GI: Toxicology Flashcards
FYI. On the exam, there will be 3 Qs on this material, concerning cases of poisoning by the agents on the flip side of this card. Did not make FCs on benzene/toluene, organophosphates that are not on this list)
Carbon monoxide
Organophosphate (carbamyl/malathion/parathion)
Iron
Lead
Arsenic
Acetaminophen
Aspirin
Benzodiazepines
Methanol, ethylene glycol
What is the range of the LD50 for various chemicals?
Bottom line is that the LD50 for chemicals covers a very wide range (9 orders of mag). Extreme ends of the lethal range: botulinum toxin is lethal at 0.00001 mg/kg, ethyl alcohol is not lethal until 10,000 mg/kg.
what is a chelator for lead with EDTA, arsenic, and mercury?
dimercaprol
what is a chelator for lead?
EDTA calcium or disodium
what is a chelator for acute arsenic, mercury or lead?
unithiol
what is a chelator for lead (kids & adults), mercury and arsenic?
succimer
what is a chelator for iron?
deferoxamine and deferasirox
what is a chelator for copper, adjunct for arsenic, gold, lead?
penicillamine
what is an antidote to acetaminophen?
N-acetylcysteine (NAC) give activated charcoal if within 1-2 h of ingestion
what is an antidote to gastric absorption?
activated charcoal
what is an antidote to benzodiazapines?
flumazenil
what is an antidote to methanol and ethylene glycol?
fomepizole
very big picture: the 10 drugs for this lecture are members of what two classes?
chelators and antidotes
define bioaccumulation
increasing concentration of a substance in the env’t, leading to accumulation in biol tissues. ex: a fish eats lots of little fish that all have a tiny bit of mercury in them, and the big fish ends up with a LOT of mercury in its tissues since it never goes away
define biomagnification
the fold increase in concentration of a substance in the food chain, resulting from bioaccumulation
define an endocrine disruptor
chemical in the env’t with endocrine effects: possible infertility, repro cancer, birth defects.
define environmental toxicology
environmental exposure to chemicals, regulated by the EPA
define acceptable daily intake (ADI)
daily intake of chemical, which over lifetime appears to carry no risk
define occupational toxicology
exposure of workers to chemicals at workplace: regulated by OSHA
define threshold limit value (TLV)
used for occupational control. exposure limit to an agent for a defined period of time. (shorter time = higher level allowed)
Carbon monoxide: what it is? what does it do in the body?
- odorless, colorless gas
- competes with O2 for hemoglobin (has a 200x greater affinity). affinity for fetal Hg even higher
Carbon monoxide: treatment? how do we detect it in the body?
tx: 100% O2, hyperbaric O2
- cannot use regular pulse ox, use a CO-oximeter to determine carboxyhemoglobin (COHb) levels
Sx of CO poisoning with 10% COHb, 40-50% COHb, 60-70% COHb?
10%: headache, dizziness
40-50%: nausea, convulsions, tachy
60-70%+: resp arrest, death
what are some cholinesterase inhibitors?
(pesticides)
Carbamates - carbaryl
Organophosphates - malathion, parathion
Cholinesterase inhibitors: what effect do they have in the body?
- Muscarinic and nicotinic activators
- SLUDGE (meaning of this is on a separate card)
Cholinesterase inhibitors: treatment?
- atropine to block receptor activation
- pralidoxime to regenerate cholinesterase
what does SLUDGE stand for? what is it associated with?
- Salivation, lacrimation, urination, defecation, GI upset, emesis
- symptoms of muscarinic and nicotinic receptor activation, possibly by a pesticide
what is Agent Orange?
Herbicide used in Vietnam War. associated with chronic disease
Common sources of CO?
- car exhaust
- spills from appliances
- building fires
- forklifts, snowblowers
- generators, heaters (boiler room malfunction!)
- zambonis (ice rinks)
- CO is the main indoor pollutant causing headaches
what is a baseline level for blood COHb in a non-smoker? what is the half life for CO?
baseline = 1-3%
half life = 5 h
What are some general clues that a person may have CO poisoning?
