KC Tox Flashcards
*What drugs cause false positives on urine drug screens?
Dextromethorphan (opiates/PCP)
Diphenhydramine (opiates/PCP)
Labetalol (amphetamines)
Tramadol (PCP)
NSAIDs (PCP/THC)
PPI (THC)
Quinolones (opiates)
Ranitidine (amphetamines)
Basically all the antidepressants
*2 properties of meds that make them able to be dialyzed
- Low molecular weight
- Low protein binding
- Low volume of distribution
- Low plasma clearance
- Low dialysate concentration
- High water solubility
*7 toxicologic causes of seizure besides alcohol and withdrawal states (different categories)
Seizures (OTIS CAMPBELL)
O organophosphates, oral hypoglycemics
T tricyclic antidepressants
I isoniazid, insulin
S sympathomimetics, strychnine, salicylates
C camphor, cocaine, carbon monoxide, cyanide, chlorinated hydrocarbons
A amphetamines, anticholinergics
M methylxanthines (theophylline, caffeine), methanol
P phencyclidine (PCP), propranolol
B benzodiazepine withdrawal, botanicals (water hemlock, nicotine), bupropion, GHB
E ethanol withdrawal, ethylene glycol
L lithium, lidocaine
L egad, lindane
*List 4 indications for emergent hemodialysis (drugs)
Dialyzable toxins
STUMBLED
S salicylates
T theophylline
U uremia
M metformin/methanol
B barbiturates
L lithium
E ethylene glycol
D Depakote (valproic acid—in massive overdose)
*List 3 reasons favouring GI decontamination
Early presentation, no antidote, deadly poisoning
*3 methods you could use to decontaminate (PO ingestion CCB)
Gastric lavage, charcoal, WBI
*2 contraindications to GI decontamination in an overdose patient
Delayed presentation, effective antidote
*List 3 potential adverse consequences of GI decontamination
Aspiration, perforation, laryngospasm, bradycardia (vagal), lytes disturbances, bradycardia, epistaxis
*List 3 toxic mechanisms of theophylline
PDEi, beta-agonist, alpha-agonist
*List 5 major clinical manifestations of severe theophylline toxicity
Seizures, dysrhythmias, N/V/D, hypotension, coma
*What is the most common cause of death in theophylline toxicity?
Dysrhythmias
*What is the definitive treatment of choice in theophylline toxicity?
Dialysis
List 3 tox agents that cause miosis and 3 that cause mydriasis
Miosis COPS:
Cholinergics, clonidine, carbamates
Opioids, organophosphates
Phenothiazines (antipsychotics), pilocarpine, pontine hemorrhage
Sedative hypnotics
Mydriasis SAW:
Sympathomimetics
Anticholinergics
Withdrawal syndromes
List 5 agents that can cause coma or seizures
LETHARGIC
Lead, lithium
Ethanol, ethylene glycol
Tricyclic antidepressants, thallium, toluene
Heroin, hemlock, hepatic encephalopathy, heavy metals, hydrogen sulfide
Arsenic, antidepressants, anticonvulsants, antipsychotics, antihistamines
Rohypnol, risperidone
GHB
Isoniazid, insulin
Carbon monoxide, cyanide, clonidine
List the toxins associated with each of the following smells
Bitter almonds
Carrots
Fruity
Garlic
Mothballs
Pears
Oil of wintergreen
Rotten eggs
Bitter almonds = cyanide
Carrots = water hemlock
Fruity = DKA, isopropanol
Garlic = organophosphates, arsenic
Mothballs = camphor
Pears = chloral hydrate
Oil of wintergreen = methylsalycylate
Rotten eggs = sulfur
List ingestions associated with bradycardia
PACED
Propranolol, poppies (opioids), physostigmine
Anticholinesterase drugs, antiarrhythmics
Clonidine, calcium channel blocks
Ethanol or alcohols
Digoxin
List ingestions associated with tachycardia
FAST
Free forms of cocaine
Anticholinergics, antihistamines, antipsychotics, amphetamines, alcohol withdrawal
Sympathomimetics (cocaine, caffeine, amphetamines, PCP)
Theophylline, TCAs, thyroid hormones
List ingestions associated with hypothermia
COOLS
Carbon monoxide
Opioids
Oral hypoglycemics, insulin
Liquors (alcohol)
Sedative-hypnotics
List ingestions associated with hyperthermia
NASA
NMS
Antihistamines, alcohol withdrawal
Salicylates, sympathomimetics, serotonin syndrome
Anticholinergics, antidepressants, antipsychotics
List ingestions associated with hypotension
CRASH
Clonidine, calcium channel blockers
Rodenticides
Antidepressants, antihypertensives
Sedative-hypnotics
Heroin or other opioids
List ingestions associated with hypertension
CT SCAN
Cocaine
Thyroid supplements
Sympathomimetics
Caffeine
Anticholinergics, amphetamines
Nicotine
List ingestions associated with tachypnea
PANT
PCP, paraquat, pneumonitis
ASA
Noncardiogenic pulmonary edema, nerve agents
Toxin induced metabolic acidosis
List ingestions associated with slow respirations
SLOW
Sedative-hypnotics (barbiturates, benzos)
Liquor (alcohol)
Opioids
Weed (marijuana)
List substances that can cause a wide anion gap metabolic acidosis
A CAT MUD PILES
Alcohol ketoacidosis
Cyanide, CO, colchicine
Acetaminophen
Toluene
Paraldehyde, phenformin
Isoniazid, iron, ibuprofen
Lactic acidosis
Ethylene glycol
Salicylates
Methanol, metformin, massive ingestions
Uremia
Diabetic ketoacidosis
How do you calculate anion gap
Na - (HCO3 + HCL)
Elevated if >12
List causes of metabolic acidosis without an anion gap
Loss of bicarb (diarrhea, renal tubular acidosis)
Gain of chloride (ammonia, calcium chloride)
HARDUP
Hyperalimentation
Acetazolamide
RTA
Diarrhea
Ureteroenterostomy
Pancreatoenterosomites
List potentially lethal toxins where activated charcoal should be used
Killer Cs
Cyanide, colchicine, calcium channel blockers, cyclic antidepressants, cardio glycosides, cyclopeptide mushrooms (amanita phalloides), cocaine, cicutoxin, salicylates
List substances that do not bind to activated charcoal
PHAILS
Pesticides, hydrocarbons, heavy metals, acid/alkalis, iron, lithium, solvents
List substances amenable to multidose activated charcoal
ABCDQ (drugs with significant enterohepatic circulation)
Aminophylline/theophylline
Barbiturates
Carbamazepine, concretion forming drugs ex. Salicylates
Dapsone
Quinine
List 3 substances amenable to serum alkalinization
Salicylates, methotrexate, phenobarbital
List 3 mechanisms for intravenous fat emulsion
Lipid sink
Enhance cardiac metabolism of free fatty acids
List drugs amenable to lipid emulsion
Refractory beta blocker overdose, calcium channel blocker overdose, bupropion, cocaine toxicity
List the antidotes for each of the following
Acetaminophen
Methanol/ethylene glycol
Organophosphates
Iron
Arsenic
Isoniazid
Acetaminophen = N-acetylcysteine
Methanol/ethylene glycol = fomepizole
Organophosphates = atropine/pralidoxime
Iron = deferoxamine
Arsenic = Dimercaprol (BAL)
Isoniazid = pyridoxine
How do you calculate serum osmols
2*Na + BUN + glucose
List 4 causes of al elevated osmolar gap
ethylene glycol, methanol, acetone, mannitol, polyethylene glycol (IV lorazepam), ketosis (diabetic, alcoholic), renal failure, multi-organ failure, IVIG, pseudohyponatremia, uremia
List 3 causes each of Type A and Type B lactic acidosis
Type A: poor perfusion: sepsis, mesenteric ischemic, hemorrhage
Type B: no hypoperfusion
- Metformin, DKA
- Seizure
- Alcohol: liver dysfunction, alcoholic ketosis, toxic alcohols
- Mitochondrial defects
- Drug s/e: Ventolin, propofol
- Tox: salicylate poisoning, carbon monoxide, cyanide, massive Tylenol
List 4 toxins that are radio-opaque
CHIPES: Calcium carbonate, heavy metals (Fe), iodized toxins (thyroxine), packer/potassium/psychotropics, enteric coated pills (ASA, slow K), solvents (halogenated hydrocarbons)
List 3 methods of GI decontamination
orogastric lavage, charcoal, whole bowel irrigation
What is the dose of activated charcoal
1g/kg PO (usually 50g) or 10g AC per 1g of toxin in a single dose
What is the dose of whole bowel irrigation
PEG 100ml/hr titrated up to 1-2L/hr until rectal effluent is clear
You are 100-1000% going to shit your pants
For what toxins is decontamination with water contraindicated
metals (potassium, magnesium, sodium) as these can ignite on contact with water
List 3 methods of elimination
Urine alkalinization, MDAC, dialysis
What is the dose for multi dose activated charcoal
loading dose (10:1) followed by 50% of initial dose every 4-6 hours for 24 hours
List 4 ingestions associated with wide complex QRS
TCAs, type 1a and 1c antidysrhythmic, cocaine, diphenhydramine
List 5 ingestions associated with hypoglycemia
Oral hypoglycemic agents, sulfonylureas, insulin
Beta blockers, isoniazid, salicylates, ethanol
List 5 one pill can kill ingestions
ABC GET MOM
A - ASA
B - BBs
C - CCBs, clonidine, cardiac glycosides, colchicine, camphor
G - glucose lowering (sulfonylureas)
E - EG
T - TCAs, Theophylline
M - methanol
O - opioids
M - MAOIs, metals (iron, lead)
List 3 side effects of levamisole
agranulocytosis, leukoencephalopathy, cutaneous vasculitides
List 4 causes of a double gap
methanol, ethylene glycol, diabetic ketoacidosis, alcoholic ketoacidosis, uremia, septic shock, multiorgan failure
*What are the 4 stages of Ethylene Glycol toxicity?
