Week 5: Toxicology Part I Flashcards
• Poison prevention/approach to the poisoned patient • Pediatric unintentional exposures • Opioid, benzos, cannabinoids, sympathomimetics (1 of 2)
Pediatric Toxicology Epidemiology
2 mill toxic exposures reporte annualy
*50% in children <6 y.o
*small rate of fatalities (<1%)
most common toxins: analgesics, cosmetics, and hosehold cleaning substances
evaluation of the poisoned child
infant/toddler:
*exploe natural curiosities and surroundings
*most exposures w.o intent ot harm and result in minimal , if any, Adverse outcomes
*if child presents w. altered level of ocnciousness, metabolic disturbances, neurologic dysfunction, cardio/pulmonary distress, important to include toxic exposure as far as differential
Supportive care for pediatrix tox
follows Pediatric Advanced Life Support (PALS) guidelines
usually begins w. airway stabilization
*early antidote administration (if indicated)
Toxin-Antidote
Organophosphates (e.g insecticides, pesticides)
atropine
Toxin-Antidote
Iron
Deferoxamine
Toxin-Antidote
digoxin
Digoxin antibody fragments (Fab)
Toxin-Antidote
benzodiazepines
Flumezanil
Toxin-Antidote
Lead
Edetate Calcium disodium (ADTA)
Toxin-Antidote
Methemoglobulinemia
methylene blue
Toxin-Antidote
heparin
Protamine
Toxin-Antidote
Salicylates, TCA’s
sodium bicarbonate
Toxin-Antidote
Warfarin
Vitamin K
Hx and Physical Exam of pediatric tox
*need a smuch detail as possible (volume ingested, tablet counts, containers of substance in question and a complete review of toxic substances in viciinty of the child when child was exposed
inquire about other places child may have been(15% occurs outside the home)
a thorough hx for adolescent is more difficult bc ingestion could be intentional an dpts may not be forthcoming
must peform physical exam and mental status and vital signs( neurologic exam including eval. of pupil size and reactivity
Lab evaluation of ped tox
lab evaluations should be directed by hx and PE
pts should have serum chemistries and acid base balanced assessed
alchool ingestion? ->serum osmolality
BB or ccb?-> electrocardiogram
serum APAP should be taken as well since APAP is widely available ad in combo with othe rproducts and SS may not occur after hours of ingestion
Gastric Decontamination use
lack of evidence of efficacy of gastirc decontamination strategies has decreased its use
Gastric decontamination MEthods
Syrup of Ipepac:
NOT RECOMMENDED
use had no impact of on either ED referral or outcomes
Gastric Lavage:
NOT RECOMMENDED
lack if evidence of efeciveness and relatively high complication rate
Activated charcoal (AC)
consider use of AC within 1 hr in pts w. a potentially toxic ingestion:
dose: 0.5-1g/kg (wiehgt based dosing preffered)
Optimal ratio: 10gAC:1g of drug(not preffered because often times because amount ingested sometimes unknown)
Multiple dose AC (MDAC)
admin of more than 2 sequential doses
prevent prolonged absoprption or enterohepatic recirculation
repeated admin of AC enhances gastric dialysis of certain drugs(e.g phenbarbital, carbamezapine, amitriptilyne, digoxin, phenytoin)
Dose: Loading dose of 1g/kg followed by 0.5g/kg q4-6h for up to 24h
Whole Bowel Irrigation (wbi)
performed uding PEG and elctrolyte solution. considered in pts who ingested sustained release products, enteric coated, or iron and other metals. can give orally, but NG route in children is easier
dose: 0.5L/hr (small children) up to 1.2-2L/hr (older shildren and adolescents) for 4-6 hrs
Products: GoLYTLELY, NuLYTELY, CoLYTE
*DO NOT USE MIRALAX) contains no electrolytes and icnreases risk of electrolyte imbalance
Select Poisonings in children
Acetominophen
Toxic ingestion range:
GI Decontamination:
Antidote:
Antidote AE:
Dosing:
Toxic ingestion range: >200 mg/kg (oral or >60mg/kg IV) in children
GI Decontamination: AC within 1 hour
Antidote: n-acetylcysteine (NAC)
Antidote AE: N/V, diarrhea, anaphylactoid reactions (rare), unpleasant taste (oral)
Dosing:
a) Oral:
*140 mg/kg x1
*70 mg/kg q4hrs x17 doses
b) IV:
*150 mg/kg infused over 1 hr
*50 mg/kg infused over 4 hours
*100 mg/kg infused over 16 hrs
*NOTE: MORE CONCENTRATION SOLUTION SHOULD BE GIVEN. to prevent hyponatremia due to excessive fluid administration. should be diluted to a conc of 40mg/mL in all 3 bags
Select Poisonings
Ethylene Glycol (engine coolant)
Toxic ingestion metabolite:
GI Decontamination:
Antidote:
Antidote AE:–
Dosing:–
Select Poisonings
Toxic ingestion range: AE-> ethylene glycol->gylcoaldehyde->glycolic acis->glycolic acid +oxalic acid
causes metabolic acidoses, cardiopulmonary compromise(12-24hrs after ingestion), nephrotixity 1-3 days, hypocalcemia
GI Decontamination: not recommended. Mainly supportive care
*pyradoxamine IV 100mg/day +thiamine IV 100 mg/dy
Antidote: ethanol (prevents metabolism of ethylene glycol by competing for alcohol dehydrogenase and has greater affinity for enzyme, inhibiting metabolism of ethylene glycol) or fomepizole
Antidote AE:–
Dosing:–
Select Poisonings
Methanol
Toxic ingestion metabolite:
GI Decontamination:
Antidote:
Antidote AE:–
Dosing:–
Select Poisonings
Methanol
Toxic ingestion: (e.g solvents, antifreeze, fuels, windshield washer fluid). methanol metbaolytes cause the toxicity.
causes metabolic acidoses, blindness due to accumulation of formic acid
methanol->formaldehyde->formic acid
GI Decontamination: not recommended
folic acid IV 1mg/kg (max 50mg) q4-6 hrs for 24 hrs
Antidote: ethanol or fomepizole (data limited, risk beenfit ratio is low)
Antidote AE:–
Dosing:–
Ethylene Glycol and Methanol Antidotes
purpose:
Ethanol:
Dosing:
notes:
Fomepizole:
purpose:
inhibiting alcohol dehydrogenase activity. prevents accumulation of toxic metabolites and allows for renal and pulmonary eliminiation of parent alcohols
Ethanol:
a)Dosing:
load: 8mL/kg over 1 hr
infusion: 0.8 mL/kg/hr
b)notes:
*serum conc. of 100-150 mg/dL
*requires central venous catheter due to high osmolality
*respiratory depression
*TDM
* continued until ethylene glycol or methanol conc are <25mg/dL
Fomepizole:
a)dosing:
load:15mg/kg
10mg/kg q12hrs x 4 hrs
15mg/kg q12hrs until serum conc of toxic alcohol are <25 mg/dL
b)notes:
*1st line therapy for toxic alcohol ingestions. more expensive, but doesnt require TDM
*4x as expensive as etoh
*less dosing errors
*less monitoring: no central venous access,no alteration of conciousness, no alteration in blood glucose or electrolytes, no ICU monitoring
Select Poisonings
Household cleaners
Toxic ingestion :
GI Decontamination:
Antidote:
Antidote AE:–
Dosing:–
Select Poisonings
Household cleaners/ caustic exposures
Toxic ingestion:
second most common reported exposures in children
*household cleaners=beaches, detergents, soaps
*caustics=toilet cleaners, drain cleaners, oven cleaners
GI Decontamination: not recommended
management: supportive (i.e fluids)
if gi injury occurs, further medical and pharm mgt (PPI’s) may be indicated
Antidote: none
Antidote AE:–
Dosing:–
Select Poisonings
Foreign Body ingestion
Toxic ingestion :
GI Decontamination:
Antidote:
Antidote AE:
Dosing:
Select Poisonings
examples: toys, disc batteries, ornaments
Toxic ingestion:
a)disc batteries
*usually pass through esophagus into stomach and pass through intestinal tract within 1-2 weeks
8battery may lodge inesophagus and result in seirous and lifethreatening complications suhc as burns, perforations, and fistulate
SS: vomiting, diarrhea, abdominal pain, fever, refusal to eat or drink, dysphagia.
