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When is toxicology actute, subacute or chronic?
- acute: occurs over 1-2 days
- subacute: repeated exposures during 3 month period
- chronic: repeated exposures >3months
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What are the three primary determinants of toxicity?
- Dose/dose rate
- duration of exposure (Concentration x time)
- route of exposure
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What is the order from most effective to least effective routes of exosure?
IV > Inhaled > IM > SC > oral > topical
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Genetically, if a drug is a fast or slow acetylator, what will be the outcome?
- fast: liver toxicity
- slow: neural toxicity
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Is a higher or lower Vd needed for effective hemodialysis of toxicity?
Low Vd
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What is the cutoff time for gastric lavage?
4 hours
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Drug that absorbs chemical toxicity?
Charcoal
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Drug that will acidify urine?
Ammonium chloride
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Drug that will alkalanize urine?
Sodium bicarbonate
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Drug that is cathartic for toxicology?
Magnesium sulfate
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Drug that is an osmotic diuretic?
Mannitol
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What are the 5 metal chelators?
- Deferoxamine
- Dimercaprol
- Edetate
- Penicillamine
- Succimer (children)
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Naloxone function?
block opiods
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Glucagon function?
inhibit beta-blockers
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Pyridoxine function?
Isoniazid toxicity
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Fomepizole function?
Ethylene glycol toxicity
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Cause: Food-borne toxin
Symptom: paralysis of muscles, double vision, vomitting
Treatment: emesis, lavage depending on time
Botulinus Toxin
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Cause: B. cereus or Salmonella
symptom: 2-4 hr. after eating, GI inflammation, fever, dehydration
treatment: fluid intake, anti-emetic
Bacterial food poisoning
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Cause: miscellaneous substance, improper handling of chemicals
Symptoms: irritation, delirium, coma
treatment: flush skin, milk, eggs, antacids
Bleach toxicity
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Cause: Cholinesterase-inhibiting insecticides
symptoms: SLUD (salivation, lacrimation, urination, defecation), headaches, slow pulse, cyanosis, coma
treatments: flush skin, Atropine, 2-PAM
Organophosphate poisoning
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Atropine function?
block cholinergic effects
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2-PAM effects
reactivate Cholinesterase enzyme
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Cause: Cholinesterase-inhibiting insecticides
symptoms: SLUD (salivation, lacrimation, urination, defecation), headaches, slow pulse, cyanosis, coma
treatments: flush skin, Atropine, 2-PAM contraindicates
Carbamates
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cause: rodenticide, antagonis of glycine
symptom: convulsion, death from respiratory failure
treatment: IV Diazepam or NMJ blockers
Strychine poisoning
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Role of glycine
inhibitory transmitter to motorneurons and interneurons
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cause: herbicide, (2,4-D) acid + (2,4,5-T) acid = (TCDD)
Chlorophenoxy compounds
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cause: herbicides, uncouple oxidative phosphorylation = increased metabolic rate & temp
dinitrophenols
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Cause: herbicide, redox recycling and ROS
Paraquat
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Cause: CCl4, methylene chloride, chloroethylene, trichloroethylene, ROS lipid peroxidation = cell death
Symptoms: liver toxicity, CNS depressant
treatment: flush skin, remove contaminated clothing
Halogenated hydrocarbons
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Cause: metabolic conversion to formaldehyde & formic acid
symptoms: visual problems, metabolis acidosis, resp. problems, death
Treat: 50% ethanol IV, Fomepizol, Sodium Bicarb
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Role of Fomepizole
alcohol dehydrogenase inhibitor
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Role of Disulfiram
- ***discourage alcohol use
- inhibits acetaldehyde dehydrogenase so acetaldehyde stays in body causing nausea and vomiting
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What are the mg levels of alcohol for acute, moderate, severe and coma poisoning?
- acute: 50-150 mg
- moderate: 150-300 mg
- severe: 300-500 mg
- coma: >500 mg`
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symptom: CNS stimulation b/c of inhibited GABA pathway followed by CNS depression at high doses.
