Week 5: Toxicology Part I

Question 1

Pediatric Toxicology Epidemiology

Answer 1

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

Question 2

evaluation of the poisoned child

Answer 2

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

Question 3

Supportive care for pediatrix tox

Answer 3

follows Pediatric Advanced Life Support (PALS) guidelines

usually begins w. airway stabilization

*early antidote administration (if indicated)

Question 4

Toxin-Antidote

Organophosphates (e.g insecticides, pesticides)

Answer 4

atropine

Question 5

Toxin-Antidote

Iron

Answer 5

Deferoxamine

Question 6

Toxin-Antidote

digoxin

Answer 6

Digoxin antibody fragments (Fab)

Question 7

Toxin-Antidote

benzodiazepines

Answer 7

Flumezanil

Question 8

Toxin-Antidote

Lead

Answer 8

Edetate Calcium disodium (ADTA)

Question 9

Toxin-Antidote

Methemoglobulinemia

Answer 9

methylene blue

Question 10

Toxin-Antidote

heparin

Answer 10

Protamine

Question 11

Toxin-Antidote

Salicylates, TCA’s

Answer 11

sodium bicarbonate

Question 12

Toxin-Antidote

Warfarin

Answer 12

Vitamin K

Question 13

Hx and Physical Exam of pediatric tox

Answer 13

*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

Question 14

Lab evaluation of ped tox

Answer 14

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

Question 15

Gastric Decontamination use

Answer 15

lack of evidence of efficacy of gastirc decontamination strategies has decreased its use

Question 16

Gastric decontamination MEthods

Answer 16

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

Question 17

Select Poisonings in children

Acetominophen

Toxic ingestion range:

GI Decontamination:

Antidote:

Antidote AE:

Dosing:

Answer 17

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

Question 18

Select Poisonings

Ethylene Glycol (engine coolant)

Toxic ingestion metabolite:

GI Decontamination:

Antidote:

Antidote AE:–

Dosing:–

Answer 18

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:–

Question 19

Select Poisonings

Methanol

Toxic ingestion metabolite:

GI Decontamination:

Antidote:

Antidote AE:–

Dosing:–

Answer 19

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:–

Question 20

Ethylene Glycol and Methanol Antidotes

purpose:

Ethanol:
Dosing:
notes:

Fomepizole:

Answer 20

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

Question 21

Select Poisonings

Household cleaners

Toxic ingestion :

GI Decontamination:

Antidote:

Antidote AE:–

Dosing:–

Answer 21

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:–

Question 22

Select Poisonings

Foreign Body ingestion

Toxic ingestion :

GI Decontamination:

Antidote:

Antidote AE:

Dosing:

Answer 22

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:–

Question 23

Select Poisonings

Cough and Cold Preperations (ex: pseudoephedrine)

Toxic ingestion:

GI Decontamination:

management:

Antidote:–

Antidote AE:–

Dosing:–

Answer 23

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:–

Question 24

Resources for poisoing

Answer 24

1) upstate NY poison center

2)poison prevention

3) poison control center hotline: 1800-222-1222

Question 25

Difference btw medical management of poisoned child or adolescent vs adult

Answer 25

similar obtaining accurate and hx and amount ingested is difficult physical and lab examination, and pt presentation is key to effective management

Question 26

Substance categories mos frequesntly involved in ped(

Answer 26

cosmetics/ personal care products household cleaning substances analgesics foreign body/toys/ misc. dietary supplements/herbals/homeopthic vitamins

Question 27

substance categories most frequently involved in ped (

Answer 27

analgesics fumes/gases/vapors cv DRUGS BATTERIES CHEMICALS ALCOHOLS

Question 28

Poison prevention methods

Answer 28

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

Question 29

general information collected when evaluating exposure

Answer 29

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)

Question 30

general treatment approach to poisonings

Answer 30

assess the pt *level of exposure *amount *symptoms selftreatment (at home) refferal to hospital *moderate-severe exposure *intentional ingestion (always refer to hosital)

