Supplemental Handout:
Specific Toxins
Melanie Madsen, MD
Last updated 12/96 for content, 9/97 for format
Outline
Acetaminophen
- toxic amounts overwhelm the normal pathway of metabolism (via sulfate
and glucuronide conjugates), resulting in metabolization through the cytochrome
P-450 system to N-acetyl-p-benzoquinoneimine (NAPQI). NAPQI is a toxic
intermediate which is conjugated with glutathione to a non-toxic compound.
Overdosing depletes glutathione, causing accumulation of NAPQI and subsequent
hepatic cell necrosis.
- toxic doses: > 140 mg/kg for children and > 7.5 grams
in adults patients that already have a stimulated P-450 system (due to
chronic use of barbiturates, anticonvulsants, etc.) require less amount
for toxicity to occur
- peak levels occur 1/2 - 4 hours after ingestion
- risk of toxicity can be determined by plotting plasma level on the
Rumack nomogram
- presentation: initially asymptomatic or may have nausea, vomiting,
diaphoresis and malaise. LFT abnormalities occur 1-2 days after ingestion.
- laboratory: initial acetaminophen level drawn at least 4 hours
after ingestion, tox screen if polypharmacy is suspected. Other laboratory
studies should be obtained as indicated: AST, ALT, bilirubin, PT, CBC,
creatinine.
- treatment:
- emesis or lavage if within 2 hours of ingestion may be of benefit
activated charcoal (1 gram/kg), single dose, minimum 1 hour before N-Acetylcysteine,
and only if emesis is not present
- N-Acetylcysteine (Mucomyst) should
be started for patients at "possible risk" or higher on the nomogram,
or if the quantity/level is unknown. Ideally this is given within 8 hours
of ingestion, but benefit has been shown when given within 24 hours of
ingestion.
- Dose: initial load of 140 mg/kg
followed by 70 mg/kg q 4 hours for 17 additional doses.
- Only the oral preparation is available in the US.
Return to top
Alcohols
- all alcohols cause inebriation, lack of coordination and muscle control,
and CNS changes
- laboratory: serum alcohol levels, ABG, electrolytes include. BUN &
creatinine, glucose, LFT's, UA
ethanol:
- found in alcoholic beverages, candies, mouthwashes, cold preparations,
perfumes
- 80% absorbed from the intestinal tract; most absorbed within 1 hour
unless there is delayed absorption (i.e., secondary to food)
- hypoglycemia (with or without seizures) is common
- treatment:
- children who are symptomatic or have serum levels > 50 mg/dl should
be hospitalized for observation and treatment within 1 hour in a conscious
patient, administer syrup of ipecac ; in an unconscious patient or after
1 hour perform gastric lavage after 1-1/2 hours supportive care is primary
focus (respiratory status, glucose maintenance)
- the amount of activated charcoal needed for adequate absorption is
so large its use is impractical
- hemodialysis with high toxic levels (esp. with renal and/or hepatic
impairment) may be indicated
isopropanol:
- found in rubbing alcohol, windshield deicers, glass cleaners, acne
preparations
- absorbed via ingestion, inhalation, or skin absorption
- 80% absorbed from the GI tract (when ingested) within 30 minutes (complete
in 2 hours)
- often presents with GI irritation, hypotension, miotic pupils, prolonged
CNS depression
- treatment:
- supportive care
- serial glucose levels (both hyper- and hypo-glycemia can be present)
- do not induce emesis (rapid
CNS depression with isopropanol), but gastric lavage is helpful
- efficacy of activated charcoal is unknown
- hemodialysis with deteriorating patient, esp. with renal and hepatic
impairment
methanol:
- found in window washer fluid, antifreeze, shellacs, gasohol, Sterno
- rapidly absorbed with peak levels in 30 - 60 minutes
- symptoms may be delayed 12 - 24 hours (toxicity is due to metabolite
formation)
- triad of symptoms: GI (N/V, pancreatitis), eyes (blurred vision,
central scotomata, fixed and dilated pupils), metabolic acidosis (caused
by the metabolite formic acid)
- treatment:
- syrup of ipecac within 30 minutes
- activated charcoal
- in a symptomatic patient, presence of acidosis, or peak level of 20
mg/dl ethanol infusion should be initiated (competition for alcohol dehydrogenase)
- bicarbonate therapy to correct acidosis
- folate (1.0 mg/kg IV q 4 hours x 6 doses) may be considered (oxidation
of ???)