1 - acute neurologic stage, 30 min - 12 hours
2 - cardiopulmonary stage, 12 - 24 hours
3 - renal stage, 24 - 72 hours
4 - delayed neurologic stage, bulbar palsy, 5 - 20 days
*What are the 3 toxic metabolites of ethylene glycol?
- Glycolic acid
- Glyoxylic acid
- Oxalic acid
*What are the 3 highly effective treatments for ethylene glycol toxicity and how do they work
- Sodium bicarbonate: Correcting metabolic acid may increase urinary excretion of EG and delay calcium oxalate- induced AKI
- Fomepizole/Ethanol: ADH blockade prevents metabolism of EG into toxic metabolites
- Dialysis: Removal of EG in the setting of acidosis (pH < 7.3)/renal failure/serum EG level > 8.1 mmol/L (level taken from Toxinz)
*What are the 2 vitamins that you can also give in ethylene glycol toxicity?
1) Pyridoxine
2) Thiamine
How do you adjust your anion gap for albumin
Albumin corrected anion gap = anion gap +2.5*(normal albumin-measured albumin)
Albumin is a negative charged protein. AG will be lowered in the presence of hypoalbuminemia, thereby masking an elevated AG - a normal AG may actually represent a metabolic acidosis
What is an abnormal anion gap
12
Normal gap 6-14, elevated if >12
How do you calculate your osmolar gap?
Osmolar gap = measured serum osmolarity – calculated serum osmolarity
Calculated serum osmolarity = 2Na + Glucose + BUN + 1.2EtOH
What is an abnormal osmolar gap
> 10
What is the delta gap?
Delta gap = (change in anion gap) - (change in bicarb)
Delta gap = (AG-12)-(24-HCO3-)
Determines if the anion gap is accounted for by the change in Bicarb
Positive delta gap = delta AG > delta bicarb = metabolic acidosis + metabolic alkalosis
No delta gap = delta AG = delta bicarb = pure AGMA
Negative delta gap = delta AG < delta bicarb = AGMA + non anion gap metabolic acidosis
What is Winter’s equation and when is it used?
PaCO2 = (1.5*serum HCO3-) + (8 +/- 2)
Used to calculate the expected arterial PCO2 for the serum bicarbonate level
Tells us if there is a mixed picture
Which two alcohols are toxic alcohols
Methanol and ethylene glycol
For methanol describe 1) common substances containing it 2) metabolism 3) clinical presentation 4) lab findings 5) management
1) Contained in windshield wiper fluid, de-icing products, paint removers, antifreeze, camping stove fluid
2) Methanol -> formaldehyde -> formic acid
3) Neurologic symptoms including optic neuritis, parkinsonism, ataxia, confusion
4) Labs show elevated osmolar gap and acidosis
5) Treated with fomepizole, folic acid 50mg, dialysis
For ethylene glycol describe 1) common substances containing it 2) metabolism 3) clinical presentation 4) lab findings 5) management
1) Found in radiator fluid, antifreeze, metal cleaners
2) Ethylene glycol -> glycolaldehyde -> glycolic acid -> oxalic acid
3) Stage 1 CNS, mimics alcohol intoxication. Stage 2 cardiopulmonary with myocardial dysfunction. Stage 3 renal failure with ATN from calcium oxalate crystals. Stage 4 late neurological sequelae i.e. bulbar palsy
4) Labs show elevated osmolar gap and acidosis. Typically high lactate. Hypocalcemia with calcium oxalate in the urine
5) Treated with fomepizole, pyridoxine 100mg, thiamine 100mg, dialysis
For isopropyl alcohol describe 1) common substances containing it 2) metabolism 3) clinical presentation 4) lab findings 5) management
1) Found in rubbing alcohol, hand sanitizer
2) Isopropyl alcohol -> acetone -> acetol
3) Intoxication, more prolonged than EtOH, fruit odor on breath
4) Ketosis and elevated osmolar gap without acidosis
5) Supportive care. No fomepizole as the metabolite is no more toxic than isopropyl alcohol itself. Fomepizole will only prolong CNS depression
How fast does ethanol metabolize
5.5 mmol/hr
What are the treatment goals in toxic alcohol
1) correction of acidosis 2) inhibition of the production of toxic metabolites 3) elimination of parent alcohol and its toxic metabolites
Is there a role for GI decontamination in toxic alcohol?
No; quickly absorbed
What are the indications for fomepizole
Methanol concentration > 6.2 mmol/L,> 3.2 for ethylene glycol
Hx of methanol or EG ingestion with an osmol gap >10
Suspected methanol or EG ingestion with at least 2 of: pH <7.3, Co2 level <20, urinary oxalate crystals present, osmolar gap >10
What is the dose of fomepizole
15mg/kg over 30 mins, then 10mg/kg over 30 mins q12 for the first 48 hours (x 4 doses) then 15 mg/kg q 12
List indications for hemodialysis in toxic alcohol
*Elderly man with alcohol use, memory impairment, wide based gait, nystagmus, ataxia. What is the likely diagnosis and treatment?
Wernicke-Korsakoff syndrome
Treatment: Thiamine and magnesium repletion
*Ddx Wernicke’s (6)
Stroke
Hepatic encephalopathy
Encephalitis
Intox
Brain tumour
Dementia
*What single lab test would be most likely to predict severe liver dysfunction in chronic EtOH use?
- AST/ALT ratio > 2 – MOST SPECIFIC TO ALCOHOL
*List three physical exam findings of Wernicke’s encephalopathy
Classic triad:
- Altered mental status
- Oculomotor dysfunction
- Gait ataxia
*List 10 side effects of ETOH withdrawal, as per the CIWA score
- Nausea or vomiting
- Tremor
- Paroxysmal sweats
- Anxiety
- Tactile disturbances
- Auditory disturbances
- Visual disturbances
- Headache
- Agitation
- Orientation and clouding of sensorium
*4 mechanisms of seizures related to alcohol use
- Withdrawal (alcohol or drugs)
- Neuro Exacerbation of idiopathic or post-traumatic seizures
- Infectious (meningitis, encephalitis, brain abscess)
4.Trauma (intracranial hemorrhage) - Metabolic (hypoglycemia, hyponatremia (Beer potomania), hypernatremia, hypocalcemia, hepatic failure)
*5 specific treatments that address the specific pathophysiology of alcohol withdrawal
- benzo: ativan, diazepam (1mg ativan = 5mg diazepam), switch to other agent after 400mg
- propofol
- phenobarb
- dexmedetomidine (for refractory)
- ketamine (for refractory)
- Thiamine (+magnesium)
*ETOH user. Dx AKA. What are the calculations for AG and DG
AG: [Na+] - ([Cl−] + [HCO − ])
Delta gap = (change in anion gap) - (change in bicarbonate) … (Anion gap - 12) - (24 - bicarbonate)
*What are FOUR causes of a double-gap acidosis (anion gap with osmolar gap)?
- Alcoholic/starvation ketoacidosis
- Diabetic ketoacidosis
- Ethylene glycol toxicity
- Methanol toxicity
*Describe the pathophysiology of alcoholic ketoacidosis.