* Increased heat & zero-order kinetics
treatment: hemodialysis if >500 mg, Diazepam if convulsions/seizures
Ethanol
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Cause: rubbing alcohol
Symptoms: CNS depression, rage
Treatment: lavage
Isopropyl alcohol (Isopropanol) poisoning
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Symptom: depression, kidney damage due to calcium oxalate crystals that precipitate
treatment: ethanol IV, Fomepizol
Ethylene glycol poisoning
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symptoms: pulmonary irritation, CNS depression
treatment: emesis & gastric lavage w/o tracheal intubation
Petroleum distillates
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symptoms: CNS stimulation & depression (high doses), kidney & liver damage, cardiac arrhythmias
treatment: lavage if aspiration can be prevented, Diazepam w/ convulsions
Aromatic hydrocarbons (benzene, toluene, xylene)
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symptoms: GI tract irritation, muscle weakness b/c of Ca chelation, renal tubular damage b/c of Ca precipitation
Treatment: precipitate drug in GI w/ Ca (milk, antacids, etc.), calcium gluconate IV
Oxalic acid toxicity
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Symptoms: GI inflammation/necrosis, hypovolemic shock after hemorrhage
treatment: dilute w/ water, analgesic pain relievers, milk of magnesia
mineral acids (hydrochloric, sulfuric, acetic, perchloric)
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symptoms: irritation, inflammation & tissue damage, penetrate more than strong acids, hypovolemic shock death
treatment: dilute w/ water
Strong Alkali (hydroxides in soap, cleansers, drain cleaners)
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cause: bind to sulhydryl groups on enzymes and inhibit cellular metabolism
symptoms: GI disturbance, convulsions, arrhythmias, kidney damage, nephritis, dermatitis, cirrhosis, personality changes
treatments: lavage or emesis, dimercarprol or penicillamine
arsenic or arsine
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Cause: paint chips
Symptoms:
- acute: GI irritation, kidney damage
- chronic: line on gums, erythrocyte strippling, aminolevulinic acid accumulation
- CNS effects: behavior disturbances, loss of
developed skills, coma
Treatment: prevent, chelate using Dimercapol, Succimer (oral children), Penicillamine
- neuromuscular effects: weakness, paralysis
Lead poisoning:
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symptom: GI, inflammation, necrosis, hemorrhage, hypotension, metabolic acidosis, shock
Treatment: Chelate w/ Deferoxamine (oral)
Iron poisoning
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Symptoms: irritation, abdominal pain, ARTN, shock, Stomatitis (bleeding gums), Erethism (emotional instability)
Treatment: milk, raw eggs, charcoal, chelate w/ IV Dimercapol
Mercury Salt poisoning
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Most common metal chelated by penicillamine?
Copper (wilson's disease)
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Main metal chelated by deferoxamine?
Iron
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Main metal chelated by succimer?
Lead
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Main two metals chelated by edetate?
Zing & Lead
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4 metals chelated by dimercaprol?
gold, arsenic, lead, mercury
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T/F dimercaprol should be given orally?
F, should be given parenterally b/c it is easily absorbed in GI tract
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Role of methemoglobin inducing agents
oxidize hemoglobin to methemoglobin so oxygen is not carried
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role of Carboxyhemoglobin producing agents
Carbon monoxide
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Role of Cytochrome oxidase inhibitors
Hydrogen cyanide
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symptoms: chocolate-colored blood, hypotension, cyanosis, convulsions, coma
treatment: methylene blue (convert methemoglobin back to hemoglobin), Oxygen administration
Nitrite toxicity
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Symptoms:headache, dizziness, stupor, Carboxyhemoglobin is cherry red
Treatment:administer oxygen
carbon monoxide poisoning
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Cause: complex with ferric iron and inhibit oxygen utilization
symptoms:dizzy, headache, hypotension, unconscious, convulsions, resp. failure
treatment: Sodium Nitrite, amyl nitrite or sodium thiosulfate, Rhodanese, oxygen treatment
Cyanide poisoning
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Role of Rhodanese (sodium thiosulfate)
Excrete cyanide as SCN- out of kidney
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symptom: dyspnea, weakness, TB disposition, heart failure/respiratory failure
treatment: symptomatic & supportive
Free crystalline silica
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symptoms: dyspnea, resp. impairment, bronchogenic carcinoma/pleural mesothelioma
treatment: symptoms and support
asbestos toxicity
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symptoms: lung cancer risk
Radon toxicity
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What drug is always used for convulsions and seizures?
diazepam
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How do emetics and Lavage come into play with mineral acid, strong base, mineral spirits and convulsion?
Don't do emetics or gastric lavage
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What organ is damaged by acetaminophen toxicity?
Liver
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What toxicity is present from a fire extinguisher, halogenated hydrocarbons and liver damage?
CCl4, chloroethylene, trichloroethylene, tetrachloroethylene
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What toxicity is from antifreeze?
ethylene glycol
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Main oral chelator of lead?
succimer
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chocolate colored blood toxicity
Nitrites
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Cherry-red blood toxicity
Carbon monoxide
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bitter almond taste toxicity
Cyanide poisoning
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