- hemodialysis in deteriorating patient
ethylene glycol:
- found in antifreeze, windshield deicers, brake fluid
- rapidly absorbed in the GI tract with peak levels in 1 - 4 hours
- symptoms are ill-defined and delayed 4 - 8 hours:
- Stage 1: CNS depression, N/V, low-grade fever, metabolic acidosis
- Stage 2: occurs in severe cases and includes cardiovascular collapse,
bronchopneumonia
- Stage 3: 2-3 days later and includes renal insufficiency hypocalcemia
(and calcium oxalate deposition in tissues and can be found in the urine),
hypomagnesemia, leukocytosis, hyperkalemia, elevated CPK
- treatment:
- in a conscious patient within 30 minutes of ingestion administer syrup
of ipecac
- gastric lavage (if within 4 hours) and activated charcoal
- ethanol therapy for symptomatic patient or serum levels > 20 mg/dl
- forced diuresis may enhance elimination and prevent oxalate crystal
deposition in the kidney
- thiamine (100 mg) and pyridoxine (100 mg) q 6 hours x 2 days to help
decrease oxalate production
- hemodilaysis in deteriorating patient
Return to top
Anticholinergics
- found with atropine, phenothiazines, antihistamines, antispasmodics,
antimotility agents, cyclic antidepressants, plants, mushrooms
- block acetylcholine action in the autonomic ganglia and at the neuromuscular
junctions of voluntary muscle
- toxicity varies with the source
- little correlation with the dose, blood concentration, and effect
on the patient
- symptoms:
- "hot as a hare, blind as a bat, dry as a bone, red as a beet,
and mad as a hatter"
- laboratory, studies:
- ECG monitoring for dysrhythmias, prolonged QT interval, ST elevation
- urine drug screening is of limited value (will detect diphenhydramine,
some antihistamines, cyclic antidepressants)
- 1% pilocarpine drops into a dilated eye is sometimes diagnostic---pupil
will constrict in patients with underlying neuropathology but not if anticholinergic
is the etiology
- treatment:
- temperature control
- continuous ECG monitoring
- dysrhythmias respond to sodium bicarbonate (alkalinize the blood to
pH > 7.5), phenytoin or lidocaine
- gastric lavage and activated charcoal (gastric emptying can be delayed
12+ hours)
- dialysis not helpful
- seizures respond to lorazepam, follow with phenobarbitol
- deteriorating patients should be given physostigmine salicylate (works
by inhibiting acetylcholinesterase); dose children at 0.02 mg/kg IV q 5
minutes to maximum total dose of 2 mg, adolescents should be given 2.0
mg IV with a second dose of 1 - 2 mg if no reversal is obtained
Return to top
Barbiturates
- inhibit neurotransmission across neuronal and neuroeffector junctions
- different time-acting preparations
- presentation:
- CNS depression, slurred speech, dizziness, ataxia, coma cardiovascular
depression
- hypothermia (but fever can occur)
- complications: RTA, shock, pulmonary edema, cerebral edema,
aspiration pneumonitis, dysrhythmias
- laboratory, studies:
- usually not tested in urine toxicology screens
- ABG to follow respiratory status
- management:
- serum levels are not indicative of brain tissue concentrations, so
treat symptomatically multiple dose charcoal is effective with phenobarbitol
elimination
- forced diuresis with alkalinzation only with long-acting preparations
- can also administer a loop-diuretic
- maintain normothermia
- hemoperfusion, hemodialysis, and peritoneal dialysis only in severe
overdoses
Return to top
Benzodiazepines
- potentiate gamma-aminobutyric acid (GABA)
- presentation:
- ataxia, lethargy, slurred speech
- visual and auditory hallucinations
- laboratory studies:
- blood levels confirm exposure but are not clinically helpful
- often found in routine toxicology screens
- management:
- flumazenil
- adult: 0.2 mg IV initially then
0.3mg, then 0.5mg every minute to a total dose of 3 mg, or response is
seen.