- more than one person affected
- pets affected
- relation of sx to use of combustion appliances
- exposure to tobacco smoke, volatile organics
acute lead poisoning: cause? sx?
acute poisoning is rare: occurs when kids eat paint chips.
abdominal colic, CNS changes.
chronic lead poisoning: cause? sx? sx particularly seen in children?
- environmental toxin, seen in low SES pts with older housing
- peripheral neuropathy (wrist drop), anorexia, anemia, tremior, GI. may see lead line on gums
- kids: growth delay, neuro deficits, dev delay
chronic lead poisoning: appearance on blood smear?
basophilic stippling of RBCs
lead poisoning: preferred chelator for kids?
oral succimer
acute arsenic poisoning: symptoms?
severe GI discomfort, rice water stools, vomiting, capillary damage with dehyd and shock (sim to cholera, typhoid)
chronic arsenic poisoning: symptoms?
skin changes, hair loss, bone marrow depression, anemia, nausea, GI disturbance
what are Mee’s lines? what do they indicate?
transverse white lines running across the nail, shape of the nail moon.
arsenic poisoning
arsenic: source of chronic poisoning?
environmental: ground water, soil
acute mercury poisoning: sx?
chest pain, SOB, n/v, kidney damage, gastroenteritis, CNS damage
chronic mercury poisoning: sx?
sore gums/teeth, GI disturbance, neuro and beh changes.
remember the ‘mad hatters’ in 18th c who had mercury pois from processing felt
mercury poisoning: tx?
chelation with succimer or dimercaprol (IM)
acute mercury poisoning: sources?
from inorganic mercury: salts and metallic.
occupational, dental labs, wood preservatives, insecticides, batteries.
organic mercury is used as what? more or less toxic than inorganic (salt/metallic mercury)?
- anti-fungal. will bioaccumulate
- MORE toxic than inorganic mercury
- highly toxic to fetuses
iron poisoning: source?
too many iron supplement pills, prenatal vits
accidental OD by child
iron overdose: sx?
vomiting, GI bleed, lethargy, grey cyanosis. may progress to GI necrosis, pneumonitis, jaundice, seiz, coma
iron OD: what is the chelating agent of choice?
deFERoxamine.
Iron OD: tx with gastric lavage with charcoal?
charcoal does not bind iron. if within 60 min, use gastric lavage. if longer than 60 min, use whole bowel irrigation
chelators: what is their overall mechanism?
form a cage around a metal ion, sequestering it and preventing binding to cells. promotes excretion. cannot reverse damage, only prevent further damage.
Bidentate v polydentate: what’s the difference?
refers to the # of electronegative groups a chelator has available to complex with cationic metal ions
of the chelators, which are bidentate? polydentate?
Bidentate are Succimer, Penicillamine, Unithiol, Dimercaprol (SPUD)
Polydentate are EDTA and deferoxamine
regardless of suspected poison, what is initial treatment for a poisoned patient?
ABCD: airway, breathing, circ, DEXTROSE if altered mental status
Organophosphate poisoning (cholinesterase inh): eye findings? skin findings? abdominal findings? (not in SLUDGE)
miosis (constricted pupil)
excessive sweating
hyperactive bowel
what type of decontamination is currently favored? (emesis, lavage, charcoal, laxatives)?
- emesis and lavage used less now: emesis increases exposure to toxin
- charcoal currently favored. large surface area, absorbs toxin.
- laxatives may help toxin exit body quickly. no hard evidence. whole bowel irrigation may help after ingestion of iron tablets, (+ other things)
what will charcoal NOT bind?
iron, lithium, potassium binds alcohols and cyanide poorly
how does N-acetylcysteine work as an antidote? antidote for what? when to give? what labs to follow?
- acetaminophen.
