Toxicology Flashcards
Initial naloxone dose for young/opioid naive children
0.1mg/kg
Initial naloxone dose for adolescent/at risk of withdrawal
0.04mg
Maximal therapeutic dose acetaminophen
Children - 90mg/kg/d
Adults - 4g/d
Toxic dose acetaminophen
150mg/kg in < 24hrs
10g in < 24hrs
What is the toxic metyabolite of acetaminophen that causes hepatotoxicity?
NAPQI
What produc detoxifies NAPQI?
glutathione
How does NAC work?
= glutathione precursor
What are the stages of acetaminophen toxicity?
Stage 1 - 0.5-24hrs post-ingestion. Asymptomatic or GI symptoms, possible ALOC and elevated anion gap acidosis
Stage 2- 24-72 hours. Hepatotoxic signs with RUQ pain, possible AKI but improvement of GI symptoms
Stage 3 - 72-96hrs. Fulminant hepatitis with return of GI symptoms, possible encephalopathy, metyabolic acidosis, AKI, coagulopathy, possible multisystem dysfunction and death
Stage 4 - 4d-2wks. Recuperation
If patient comes in with ingestion > 8hrs ago or unknown time, how do you manage?
Start NAC immediately and refer to nomogram once results available
What are the criteria for being able to use the nomogram?
Single ingestion or over < 8hrs
bloodwork done 4-24hrs post-ingestion
What are indications for use of NAC?
APAP > 66
Abnormal transaminases (do at least 2 checks)
When can NAC treatment be stopped?
If APAP dose not toxic based on nomogram
At end of treatment if acetaminophen negative and normal transaminases
What are secondary effects of NAC?
elevated INR
flushing
urticaria
angioedema
dyspnea/hypotension
What is the therapeutic dose of activated charcoal?
1g/kg, max 50g
When would you consider more than one dose of activated charcoal?
large quantity of ingested pills, especially if salicylate
ingestion of substance that slows gastric emptyin
extended release pill
enterosoluble pill
blood concentration of substance continues to increase
What are contraindications to use of charcoal?
lithium, heavy metals, alcohols
inadequate protection of airways
intestinal occlusion
ingestion of corrosive substance
What substances warrant repeated charcoal doses?
theophylline, caffeine, phenobarbital, carbamazepine, dapsone, quinine, amatotoxine (mushrooms)
What are the doses for repeated activated charcoal?
1g/kg q4h or 0.5g/kg q2h
What bloodwork should be done if not able to get history in comatose/ALC patients?
CBC, uric acid, Cr, lytes, transaminases, gas, serum osmolality, EtOH, ECG, APAP/ASA dosing
What is the calculation for anion gap?
Na - (Cl + HCO3)
What are the substances that cause elevated anion gap metabolic acidosis
Methanol
Uremia
Diabetic ketoacidosis (DKA)
Paraldehyde, phenformin;
Iron, isoniazid
Lactic (ie, carbon monoxide [CO], cyanide)
Ethylene glycol
Salicylates
How do you calculate osmolality?
2Na + Glucose + BUN (2 salts and a sugar bun)
What is a normal osmolar gap value?
< 10
What toxins cause elevated osmolar gap?
Ketones
Alcohols**
What anti-arhythmic medication should be avoided in cases of toxic OD?
Amiodarone
What is the electrolyte-channel associated with enlarged QRS?
Sodium channel blocker
What is the electrolyte-channel assoiciated with prolonged QTc?
Potassium channel blocker
In what toxidromes should beta-blockers be avoided?
sympathomimetic, anticholinergic, serotoninergic
What drug should be dosed + consider administration of its antidote in tachycardia?
digoxin
What substances are sodium channel blockers?
quinine
procainamide
TCA
lidocaine
phenytoine
local anesthetics
cocaine
chloroquine
How do you treat widened QRS caused by sodium channel blockers?
Sodium carbonate 1-2mmol/kg IV in 1-2 mins
Repeat until QRS < 100 or until BP stabilized and ECG normal
OR
Try NaCl 3%
What substances cause long QTc/torsades de pointe by Potassium cannel blockers?
sotalol etc
macrolides
psychotropic meds
methadone
domperidone
How do you treat long QTc/torsades de pointe caused by Potassium cannel blockers?
Magnesium sulfate 1-2g IV
What are the symptoms of anticholinergic toxidromes?
