10: Household Poisons Flashcards
APAP has what effects
analgesics, antipyretic, weak aniinflam
APAP effect on COX
nonselective inhibitor
COX 2> 1
APAP blocks production of prostaglandins by
reducing heme on peroxidases
APAP has evidence of analgesic effects by affecting
serotonergic, opioid, cannabinoid, and TRV 1 receptors
APAP is absorbed within ___, peaks at ___
abs 2hrs, peaks 4hrs
APAP metabolism includes
glucuronidation, sulfation, CYP2A1 oxidation
most APAP metabolism is _________, the rest is
most = hepatic conjugation
rest = oxidized by CYP2A1 to NAPQI
MOA of APAP toxicity
amount of NAPQI overwhelms glutathione and accumulates in hepatocytes = cell death by mitochondrial effects
describe stage 1 APAP toxicity
incubation (quiescent- might be missed)
Asymptomatic or nonspecific sx (N/V, malaise, diaphoresis)
describe stage 2 APAP toxicity
latent period
resolution/ improvement of stage 1 sx
Onset of hepatic injury (5% of patients who overdose), AST/ALT lab value abnormalities, elevated AST then ALT (1000IU/L)
Nephrotoxicity may occur as toxic metabolites are produced
describe stage 2 APAP toxicity
latent period
resolution/ improvement of stage 1 sx
Onset of hepatic injury (5% of patients who overdose), AST/ALT lab value abnormalities, elevated AST then ALT (1000IU/L)
Nephrotoxicity may occur as toxic metabolites are produced
describe stage 3 APAP toxicity
peak liver toxicity
Systemic sx reappear
Fulminant hepatic failure (encephalopathy, jaundice, coagulopathy, hypoglycemia)
Abnormalities in transaminase peak (3-4d), PT, INR, glucose, lactic acidosis
Highest risk of death
describe stage 4 APAP toxicity
resolution
Survivors make a complete recovery and/or death
what is the antidote for APAP toxicity
NAC
NAC must be administered within_____ of APAP OD
4-8hrs
NAC is given as a ____IV infusion or ____ oral schedule
24h IV
72hr oral
which is preferred? NAC iV or PO
IV preferred- faster, safer, rare ADRs
PO = strong smell, makes pt vomit, logically hard if unconscious
what is NAC?
a precursor for glutathione synthesis
NAC detoxifies NAPQI by (4)
Free radical scavenger
Increasing oxygen delivery/ microvascular tone
Increasing mitochondrial ATP production
Antioxidant effects
4 clinical tests for APAP OD
serum APAP
aminotransferases (ALT/AST)
INR
serum creatinine
traditionally, NAC IV is a ________ regimen
3 bag- AHS has new 2 step regimen
what is the Rumack- Matthew Nomogram used for
to see if NAC needs to be initiated in APAP toxicity
how is the slop of the Rumack-Matthew nomogram determined
1. clinical data
2. APAP half life
3. kinetics of hepatic failure
4. all of the above
- based on clinical data
what are some factors that impact interpretation of the RM nomogram
incorrect hx/ when they took it, multiple/ chronic ingestions, CYP inducers (ethanol), chronic alcohol use, extended release
what is the goal of the RM nomogram
to determine the risk of hepatotoxicity and need to initiate NAC tx
NAC reactions may be
anaphylactic or anaphylactoid
anaphylactic reactions are ADR type ___, type ____ hypersensitivity reactions
type B, type 1 hypersens
how do anaphylactic reactions happen
Cross linking allergen to specific IgE molecules (bound to mast cells and basophils)
Reexposure = degranulation release of histamine
what is an anaphylactoid reaction? what happens after the drug triggers the reaction?