- acts as a glutathione substitute, binds hepatotoxic metabolite as it is made. also replenishes glutathione reserve, preventing formation of metabolite
- give within 8-10 h (as soon as possible)
- follow LFTs and serum drug levels
aspirin toxicity: what will be the course? what is treatment & how does it work? treatment for severe cases?
- resp alkalosis followed by metabolic acidosis
- IV sodium bicarb alkalizes urine and promotes salicylate excretion
- severe: hemodialysis
cholinesterase inhibitors: tx? mechanism?
Atropine: competes for muscarinic receptors
Pralidoxime (2-PAM) can regenerate cholinesterase activity
treatment for benzodiazepine OD? mechanism?
- flumazenil
- blocks site of benzo action.
treatment for methanol/ethylene glycol toxicity? mechanism?
- fomepizole
- competes for alcohol dehydrogenase, thus reduces production of toxic metabolites
methanol poisoning causes what sx (eyes)?
severe vision disturbances
acetominophen OD: how does it cause liver necrosis?
normal metabolism is saturated, so acetaminophen is metabolized in liver to a toxic metabolite. the metabolite binds to proteins and the lipid bilayer of hepatocytes; yields hepatic injury and centrilobular liver necrosis.
what is one of the most common pharmaceuticals seen in both intentional and accidental poisoning?
acetaminophen
urinary pH manipulation: urinary alkalinazation is useful in what kind of OD?
salicylate (aspirin)
salicylates: what do they cause, metabolically?
uncoupling of oxidative phosphorylation.
results in incr O2 consumption, incr CO production, incr glycolysis, incr lipolysis. –>resp alkalosis and met acidosis –>incr anion gap due to accumulated lactate
clinical picture of salicylate OD?
- hyperpnea (deep, quick breaths)
- hyperthermia
- GI hemorrhage
- N/V
- ototoxicity
tx for aspirin/salicylate OD?
- gastric lavage up to 60 min
- activated charcoal after 60 min -bicarb to alkalinize urine, incr salicylate excr, correct acidosis
- hemodialysis to remove salicylate, restore fluids
aspirin/salicylate OD - when might you consider whole bowel irrigation?
if large mass of enteric coated pills were ingested
5yo in ER in December. Confused, headaches, lethargy, joint aches, nausea. HR 120, HP 130/85, RR 25. Mom also has headache. Moved to old building 6 mo ago. What is the likely toxin? what test should we do?
- CO
- test carboxyhemoglobin level
- older apt suggests lead
- shared symptoms of both mother and daughter suggests CO
crop duster in ER with weakness, sweating, wheezing, abd cramps, diarrhea, miosis, bradycardia, muscle twitches. what is he poisoned with? how do we treat his weakness, labored breathing?
- malathion (organophosphate)
- SLUDGE sx
-treat with atropine (block receptor binding), pralidoxime (reactivate AChE)
3yo in ER, vomiting (some blood), abdominal pain. non bloody diarrhea, listless. HR 170, RR 28, BP 98/58. Dry mucous membranes. low serum bicarb. what is toxin?
Iron, from mom’s prenatal vitamins. for a small child, only 4 pills could be toxic
Iron OD 3 hrs ago, has been vomiting: best treatment is whole bowel lavage, gastric lavage, activated charcoal, or ipecac?
whole bowel irrigation with polyethylene glycol solution too late for lavage, charcoal doesn’t bind iron well, more vomiting will not help
chelating agent for iron overdose?
deferoxamine - chelates iron, but poorly binds other trace metals
42 yo, ingested 30 pain pills yesterday. (taken to ER and was treated). Today she re-presents with RUQ pain, elevated AST and ALT. what is best antidote?
-NAC. acetaminophen OD: accumulation of a metabolite. NAC replenishes glutathione reserves, preventing this
74 yo women with confusion, fever, hearing loss over past 2 days. takes OTC aspirin for her osteoarthritis. best treatment?
activated charcoal, IV fluids, urine alkalization. ingestion was chronic so gastric lavage will not help a lot. activated charcoal is especially indicated for enteric-coated drugs. raising the pH of urine can incr aspirin excretion by 10x