1 - Long-standing ethanol user abruptly stops drinking (acute starvation on top of malnutrition)
2 - Ketones are generated (ketogenesis blocked by drinking) and accumulation of β-hydroxybutyrate and the inhibition of gluconeogenesis
*Treatment of AKA
- Fluids (D5NS)
- Thiamine
- Electrolyte replacement
- Correction of acidosis (should correct with above)
*In AKA, serum levels of which of the following would be elevated or depressed? Insulin, Ketones, Catecholamines, Lipolysis
Insulin - down
Ketones - up
Catecholamines - up
Lipolysis - up
What is the metabolism of alcohol
Alcohol by AHD -> alcohol dehydrogenase -> acetaldehyde -> acetyl coenzyme A _ CO2 + H20 (acetate)
What is the legal limit of alcohol
17 mmol/L
What is the pathophysiology of alcohol withdrawal
Decrease in GABA with the cessation of alcohol. Low GABA and high glutamate cause CNS excitation
What are the stages of alcohol withdrawal
Stage 1 (12-18hrs onset): shakes, sweating, agitation, anorexia, anxiety
Stage 2 (12-24): seizures
Stage 3 (12-24, often later): hallucinations
Stage 4: (3-5 days): delirium tremens
What is delirium tremens
Life threatening form of alcohol withdrawal characterized by altered sensorium (confusion, delusions) + autonomic hyperactivity (fever, tachycardia, hypertension)
Describe an approach to manage alcohol withdrawal
Diazepam 10-20mg PO or IV q15 until tachycardia is resolved and patient is comfortable. Phenobarbitals 5-10mg/kg (~65mg, can double each dose) as a second line agent
Alternatives would be to follow the CIWA protocol and give benzos if score >10
List 3 medications that can be used as anti relapse drugs in alcohol withdrawal
Naltrexone, gabapentin, disulfiram, acamprosate
List 10 long term effects of alcohol use
Neurological: withdrawal seizures, polyneuropathy, tremor, cerebellar dysfunction, ataxia, Wernicke’s, Korsakoff
Cardiovascular: increased HR/HTN, contribute to CAD and arrhythmias ex. Holiday heart
Resp: increased pneumonia, often concurrent smoking
GI: esophagitis, GERD, GI bleeding from varices, alcoholic hepatitis (AST/ALT >2), cirrhosis, pancreatitis
ID: immunosuppression
Heme: anemia, leukopenia, thrombocytopenia
Metabolic: hypoglycemia (likely due to starvation and depletion of liver glycogen stores) electrolyte deficiencies
List the components of the CAGE questionnaire
desire to cut back, annoyed when people ask, guilty about drinking, eye opener in the morning
What are the safe drinking guidelines
2023 Canadian guidelines
0 - health benefits, sleep benefits
1-2 - likely avoid harms
3-6 - increase CA risk (breast and colon)
>7 - increase MI and stroke risk
Don’t have more than 2 on one day per week
0 in pregnancy
List the components of SBIRT
Screening, brief intervention, referral to treatment
*Table of 4 stages of APAP toxicity
Stage 1 = Pre – Injury (<24hrs – 36hrs)
Asymptomatic
Possible N/V/Abdo Pain
Stage 2 = Liver Injury (8 – 36hrs)
N/V/Abdo Pain
Elevated AST/ALT
Stage 3 = Maximal Liver Injury (2-4 days)
Fulminant hepatic failure (enceph / coagulopathy / acidosis etc)
Stage 4 = Recovery (> 4 days)
Death or recovery
*4 criteria for liver transplant (APAP toxicity)
Kings College criteria:
pH < 7.30
INR > 6.5 (PT > 100 sec)
Creatinine 300 µmol/L
Grade III or IV hepatic encephalopathy
*Patient meets Kings College transplant criteria on BW. 6 things to do in the ED while waiting.
- IV crystalloid resuscitation
- IV NAC
- Intubation
- Consult transplant service
- Consult nephrology service regarding hemodialysis
- Regular monitoring of CBC/INR/PTT/VBG/glucose/LFT
*APAP level is zero. 2 reasons to still give NAC
For delayed, chronic, or supratherapeutic toxicity, NAC therapy should continue until acetaminophen is undetectable in the serum (<10 mcg/mL) AND:
- Any signs of liver injury have resolved (ie, encephalopathy has cleared, normalization of the coagulation profile, resolution of metabolic acidosis)
- AST is less than 1000 IU/L with demonstration of a downward trend
*If APAP is zero (pre-Tx) how is NAC still useful?
Decreases rates of cerebral edema, hypotension and death
*Describe the metabolism of APAP
Glucuronidation (50% range 40-67%)
Sulfation (30% range 20-46%)
CYP (~10%); this is what produces NAPQI
Direct Renal Clearance (~10%)
*What drug is used as an antidote to acetaminophen toxicity? List 3 ways in which it works.
Decrease toxic / free NAPQI
Glutathione precursor
Glutathione substitute
Direct reduction of NAPQI-APAP
Increase Sulfation route
Free radical scavenger
Hepatocyte stabilizing effect
*Describe the Rumack Matthews nomogram. What are 2 situations in which it is inapplicable? Describes level at which hepatic injury is likely.
Reference graph plotting serum APAP level and time in hours.
At 4h - levels greater than 1000 umol/L toxic
8h - greater than 500
12h - greater than 250
Not to be used in chronic ingestions, extended release preparations, co-ingestions etc.
*Acute EtOH ingestion increases the risk of Tylenol ingestion (T/F)
Chronic EtOH ingestion increases the risk of Tylenol ingestion (T/F)
False - CYP inducer is busy so less NAPQI is produced
True - more NAPQI is produced
*Concomitant ingestion of cimetidine is likely to worsen Tylenol toxicity (T/F)
10‐15% of Tylenol is metabolized by CYP450 pathway (T/F)
False (CYP450 inhibitor)
True
*Glucuronidation exceeds sulfonation metabolic pathway for Tylenol metabolism in adults (T/F)
Sulfonation exceeds glucuronidation as the dominant pathway in kids (T/F)
True
True
What is a massive Tylenol ingestion
> 500mg/kg or >50gm or acetaminophen ingestion + rapid onset of lactic acidosis, hyperthermia, hyperglycemia, altered mental status
List 4 risk factors for severe Tylenol toxicity
chronic use, chronic EtOH, pre-existing liver disease, malnourished, other CYP meds (ex. Rifampin, phenobarbital, phenytoin)
When should acetaminophen levels be measured
4 hours after ingestion and q4 hours until peaked
What Tylenol ingestion is likely toxic
200mg/kg or ~ 10-12g [OPC]
List indications for NAC
Acetaminophen level about the treatment line, chronic acetaminophen toxicity with signs of toxicity (clinical symptoms, elevated AST x2 limits, elevated APAP), clinical suspicion for massive ingestion, unable to get APAP level back within 8 hours of ingestion, acetaminophen ingestion + elevated liver enzymes
What is the dose for NAC
Will vary based on local poison control protocol
3% NAC 60mg/kg/hr for 4 hours + 6mg/kg/hr (max 600mg/hr) until stopping criteria reached
What is the stopping criteria for NAC
Tylenol level is undetectable AND
N-acetylcysteine has been given for at least 12 hours AND
AST/ALT <100 and falling and INR <2
What are the indications for dialysis in Tylenol poisoning
APAP >1000mg/L or 6620 umol/L without NAC
APAP >700mg/L or 4630 umol/L with altered mental status, acidosis, elevated lactate and without NAC
APAP >900mg/L or 5960 umol/L with altered mental status, acidosis, elevated lactate with NAC
*List 3 reasons why the elderly are at increased susceptibility to ASA toxicity.
Decreased liver blood flow limits biotransformation of salicylate
Decreased renal function reduces salicylate clearance
Chronic ingestion decreases albumin binding, increasing the free salicylate that can enter the cell, and allows salicylates more time to pass through the blood-brain barrier.
*Explain why serum level of ASA is incongruent with degree of symptoms
Falling concentration may reflect redistribution rather than clearance
List 4 products that contain salicylates
ASA, oil of wintergreen methyl cold products, bismuth (pepto bismol)
What is a toxic dose of ASA
200mg/kg or ASA 10-30g
List 4 clinical signs of asa toxicity
Tachypnea, hyperpnea, hyperthermia
Resp: pulmonary edema
GI: Abdo pain, nausea/vomiting
Neuro: altered mental status, irritability, ototoxicity
Heme: coagulopathy
Describe the progress of the acid base status in a patient with salicylate toxicity
Respiratory alkalosis 0-4 hrs - tachypnea from stimulation of the medulla.
Neutral 2-12 hours - metabolic acidosis from uncoupling of oxidative phosphorylation + metabolic alkalosis from vomiting
Metabolic acidosis 6-12 hours - respiratory acidosis if preterminal due to respiratory muscle fatigue
Why can chronic salicylate toxicity present with lower serum levels
serum levels may underestimate the severity of the intoxication because salicylate has already accumulated in the brain
List 6 management priorities in ASA toxicity
- GI decontamination
- IV fluids
- Urine alkalinization
- Glucose supplementation
- Potassium correction
- Dialysis if refractory
Describe the process for urinary alkalinization with targets
1-2 mEq/kg bicarb bolus then bicarb drip (3 amps of sodium bicarb in 1L D5 with 40mEq at 2.5*maintenance)
Target urine pH 7.5-8.0 and serum pH of 7.55
What are the indications for urinary alkalinization
Acute ASA level >3.5 [OPC]
Chronic ASA level >2.9
ASA ingestion + clinical symptoms
How does urinary alkalinization work
Salicylate are acidic and readily ionize in an alkali environment
Only the non ionized state can traverse cell membrane and cause toxicity. The non ionized state is the one that causes clinical harm
Once ionized in the urine they are ’trapped’ there
Alkaline urine traps the salicylate on and increased excretion
Reduces reabsorption of salicylate molecules and encourages secretions down a concentration gradient
List indications for dialysis in salicylate toxicity
Salicylate >7.2 mmol/L or >6.5 mmol/L in the presence of impaired kidney function
Salicylate toxicity + altered mental status, hypoxia,
Failure of standard therapy (ex. urine alkalinization)
In general, lower threshold for chronic ingestions
Discuss an approach to intubation a patient with salicylate toxicity
Caution as it is difficult to match the patient’s ventilation. If intubation is necessary:
- VBG beforehand
- Bicarb boluses before hand
- Intubation without paralysis
- Bag during the apneic period
- Match pt’s pre intubation RR on the vent
Describe the physiology of an anticholinergic overdose
Anticholinergic ingestions antagonize the muscarinic receptors (ex. Salivary glands, SA node, pupils, skin)
Do not affect the nicotinic receptors at the neuromuscular junction
List 5 examples of anticholinergic agents. Include 3 plants
Diphenhydramine, toxic at >2.5mg/kg, also act as a sodium channel blocker
TCAs, toxic at >2,5mg/kg, also act as a sodium channel blocker
Antihistamines
Antipsychotics
Antiparkinsonian agents ex. Cogentin
Atropine, scopolamine, glycopyrrolate
Antiemetics dimenhydrinate
Jimson weed, belladonna, amanita mushrooms
List 5 clinical signs of anticholinergic toxidrome
“Dry as a bone (dry mucous membranes, decreased motility, urinary retention, dry skin), hot as a hare, red as a beet, mad as a hatter, blind as a bat (mydriasis)”
Tachycardic, hypertensive, hyperthermic
Warm, dry skin
Large pupils
Delirium, agitation, hallucinations, picking gestures, myoclonus
What is a diagnostic and therapeutic agent that can be used in anticholinergic toxidrome, along with its dose
Physostigmine 0.5-2mg IV slow bolus over 5 mins[OPC] [1-2mg IV in Rosens]
What is the mechanism of action of physostigmine? What is one important pharmacological feature?
