37/38: Intentional Poisonings Flashcards
nerve agents are designed to be
undetectable
nerve agents are very potent _____ that inhibit _______
organophosphates
cholinesterase
nerve agent properties
colorless, odorless, tasteless, clear
which nerve agents are volatile
GA, GB, GD
which nerve agents are oily liquids
VX
what is the LD50 for aerosol doses of GA and GB
10-400mg-min/m3
what is the dermal dose LD50 for VX and sarin (GB)
10-1700mg
GA is
tabun
GB is
sarin
GD is
soman
nerve agents are part of the _____ toxidrome
cholinergic
onset of nerve agents (vapors and liquids)
Vapors = seconds to minutes
Liquids = slightly delayed due to absorption
AEs of nerve agent vapors
most common eye issues (miosis, pain, dim vision, loss of acuity), HA, nausea, cough
AEs of dermal exposure from nerve agent
sweating, fasciculations, vomiting, diarrhea, weakness, seizures, loss of consciousness
LT effects of nerve agents are mostly
psychological sequelae
the lethality of nerve agents comes from
asphyxiation or cardiac arrest
T or F: secondary exposure is a major issue for nerve agents
T- can evaporate from pt’s clothing and permeate HCP’s clothing
5 tx for nerve agent toxicity
atropine
2-PAM
decontamination
antiepileptics
pyridostigmine
what is always the first step to treating a patient exposed to a nerve agent`
decontamination to limit secondary exposure
atropine is a _______ antidote for nerve agents due to it’s _______ effects
anticholinergic
muscarinic
2-PAM are _____ which are nucleophilic. Their MOA is _____________
oximes
reactivate cholinesterase by removing dialkyl phosphoryl moiety
2-PAM has ________ dependent use
time
2-PAM must be used within ____ (time) for
- soman
- sarin
- tabun
- VX
Soman = 2-6 min
Sarin = 3-5hrs
Tabun = 14h
VX = 48h
pyridostigmine MOA in soman exposure
pretreatment often- is a carbamate acetylcholinesterase inhibitor which outcompetes nerve agents
describe the structure of dioxin
is part of a family of isomers- dibenzo-p-dioxin
dioxin is
1 highly lipophilic
2. very specific in dose response
3. a minor environmental pollutant
4. has a half life of 7-11rhs
1
- is very wide variation in dose response, major pollutant, half life 7-11yrs
what is the most potent dioxin
TCDD
dioxin MOA
binds to AHR = inappropriate activation of CYP and phase 2 enzymes
dioxins are considered class ________ and _______ disruptors
class 1 carcinogens
endocrine disruptors
what is the impact of dioxin
impact on repro function, immunologically suppressive, carcinogenic
causes chloracne
what happens when someone gets chloracne
is a systemic toxicity which starts with excessively oily skin = whiteheads, balckheads, cysts, thickened skin, flakiness, scaring, and change in coloration
what is the MOA of chloracne
MOA unknown- probably involves alterations of cellularty
ricin can be exposed via
injection, inhalation, ingestion
select all of the above that is true about ricin
1. is water soluble
2. is composed of 2 proteins linked by disulfide bond
3. is 1C + 3N
4. there are no tx for ricin toxicity
5. inhibits many enzymes
1, 2, 4
what does ricin’s chain B do?
facilitates binding and entry into the cell + localizing into ER
what does chain A of ricin do?