- children: 10 mcg/kg x 2 doses
(checking on this dose)
- support respiratory status
Return to top
Cyclic Antidepressants
- responsible for the largest number of acute drug fatalities in the
past 2 decades
- block the reuptake of norepinephrine into the postganglionic neurons
with side effects:
- anticholinergic, blockade of norepinephrine reuptake, quinidine-like
effects on the myocardium
- rapidly absorbed from the GI tract, but absorption may be delayed with
an overdose due to delayed gastric emptying
- presentation:
- symptoms usually develop in 4 - 6 hours, but may be delayed for up
to 24 hours
- anticholinergic effects, increased sympathetic tone (secondary to blocked
norepinephine uptake), prolonged QRS, QT or PR interval, any type of dysrhythmia
including complete heart block and torsades de pointes
- children often present with seizures, coma and dysrhythmias
- laboratory studies:
- comprehensive drug screen
- ECG, with QRS segment and QT interval determination
- serial monitoring of electrolytes, magnesium, calcium, ABG's, renal
and liver
- CXR can indicate pulmonary edema or cardiac enlargement
- management:
- no emesis (CNS depression can be rapid)
- gastric lavage, charcoal decontamination (multiple doses due to enterohepatic
recirculation), and cathartics can be initiated hours after ingestion due
to decreased gastric motility
- cardiac monitoring
- dysrhythmias should be treated with alkalanization (sodium bicarbonate
or hyperventilation to achieve pH around 7.50) and phenytoin
- ventricular fibrillation and pulseless ventricular tachycardia should
be treated with electric cardioversion
- unresponsive dysrhythmias may respond to lidocaine, propranolol, or
physostigmine (lidocaine is the drug of choice for ventricular dysrhythmias)
- phenytoin acts as an antidysrhythmic as well as anticonvulsant
- physostigmine trial should only be used as last resort
- treat hypotension as needed with fluids and inotropic support
- treat seizures with benzodiazepine, phenytoin, or barbiturate
- forced diuresis and hemodialysis are not effective
- monitor for at least 6 hours; symptomatic patients need to be monitored
for 24 hours after asymptomatic
Return to top
Cocaine
- well absorbed via mucous membranes
- presentation:
- tachypnea, cyanosis, dyspnea, respiratory failure
- hypertension, dysrhythmias, CV collapse
- excitement, paranoia, seizures, irritability
- hyperthermia, muscle paralysis
- complications: myocardial infarction, subarachnoid hemorrhage,
aortic dissection, pulmonary edema, renal infarction, hepatotoxicity
- laboratory, studies:
- blood and urine screens levels not helpful clinically
- ECG for symptomatic patients
- management:
- supportive care for mild intoxifications
- GI decontamination
- do NOT nduce emesis
- support blood pressure and CV status
- propanolol only with life-threatening dysrhythmias (may cause paradoxic
hypertension and worsen coronary artery spasm)
- aggressively treat hyperthermia
- benzodiazepines may be needed to treat agitation
- given rapid metabolism, no elimination enhancement is necessary
Return to top
Iron
- rapidly absorbed from the small intestine with peak levels in 2-6 hours
after ingestion
- presentation: (4 clinical stages)
- 1st stage: occurs within a few hours; GI symptoms of nausea, abdominal
pain, corrosive iron effects in the GI tract
- 2nd stage: "honeymoon phase"; apparent improvement; lasts
as long as 36 hours
- 3rd stage: "shock phase"; variable when this occurs; free
iron causes venous pooling and third-spacing; also see heart failure, renal
failure, coagulopathies, hypoglycemia
- 4th stage: occurs days to weeks after the insult; GI tract scarring
- laboratory studies:
- CBC, glucose, TIBC, renal and hepatic functions, blood type and cross
are baseline
- stools and emesis tested for blood
- serum levels of iron should be drawn 2-4 hours after ingestion--a
later time period may be falsely low secondary to tissue distribution
- a negative x-ray does not necessarily exclude iron overdose
- deferoxamine challenge causes discoloration of the urine ("vin
rose")
- management:
- treat if symptomatic, regardless of serum iron level
- ingestions > 20 mg/kg require gastric emptying, lavage, and/or cathartics
- lavage with 1%-5% sodium bicarbonate solution may enhance results (precipitates
iron complex)
- charcoal is not effective
- deferoxamine mesylate
- chelates iron
- 15 mg/kg/hr IV
- give to patients who: are symptomatic, have iron concentration greater
than the TIBC, or have an iron concentration greater than 300-350 mg/dl
- hemodialysis only with renal failure
- exchange transfusion only with severe intoxications
- aggressive supportive care