a nonIgE medated response that does not require previous exposure
Drug triggers sudden and massive mast cell and basophil degranulation (release of histamine) in absence of imunoglobulins
which of the following may be rechallenged
1. anaphylactic reactions
2. anaphylactoid reactions
2
treatment for anaphylactoid reactions
antihistamines, beta 2 agonists, corticosteroids
COX1 is
constitutive
COX2 is
inducible
ASA causes ____ inhibition of COX ____
irreversible inhibition of COX 1 and 2
NSAIDs cause _____ inhibition of COX ___
reversible inhibition of COX 2
prostacycline synthase produces _________ which are ___ inflammatory
prostacyclines
antiinflammatory
thromboxane synthase produces _________ and ________ which are ___________
prostaglandins and thromboxanes
proinflammatory
T or F: All NSAIDs have similar presentations in OD situations
T
which of the following is false about NSAIDs
1. asymptomatic or nonspecific sx appear within 0-4hrs
2. there is no specific test to check for NSAID toxicity
3. treatment may include GI decontamination with charcoal
4. causes irreversible inhibition of COX 2 more than COX 1
4 - reversible
sx of mod-severe NSAID toxicity include
coma, seizures, CNS depression, metabolic acidosis, hypotension, hypothermia, rhabdomyolysis, lethargy, unresponsiveness
what labs should be ordered in NSAID OD
no spec test, but rec to check APAP levels
Ts for NSAID OD includes
supportive care, antacids for GI upset, GI decont w/ charcoal for children that had >400mg/kg
aspirin has 3 properties
analgesic, antiinglam, antipyretic
aspirin is a _____ inhibitor of _____
irreversible inhibitor of COX 1 + 2
platelets do not express COX
2
ASA daily dose inhibits COX __ for the duration of the platelet’s lifespan (8-12d)
2
ADME of aspirin
rapid absorption, highly protein bound, half life 15min-2-3h, hepatic metabolism, absorbed and excreted unchanged in urine
in an aspirin OD, what happens to ADME?
decreased protein binding (runs out) = more into tissues = more SEs
characteristics of patients more likely to have acute aspirin toxicity- list 3
younger, intentional, easily recognized (absent coingestion), no other diseases, suicidal ideation typical, marked elevations in serum concs, mortality uncommon when recognized and properly tx
acute aspirin toxicity may see development of ___________ by impacting ___________
anion gap metabolic acidosis
impacting mitochondria
worsening acute aspirin toxicity may result in
severe CNS toxicity
characteristics of patients more likely to have acute aspirin toxicity- list 3
older, therapeutic misadventures/ iatrogenic, frequently undiagnosed, many underlying diseases (esp chronic pain), suicidal ideation not typical, intermediate elevation in serum concs, mortality more common due to delayed recognition
mortality is more common with _____ aspirin toxicity due to __________
chronic
delayed recognition
intermediate elevations in serum concs are more likely in ____ aspirin toxicity
chronic
anion gap =
unmeasured cation – unmeasured anion = [Na+] – ([Cl- ] +[HCO3 - ]
2 acronyms for poisons/ diseases that can increase anion gap
MUDPILES and GOLDMARK
what does MUDPILES stand for
methanol/ metformin, uremia, DKA, paraldehyde, iron/ isoniazid/ ischemia, lactic acidosis (CO, CN), ethylene glycol, salicylates
what does GOLDMARK stand for
glycols, 5-oxoproline, L-lactate, D-lactate, methanol, aspirin, renal failure, ketoacidosis
metabolic acidosis may be due to ___________ or ___________
acid accumulation of HCO3 loss
treatment for aspirin OD includes
supportive care- no true antidote
may use GI decontamination with activated charcoal
Cornerstone = shift salicylate out of brain and tissues in serum (alkalinization of serum and urine = ion trapping by adding serum IV sodium bicarbonate)
Hemodialysis: aims to remove salicylate from tissues but may not correct severe organ toxicity
Glucose supplementation (pts altered mental state)
what is the cornerstone of treating aspirin OD
adding IV sodium bicarb to shift salicylate out of tissues into serum and urine by ion trapping it
____ is produced by activated platelets and is prothrombotic
TxA2
TxA2 increases platelet ______ (3)
aggregation, vasoconstriction, inflammation
why do COXIBs result in an overall net inflammatory state
COXIBs only inhibit COX 2, but do not inhibit platelet COX 1 derived TxA2 = TxA2 effects are exaggerated while endothelial cell’s COX1/2 PGI2 process is inhibited = overall prothrombotic and hypertensive result