inhibits protein synthesis by inactivating ribosomes by removing an adenine residue from rRNA = rRNA can’t bind to protein elongation factors
clinical sx of ricin toxicity
resp distress (inh within few hrs), severe vomiting (ingestion), gastroenteritis, hemorrhage, and inflammation, multiple organ failure, death within 48-72hrs
what are the tx for ricin toxicity
no tx available
describe the tylenol poisoning series and outcome
drug was tampered with to lace with potassium cyanide = led to development of tamper resistant packaging such as induction seals and quality control measures
anthrax, AKA ___________ is a , gram ____, ____ forming bacillus found in soil worldwide
bacillus anthracis
gram +
spore forming
inhalation of anthrax can cause
mediastinitis
spores of anthrax taken into the lymphatic sytem can
germinate
cyanide is a chemical group that consists of
1C and 3N
plant sources of cyanide include
cassava roots, apricot pits, peach pits, almonds
which HPTN drug can cause cyanide poisoning
nitroprusside
________ can react with water to form hydrogen cyanide gas
common salts like NaCN, KCN
why is cyanide gas the most dangerous
less dense than air = rise/ disperse quickly
T or F; cyanide crosses membranes easily
T - due to low MW
nonionized cyanide is metabolized to
thiocyanate
cyanide metabolism is limited by
endogenous stores of sulfur
nonionized cyanide is metabolized to thiocyanate by
rhodanese, b-mercaptopyruvate, CN sulfurtransferase
what is the MOA of cyanide toxicity
induces cellular hypoxia and metabolic acidosis by shutting down oxphos = no ATP = enzymes to metabolize cyanide can’t run
inhibits multiple enzymes, succinic acid dehydrogenase, superoxide dismutase, carbonic anhydrase, cytochrome oxidase
which 2 organs are majorly impacted by cyanide
heart and CNS
cyanide survivors can develop delayed _________
neuro sequelae
cyanide toxicity onset
v rapid (seconds to minutes)
tx for cyanide toxicity besides antidotes
supportive care- ventilate, give 100% oxygen, vasopressors for hypotension, sodium bicarbonate
antidotes for cyanide toxicity
Hydroxocobalamin
Cyanide antidote kit: amyl nitrile, sodium nitrile, sodium thiosulfate
how does hydroxocobalmin work as a cyanide antidote
is a metalloprotein with a central cobalt atom that complexes CN forming cyanocobalamin (pref)
what is the preferred tx for cyanide toxicity
hydroxocobalamin
what is the MOA for the cyanide antidote kit
the amyl nitrile generates methemoglobin which CN has a higher affinity to compared to cytochrome a3
anthrax produces which 3 toxins
protective antigen
edema factor
lethal factor
what does PA do
pore forming that allows EF and LF into cell
what does EF do
produces cAMP = imbalance in water homeostasis = cellular edema
what does lethal factor do
metallic protease that breaks down cell and activates immune response to kill cell off
anthrax sx starts with ______________ and progresses to ________________
Starts with fever, malaise, cough, chest discomfort (2-3 days)
Progresses to severe respiratory distress, dyspnea, diaphoresis, stridor, cyanosis
anthrax tx (3)
antibiotics (cipro, doxy)
raxibacumab
vaccine
what is raxibacumab
a monoclonal antibody that blocks the binding of anthrax PA
the anthrax vaccine is a __________ strain that produces the PA antigen
avirulent nonencapsulated strain
the ______ test is used to detect arsenic poisonigns
arsenic
arsenic is a metalloid existing in multiple forms, including
elemental, gaseous (arsine), organic and inorganic (As3+, As 5+)
Arsenic trioxide (As2O3) is a __________= easily incorporated into food and drink
flavorless, odorless
As3+ inhibits
pyruvate dehydrogenase
As3+ 4 impacts
inhibits PDH
inhibits citric acid cycle
decreases gluconeogenesis
affects cardiac repolarization
As5+ is readily reduced to ____ and ________
As3+ and pentavalent arsenic resembles phosphate (ex- gets incorporated wherever phosphate would be) = uncouple OSPHOS
arsenic has ____ metabolism
hepatic
acute toxicity to arsenic resembles
cholera- diarrhea rice water
death from acute arsenic poisoning is mostly due to
CV collapse and hypovolemic shock
chronic arsenic toxicity causes
arseniasis
mees lines
GIT, skin, CNS, primary organ damage
N, epigastric pain, colic, diarrhea, paresthesias
cancer
arsenic toxicity tx
chelation tx with BAL, 2,3-dimercaptosuccinic acid, and dimercaptopropane sulfonate which are vicinal dithiol moieties that bind arsenic