- follow volume and cardiovascular status closely
- monitor blood loss
Return to top
Opioids
- common accidental ingestions due to cough preparations
- absorbed well by all routes except externally (through skin)
- presentation:
- most effects on the CNS and GI tract
- CNS: pinpoint pupils are usually present (not always) , coma, drowsiness,
seizures (especially with meperidine), ataxia
- CV: bradycardia, hypotension
- resp: respiratory depression
- GI: nausea, vomiting, constipation, urinary retention
- other: rash, itching
- laboratory studies:
- drug screen
- CV monitoring if symptomatic
- management:
- GI decontamination
- do NOT induce vomiting because of rapid onset of CNS symptoms
- naloxone
- < 20 kg: 0.1 mg/kg IV; > 20 kg 2.0 mg; repeat every 2-5 min to
max of 10 mg
- manage symptomatically; supportive care
Return to top
Organophosphates and Carbamates
- insecticides cholinesterase inhibitors
- prevent breakdown of acetylcholine
- clinical effects are due to overstimulation by acetylcholine of the
peripheral muscarinic junctions
- presentation:
- "DUMBELS" or "SLUDGE": Diarrhea, Urination, Miosis,
Bronchospasm, Emesis, Lacrimation, Salivation; or Salivation, Lacrimation,
Urination, Diarrhea, GI complaints, Emesis
- other effects: bradycardia or tachycardia, muscle fasciculations,
pallor, hypertension, hyperglycemia, lethargy, emotional lability, ataxia,
coma, convulsions, depression of cardiorespiratory drive, and dysrhythmias
- odor of garlic on the breath
- laboratory studies:
- RBC cholinesterase
- common abnormalities: hyperglycemia, glycosuria, albuminuria, ketoacidosis,
- leukocytosis with left shift
- management:
- gastric decontamination with lavage, activated charcoal, and cathartics
- clothes removed and skin cleaned thoroughly (even as late as 6 hour
after exposure)
- atropine antidote should be used immediately
- blocks acetylcholine at the muscarinic receptors, but does not reverse
nicotinic
- receptor overstimulation
- 12 yo or less: 0.05 mg/kg slow IV push followed by 0.02 - 0.05 mg/kg
every 5 - 20 minutes until adequate atropinized; > 12 yo 1 - 2 mg IV
as needed (high doses are required: adult average dosage is 40 mg/24
hr)
- atropinization is achieved when skin is dry and flushed, pupils are
dilated, rapid heartrate
- NOTE: because atropine does not reverse nicotinic effects, the fully
atropinized patient will still have respiratory muscle impairment due to
muscle weakness pralidoxime is useful to counteract nicotinic effects only
for organophosphate toxicity works as a cholinesterase reactivator at the
neuromuscular junction CNS function is unaffected (does not cross the blood-brain
barrier) give after atropinization (should begin within 36 hours of exposure)
12 yo or less: 25 - 50 mg/kg IV; adults 0.5 - 1 gm; repeat dose in 1-2
hours and then at 6-12 hour intervals if symptoms persist
- contraindicated medications: morphine (respiratory depression), methylxanthines
(lowers seizure threshold), and loop diuretics
Return to top
Phencyclidine
- PCP
- stimulates alpha-adrenergic receptors and potentiates catecholamines
- similar to ketamine
- rapid onset with duration of action up to 24 hours or longer, with
drug-induced psychosis lasting weeks with flashbacks
- presentation:
- symptoms vary with level of toxicity
- major effects are psychologic, sympathomimetic, cholinergic and cerebellar
- emotional lability, combative, panic reactions, coma, seizures
- rhabdomyolysis
- tachycardia, hypertension
- miosis, flushing
- nystagmus, ataxia
- most fatalities related to violent actions, not toxicity of the dose
- laboratory studies:
- routine drug screens
- levels are not useful clinically
- CBC, CPK, electrolytes, BUN, creatinine and UA for rhabdomyolysis
- management:
- supportive treatment
- GI decontamination
- keep well hydrated to less effects of rhabdomyolysis
- benzodiazepine for seizures and treatment of agitation
- treat hyperthermia
- support blood pressure
Return to top
Phenothiazines
- anti-cholinergic, adrenergic blocking, and quinidine-like effects
- presentation:
- dystonic reactions, coma, seizures
- neuroleptic syndrome: hyperthermia, skeletal muscle activity, autonomic
disturbances, extrapyramidal dysfunction
- extrapyramidal reactions of acute dystonia are common with pediatric
overdoses (can be delayed and recur up to a week later)
- laboratory studies:
- routine drug urine screens
- ferric chloride test: add ferric chloride to urine--purple color change
is positive result
- blood levels do not correlate with clinical symptoms
- may be detectable per x-ray
- ECG monitoring to detect QT prolongation and other dysrhythmias
- management:
