34: Toxic Alcohols Flashcards
ethanol key effect
metabolic acidosis
methanol key effect
metabolic acidosis, hyperosmolality, retinal damage, neuro dysfunction
methanol is metabolized to 3 substances which causes toxicity
formic acid, lactic acid, ketone
ethylene glycol is metabolized to 2 substances which causes toxicity
glycolic aid
calcium oxalate
isopropranolol is metabolized to _____ which causes ______
acetone, causes ketosis (only alcohol that deoesnt produce organic acids and therefore does not cause met acidosis).
what is the tx for ketosis
no tx, just time and IV fluids
3 types of exposure for methanol and ethylene glycol
suicide/ homicide
accidental
recreational
T or F: methanol poisonings are often repeat pts
T
list 2 sources of MeOH
windshield wiper fluid, varnish, pain thinner (huffing), fuel, industrial denaturant, moonshine
list 2 sources of EG
antifreeze, natural gas industry, liquid cooled computers, household cleaning products, pesticides, industrial solvents (for paints, plastics)
methanol is metabolized by ADH into _________ then metabolized by formaldehyde dehydrogenase into ________
formaldehyde
formic acid
ethylene glycol is metabolized by ADH into ________ then aldehyde dehydrogenase into _____ and later _______
glycoaldehyde
glycolic acid
oxalic acid
fomepizole and ethanol are both competitive inhibitors of
ADH
EtOH becomes zero order at
1mM (DUI 17mM)
what is zero order
when an enzyme is saturated and rate of metabolism is indep of drug conc
what is first order
when rate is directly proportional to substrate conc (rate dep on drug conc)
which of well absorbed inhalational + dermal
1. MeOH
2. EG
3. both
4. neither
1
which of not well absorbed INH and topical
1. MeOH
2. EG
3. both
4. neither
2
what is the decontamination protocol for MeOH and EG
use NG tube within 1hr to suction stomach
no role for AC as it does not absorb alcohols
T or F: AC may be used in MeOH and EG toxicity
F- can’t absorb alcohols
hallmarks of methanol toxicity
metabolic acidosis and visual problems
formic acid MOA (formed from methanol)
inhibits cytochrome C oxidase (mitochondrial ETC) = stops OXPHOS, ATP production = tissue hypoxia
________ is the metabolite of methanol responsible for photoreceptor death, decreased visual acuity, photophobia, blurred vision, abd pain
formic acid
describe stage 1 of methanol toxicity
mimics ethanol intoxication
inebriation, gastric irritation
absence doesn’t rule out toxic concs
when does stage 2 methanol toxicity set in
6-30h
describe stage 2 methanol toxicity
latent period- critical
inebriation resolves
may be asymptomatic (coingestionof EtOH common)
describe stage 3 methanol toxicity
visual sx start to appear (blurred vision, blindness)
seizures, coma, cerebral edema, herniation
cardiac failure, resp arrest`
ethylene glycol causes metabolic acidosis and organ dysfunction primarily from ________ and _______
glycolic and oxalic acid
glycolic acid MOA toxicity
overwhelms HCO3- buffering ability = impairmet of celular resp
oxalic acid MOA toxicity
forms calcium oxalic crystals = precipitate in blood = clugs renal microcirc = tubular necrosis (oxalic acid + Ca2+)
leads to hypocalcemia = myocardial dysfxn and renal failure
stage 1 of EG toxicity time + sx
30min-12hrs
mimics ethanol intoxication, early neuro CNS depression, cerebral edema, seizures
stage 2 EG toxicity time + sx
12-24hrs
cardiopulmonary stage- cardiac dysfxn, shock, tachypnea, ARDs
stage 3 EG toxicity time + sx
24-72hrs
renal failure stage
stage 3 EG toxiicty sx
late neurologic damage
describe anion and osmolal gap changes in alcohol intoxication
osmolal gap decreases while anion gap increases
is there osmolal gap standardization?
no- many different equations and no consensus on upper limit (between 10-20 mOsm)
ranges may vary between labs
osmolal gap sensitivity and specificity?
low for both
why is there low sensitivity in measuring osmolal gap
values range ~20mOsm
EG level >20mg/dL shift in osmolal gap only 3mOsm/L
baseline is at lower end of normal- clinically sig intoxication within normal gap
later stages of intoxication as EG or meOH are metabolized = osmolal gap may eb absent
EG lvl >20mg/dL shifts the osmolal gap _______
2mOsm/L
why is there low specificity in measuring the osmolal gap
elevated osmolal gap may be caused by any uncharged molecule (ex- EG, MeOH, EtOH, ketoacidosis, renal failure, shock) = doesn’t prove EG or MeOH intoxication
why is a serial anion gap sometimes used in determining EG and MeOH toxicity?
clinically significant poisoning will elevate anion gap
MeoH and EG metabolized to acidic metabolites = rise anion gap
how is a serial anion gap done
measured at baseline then repeated q2-4hrs for 6-12h passed ingestion
EG ad MeOH poisoning can elevate lactate levels by
mitochondrial poison, pts often have low thiamine levels, stress response
generally in EG and MeOH poisoning, lactate is ______ and does not fully account for elevated anion gap (attributed to formate and glyoxylate)
low <5mM
what are the issues with sensitivity of assays used (2)
portable blood gas (lactate oxidase) can’t differentiate
lab assay (GC specific) uses lactate dehydrogenase
3 goals of tx in alcohol poisonings
block toxic metabolite formation (inhibit ADH with fomepizole, EtOH)
correct pH to 7.2 (with bicarb)
eliminate toxic metabolites with dialysis
what is the pref tx in alcohol poisoning
fomepizole
how to use fomepizole
initial dose 15mg/kg IV, then 10mg/kg IV q12h for 4 doses (2 days, then 15mg/kg IV q12h until toxic alcohol levels were safe (can take a long time as elimination is slow)
- dialysis may be req to clear parent alcohol
what is 2nd line tx if fomepizole is not available
ethanol
target blood alcohol level should be ______ with ethanol
22-23mM
what is the PO alcohol LD and MD for ethanol
17mmol/kg LD
1.4-2.8mmol/kg/hr MD (~1/2 standard drink perhr)
what should be monitored when giving ethanol to inhibit ADH
anion gap- if increasing = ADHi not adequate
what type of alcohol is preferred for ADHi
hard alcohol- less volume
what tx besides ADHi may be used in alcohol toxicity
dialysis
bicarbonate for pH
vitamins
T or F: ADHi should be continued during dialysis
T
bicarbonate is used in alcohol toxicity to
normalize pH to keep metabolites in ionized state = prevent penetration into tissues + increase urinary excretion
______ may cause hypocalcemia due to chelation with oxalic acid
EG
T or F; in hypocalcemia caused by EG, avoid giving Ca
T- may exacerbate precipitation of calcium oxalate
why might vitamins be used in alcohol toxicity
to facilitate metabolism- MOA not completely known
what vitamins may be used in EG toxicity
thiamine, pyridoxine (vit B6)
what vitamins may be used in MeOH toxicity
folic acid (folic acid)