Acetylcholinesterase inhibitor, allowing for acetylcholine accumulation and competition with the antimuscarinic blocking agents. Crosses the blood brain barrier so can reverse the central and peripheral anti-muscarinic effects
What are the contraindications to physostigmine
wide QRS, narrow angle glaucoma, bradycardia or heart block, seizures, salicylate allergy, ileus, urinary retention, asthma
Will worsen any existing cholinergic symptoms
*What are 6 symptoms of SSRI discontinuation syndrome
The mnemonic FINISH summarizes the symptoms of antidepressant discontinuation syndrome:
Flu-like symptoms (lethargy, fatigue, headache, achiness, sweating),
Insomnia (with vivid dreams or nightmares),
Nausea (sometimes vomiting),
Imbalance (dizziness, vertigo, light-headedness),
Sensory disturbances (“burning,” “tingling,” “electric-like” or “shock-like” sensations) and
Hyperarousal (anxiety, irritability, agitation, aggression, mania, jerkiness).
*FOUR mechanisms of TCA toxicity
7 mechanisms
- Na channel blockade (wide QRS)
- K Efflux blockade (prolonged QT)
- Alpha 1 blockage (hypotension)
- Amine reuptake inhibition (norepinephrine, serotonin - serotonin syndrome)
- Anticholinergic (muscarinic - hot as a hair, mad as a hatter)
- Antihistamine (sedation, altered LOC)
- Indirect GABA antagonism (CNS, seizure)
*An 18 year old with her life together decides to OD on citalopram and amitriptyline. The patient is tremulous, altered GCS with ECG changes. Her pupils are dilated, and she is hyper-reflexic. She his hyperthermic. Given her 2 ingestions, outline your initial pharmacotherapy and Rx if refractive.
- Benzodiazepine
- Sodium bicarbonate
- Phenobarbital/Propofol
- Intralipid
*Complications of TCA toxicity (4)
- Prolonged QT
- Delayed Seizures
- Ventricular Tachycardia
- Serotonin Syndrome
*What is one medication you could use to counter the serotonergic effects of citalopram, following supportive care and benzodiazepine use?
Cyproheptadine
*List 6 txs which can be used in TCA OD
Cooling
IVF
Benzos
Bicarb + potassium
Hypertonic saline
Lidocaine
Intralipid
Propofol
Two alternatives to Bicarb, one extra that goes with bicarb
List 5 medications that may cause serotonin syndrome
SSRIs: escitalopram, citalopram, fluoxetine, paroxetine, sertraline
SNRIs: Duloxetine, venlafaxine
TCA: amitriptyline MAOIs: Selegiline, Rasagiline
Metoclopramide, Linezolid, Tramadol
Cocaine, NMDA, LSD, St. John’s wort
What is the Hunter criteria for serotonin syndrome
In the setting of exposure to a known serotonergic agent, serotonin syndrome can be diagnosed in the presence of any of:
Spontaneous clonus
Inducible clonus AND agitation/diaphoresis
Ocular clonus AND agitation/diaphoresis
Tremor and hyperreflexia
Elevated temp AND ocular or inducible clonus
SETH - vowels in the middle
What symptoms are seen with serotonin syndrome
Triad of symptoms
- Psychiatric - confusion, altered LOC, agitation, restlessness
- Autonomic - increased BP, HR, nausea, vomiting, sweating, hyperthermia
- Neurologic - tremor, myoclonus, hyperreflexia, ocular flutter
How would an SNRI overdose present compared to an SSRI overdose
Similar presentations
Risk of more serious overdose with more cardiac complications (prolonged Qtc and prolonged QRS) with an SNRI overdose
List 4 ECG findings that may be seen in TCA overdose
Prolonged QRS, R/S ratio >0.7, R wave >3mm
R bundle branch block, Brugada pattern, rightward access
Prolonged QTC
Tachycardia
List 4 management priorities in TCA overdose
Sodium bicarbonate for wide QRS
Correction of acidemia target pH 7.50-7.55
Benzos for agitation or seizures
Fluid for hypotension
Activated charcoal if within 2 hours
List 3 management steps for cardiac TCA toxicity refractory to sodium bicarbonate
Hypertonic saline (100ml bolus of 3%) if cannot give bicarb due to alkalemia or hypernatremia
Lidocaine 1 mg/kg; also acts a sodium channel blocker so will compete with TCA
Intralipid if cardiac arrest
Magnesium for prolonged Qtc
Why is sodium bicarb ineffective in bupropion overdose
Wide QRS is due to blockage of potassium channel and cardiac gap junction; NOT sodium channels
What one clinical symptoms is most likely in bupropion overdose
Seizure
List 3 mechanisms of MAO toxicity
Explain the first mechanism in detail
- Drug food interactions/hypertensive crisis
- Dietary tyramine in cheese, pickles, alcohol, soy sauce, sausage
- Tyramine is a sympathomimetic amine that is usually broken down by MAO
- When MAO A is inhibited tyramine is systemically absorbed causing the release of norepinephrine and serotonin, leading to a hypertensive crisis
- Tyramine syndrome presents as headache, hypertension, flushing, diaphoresis - Drug interactions (amphetamines, phenylephrine/ephedrine)
- Overdose
List 5 drugs that can cause sodium channel blockade
TCA
Type 1a antiarrhythmic: quinidine, procainamide
Type Ic antiarrhythmic: flecainide
Cocaine
Antimalarial: chloroquine
Anesthetic
Other: propranolol, carbamazepine, quinine, certain antipsychotics, gravol, phenytoin (don’t use in Na block-induced seizures)
*4 ECG abnormalities of obvious dig toxicity
- Atrial fibrillation with slow, regular ventricular rate (AV dissociation)
- Nonparoxysmal junctional tachycardia (rate 70 to 130 beats/min)
- Atrial tachycardia with block (atrial rate usually 150 to 200 beats/min)
- Bidirectional ventricular tachycardia
*5 initial treatments in dig toxicity (patient with hyperkalemia and AKI)
Digibind
Temporize bradycardia with atropine
Watch the K+ (helps guide acute Fab treatment or chronic OD’s need repletion)
Correct the Mg+
Temporizing measures while waiting for DigiFab:
Consider pacing and cardioversion (avoid if possible!)
Consider Phenytoin or lidocaine for tachydysrhythmias
Caution with calcium (theoretical risk of stone heart)
*5 commonly accepted indications for digibind
History:
Other cardiac toxic drug ingestion – CCB, BB, TCA with shock
Acute ingestion > 10 mg plus clinical toxicity
Ingestion of plant containing cardioactive steroids plus dysrhythmias
Physical:
Too fast and deadly: unstable ventricular dysrhythmias (not PVCs)
Too slow and deadly: unstable dysrhythmias (hemodynamic compromise) such as symptomatic sinus bradycardia, or second- or third-degree heart block unresponsive to atropine.