DRY
Delirium/agitation/hallucinations
Mydriasis
Hypertension
Tachycardia
Tachympia
Possible urinary retention
Hyperthermia
Redness
Hyperreflexia/trembling
What are the symptoms of Cholinergic toxidromes? (Muscarinic)
WET
- delirium/depression
- Myosis
- Salivation + tearing
- Hypotension
- Bradycardia
Bronchospasm
Increased GI motility
Incontinence
Vomiting/cramps/diarrhea
Diaphoresis
Cholinergic (nicotinic) toxidrome?
WET
mydriasis
hypertension
tachycardia
fasciculations
weakness
hyper then hyporeflexia + paresis
Sympathomimetic toxidrome
delirium/agitation
mydriasis
hypertension
tachycardia
tachypnea
no GI/Urinary symptoms
hyperthermia
diaphoresis
hyperreflexia
trembling
Opioid toxidrome
confusion/somnolence
myosis
hypotension
bradycardia
bradypnea
hypothermia
hyporeflexia
Serotoninergic toxidrome
delirium/agitation
mydriasis
hypertension
tachycardia
tachypnea
increased GI peristalsis
hyperthermia
diaphoresis
clonus
hypertonia
hyperreflexia
tremors
bruxism
Examples of methanol-containing toxins
fondue liquid
anti-freeze
Lab findings in methanol + ethylene glycol poisoning
starts with elevated osmolar gap
then elevated anion gap
metabolic acidosis (methanol = elevated formic acid, ethylene glycol = oxalic acid)
Antidotes to methanol + ethylene glycol poisoning
Fomepizole
Ethanol
How much methanol can cause significant intoxication
0.25ml/kg
4-10 mL can cause permanent blindness
What are the clinical symptoms of methanol poisoning?
GI symptoms - nausea, vomiting, anorexia, abdo pain, pancreatitis
neurologic symptoms - depression, headache, compa, convulsions, cerebral edema, possible basal ganglia effects
Visual disturbance - “snowstorm”, central scotoma, papilledema
Tachycardia, hypotension
Tachypnea initially followed by respiratory depression
What are examples of ethylene glycol containing toxins?
antifreeze
Toxic quantity of ethylene glycol
0.2ml/kg
1-1.5ml/kg = lethal
Clinical symptoms of ethylene glycol poisoning
GI - nausea, vomiting, ado pain
Neuro - depression, seizure, cerebral edema, coma, polyradiculopathy, IC hemorrhage
Renal - AKI, oxaluria, hypocalcemia, tetany
Leucocytosis, hyperglycemia
tachycardia
QTc prolongation
CHF
tachypnea then resp failure
pulmonary edema
What labs need to be done for toxic alcohol poisoning?
Concentration 1.5-2hrs post ingestion then repeat q 4-8hrs
CBC, Electrolytes inc Ca, BUN. Cr, glycemia, hepatic enzymes, lipase, troponin, CK
EtOH, serum osmolality, gas, lactate
ethylene glycol - UA looking for calcium oxalate crystals
Products containing isopropanol
rubbing alcohol, solvants, some antifreeze
Lab changes in isopropanol poisoning
elevated Ketones
Elevated osmolar gap
NO metabolic acidosis
Clinical symptoms of isopropanol poisoning
Fruity breath (acetone)
CNS depression
nausea, vomiting, abdo pain
hemorrhagic gastritis
acute pancreatitis (rare)
Severe - coma, hypotension, hypothermia, arhythmias, AKI
Labs to do for suspected isopropanol poisoning
CBC, Lytes, BUN, Cr, glucose
Hepatic enzymes, lipase
concentration of isopropanol and acetone (metabolizes to acetone)
other alcohols
ketones
blood gas
serum osmolality
UA - ketones
Treatment for isopropanol poisoning
symptomatic treatment
Indications for use of Fomepizole
Methanol > 6mmol/L
Ethylene glycol > 3mmol/L
Metabolic acidosis with osmolar gap > 10 without clear reason
false hyperlactatemia
Dose of fomepizole
15mg/kg IV over 30 mins
12 hrs later give 10mg/kg iV over 30 mins - repeat q12h x 4 doses
When can fomepizole be stopped?
resolution of metabolic acidosis
methanol < 6 mmol/L or ethylene glycol < 3 mmol/L
What adjunct treatments can be given in methanol poisoning?
leucovorin (folic acid) 1mg/kg/dose IV
What adjunct treatment can be given for ethylene glycol poisoning?