Question 31

ABC's of poison management

Answer 31

Airway Breathing Circulation Dextrose/decontamination Ekg/elimination

Question 32

non pharm therapies for poisonings

Answer 32

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

Question 33

pharm elimination strategies syrup of irepac: activated charcoal whole bowel irrigtion

Answer 33

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

Question 34

non pharm elimination strategies for poisoning

Answer 34

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

Question 35

Toxidromes what is it

Answer 35

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

Question 36

common toxicdome chategories

Answer 36

agrenergic/sympathomimemtic cholinergic anticholinergic sedative-hypnotic opioid

Question 37

Anticholinergic toxidrome causative agents: SS: *mental status: *vitals: *pupils *bowel sounds Anitidote:

Answer 37

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

Question 38

Sedative-Hypnotic toxidrome causative agents: SS: Anitidote:

Answer 38

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

Question 39

Adrenergic/ Sympathomimetic Toxidrome causative agents: SS: Anitidote:

Answer 39

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:--

Question 40

Opioid Toxidrome causative agents: SS: Anitidote:

Answer 40

causative agents: opioids SS: unresponsive unrepsonsive to painful stimuli lower vitals hyporeflexic bowel sounds absent pinpoint pupils normal mucous membranes antidone: naloxone

Question 41

Cholinergic Toxidrome causative agents: SS: antidote:

Answer 41

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

Question 42

Notable toxidrome exclusions

Answer 42

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

Question 43

opioid effects on receptors

Answer 43

mu receptor: central pain analgesia, resp depresion kappa receptor: spinal analgesia, miosis delta receptor: central and spinal analgesia, cough supression

Question 44

opioid categories agoinsts

Answer 44

codeine fentanyl heorin morphine hydrocodone oxycodone hydromorphone loperamide meperidine tapentadol tramadol

Question 45

opioid categories partial agonist

Answer 45

buprenorphine

Question 46

opioid categories agonist-antagonist

Answer 46

nalbuphine butorphanol pentazocine

Question 47

opioid categories antagonist

Answer 47

naloxone methylnaltrexone naltrexone alvimopan

Question 48

genomic considerations for opioids

Answer 48

cyp2d6 genetic polymorphisms may effect opioids such as codeine: codeine metabolized to morphine by cyp2d6. risks for ultrametabolizers, can increase resp depression

Question 49

opioid toxidrome clinical presentation: management: antidote:

Answer 49

clinical presentation: decreased mental status pinpoint pupils decreased bowel sounds depressed respiration management: administer antidote protect airway anitidote: naloxone

Question 50

Naloxone route of admin

Answer 50

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

Question 51

Naloxone dosing strategies

Answer 51

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

Question 52

AE of naloxone treatment

Answer 52

runny nose, flash pulmonary edema, acute precipitated withdrawal

Question 53

Duration of actions of different opioids and comparison of duration of actions of opioids to duration of action of naloxone

Answer 53

Heroin 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

Question 54

Naloxone Induced Pulmonary Edema

Answer 54

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

Question 55

Loperimide (immodium) Overdose

Answer 55

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 (+)

Question 56

management of Loperomide overdose

Answer 56

Respiratory depression *naloxone cardiac disturbances: *IV Mg for long qt intervals *sodium bicarb * iV isoproternol *transcutaneous pacing CPR and ACLS

Question 57

benzodiazepines

Answer 57

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

Question 58

flumezanil

Answer 58

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?

Question 59

benzo withdrawal SS

Answer 59

slevere sleep disturbances irritability increase tension and anxiety panic attacks sweating difficulty in concentration dry retching and nausea palpitations headache psychotic reaction seizures

Question 60

to use or not use flumazenil

Answer 60

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

Question 61

Polysubstance Overdose manegement

Answer 61

elimination: e.g activated charcoal administer antidote: i.e NAC supportive care: benzodiazepines

Question 62

indications for flumazenil

Answer 62

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