GI Decontamination: manual removal if esophageal impaction suspected.
NOTE: national battery ingestion hotline: 1800-498-8666
Antidote:–
Antidote AE:–
Dosing:–
Select Poisonings
Cough and Cold Preperations (ex: pseudoephedrine)
Toxic ingestion:
GI Decontamination:
management:
Antidote:–
Antidote AE:–
Dosing:–
Select Poisonings
Cough and Cold Preperations (ex: pseudoephedrine)
Toxic ingestion:
*2007: FDA advisory panel recommended that these drugs be avoided in children <6 y.o
GI Decontamination: AC if pt presents early enough
management:
*symptomatic management of HTN (e.g labetolol, nicardipine), arryhtmias (e.g amiodarone), and seizures (benzos)
Antidote:–
Antidote AE:–
Dosing:–
Resources for poisoing
1) upstate NY poison center
2)poison prevention
3) poison control center hotline: 1800-222-1222
Difference btw medical management of poisoned child or adolescent vs adult
similar
obtaining accurate and hx and amount ingested is difficult
physical and lab examination, and pt presentation is key to effective management
Substance categories mos frequesntly involved in ped(</5) exposures (top 25)
cosmetics/ personal care products
household cleaning substances
analgesics
foreign body/toys/ misc.
dietary supplements/herbals/homeopthic
vitamins
substance categories most frequently involved in ped (</5) deaths
analgesics
fumes/gases/vapors
cv DRUGS
BATTERIES
CHEMICALS
ALCOHOLS
Poison prevention methods
child proof caps/ containers
storage location
environmental precautions(e.g opening the garage door)
taking appropriate doses
disposing of unused, expired drugs
never mix household products
general information collected when evaluating exposure
age and weight
health hx
time of exposure
route of exposure
present symptoms
exact name of product, if available
estimate to how much may have been ingested
strength of product
formulation of product (IR, XR, etc.)
occupation?
notes: (i.e suicide note)
general treatment approach to poisonings
assess the pt
*level of exposure
*amount
*symptoms
selftreatment (at home)
refferal to hospital
*moderate-severe exposure
*intentional ingestion (always refer to hosital)
ABC’s of poison management
Airway
Breathing
Circulation
Dextrose/decontamination
Ekg/elimination
non pharm therapies for poisonings
inhalational
*remove pt form exposure area
topical/dermal
*irrigation w. soap and water
ingestions
*fluids?: sometimes fluids can increase absoprtion potential
*gag reflex?: not recommended in most situations
pharm elimination strategies
syrup of irepac:
activated charcoal
whole bowel irrigtion
syrup of ipecac:
*no documented benefit
*no longer commercially available
activated charcoal
*adsorbent 950-2000m^2/g surface area
time window: 1 hr
*substances which will not bind: ionized metals(ex lithium), alcohols, gasoline
*sorbitol to improve palatability
*ADR: vomiting, black tarry stools
*notes: pneumonitis if aspirated. make sure to maintain airway
whole bowel irrigation
*PEG+electrolyte formulation
1-2L/hr PO/NG until rectal effluent is clear
*minimizes time in GI tract fo absoprtion
*beneficial for XR products and packers
non pharm elimination strategies for poisoning
orogastric lavage:
*stomach pumping
*potentially utilized if agent toxicity can prduce serios toxicity and no antidote exists