Pyridoxine 50mg q6h + thiamine 100mg IV q8h
What are indications for hemodialysis in methanol poisoning?
visual symptoms
coma
seizures
methanol > 15-22
pH < 7.15
What are indications for hemodialysis in ethylene glycol poisoning?
AKI
EG > 8
pH < 7.15
What is a possible systemic toxic effect of OD of local anesthetics?
Methemoglobinemia - topical and oral use of benzocaine
CNS - tinnitus, dizziness, lingual/peribuvval numbness, visual changes, hearing changes, confusion, tremor, seizures, coma
CV (higher concentrations) - shock, vascular collapse, sodium channel block
What local anesthetic is most cardiotoxic?
Bupivacaine
What is the antidote for local anesthetic OD?
Intralipids
What medications have anticholinergic effects?
atropine
scopolamine
glycopyrrolate
TCAs
antihistamines
antipsychotics
antispasmodics
antiparkinsoniens (benztropine)
muscle relaxants
anticonvulsants - carbamazepine
belladonna plant
What labs need to be done for anticholinergic ingestion?
Cardiac monitoring
CK - if agitation, convulsion, compa
Lytes, BUN, Cr
UA - myoglobinuria if suspected rhabdomyolysis
What is the antidote for anticholinergics?
Physostigmine
- only if pure anticholinergic ingestion, severe and refractory to other treatments
Dose 0.02mg/kg (max 0.5mg) IV max rate 1mg/min
Can repeat q 10-30 mins - max 2mg cumulative dose
What is a contraindication to physostigmine use?
evidence of sodium channel block
Symptoms of TCA overdose
Antihistamine - Sedation
Anti-muscarinic - agitation, hallucinations, delirium, tachycardia, hyperthermia, mydriasis, dryness, ileus, urinary retention
Alpha adrenergic - hypotension, reflex tachycardia
Diaphoresis, tachycardia
Serotonin syndrome
Sodium channel blocker - large QRS, brugada, seizures
Potassium channel blocker - QTc prolongation
GABA antagonists
What is the best prognostic parameter to prognosticate risk of arrhythmia and seizure in TCA intox?
ECG - R wave in aVR > 3mm
Treatment of TCA overdose
Consider if in cardiogenic shock. If yes, will respond well to NaHCO3 administration
If large QRS give 1-2mmol/kg IV of NaHCO3 boluses
- goal = pH 7.45-7.55
What medications are “one pill killers”?
- benzocaine – methemoglobinemia and seizures
- β-blockers – bradycardia, hypotension, seizures
- calcium channel blockers - bradycardia, hypotension
- camphor – seizures, CNS depressant
- chloroquine – seizures, arrhythmia
- clonidine – bradycardia, CNS depression
- diphenoxylate/lomotil – CNS and respiratory depression
- hypoglycemics (sulfonylureas) – hypoglycemia
- Lindane – seizures, CNS depression
- methyl salicylate (oil of wintergreen) – seizures, CVS collapse
- phenothiazines – seizures, arrhythmia
- quinidine – seizures, arrhythmia
- theophylline – seizures, arrhythmia
- TCAs – Seizures, CVS collapse, hypotension
What medication does oleander ingestion mimic?
digoxin
What are the signs of oleander toxicity?
vomiting, diarrhea, abdominal pain, weakness, confusion, hyperkalemia, and bradyarrhythmias, especially high grade atrioventricular block
What are the signs of hemlock toxicity?
spontaneous vomiting within 1 hour. Salivation, headache, fever, mental confusion, and muscular
weakness may follow, and the child may deteriorate to convulsions, coma, and death from respiratory failure.
what is the toxidrome of jimsonweed toxicity?
