10: Household Poisons Flashcards by Linda Chen

APAP has what effects

analgesics, antipyretic, weak aniinflam

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APAP effect on COX

nonselective inhibitor
COX 2> 1

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APAP blocks production of prostaglandins by

reducing heme on peroxidases

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APAP has evidence of analgesic effects by affecting

serotonergic, opioid, cannabinoid, and TRV 1 receptors

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APAP is absorbed within ___, peaks at ___

abs 2hrs, peaks 4hrs

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APAP metabolism includes

glucuronidation, sulfation, CYP2A1 oxidation

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most APAP metabolism is _________, the rest is

most = hepatic conjugation
rest = oxidized by CYP2A1 to NAPQI

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MOA of APAP toxicity

amount of NAPQI overwhelms glutathione and accumulates in hepatocytes = cell death by mitochondrial effects

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describe stage 1 APAP toxicity

incubation (quiescent- might be missed)
Asymptomatic or nonspecific sx (N/V, malaise, diaphoresis)

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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

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describe stage 2 APAP toxicity

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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

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describe stage 4 APAP toxicity

resolution
Survivors make a complete recovery and/or death

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what is the antidote for APAP toxicity

NAC

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NAC must be administered within_____ of APAP OD

4-8hrs

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NAC is given as a ____IV infusion or ____ oral schedule

24h IV
72hr oral

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which is preferred? NAC iV or PO

IV preferred- faster, safer, rare ADRs
PO = strong smell, makes pt vomit, logically hard if unconscious

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what is NAC?

a precursor for glutathione synthesis

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NAC detoxifies NAPQI by (4)

Free radical scavenger
Increasing oxygen delivery/ microvascular tone
Increasing mitochondrial ATP production
Antioxidant effects

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4 clinical tests for APAP OD

serum APAP
aminotransferases (ALT/AST)
INR
serum creatinine

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traditionally, NAC IV is a ________ regimen

3 bag- AHS has new 2 step regimen

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what is the Rumack- Matthew Nomogram used for

to see if NAC needs to be initiated in APAP toxicity

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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

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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

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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

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

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

ASA daily dose inhibits COX __ for the duration of the platelet's lifespan (8-12d)

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