use benzos benzos benzos
Name 7 hyperthermic syndromes in toxicology
1) sympathomimetic
2) anticholinergic
3) neuroleptic malignant syndrome
4) malignant hyperthermia
5) serotonin syndrome
6) uncoupling oxidative phosphorylation (salicylate)
7) acute withdrawal
What findings characterize serotonin syndrome?
autonomic hyperactivity
increased neuromuscular tone (LEs especially)
hyperreflexia
CNS depression
What are bath salts?
synthetic canthiones, related to khat
has similar features to amphetamine overdose
notable for prolonged agitation, aggressive and violent behaviour, hallucinations, paranoia, seizures
How is the osmolar gap calculated?
What is normal
osmolar gap=
measured osmolality - calculated osmolality
calculated osmolality= 2(Na) + BUN + glucose
Normal gap -7 to 10 mOsm
List causes of a large osmolar gap
acetone ethanol glycols isopropanol magnesium mannitol methanol renal failure severe ketoacidemia severe lactic acidemia
What are symptoms of TCA overdose?
What is the treatment?
What should you NEVER give?
Present with altered mental status, anticholinergic toxicity, seizures, wide-complex tachycardias (QRS >100msec).
Treat with NaHCO3, secure airway, activated charcoal if <2hrs.
Do not give:
- procainamide (worsens cardiac delay)
- physostigmine (increases seizures)
- dopamine (ass’ w/ vent dysrhythmias)
What is the antidote of choice for beta-blocker toxicity?
Glucagon
How is the osmolar gap calculated?
What is normal?
2{Na}+BUN+glucose
-7 to 10 mOsm
List potential causes of an osmolar gap
- acetone
- ethanol
- glycols
- isopropanolol
- magnesium
- mannitol
- methanol
- renal failure
- severe ketoacidemia
- severe lactic acidemia
How is alcohol metabolized?
According to zero order kinetics, typically it decreases by 15mg/dL/hr
What are the toxic metabolites of ethylene glycol and methanol?
What tissues do they damage?
How to treat
methanol -> formic acid, toxic to the retina
ethylene glycol -> glycolic and oxalic acids, toxic to the kidneys
alcohol dehydrogenase is responsible for the dangerous transformation, therefore keep it busy with ethanol or fomepizole
adjunctive treatments are folic acid for formic acid
pyridoxine and thiamine for glycolic acids
What characteristics of hydrocarbon ingestion make them prone to aspiration?
What’s the clinical presentation?
- low viscosity
- low surface tension
- high volatility
Children may cough, gag or sputter at the time. Gradually pneumonitis may develop, usually within 6hrs and 98% within 24hrs.
Which hydrocarbons are notable for systemic toxicity?
CHAMPs Camphor Halogenated hydrocarbons (carbon tetrachloride, tricholoethane) Aromatic hydrocarbons (benzene, toluene) Metal-containing hydrocarbons Pesticide-containing hydrocarbons
CNS depression, seizures, hepatotoxicity, nephrotoxicity, bone marrow toxicity
What are the clinical manifestations of organophosphate or carbamate insecticide poisoning?
1) Muscarinic effects (pre&post ganglionic parasympathomimetic)
DUMBELS or SLUDGE with killer B’s
2) Nicotinic effects (preganglionic sympathomimetic)
tachycardia
3) Nicotinic effects (neuromuscular endplate)
muscle fasciculations and weakness
4) CNS system effects
depressed consciousness and seizures
DUMBELS: diarrhea, diaphoresis, urination, myosis, bradycardia and bronchorrhea, lacrimations, salivation
SLUDGE B’s: salivation, lacrimation, urination, diarrhea, GI cramping, emesis, bronchorrhea, bradycardia, bronchospasm
What is the treatment for organophosphate or carbamate poisoning?
Atropine; repeat dose every 5 minutes with doubling (targets muscarinic effects) END POINT OF THERAPY IS THE DRYING OF SECRETIONS **PULMONARY
Pralidoxime (2-PAM) for organophosphates only, dislodges the aged acetylcholine esterase inhibitor (it regenerates active acetylcholinesterases)
Benzodiazepine
What toxins would you consider for hemodialysis?
alcohols
salicylates
theophylline
lithium
NO digoxing, NO TCAs (large volume of distribution)
How do you calculate an anion gap? What is the normal range?
AG= [Na] - [Cl] - [HCO3]
normally <11
What is the antidote for acetaminophen
NAC
What is the antidote for aspirin
NaHCO3 & hemodialysis
What is the antidote for carbamate
atropine and diazepam
not pralidoxime
What is the antidote for warfarin
vitK FFP
What is the antidote for hydrofluoric acid
Calcium, magnesium
What is the antidote for isoniazid
pyridoxine
What is the antidote for TCAs
NaHCO3
What is the antidote for CO
oxygen
hyperbaric oxygen
What is the antidote for beta blockers
glucagon, calcium, insulin, lipid emulsions
What is the antidote for calcium channel blockers
glucagon, insulin, calcium, intralipid
What is the antidote for heavy metals
chelators (BAL, EDTA)
What is the antidote for iron
Defuroximine
What is the antidote for cyanide
hydroxycobalamine
How can you differentiate bradycardic intoxications from digoxin, clonidine, beta-blockers and calcium channel blockers ?
digoxin: hyperkalemia, arrhythmias in atria and ventricle, AV block, give Fab fragments
clonidine: looks like opioid with coma, pinpoint, resp depression. Supportive care
beta-blockers: hypoglycemia, treat with IVF, pressors, glucagon, calcium, insulin… ECMO
calcium-channel blockers: inhibits insulin release therefore hyperglycemia… ECMO
What is the suffix for sulfonylureas?
What is the mechanism of action?
What is the antidote in intoxications?
-ide, like glipizide
increases insulin release from the pancreas
Rx Octreotide (somatostatin analogue) and 2nd line glucagon
What is the differential diagnosis for a wide osmolar gap?
(ShARP)
¤ Sugar (mannitol,sorbitol)
¤ Alcohols(Ethanol, methanol, ethylene glycol, isopropyl)
¤ Renal Failure
¤ Pseudo-hyponatremia (hyperlipidemia, hyperproteinemia)
Name drugs that are readily removed by dialysis
STUMBLED ¤ Salicylates ¤ Theophylline/Caffeine ¤ Uremia ¤ Methanol ¤ Barbiturates ¤ Lithium ¤ Ethylene Glycol ¤ Depakote (Valproic Acid)
Name indications for hyperbaric oxygen therapy in carbon monoxide poisoning
̈ Neuro symptoms: Syncope, Coma, Seizure, Altered Mental Status/Confusion
̈ Acidosis
̈ COHgB >25%
̈ COHgB>20% in pregnancy
What are indications for urine drug screening?
No absolute indications, only relative indications ¤ Child abuse ¤ Acute psychosis NYD ¤ Altered LOC NYD ¤ Drug packer
Which people should drink charcoal quickly?
These People Should Drink Charcoal Quickly Theophylline Phenobarbital Salicylates Dapsone Carbamazepine Quinine