anticholinergic
Antidotes for the following med classes:
Acetaminophen
Antichoninergic
Anticholinesterase
Organophosphates
Benzos
Beta blockers
Calcium channel blockers
Digitalis
Fluoride
Iron
Isoniazid
Methanol/ethylene glycol
Methemoglobinemia
Opoioids
Sulfonylureas
TCAs
Warfarin
Acetaminophen - NAC
Antichoninergic - Physostigmine
Anticholinesterase - atropine
Organophosphates - pralidoxime
Benzos - flumazenil
Beta blockers - glucagon
Calcium channel blockers - CaCl or CaGluconate + insulin/glucose
Digitalis - digibind
Fluoride - calcium gluconate
Iron - deferoxamine
Isoniazid - pyridoxine
Methanol/ethylene glycol - fomepizoe, ethanol, folate, thiamine
Methemoglobinemia
Opioids - naloxone
Sulfonylureas - octreotide
TCAs - sodium bicarb
Warfarin - vit K
Possible side effect of repeated doses of succinylcholine
*bradycardia
Hypotension
Arrhythmia
MI
Prolonged paralysis
Hyperkalemia and ventricular arrhythmias in patients in catabolism or with muscular trauma
Stages of ethylene glycol poisoning
Stage 1 CNS – profound metabolic acidosis, tachycardia, mild HTN, leukocytosis, nausea/vomiting, convulsions + coma, hypocalcemia
Stage 2 Coma + cardiopulmonary failure – result of acidosis
Stage 3 Renal failure – ATN requiring dialysis
What are the final toxic products in the metabolism of ethylene glycol?
Glycoaldehyde, glycolic acid, oxalate
What chemicals should not be immediately irrigated?
Dry lime
Elemental metals
Phenol
Side effects of physostigmine
seizures
asystole
cholinergic crisis
3 antidotes for methanol
ethanol
folate
fomepizole
Meds that are dangerous to toddlers in 1-2 doses
benzocaine
betablockers
calcium antagonists/calcium channel blockers
camphor (eg. vicks vapo rub)
chloroquine
clonidine
lomotil
glyburide
lindane
methyl salicylate
opioids
chlorpromazine
quinidine
quinine
theophylline
TCAs
5 stages of iron toxicity
Stage 1 (0-6h) - GI symptoms, if severe can have GI bleeding
Stage 2 (6-24h) - latent, no GI sx, lethargy, tachycardia, metabolic acidosis
Stage 3 (24-72h) - shock, GI hemorrhage, coagulopathy, worsening metabolic acidosis, convulsion, coma
Stage 4 (2-3d) - hepatic failure
Stage 5 (long term) - intestinal stenosis, scarring, pyloric stenosis
Indications for deferoxamine
ingestion > 40mg/kg of elemental iron with GI symptoms or lethargy
Iron > 90 micromol/L OR
iron > 63micromol/L with CV symptoms or metabolic acidosis
Starting dose of deferoxamine
15mg/kg/hr
When can deferoxamine treatment be stopped?
decontamination is done
no more symptoms
no more lactic acidosis
side effects of deferoxamine
urticaria or erythema
hypotension
ARDS
RED/PINK URINE
TCA clinical findings in OD
sedation or agitation
hallucinations/delirium
tachycardia
hyperthermia
mydriasis
dry mouth/skin
ileus
urinary retension
hypotension
QRS prolongation, brugada
seizures
QTc prolongation
Most accurate way to predict arrhythmogenic and convulsive risk in TCA overdose
ECG shows R in aVR > 3mm
Labs in TCA OD
lytes, BUN, creatinine, hepatic enzymes, CK
lactate, gas
Urinalysis for myoglobinuria
Signs of mild to moderate bupropion toxicity
tachycardia and hypertension
agitation
dizziness
tremors
paresthesias
lethargy
confusion
seizures
Signs of severe bupropion toxicity
hyperthermia
hypotension
QRS prolongation
QTc prolongation
ventricula arrhythmias
status epilepticus
coma
How long does patient with toxic ingestion of bupropion need to have ECG monitoring?
18-20 hours post ingestion if asymptomatic or minimum 12h post end of symptoms
Symptoms of IMAO toxicity
hyperthermia
nausea/vomiting/diarrhea
mydriasis
ocular clonus
redness
diaphoresis
headache
delirium
neuromuscular symptoms
hypertension initially followed by hypotension
possible MI
which SSRI is at risk of causing late-presenting torsades de pointes/
citalopram
How long does ECG monitoring need to continue for citalopram or escitalopram ingestion?
24hrs minimum
How long does clinical monitoring need to continue for SSRI ingestion?
