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48 Cards in this Set
- Front
- Back
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toxicant
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any agent that causes adverse effects
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toxin
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an extracellular substance elaborated by a cell. i.e.: from a living organism
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5 steps before patient's arrival at treatment center in cases of acute poisoning
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obtain useful information
emesis adsorbents (activated charcoal) decontaminat skin and eyes get pt to tx center |
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6 signs of acute poisoning on physical exam
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coma
hyperactivity arrhythmia metabolic acidosis seizure GI symptoms |
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4 means of removing unabsorbed toxicants
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emesis
gastric lavage cathartic adsorbents |
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supportive treatment for acute poisoning
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maintain respiration
maintain circulation maintain body temp suppress pain hasten elimination of absorbed toxicant |
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means of hastening elimination of absorbed toxicants
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forced diuresis
urinary pH adjustment peritoneal dialysis hemodialysis |
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extent of cell or tissue damage from a xenobiotic agent depends on what 4 things?
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dose and nature of exposure
tissue or cell characteristics rate at which insult occurs progression factors |
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digoxin class of toxicity
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receptor-mediated
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chemical characteristics of digoxin
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planar
stable highly lipid soluble |
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digoxin toxicity mechanism
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binding to cytosolic Ah-receptor
translocation to nucleus altered gene expression |
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example of drug with digoxin like toxicity
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polychlorinated biphenyls (PCBs) spend time in a coplanar configuration and can fit into the Ah receptor (with less affinity)
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coplanar PCBs
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meta-, para-substituted
bind with high affinity to the Ah receptor mediate many effects thru changes in gene transcription |
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noncoplanar PCBs
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ortho-substitution
are not good ligands for the Ah receptor mechanisms of action are unknown but initated by changes in cell signaling |
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endocrine disruptors
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estrogen agonists/antagonists
e.g.: chlorinated compounds, furane coumarins (soy), diethylstilbestrol, tamosifen, RU 486 |
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interference with excitable membranes
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saxitoxin
tetrodotoxin organic solvents DDT organophosphates carbamates |
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effects of volatile organic solvents
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disorientation
euphoria unconsciousness paralysis convusion death - resp. and cardiac arrest |
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mechanism behind effects of volatile organic solvents
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physical interaction with CNS
alters characteristics of lipid bilayers (membrane fluidity) |
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specific toxic effects of benzene
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hematopoietic toxicity:
- aplastic anemia - leukemia |
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specific toxic effects of carbon tetrachloride
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hepatotoxicity
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specific toxic effects of methanol
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retinal toxicity
metabolic acidosis |
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specific toxic effects of n-hexane
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neurotoxicity
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specific toxic effects of ethylene glycol ethers
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reproductive toxicity
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specific toxic effects of dioxane
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carcinogenesis
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direct and indirect (bioactivation) effects of EtOH
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depressant
Wernicke-Korsakoff's syndrome liver steatosis, hepatitis gastritis, peptic ulcer pancreatitis heart vasodilation, cardiomyopathy, arrhythmias feminization in males upper GI & liver cancer fAS immune compromise |
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drugs that interfere with energy production
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CO
nitrite cyanide, HS, azide nitrophenols fluoroacetate |
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sources of nitrites (NO2-)
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drugs
food preparation well water drug abuse of nitrites |
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effects of nitrite
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cyanosis
hypotension AP, N/V HA, vertigo altered HR & RR increased intraocular pressure elevated intracranial pressure coma |
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mechanism of action of nitrites
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Hb-Fe2+ --> Hb-Fe3+ (metHb)
40% MetHb - toxicity 70-80% - MetHb - death due to hypoxia, vasodilation |
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treatment of nitrite poisoning
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maintain circulation and respiration
transfusion methylene blue ascorbic acid |
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sources of cyanide
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industry
fumigant rodenticide criminal tampereing iwth drugs smoke inhalation nitroprusside metabolism |
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cyanide toxicity
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HA, anxiety (early)
N/V arrhythmias & other cardiac effects PE coma convusion shock respiratory failure death lack of cyanosis |
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CN reacts with ...
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HEME
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treatment for cyanide poisoning
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supportive therapy (antiarrhythmics, anticonvulsants, NaHCO3 for acidosis, 100% O2)
antidotes sodium nitrite sodium thiosulfate |
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cyanide binds to...
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cytochrome oxidase
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carbon monoxide binds to...
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hemoglobin
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heavy metals bind to...
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protein sulfhydryl groups (-SH)
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glutathione (GSH)
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cellular protectant
many toxicants only attack cell after GSH levels depleted |
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example of toxicant that depletes soluble intracellular thiols
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acetaminophen
bioactivated to an electrophilic species which depletes glutathione and then binds to cellular proteins |
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most frequent cause of drug induced liver failure
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acetaminophen (APAP) toxicity
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metabolism of acetaminophen
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see p. 492
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Aflatoxin B1
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mycotoxin produced by Aspergillus strains
causes acute livery injury and hepatocarcinogenesis metabolized yo active forms by mixed function oxidases (P450s) |
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most active metabolite of Aflatoxin B1
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8,9-epoxide, which forms covalent bonds with cellular macromolecules (proteins and DNA)
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Effect of LPS/inflammation on Aflatoxin B1 toxicity
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inflammation potentiates hepatotoxicity
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____ chemicals bind to DNA, altering genes
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electrophilic chemicals can bind to nucleophilic sites within DNA, thus altering expression of critical genes
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example of electrophilic chemical that binds DNA
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benzopyrene
polycyclic aromatic hydrocarbon bioactivated by mixed function oxidases to an electrophile that binds DNA |
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Delaney Ammendment to Food and Drug Laws
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prohibits addition to foods of any substance which produces CA at any does in any experimental animal
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2 problems with animal testing wrt carcinogenicity
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latent periods/longevity
spontaneous tumors |