Cardiac arrest
Labs:
Serum potassium level above 5.0 mEq/L (acute ingestion)
Acute steady state > 12 nmol/L and one clinical sign or chronic >7 nmol/L
Any serum level > 19 nmol/L (this is not a steady state level, will change after drug distributes)
*6 classes of medications that can cause acute decreased LOC in a toddler
Benzodiazepines
EtOH
Cannabis
Cardioactive steroids
BB
CCB
Opioids
Hypoglycemics
…
*4 medications that can cause bradycardia and hypotension in a toddler
Clonidine
BB
CCB
Digoxin
*List 4 pharmacologic treatments (empirically) that you would try and their specific MOA for an unknown antihypertensive OD
IV fluids → increase preload
Atropine → anticholinergic, increases firing through SA and AV node
Calcium → replaced depleted intracellular calcium
High dose insulin + glucose → provides substrate to heart, may be inotropic
What is the pathophysiology of digoxin toxicity
Paralyzes the Na/K/ATP pump. Potassium cannot enter the cells, conduction is depressed through the AV node creating AV blocks/bradyarrhythmias, and Purkinje fibres are more sensitive to electrical stimulation creating enhanced automaticity
Also why you get hyperkalemia - none of the K can get into cells just sits outside can be over 10
List 10 symptoms of digoxin toxicity
General: weakness, fatigue, malaise
GI: nausea and vomiting, abdominal pain, diarrhea
Optho: blurry or snowy vision, photophobia, visual changes to colour
Neurologic: dizziness, headache, confusion, hallucinations, parasthesias, seizures
Cardiac: bradyarrhythmia, tachyarrhythmia, PVCs
List 5 risk factors for chronic digoxin toxicity
Drug-drug interactions (antibiotics, diuretics, other cardiac meds), declining renal function, electrolyte imbalance, hypothyroidism, elderly, female patient
List 2 way of calculating digiFab
1) Serum dig level 5.6 L/kg kg /1000
2) # of vials = [(PO digoxin in mg)0.8]2
- 1 vial brings down the dig level by 0.5 mg
List examples of B1 and B2 receptors
B1: myocardium, kidney, eye - increases inotropy, chronotropy, renin release, aqueous humour production
B2: bronchial and visceral smooth muscle - increases bronchodilator, vasodilation
Describe the naming convention for beta blockers
A-M cardioselective block B1 ex. Atenolol, metoprolol
N-Z nonspecific B1 and B2 (can cause bronchospasm in asthmatics) ex. Nadolol, propranolol
Olol - pure beta blocker
Vowel -lol alpha and beta blocker ex. Labetalol
Describe a stepwise approach to managing beta blocker overdose
Supportive care:
IVF
GI decontamination if large overdose
Atropine 1mg IV
Calcium supplementation
Treatment:
Glucagon 5-10mg IV bolus
High dose insulin
- 0.5-1U/kg IV bolus then 1-10 U/kg/hr titrate to effect
- 1g/kg IV D50 bolus then 0.5-1g/kg/hr of glucose
Salvage:
Intralipid 1.5ml/kg bolus then 0.025 ml/kg/min infusion
Dialysis if applicable
Circulatory support LVAD, ECMO, IAMP
Which beta blockers are dialysable
SATAN - sotalol, atenolol, timolol, acebutolol, nadolol
Why is propranolol the most toxic overdose
Propranolol: most toxic due to lipophilic nature, allows it to penetrate the CNS resulting in seizures
Which beta blockers have membrane stabilizing effects
Membrane stabilizing: can result in sodium channel inhibition and wide QRS ex. Propranolol, acebutolol, nadolol
Which beta blockers have potassium channel blocking effects
Sotalol, Acebutolol: can resulted in prolonged QT + TdP
Describe a stepwise approach to managing a calcium channel blocker overdose
What is different between this one and BB OD?
Supportive care:
IVF (caution due to increased risk of pulmonary edema)
GI decontamination if large overdose
Atropine 1mg IV
Calcium supplementation
Treatment:
High dose insulin
- 0.5-1U/kg IV bolus then 1-10 U/kg/hr titrate to effect
- 1g/kg IV D50 bolus then 0.5-1g/kg/hr of glucose
Pressors
Salvage:
Intralipid 1.5ml/kg bolus then 0.025 ml/kg/min infusion
Methylene blue 1-2mg/kg bolus
Circulatory support LVAD, ECMO, IAMP
What one lab abnormality may be able to distinguish an beta blocker overdose from a calcium channel blocker overdose
Glucose
Hyperglycemia -> CCB
Hypoglycemia -> BB
*Hydrofluoric acid spill on arm young guy, Two ways of decontamination (physical?)
- Irrigation with copious amounts of water for at least 15-30 minutes
- Removal of blisters, as necrotic tissue may harbour fluoride ions
- Clothing removal
*4 treatments for dermal HFA exposure
- Topical calcium gluconate gel, which can be made by mixing 3.5 g of calcium gluconate powder in 150 ml of water-soluble lubricant (e.g. K-Y jelly) and secured with an occlusive cover
- Infiltration of subcutaneous calcium gluconate for deeper burns (note: this is painful, so consider a regional nerve block)
- Intravenous calcium gluconate
- Intra-arterial calcium gluconate
Pain control
*2 most common metabolic complications of HFA
Hypocalcemia hypomagnesemia hyperkalemia
*One most serious complication for large volume HF inhalation
Inhalation and skin exposure to 70% hydrofluoric acid can result in pulmonary edema and death within 2 hours. However, delayed pneumonitis and adult respiratory distress syndrome can also occur, and they can be present for months. Pneumonitis can be severe and require ventilatory support.
*young patient ingests 80% acetic acid 30 min ago. Stable looks unwell. 5 initial resuscitation steps
Secure IV access/crystalloid resuscitation as indicated
• Secure airway/intubate
• Pain management
• Consult surgical service as indicated
• Antibiotics if suspected/confirmed perforation
• Consult poison centre
• consider careful nasogastric aspiration if ingestion within 30-45 mins, other forms of GI decontamination/charcoal contraindicated
• Monitoring in ICU
*3 tests you would do to determine extent of injury in acid ingestion
• Scope (12-24h post ingestion)
• Barium
• CT
*4 systemic complications of acid ingestion
• - Renal failure
• - Hepatic failure
• - Hemolysis
• - DIC
• - Metabolic acidosis
Metabolic acidosis, renal and liver crap out, then blood says screw this and taps out
*3 complications of hydrofluoric acid ingestion (aside from death)
• - Burns, pneumonitis, esophageal perforation
• - Hypocalcemia (calcium scavenged by free fluoride ions)
• - Hypomagnesaemia (magnesium scavenged by free fluoride ions)
• - Hyperkalemia (per Rosen’s 9, due to inhibition of sodium-potassium ATPase and cellular destruction
List 5 factors that determine the extent of injury in a caustic ingestion
pH: injury increases with pH <3 or >11
Concentration, volume, viscosity
Duration of contact: greater with crystals/solid particles than liquids
Presence of food in stomach
What are the 4 phases of caustic and chemical injury
Phase 1 - initial necrosis occurs, with invasion by bacteria and leukocytes
Phase 2 - vascular thrombosis
Phase 3 - superficial layers of injured tissue begin to slough, lowering the tensile strength of the healing tissue and potentially risking delayed perforation
Phase 4 - granulation tissue forms, collagen is deposit, strictures may form
Describe the grading system for caustic injuries
Similar to a burn
- Grade 1 - edema and hyperemia
- Grade 2 - superficial ulcers, whitish membranes, friability, hemorrhage
- Grade 2a - non circumferential
- Grade 2b - nearly circumferential
- Grade 3 - transmittal involvement with deep tissue injury, necrotic mucosa, frank perforation of the stomach or esophagus. 90% result in strictures
What is the ideal time for endoscopy post caustic ingestion
12 to 24 hours, endoscopy too soon is more likely to miss injury and too late is more likely to cause perforation
When is the highest risk for perforation post caustic ingestion
5-14 days
Why are alkali burns more serious
Cause liquefaction necrosis
Generally easily penetrates tissues leading to protein denaturation, liquid saponification, and liquefaction necrosis.
Minimal pain on ingestion so self harm tends to be more serious
*“Hot and bothered” “hot and crazy” Drugs of abuse (6)
- Cocaine
- Amphetamines
- MDMA/ecstasy
- Methamphetamine/crystal meth
- Ephedrine
- Khat
- Bath salts
*“Hot and bothered” “hot and crazy” Plus seizure, Ddx:
DIMES
Drugs Amphetamines, cocaine, caffeine, anticholinergics, lithium, ASA OD, EtOH withdrawal, DRESS syndrome, synthroid OD
Infectious Meningitis, Encephalitis
Metabolic Thyrotoxicosis, Hyperammonemia, Hypoglycemia, Hypoxia, Uremia
Environmental Heat stroke
Structural Hemorrhage, mass, stroke, trauma
*13. 18F college student, hx of depression on multiple medications, found with altered LOC in her bathroom by roommates. Hyperthermic. You suspect serotonin syndrome. List 6 Ddx.
DIMES
Drugs Amphetamines, cocaine, caffeine, anticholinergics, lithium, ASA OD, EtOH withdrawal, DRESS syndrome, Synthroid OD
Infectious Meningitis, Encephalitis
Metabolic Thyrotoxicosis, Hyperammonemia, Hypoglycemia, Hypoxia, Uremia
Environmental Heat stroke
Structural Hemorrhage, mass, stroke, trauma
*List 5 drugs other than SSRIs that can cause serotonin syndrome
i. SSRIs
ii. SNRIs
iii. MAOi
iv. TCA
v. Dextromethorphan
vi. Amphetamines
vii. Lithium
viii. Cocaine
ix. Meperidine
x. LSD
xi. Buspirone
xii. Ecstasy
*If this was severe toxicity (serotonin syndrome) what is one medication you could use to treat this syndrome?
Cyproheptadine
*What initial screening test could you to test for packets?
Abdo XR
*Name 2 treatments that are indicated in this patient (asymptomatic young body packer)
- Laxatives
- Whole bowel irrigation (PEG)
*What one test might help determine the contents of the packages (body packer)
Urine drug screen
*The young body packer, previously asymptomatic becomes agitated with a BP 232/115. What agent would be most appropriate to lower her BP? And what ultimate treatment is now indicated?
Phentolamine (acute cocaine hypertension)
Laparoscopic removal of packets
*Multiple drug Hx presenting with increased muscle tone and AMS, 2 Ddx:
i. Serotonin syndrome
ii. Neuroleptic malignant syndrome
*What 6 lab investigations would you do to assess for complications of SS/NMS?