18-20 hours post ingestion if asymptomatic or minimum 12h post end of symptoms
Mirtazipine toxicity clinical signs
tachycardia
dizziness
altered LOC
hypothermia
dry mouth
constipation
elevated transaminases
QRS prolongation
Trazodone toxicity clinical signs
lethargy
dizziness
myoclonus
ataxia
seizures
nausea/vomiting
respiratory depression
hypotension
bradycardia
mydriasis
priapism
hyponatremia
hypokalemia
Venlafaxine + Duloxetine toxicity
seizures
altered LOC
nausea/vomiting
tachycardia
hypotension
diaphoresis
hyperthermia
QRS and QTc prolongation
hyponatremia
rhabdomyolysis
transaminitis
Clinical presentation of neuroleptic malignant syndrome
hyperthermia
rigidity (cogwheel)
altered LOC
autonomic instability - tachycardia, diaphoresis, hypersalivation, incontinence, irregular respiration, arrhythmia, hyper or hypotension
leucocytosis
rhabdomyolysis
myoglobinuria
AKI
Risk factors for neuroleptic malignant syndrome
recent initiation of antipsychotic medication or dose increase
young age
male
dehydration
co-treatment with lithium
combination of multiple agent
rapid dose increases
Betablocker toxicity
decreased contractility
bradycardia
confusion
altered LOC/coma
nausea/vomiting
bronchospasm
hyperkalemia
pulmonary edema
HypOglycemia
Which betablocker can cause torsades de pointe?
sotalol
Calcium channel blocker toxicity
vasodilation of arteries
decreased contractility
bradycardia
confusion
altered LOC/coma
nausea/vomiting
pulmonary edema
HypERglycemia
Indications for pralidoxime use in cholinergic toxicity
presence of nicotinic signs or CNS signs with only an organophosphate or mixed with carbamate insecticide
Acute digoxin intoxication
nausea + vomiting*
hyperkalemia (marker of severity in acute ingestion)
bradycardia, AV block, VT/VF
lethargy
comfusion
weaknessA
Chronic digoxin intoxication
predominant neuro symtoms - delirium, comfusion, somnolence, hallucinations, photophobia, blurred vision, scotoma, chromatopsy (seeing yellow haloes)
GI symtpoms
Electrolyte abnormalities secondary to chronic renal insufficiency
bradycardia
slow AF
AV block
bigeminy/trigeminy
VT
Pathognomonic arrhythmia for chronic digoxin intoxication
Bidirectional ventricular tachycardia
When should digoxin levels be drawn
6hrs post ingestion
What is the antidote for digoxin intoxication?
Digoxin-specific antibody antigen-binding fragments (DSFab)
Indications for use of Digoxin-specific antibody antigen-binding fragments (DSFab)
symptomatic and progressive bradyarrhythmia
2nd or 3rd degree AV block resistant to atropine
tachycardia or Vfib
Digoxin level > 12.8 6hrs+ post ingestion
Potassium > or equal to 5
What dose of iron is toxic?
> 30mg/kg of elemental iron or iron > 32micromol/L 4h post-ingestion
Examples of oral hypoglycemic agents that increase insulin release
sulfonylureas - eg. glipizide, glyburide, chlorpropamide
Gliptines - sitagliptine, saxagliptin
GLP-1 analogs - exenatide
meglitinides - nateglinide, repaglinide
Up to when can symptoms of sulfonylurea toxicity appear
up to 24hrs post
Effects of oral hypoglycemics with increased insulin release - toxicity
hypoglycemia**
Neuro sx - seizure, delirium, coma
tremor
sweating
tachycardia
hypokalemia
hypomagnesemia
hypophosphatemia
mild hypothermia
Effects of metformin OD
unlikely to cause hypoglycemia
mild-moderate: nausea, vomiting, abdo pain, myalgia
Severe: severe lactic acidosis, cNS depression, hypothermia, tahypnea, hypotension, AKI
Toxic dose of metformin for children
> 1.7g
Which oral hypoglycemic can cause QTc prolongation?
sitagliptin
What is the antidote for oral hypoglycemics?