- acute dystonic reactions:
- diphenhydramine (can schedule dosing)
- do NOT use benztropine mesylate (Cogentin) because it aggravates anticholinergic
effects
- diazepam
- malignant hyperthermia:
- dantrolene 2.5 mg/kg (maximum to 10 mg/kg) every 6 hours
- cooling blankets
- activated charcoal, forced diuresis, dialysis are not helpful
Return to top
Salicylates
- found in aspirin tablets as well as many topical preparations (Ben
Gay)
- many systemic effects
- presentation:
- metabolic acidosis with a deep, driven, normal rate hyperpnea
- dehydration causes tachycardia, orthostatic changes
- fever, hyperglycemia (hypoglycemia is late occurrence), tetany, parethesias
cerebral edema, hepatotoxicity
- lethargy or excitability, coma, seizures
- hyponatremia, hypernatremia, hypocalcemia or hypokalemia
- laboratory studies:
- Done nomogram with first level obtained 6 hours after ingestion
- ferric chloride test: add 10% ferric chloride to urine--purple color
is a positive test
- electrolytes, ABG, BUN, creatinine, glucose, CBC, urinalysis as baseline
- may need calcium, LFTs, PT
- serum level 6 and 10 hours after ingestion
- often an acetaminophen level is indicated because of unreliable history
- chest x-ray if pulmonary edema is suspected
- head CT if cerebral edema is suspected
- management:
- gastric decontamination
- activated charcoal (multiple doses)
- * fluid management
- goal for urine output is 3-6 ml/100 ml maintenance fluid/hr
- aggressive diuresis contraindicated with cerebral or pulmonary edema
- follow electrolytes closely
- alkalinization
- titrate to serum pH 7.5 over 4-8 hours
- optimal urine pH is 8.0-8.5
- treat seizures - make sure electrolyte imbalance is not the etiology
- dialysis indicated only for severe symptoms that are not responding
to treatment
Return to top
Sympathomimetics
- diet aids, cold and cough preparations
- readily absorbed from GI tract
- presentation:
- restlessness, irritability, tremors, hyperreflexia, confusion, coma,
seizures
- dilated pupils, flushed skin, diaphoresis
- hypertension, dysrhythmias, CV collapse
- tachypnea, fever, rhabdomyolysis
- laboratory studies:
- routine drug screen
- levels are not helpful
- electrolytes, CPK, and myoglobin in the agitated patient
- CT for neurologic deficits
- management:
- support CV status (treat hypertension, dysrhythmias)
- GI decontamination
- persistent neurologic changes require CT imaging
- supportive care
Return to top
BIBLIOGRAPHY
- Anderson, Angela C. Iron Poisoning in Children Current Opinion
in Pediatrics, 1994, 6: 289-294.
- Barkin, Roger M. and Rosen, Peter. Emergency Pediatrics. A Guide
to Ambulatory Care Mosby Year Book, St. Louis, 1994: 324-368.
- Barkin, Roger M..et al. Pediatric Emergency Medicine. Concepts
and Clinical Practice Mosby Year Book, St. Louis, 1992: 463-530.
- Blumer, Jeffrey L. A Practical Guide to Pediatric Intensive Care
Mosby Yearbook, St. Louis, 1990: 660-739.
- Conway Jr., Edward E. Recognizing Carbon Monoxide Toxicity Contemporary
Pediatrics, Feb. 1994: 24-32.
- Fuhrman, Bradley P. and Zimmerman, Jerry J. Pediatric Critical
Care Mosby Yearbook, St. Louis, 1992: 1109-1153.
- Henretig, Fred M. A Guide to Acute Medical Management of Intoxication
in Adolescents Adolescent Health Update, June 1994, 6(3).
- Johnson, Kevin B. The Harriet Lane Handbook Thirteenth Edition.
Mosby Year Book, St. Louis, 1993: 29-56.
- Kulig, Kenneth. Initial Management of Ingestions of Toxic Substances
The New England Journal of Medicine, June 1992, 326(25): 1677-1681.
- Levin, Daniel L. and Morris, Francis C. Essentials of Pediatric
Intensive Care Quality Medical Publishing, Inc., St. Louis, 1990:
593-670.
- Liebelt, Erica L. and Shannon, Michael W. Small Doses, Big Problems:
A Selected Review of Highly Toxic Common Medications Pediatric Emergency
Care, 1993, 9(5): 292-296.
- Lovejoy, Frederick H. et al. Common Etiologies and New Approaches
to Management of Poisoning in Pediatric Practice Current Opinion in
Pediatrics, 1993, 5: 524-530.
- Mack, Ronald B. Dishwasher Detergent Toxicity--Here's Looking at You,
Kid Contemporary Pediatrics, Nov. 1993: 49-58.
- Tinker, Thomas D. Hydrocarbon Ingestion in Children: Its Sequelae
and Management Oklahoma State Medical Journal, Feb. 1986: 95-100.
- Woolf, Alan D. Poisoning in Children and Adolescents Pediatrics
in Review, Nov. 1993, 14(11): 411-422.
Return to top
Return to Acute Care Index
This page is meant for educational purposes only, drug dosing should
be verified from appropriate sources prior to any use in patient care.
Questions or comments regarding his outline can be sent to the author
at:
mmadsen@inet-serv.net
This page last updated on 9/5/97 at 0950CDT