CK, WBC, LFTs, VBG, lactate, Creatinine, electrolytes, coags, serum catecholamines
*3 treatments for SS/NMS
Stop offending agent
Benzos
IV fluids
Cyproheptadine for severe cases
List 5 causes of cocaine induced MI
atherosclerosis, platelet aggregation, vasospasm, demand ischemia, LVH, dissection
List 2 complications of levamisole
agranulocytosis, thrombosis, ulcers esp. on the ear
List 4 agents that can be used to treat a hypertensive crisis in a sympathomimetic patient
Benzos, phentolamine 1mg q3min, IV nitro, hydralazine
Avoid beta blockers due to unopposed alpha activity
List 3 reasons why a patient with MDMA use presents with hyponatremia
Increased free water retention (affects release of vasopressin, SIADH)
Increased free water consumption
Patient with cocaine use presents with chest pain and elevated troponins. What is their management
ASA, DAPT
Should be treated as ACS if meeting criteria as a significant number of cocaine users end up having angiographically significant disease
What are methylxanthines
Plant derived alkaloids ex. Theophylline, caffeine
*Hyperemesis cannabinoid: 4 antiemetics
Zofran
Haldol
Gravol
Metoclopramide
Seroquel
Risperidone
Ativan
*4 non pharmacologic options for cannabis hyperemesis
Hot shower/bath
Capsaicin cream
Stop smoking
PO fluids
2 active components of marijuana
THC and CBD
*Drug interactions of marijuana (foolish) had like 8 drugs, and how each was effected by marijuana
Warfarin
Fluoxetine
Glyburide
Acetaminophen
NSAIDs
Indinovir
Verapamil
Warfarin (increases INR)
Fluoxetine (serotonin syndrome)
Glyburide
Acetaminophen (increased hepatoxicity)
NSAIDs (less GI bleeding)
Indinovir (reduces effectiveness)
Verapamil (decreases activity)
List 5 hallucinogens
LSD
‘Natural’ morning glory seeds, nutmeg, jimson weed, amanita muscaria mushrooms, buff toad, Mescaline, Salvia, THC/marijuana, peyote, Kratom
What is the % of elemental iron in each of the following: ferrous gluconate, ferrous sulfate, ferrous fumarate
Ferrous gluconate 12%, ferrous sulfate 20%, ferrous fumarate 33%
What levels of ingested iron correlate with toxicity?
<20 mg/kg benign
20-40mg/kg if asymptomatic likely benign
>40mg/kg mild to moderate toxicity; needs referral
>60mg/kg is considered severe
Describe the stages of iron toxicity
1: GI stage <6 hours - sx from direct caustic effects of iron, causes vomiting, abdominal pain, GI bleeding
2: Latent 6-24 hours - resolution of gastric symptoms, may be asymptomatic. May start developing systemic symptoms due to ongoing cellular toxicity and organ damage
3: Systemic 12-24 hours - return of GI symptoms, systemic symptoms including coagulopathy, lethargy, cardiovascular collapse, metabolic acidosis
4: Hepatic 2-5 days - fulminant liver failure
5: Obstructive 3-6 weeks - pyloric or bowel scarring, obstruction, gastric outlet obstruction
What serum levels of iron correspond to toxicity
Rosens: <30 micromol/L mild, >60 micromol/L moderate, >90 micromol/dL considered severe
What form of decontamination can be used in iron ingestion
Whole bowel irrigation (iron can clump and form bezoars)
Activated charcoal does not bind
What is the treatment for iron toxicity? What are common side effects
Deferoxamine 15mg/kg/hr IV x 24 hours, repeated up to 6 g in the fist 24 hours
S/E include hypotension, anaphylactoid reactions, ARDS, yersinia enterocolitis, oto and visual toxicity, vin rose urine
List 5 symptoms of lead toxicity
CNS: Encephalopathy, seizures, ataxia, HA, mood disturbances, peripheral neuropathy, absent DTR - due to segmental demyelination of degeneration of motor axons, decreased IQ
Resp: acute lung injury and pulmonary edema if acute inhalation
GI: Abdo pain, constipation, hepatitis, diarrhea
Renal: ATN, nephritis, HTN, gout
Heme: hemolytic anemia
What are indications for chelation in lead toxicity. What levels should be used?
Lead levels >70 ug/dL or >45 with clinical toxicity
Chelation via succimer 10mg/kg q 8 PO x 5 days then 10mg/kg q 12 PO for mild cases
Chelation via dimercaprol BAL 4mg/kg IM Q4H for 5 daysfor severe cases
List one contraindication for dimercaprol BAL
Peanut allergy
What are indications for deferoxamine
Serum >90 (or >60 + systemically unwell), systemic toxicity, metabolic acidosis
Which form of arsenic is toxic
Inorganic arsenic and arsine gas is toxic
Elemental arsenic is poorly absorbed and non toxic, organic arsenic (in shellfish) is also non toxic
List 5 symptoms of arsenic toxicity
GI: nausea, vomiting, diarrhea (rice water), abdominal pain, jaundice, pancreatitis, hepatosplenomegaly
Neuro: encephalopathy with seizures and coma, sensorimotor neuropathy (appears after months)
Resp: Respiratory failure, ARDS, pulmonary edema
Cardiac: dysrhythmias, prolonged Qt, Torsade’s
Renal: proteinuria, hematuria, oliguria, renal failure
Derm: characteristic Aldrich-Mees lines (appears after months)
What chelation agent is used in arsenic toxicity
Intramuscular BAL is the preferred chelator
Succimer can be given orally but is limited due to gastroenteritis symptoms
Chelation is not useful for arsine gas exposures (needs hemodialysis and plasma exchange)
What forms of mercury are toxic
Organic: may be absorbed through the skin in chronic exposures
Inorganic (mercury salts): caustic with oral ingestion
Elemental (ex. Thermometers): volatile at room temperature, may deposit in the lungs. Poorly absorbed from the GI tract and poses no risk
List clinical signs of mercury toxicity
Resp: tachypnea, wheezing, respiratory distress, burning sensation, pneumonitis, ARDS (esp. if inhalation or aspirated)
CNS: Altered mental status, tremors, visual field changes, hearing loss, hyperreflexia
GI: gastroenteritis, anemia, elevated in liver enzymes, abdo pain (especially if ingested)
Renal: renal tubular necrosis
List the 4 structural classes of hydrocarbons and an example from each
Aliphatic (straight chain): ex. Petroleum
Aromatic (ring) ex. Solvents, toluene
Halogenated (side chain) ex. Chloroform
Terpene ex. turpentine
What clinical features are associated with 1) camphor 2) halogenated hydrocarbons 3) aromatic hydrocarbons 4) toluene 5) benzene
Camphor: neurotoxicity and seizures
Halogenated: dysrhythmias and hepatotoxicity
Aromatic: bone marrow suppression and leukemia
Toluene: renal tubular acidosis
Benzene: bone marrow toxicity
Camphor = crazy, halogenated haptotoxic, aromatic anemia, toulene tubular, beneze bone marrow
List 4 features of hydrocarbons that impact toxicity
Viscosity: lower viscosity = more toxic
Volatility: higher volatility = more toxic
Surface tension: lower surface tension = more toxic
Chemical side chains: may produce their own symptoms ex. Arsenic
Lipophilicity: more toxic if can cross BBB
List 5 effects of hydrocarbons on the respiratory system
Chemical pneumonitis, destruction of surfactant, atelectasis, bronchospasms, hypoxia (due to volatility), hyaline membrane formation, interstitial inflammation
Other than respiratory, list 5 clinical effects of hydrocarbons
Cardiac arrhythmias
CNS depression, coma
Hepatotoxicity
Renal tubular acidosis
Direct chemical burns, angioedema
Should activated charcoal be given in hydrocarbon toxicity
No; GI effects less toxic than respiratory effect
When can a patient with a hydrocarbon exposure be discharged?
1) asymptomatic after 6 hours 2) normal CXR
Patient with hydrocarbon exposure comes in with a VF arrest. List 3 changes to management
Avoidance of epinephrine
Vasopressin and phenylephrine as preferred pressors
Esmolol (beta blockers) for ventricular dysrhythmias
*5 symptoms of CO poisoning
Symptoms: headache, nausea, vomiting, dizziness, myalgia, and confusion
Presents with: altered mental status, including coma and seizures; extremely abnormal vital signs, including hypotension and cardiac arrest; and metabolic acidosis
*Patient’s CO level is 40. They asked how long will it take for the level to go to 10 on: Room Air, NRB 100% O2, HBO at 3ATA.
Half life on room air is 5 h.
NRB: 60-90mins
HBO at 3ATA: 30min
so:
Room air: 10 hour
NRB: 2 hour
HBO: 1 Hour
*What are 5 tests that you order immediately in the ED for suspect CO poisoning?
Co-oximetry
VBG
Lactate
Beta HCG
CBC
Electrolyte panel
*Name 5 widely accepted reasons for initiation of hyperbaric therapy.
o COHgb > 25% in adult
o COHgb > 15% in pregnant patient, child
Elevation in CO plus:
- Associated Hemodynamic instability: MI, Arrhythmias
- Associated Neurologic impairment: SZ, Coma
o Decompression sickness I, II
o Arterial Gas embolism
o Increased wound healing (ex. Malignant Otitis externa)
o Hydrogen peroxide ingestion
What are the 4 delayed sequelae of CO toxicity? ** verify question
Focal deficits
Seizures
Memory deficits
Personality changes
Apathy
*What are the 2 risk factors for getting the delayed neurologic sequelae of CO toxicity?