*time window gives reason to believe agent may still be in stomach
hemodialysis:
*used when other elimination strategies not effective/ CI
*potential to produce serious toxicity
*agent able to be removed through filtration
*EXTRIP workgroup
Toxidromes
what is it
constellation of signs and symptoms that point to a class of toxin based upon understanding of pharmacology
*helps provide information in unkown overdose
helps provide consistency in known overdoses
common toxicdome chategories
agrenergic/sympathomimemtic
cholinergic
anticholinergic
sedative-hypnotic
opioid
Anticholinergic toxidrome
causative agents:
SS:
*mental status:
*vitals:
*pupils
*bowel sounds
Anitidote:
causative agents: antcholinergics (ex: antihistmaines, TCAs)
SS:
blind as a bat (mydriasis)
Hot as a desert
dry as a bone
red as a beat
mad as a hatter
also.. tachycardic, absent bowel sounds
mental status: decreases, agitated, seizures
vitals: inc bp, hr, rr, temp
pupils: inc size
bowel sounds: absent
antidote: physostigmine
0.5mg-2mg IV
anticholiesterase inhibitor
unpopular in use
Sedative-Hypnotic toxidrome
causative agents:
SS:
Anitidote:
causative agents: (ex: benzos, cns depressants,ETOH)
SS:
*relatively stable vitals
* Repsonse to painful stimuli
mental status: decreased
vitals: dec bp, hr, rr, no change in temp
pupils: no change in size
bowel sound spresent
Adrenergic/ Sympathomimetic Toxidrome
causative agents:
SS:
Anitidote:
causative agents: (ex:cocaine, amphetamines)
SS: vitals: incr. HR, BP, RR, T
pt may prsent accutely aggitated, alert;seizures
*diaphoretic
*bowel sounds present
*tremor
*increased pupil size
antidote:–
Opioid Toxidrome
causative agents:
SS:
Anitidote:
causative agents: opioids
SS: unresponsive
unrepsonsive to painful stimuli
lower vitals
hyporeflexic
bowel sounds absent
pinpoint pupils
normal mucous membranes
antidone: naloxone
Cholinergic Toxidrome
causative agents:
SS:
antidote:
causative agent: cholinergics (ex: organophosphates)
SS:
SLUDGE
S: salivation
L:lacrimation
U:urination
D: defecation
G: gastric cramps
E: emesis
Killer B’s
B: bradycardia
B: bronchorrhea (secretions in lungs)
B: bronchospasm
decreased pupil size. bowel sounds present
antidote:
*atropine
1mg IV-titrate to effect (no max dose in cholinergic toxidrome)
inhibits muscarinic actions of Ach
*Pralidoxime (2-PAM)
30mg/kg IV load
8-10mg/kg/hr continuous infusion
*reactivates cholinesterase
Notable toxidrome exclusions
APAP:
*no toxidrome
*level w. every intentional or unknown ingestion
*4 hr level
*easy access
*fatal
Salicylates
*unique toxidrome
*level w. every intentional or unknown ingestion
*serial levels
*easy access
*fatal
opioid effects on receptors
mu receptor: central pain analgesia, resp depresion
kappa receptor: spinal analgesia, miosis
delta receptor: central and spinal analgesia, cough supression
opioid categories
agoinsts
codeine
fentanyl
heorin
morphine
hydrocodone
oxycodone
hydromorphone
loperamide
meperidine
tapentadol
tramadol
opioid categories
partial agonist
buprenorphine
opioid categories
agonist-antagonist
nalbuphine
butorphanol
pentazocine
opioid categories
antagonist
naloxone
methylnaltrexone
naltrexone
alvimopan
genomic considerations for opioids
cyp2d6 genetic polymorphisms may effect opioids such as codeine:
codeine metabolized to morphine by cyp2d6.