Octreotide
When is octreotide administration indicated
recidivant hypoglycemia induced by a sulfonylurea or no IV access
When can octreotide treatment cease?
absence of hypoglycemia x 24h after last dose of octreotide including an 8hr period of fasting
Dose of dextrose to give to correct hypoglycemia caused by oral hypoglycemics
0.5g/kg followed by a perfusion of 0.5g/kg/h
Dose of glucagon for hypoglycemia
20-30mcg/kg IM
Risk associated with intox by hypoglycemic agents in a patient already on beta blockers or co-ingested with beta-blocker
may not present adrenergic manifestations of hypoglycemia
Causes of methemoglobinemia
Local anesthetics (Eg. benzocaine, lidocaine)
Nitrates and Nitrites
Antimicrobials (eg. chloroquine, dapsone)
bromates
chlorates
metoclopramide
nitrous oxide
nitroglycerin
napthelene
What age group is most at risk for methemoglobinemia in pediatrics?
< 36 months
Risk factors for developing methemoglobinemia
anemia
malnutrition
renal insufficiency
sepsis
acidosis
G6PD deficiency
In which patients should methemoglobinemia be considered?
cyanosis that does not fit with clinical picture and does not respond to O2 administration
Antidote for methemoglobinemia
methylene blue 1% 1-2mg/kg in 5 min IV repeated 30-60 mins later if needed
When can methylene blue treatment be stopped?
max dose 7mg/kg
no more symptoms
Secondary effects of methylene blue
blue/green coloured urine, stool and skin
nausea, vomiting, headache, abdo pain, vertigo, hypotension, dyspnea
superficial thrombophlebitis
Lithium toxicity (acute)
GI predominant - nausea, vomiting, diarrhea
CNS (late signs)
ECG - flattened or inverted T waves, QTc prolongation, bradycardia
Lithium toxicity (chronic)
Nervous predominant - tremor, hyperreflexia, clonus, fasciculations, nystagmus, ataxia, dysarthria, seizures somnolence, confusion, coma
what is SILENT?
syndrome of irreversible lithium-effectuated neurotoxicity
Treatment of lithium toxicity
hydration at 1.5-2x maintenance
regular monitoring of electrolytes and renal function
hemodialysis - consider
Salicylate toxic dose
150-200mg/kg
Examples of salicylate-containing products
ASA
Methyl salicylate (tea tree essential oil + wintergreen)
pepto-bismol
3 stages of salicylate toxicity
1 - hyperventilation
diaphoresis
vomiting
tinnitus
hypoacusis
respiratory alkalosis
hypokalemia
alkaline urine with high K+
2 - hyperglycemia
volume contraction
deterioration
elevated anion gap
hypokalemia
acid urine
3 - hyperthermia
pulmonary edema
possible hepatotoxicity
hypoglycemia
confusion/coma
seizures
CV collapse
acid urine
acidosis (blood)
Also: SIADH (hyponatremia) or dehydration (hypernatremia), ketonuria
more rarely: rhabdomyolysis, GI hemorrhage
How often to monitor salicylate levels?
q2hrs
how often to measure urine pH in salicylate toxicity?
q1h
Treatment of salicylate toxicity
charcoal decontamination
administer dextrose
Urine alkalanization - pH 7.5-8, plasma alkalanization (ifpH < 7.4) using sodium bicarbonate (2-3ml/kg/hr max 150-200ml/hr)
prevent hypokalemia
consider hemodialysis
Why do we do urine/plasma alkalanization in salicylate toxicity?
higher pH = salicylates more ionized = decreased absorption in the renal tubules = increased excretion
Serotonin syndrome
myoclonia, tremor and hyperreflexia (predominant sxs)
clonus
hyperthermia
ocular clonus
rigidity
Medications that are NOT SSRI/SNRI that can cause serotonin syndrome
methylene blue
linezolid
bupropion
cocaine
dextromethorphan
fentanyl
tramadol
trazodone
LSD
amphetamines
MDM
buspirone
lithium
mirtazapine
Major differentiating factor between NMS vs serotonin syndrome
Serotonin syndrome = faster onset, more tremor, myoclonia and hyperreflexia
NMS = slower/delayed onset, rigidity and bradykinesia more prominent
antidote to serotonin syndrome
cyproheptadine 1-2mg PO or NG q 1-4h until end of symptoms or max 12mg/24h
indicated for severe SS
Secondary effects of cyproheptadine
mydriasis
urinary retention
Amanita toxicity
Phallotoxin acts first, causing nausea, vomiting, abdominal pain, and diarrhea. Fever, tachycardia, and hyperglycemia may also occur during this stage. The other toxin, amatoxin, causes renal tubular and hepatic necrosis.