Extremes of age
LOC
*Three mechanisms by which carbon monoxide impairs cellular oxygen delivery
Bind de-oxyhemoglobin, preventing binding of O2
Shift Hbg-SpO2 curve to LEFT, impairing release of O2 in tissue
Inhibits cytochrome complex leading to anaerobic metabolism
Inhibits oxidative phosphorylation
Binds myoglobin causing atraumatic rhabdo
Generation of free radicals leading to inflammatory cascade
Release of excitatory neurotransmitters
Vasodilation and myocardial depression
Lipid peroxidation
*Inhalation : List 2 examples and 3 symptoms of each.
i) Simple asphyxiants
ii) Upper A/W irritants
iii) Lower A/W irritants
iv) Cellular toxins
i) Simple asphyxiants: CO2; methane; nitrogen gas; nitrous oxide; noble gases (tachycardia, dyspnea, AMS)
ii) Upper A/W irritants: Ammonia, Chloramine, Hydrogen chloride, Sulfur dioxide (lacrimation, cough) - these have high water solubility
iii) Lower A/W irritants: Phosgene, nitric oxide (resp failure, ARDS - these have low water solubility
iv) Cellular toxins: CO, CN, HS (seizures, coma)
*What is the toxic substance that can occur from methylene chloride?
Carbon monoxide
*19M found down in shed with motorcycle running. T 40.5 HR 130 BP N aLOC. Smells like gasoline. List 4 most likely causes of his altered mental status
- CO
- huffing/bagging/sniffing
- other ingestion?
- heat stroke?
- based on this stem, hard to say what specifically they were looking for from the “hot and altered” list
*4 possible causes of rhabdo in 19M found down in his garage with motorcycle running.
- prolonged immobilization
- hyperthermia
- illicit drugs
- CO (binds myoglobin and causes atraumatic rhabdo, pg 2041)
- seizures
*Worker collapses at a site after exposure to gas smelling of rotten eggs. Likely toxin?
3 biochem. mechanism of toxicity?
Tx?
Hydrogen sulfide
Pulmonary irritant, cellular asphyxiant, shifts curve to right
Supportive, remove from source
In severe cases can use sodium nitrite from cyanide kit
List 10 cases of elevated lactate
Increased production
- Type A: poor perfusion: sepsis, mesenteric ischemic
- Type B: no hypoperfusion
- DKA, metformin
- Seizure
- Alcohol: liver dysfunction, alcoholic ketosis, toxic alcohols
- Leukemia, lymphoma
- Inborn errors of metabolism
- Drug s/e: Ventolin, propofol
- Tox: salicylate poisoning, carbon monoxide, cyanide, massive Tylenol
Poor clearance: liver disease, renal disease
What are the two main categories of inhalational injuries
- Asphyxiants (simple and chemical); cause damage through displacement of oxygen or direct chemical injury
- Pulmonary irritants; cause damage through the destruction of the mucosal barrier of the respiratory tract, leading to inflammation
List 3 examples of asphyxiants
carbon monoxide, carbon dioxide, methane (natural gas), nitrogen (mines, scuba), nitrous oxide (inhalant of abuse), helium, neon
Describe the clinical symptoms associated with the fall in FiO2
21%: None
16-12%: tachypnea, hyperpnea, tachycardia, reduced attention and alertness, headache
- Dyspnea is not an early finding because hypoxemia is not as potent a stimulus to the respiratory centre as hypercarbia and acidemia
14-10% altered judgement, incoordination, muscular fatigue, cyanosis
10-6%: nausea/vomiting, lethargy, air hunger, severe incoordination
- Lethargy starts as FiO2 falls below 10%
<6: gasping, seizure, coma, cherry red skin (terminal)
List 5 examples of pulmonary irritants
Ammonia (fertilizer, combustion), hydrogen chloride (industrial), sulfur dioxide (photochemical smog)
What is the treatment for exposure to a pulmonary irritant
Supportive care
Beta agonist for bronchospasm
List one specific therapy for exposure to chlorine gas
Nebulized 2% sodium bicarb solution for patients exposed to chlorine
Describe how cyanide cause toxicity
Inhibits oxidative metabolism in the electron transport chain -> depletes ATP -> cellular hypoxia and death -> anaerobic metabolism (high lactate). No effect on hemoglobin
List 3 lab findings of cyanide toxicity
- Anion gap metabolic acidosis
- Elevated lactate
- Elevated cyanide level
- Similar PO2 levels between arterial and venous gas
List 4 treatments for the treatment of cyanide toxicity
- Hydroxycobalamin 5g IV
- Sodium thiosulfate 12.5g IV
- Sodium nitrite 10mls
- Amyl nitrite
What is the byproduct formed by hydroxycobalamin
B12
What is the risk of using sodium nitrite or amyl nitrite
Methemoglobinemia
List the clinical symptoms associated with each of the following CO level: 5-10%, 10-30%, >30%
Mild 5-10% - headache, nausea, dizziness, myalgia, and confusion. Consider if there is a group of people with a similar symptom
Mod 10-30% - headache, weakness, dizziness, dyspnea, irritability, N/V, impaired judgement
Severe 30-50% - coma, seizure death
What will the SpO2 be in carbon monoxide? The PaO2? PvO2?
All normal
What is the treatment of CO
Oxygen, hyperbarics if severe
List 3 causes of left shift and 3 causes of right shift on the oxygen-hemoglobin curve
Left (difficulty unloading O2): decreased temp, decreased 2-3 DPG, decreased H+ (alkalotic), CO
Right (easier to unload O2): increased temp, increased 2-3 DPG, acidosis
*What TWO lab tests have to be done in chronic lithium toxicity (other than lithium level)? and why
- Urine lytes for nephrogenic DI
- Thyroid function studies ** big increased risk of severe neurotox in hypothyroid
- Creatinine (renal impairment)
- Beta?
- Tox screen
*What are the TWO preferred methods for enhanced elimination in lithium toxicity?
- Fluid resus (NaCl)
- ECTR
*If the patient takes dextromethorphan with the lithium, what are two complications that can result?
CHECK QUESTION. WAS IT REALLY DM THEY ASKED ABOUT?
Regardless, NMS and serotonin syndrome could result.
*If it’s slow release, what is the decontamination that you’ll do? Describe how you will do it.
Whole bowel irrigation
NG, 2L PEG per hour until effluent is clear
*** Rosen’s very clearly does not endorse WBI, but 2016 paper by Dr. Gosselin does.
*What is on your differential for ingestions that make you hyperthermic, altered, and rigid.
NMS - antipsychotics
MH - volatile agents, succinylcholine
SS - SSRIs, MAOIs, lithium, dextromethorphan, meperidine, tramadol
*Dialysis drains serum and CNS lithium levels (T/F)?
False
*If you are chronic toxic and have CNS symptoms you should get dialysis(T/F)?
True
*Asymptomatic lithium level of 5 mEq/L needs dialysis(T/F)?
True
*Those who get dialysis are prone to later “rebound” lithium toxicity(T/F)?
True
*Li+ is metabolized by the liver, excreted by the kidneys(T/F)?
False not metabolized, excreted renally 95% unchanged
*List 5 CNS symptoms of Li+ toxicity
Tremors
Clonus
Hyperreflexia
Somnolence
Extrapyramidal symptoms
Coma
Seizures
*3 ECG manifestations of Li+ toxicity
Bradycardia
Junctional rhythm / AV blockade
ST changes
QT prolongation
Flattened or inverted T-waves
Brugada pattern on ECG
Ischemic changes on ECG
*List 4 medications that are associated with causing lithium toxicity/increasing its serum level
BZD, carbamazepine, diuretics, ACEi, ARB, NSAIDs
List 4 chronic side effects of lithium use
Diabetes insipidus, hypothyroid, hypercalcemia, hyperparathyroidism
What is the difference in clinical presentation between acute and chronic lithium toxicity
Acute: more GI symptoms predominate ex. Nausea, vomiting, diarrhea
Chronic: more neuro symptoms; these patients are already saturated
List the indications for dialysis in lithium toxicity
Acute >4.0 mEq and chronic >2.5 [Rosens]
- >4.0 and impaired kidney function [ExTrip - no specific chronic level]
- Can consider at low levels if symptomatic
Severely symptomatic
Renal impairment
Unable to tolerate fluid hydration
*Girl has been out partying and took some random drug. Comes in altered and yelling about green elves. You give her Ativan and Haldol.
After 2 hours, she’s chill but she can’t move her neck; what 2 medications and doses would you consider?
Dystonia will usually respond within 30 minutes to diphenhydramine 25 to 50 mg or benztropine 1 to 2 mg intravenously, intramuscularly, or orally. Lorazepam 1 to 2 mg IV may also be effective in patients who do not respond within 1 hour to diphenhydramine or benztropine.