risks for ultrametabolizers, can increase resp depression
opioid toxidrome
clinical presentation:
management:
antidote:
clinical presentation:
decreased mental status
pinpoint pupils
decreased bowel sounds
depressed respiration
management:
administer antidote
protect airway
anitidote: naloxone
Naloxone route of admin
IM:
dose: 0.4mg
peak conc: low peak
IV
dose: 0.4 mg
peakconc: high peak and fast time to peak
has smallest duration of effect
IN
dose: 1mg, 2mg, 4mg
*IN 4 mg highest peak, slower time to peak than iV
Naloxone dosing strategies
non-opioid dependent dose: IV 0.4 mg
opioid dependent pt.: IV 0.04 mg and titrate to effect (avoids withdrawal)
bystanders:
*IM 2mg (Evzio: D/C)
*IN 4mg (Narcan)
continuous infusion: calculate dose needed to respond to naloxone, give 1/2 initial dose as bolus, then start 2/3 of new bolus dose per hour
AE of naloxone treatment
runny nose, flash pulmonary edema, acute precipitated withdrawal
Duration of actions of different opioids
and comparison of duration of actions of opioids to duration of action of naloxone
Heroin<oxycodone<morphine<methdone
heroin DOA~=naloxone DUA
oxydone DOA~3x> naloxone doa
Morphine DOA~3x> naloxone DOA
methadone DOA~8x> naloxone DOA
overdose w. opioids with longer durations than naloxone may need to be dosed multiple times or consider continuous infusion
Naloxone Induced Pulmonary Edema
incidence: 0.2-3.6%
moa: adrenergic response, caecholamine curge causing tachycardia, tachypnea, HTN
*shift in blood volume into pulmonary vasculature, causing pulmonary vasoconstrictoin, pulmonary htn, Fluid leakage into lungs
Treatment: diuretics
prevention: smaller initial doses of naloxone
Loperimide (immodium) Overdose
indication: otc anti-diarrheal
moa: inhibits intestinal peristalsis through mu-opioid receptor agonism
toxidrome: opioid
clinical presentation: opioid overdose,
severe cardiac arrythmias
*BBB effects
*P-GLYCOPROTEIN carrier brings loperimide through bbb
*co admin of PGP inhibitor also enhances effects
dose:
2-4 mg PRN (max 16mg/day
overdose: 30mg-200 mg (+)
management of Loperomide overdose
Respiratory depression
*naloxone
cardiac disturbances:
*IV Mg for long qt intervals
*sodium bicarb
* iV isoproternol
*transcutaneous pacing
CPR and ACLS
benzodiazepines
end in -AM
moa: bind to benzo rceptors on postsynaptic GABA neurons. inhibition of gaba increase Cl- ion permability, causing hyperpolarization (less excitable) and stabilization. causing inhibition of cns
flumezanil
moa: compettive antagonist of benzo receptor site
dose: 0.2 mg IV over 15 seconds
peds: 0.01 mg/kg IV
onset: 1-2 min
duration: variable, re-dosing may be necessary
indication?
benzo withdrawal SS
slevere sleep disturbances
irritability
increase tension and anxiety
panic attacks
sweating
difficulty in concentration
dry retching and nausea
palpitations
headache
psychotic reaction
seizures
to use or not use flumazenil
contraversial
benzos have protectant effect, relatively non lethal component of toxicity. can cause resp depression
benzo reversals with flumezanil can potentiate lethal seizures, may not even reverse resp depression
Polysubstance Overdose manegement
elimination: e.g activated charcoal
administer antidote: i.e NAC
supportive care: benzodiazepines
indications for flumazenil
Procedural sedation:
*okay to use if pt is not benzo depndent(so u wont precipitate withdrawal) or has hx of epilepsy
unintentional, pediatric exposure:
*can be pretty certain pt is not benzo dependent, wont precipitate withdrawal