*What are 2 other side effects of Haldol (other than dystonia)
Extrapyramidal: akathisias, parkinsonism, NMS, tardive dyskinesia
Prolonged QtC
*What is one ECG side effect of haldol
Prolonged Qtc
List 7 receptors affected by antipsychotics
Dopamine + TCA list
Dopamine (main effect)
Muscarinic (anticholinergic symptoms)
Histamine (sedation)
Alpha (vasodilation)
Sodium channel (wide QRS)
Potassium channel (prolonged Qtc)
Gaba (leads to seizures
Serotonin
Compare first and second generation antipsychotics and given 2 examples of each
First: Dopamine >serotonin, higher incidence of EPS, more sedating ex. loxapine, haloperidol
Second: Serotonin >dopamine, lower incidence of EPS, less sedating but more metabolic side effects, treats positive and negative symptoms ex. Clozapine, quetiapine, olanzapine, aripiprazole
List 3 risk factors for NMS
Rapid dose escalation, cumulative drug dosage, high potency antipsychotics, prior brain injury, poorly controlled extrapyramidal symptoms, previous episodes of NMS
Describe the clinical features of NMS
FARM
Fever, autonomic dysfunction, rigidity with rhabdomyolysis and CK>1000, mental status changes
Contrast NMS to serotonin syndrome
NMS: patient rigid, always has a fever, diminished reflexes, can occur at any time
SS: no rigidity, fever late sign, hyperreflexia, temporally related to acute overdose
*List 4 serious side effects of Demerol
Serotonin syndrome
Hypertonicity
Myoclonus
Seizures
Apnea
*6 signs of opiate withdrawal
- Yawning
- Piloerection
- CNS excitation (e.g. restlessness, agitation, dysphoria, insomnia)
- Tachypnea
- Mydriasis
- Tachycardia
- Hypertension
- Nausea
- Vomiting
- Diarrhea
- Abdominal cramps
- Myalgias
*4 drugs of different classes to treat opiate withdrawal
- Suboxone or methadone
- IV fluids
- Clonidine (for tachycardia, hypertension, sweating, anxiety, restlessness)
- Ondansetron (for nausea/vomiting)
*Chronic user crushes and injects Suboxone what will happen
Potential precipitation of withdrawal symptoms due to suboxone containing naloxone, which has little to no activity when administered sublingually
(MOA of clonidine as it pertains to treatment of opioid withdrawal
Alpha 2 -agonist, can be used to suppress sympathetic hyperactivity and shorten the duration of withdrawal.
*What is the duration of action of naloxone
~30 mins
*What are the components of the COWS score
11 items
Tachycardia
Chills/flushing, mydriasis, bone and joint aches, runny nose, GI upset, tremor, yawning, goosebumps
Restlessness, anxiety
*Describe the mechanism of action of suboxone and precipitated withdrawal
Suboxone is a partial opioid agonist with high affinity
Provides some stimulation at the opioid receptors preventing symptoms of withdrawal
Precipitated withdrawal occurs when suboxone is given while there is still native opioid in the system. The high affinity suboxone displaces the existing opioid. The suboxone is a less potent stimulator of the receptor, so overall the patient feels profound withdrawal
*What does the naloxone do in suboxone
Nothing if ingested orally
Deactivates the suboxone if given IV
What is the dose of naloxone
Generally 0.4 (can range 0.04-4mg) target to RR>10
If multiple doses are needed an infusion can be started at 1/3 of the wake up dose
*List 10 clinical manifestations of organophosphate toxicity?
S = Salivation
L = Lacrimation
U = Urinary incontinence
D = Diarrhea/Diaphoresis
G = Gastrointestinal cramps
E = Emesis
(Killer) Bs: Bradycardia/bronchorrhea/bronchospasm
*What are 3 general measures for tx other than supportive ie controlling airway in organophosphate toxicity?
(1) Decontamination
(2) Supportive care with an emphasis on respiratory stabilization
(3) Reversal of acetylcholine excess (atropine)
(4) Reversal of toxin binding at receptor sites on the cholinesterase molecule (2-PAM)
*What are 2 antidotes in organophosphate toxicity?
Atropine, 2-PAM
What is the mechanisms of toxicity in organophosphate poisoning
Compounds bind to acetylcholinesterase, inhibiting the break down of acetylcholine and causing a cholinergic crisis
What are the clinical symptoms of an organophosphate poisoning. Which receptors are affected?
Muscarinic: SLUDGE DUMBELLS - salivation, lacrimination, urinary incontinence, defecation, GI upset, emesis, diaphoresis, urination, bronchorrhea/bradycardia/bronchospasm, excitation, lacrimination, lethargy, salivation
Nicotinic: MATCH - muscle fasciculations, adrenergic stimulation, tachycardia, cramping, hypertension; may eventually lead to paralysis with prolonged stimulation
What is aging? With what agents does it occur?
Occurs when an agent forms an irreversible bond with the acetylcholinesterase leading to prolonged effects. Occurs with organophosphates but not carbamates
Describe the non pharmacologic management of organophosphate poisoning
Decontamination: dermal absorption is contributory; remove clothes and flush skin. GI decontamination is often not helpful
Supportive care: suctioning, correction of electrolytes
Describe 2 agents that can be used in the management of organophosphate poisoning
Atropine 1mg doubling q5 mins until secretions dry up, with infusion of 10-20% of the cumulative dose over an hour
Pralidoxime 1mg bolus (limited evidence)
Briefly describe the clinical symptoms associated with each of the following compounds:
1. Chlorinated hydrocarbons ex. DDT, lindane
2. Substituted phenols ex. DNP
3. Chlorhenoxy compounds
4. Bipyridyl compounds ex. Paraquat
5. Pyrethrins ex. chrysanthemum
6. Glycophosphate ex. Roundup
- Highly lipid soluble and absorbed dermally. Can result in seizures, neurologic sx, risk of V tachy due to myocardial sensitization to catecholamines. Needs decontamination, betablockers for arrhythmias
- Presents like sympathomimetic toxidrome: hyperthermia, tachycardia, diaphoresis, agitation, rhabdo, yellowing of skin, hypoglycemia (used as weight loss medication)
- Diffuse fasciculations can lead to rhabdo, hyperthermia, hypermetabolic state
- Risk of pulmonary injury, concentrates in the lung with toxicity through oxygen free radicals, avoid excessive oxygen, common agent of suicide
- Allergic like reaction; dermatitis, wheezing, vomiting
- Poorly absorbed dermally, absorbed through GI tract
What is the safe recommended dose of DEET in children
<2 do not use
>2 10% DEET
>30% DEET can result in seizures
List 2 main categories of rodenticides
Anticoagulants: 90% of all exposures, managed with RBCs, transfusion, PCC, vitamin K
Non anticoagulants: uncouple oxidative phosphorylation ex. Arsenic, barium, phosphorus
Describe the identification, clinical symptoms, and management of amanita phalloides ingestion
White mushroom with a ring at the bottom and veil on the stalk
Sx include severe liver toxicity, renal toxicity, GI symptoms
Decontamination and supportive care, can consider NAC, needs serial monitoring of liver enzymes
Describe the identification, clinical symptoms, and management of the false morel (gyomitrin mushrooms)
Brown ribbed mushroom, looks similar to true morel
Sx include refractory seizures due to the inhibitory effects on pyridoxine. May also cause hepatotoxicity and methemoglobinemia
Seizures managed with IV pyridoxine 5g
Briefly describe the clinical symptoms associated with each of the following mushrooms:
1. Amanita muscaria
2. Psilocybin
3. Amanita smitthiana
4. Clitocybe
5. Coprinus
- Hallucinogenic
- Hallucinogenic
- Renal failure
- Cholinergic toxidrome
- Disulfram reaction
Which mushrooms ingestions may present with a delayed presentation of toxicity
Amanita phalloides, gyromitrin
Briefly describe the clinical symptoms associated with each of the following plants:
1. Jimson weed, belladona
2. Autumn crocus
3. Foxglove
4. Water hemlock
5. Poison hemlock
6. Dumbcane
7. Castor bean
8. Yew
9. Monkshood, wolfsbane
- Anticholinergic toxidrome
- Contains colchicine; GI symptoms -> multi organ failure -> sepsis
- Cardiac glycosides, like digoxin toxicity
- Intractable and life threatening seizures
- Nicotinic/cholinergic poisoning
- Vomiting, mucosal and airway edema
- Ricin if chewed
- Sodium channel blockage can lead to arrhythmia and cardiac arrest
- Sodium channel blockage can lead to arrhythmia and cardiac arrest
List 5 drugs that can cause a sedative hypnotic toxidrome
Benzos, barbiturates, GHB, chloral hydrate, rohypnol, zopiclone
List 4 contraindications for flumazenil
Co-ingestions (esp. those suspected at lowering seizure threshold)
Chronic benzos use
Seizure
Ongoing withdrawal
Hypersensitivity to flumazenil or benzos
Muscular blockage
What is the clinical presentation of chloral hydrate toxicity
Pear odor, CNS depression, arrhythmias
List 3 diabetic medications that can cause hypoglycemia
Insulin, sulfonylureas (ex. Glicizide, glyburide), meglitindes
List one unique antidote that can be used in sulfonylurea toxicity
Octreotide; inhibits insulin release
Compare acute vs chronic dig toxicity?
Components of Audit C questionnaire?
How often have you had a drink of alcohol in the past year?
(Monthly, 2x a month, 2x a week, 4x a week)
If you were drinking in the past year, how many drinks did you have on a typical day?
)0,3,5,7,10)
How often did you have 6 or more drinks in the past year?
Never, monthly, weekly daily)
