ABT EXAM Flashcards
LEAD
10% abs in adult; 50% in kids initial distribution: liver, kidneys; redistributes to bone exreted in urine acute poisoning is rare Chronic poisoning Adults: GI, neuromuscular Children: CNS Blood: basophilic stippling
ARSENIC
distributes to liver, kidney, hair, nails excreted: feces(ite) urine (ate) competes with PO4+ Diarrhea, dimentia, dermatitis hepatic fatty infiltration and necrosis carcinogen: skin llung, liver, bladder hyperkeratosis
Mercury
electrical equipment, pain, fugicides, fish
elemental (Vapor)
Salt (drinking water)
organo (methylHg) - fish
Chronic Vapors - CNS, psychotic
Chronic Organic: vision, hearing speech, ataxia, teratogen
Therapy
Dimercaprol: unable to reduce brain levels
Peniclliamine: goodfor vapor
polythiol resins: bine Hg in GI tract
CHROMIUM
lung cancer, oxidative injury
BERYLLIUM
effects on skin, conjuctivitis, chronic granuloma, carcinogen; zone 2 of liver
genetic polymorphism
LEAD EFFECTS
Peripheral neuropathy (Adults) Fatigue / Irritability Impaired concentration Hearing loss Wrist / Foot drop Seizures Encephalopathy (Children) Gastrointestinal Effects Nausea Dyspepsia Constipation Colic Lead line on gingival tissue Reproductive Effects Miscarriages/Stillbirths Reduced sperm count & motility Abnormal sperm Heme Synthesis Anemia Erythrocyte protoporphyrin elevation Renal Effects Chronic nephropathy with proximal tubular damage Hypertension Other Arthralgia Myalgia
EXCRETED INTO MILK
simple diffusion
basic compounds more likely because milk is acidic
lipid soluble
aldrin, chlordane, DDT,PCB, PBB, DBpD, furans
CARBON MONOXIDE
focal intimal damage and edema at 180ppm
direct damage to vasc enothelial and smooth muscle
increase permeability
induce atherosclerotic lesions
reversible interaction with Hemoglobin
carboxyhemoglobin decreases the O2 carrying capacity of blood leading to functional anemia
interacts with myoglobin and cytochrome C oxidase. vasodilatory
SALICYLATE
Ph1: hyperventilation leading to resp alkalosis
Ph2: paradoxic aciduria, with resp alkalosis
Ph3: dehydration, hypokalemia, metabolic acidosis
ALPHA RADIATION
most cannot penetrate skin
BETA RADIATION
short range
ejected electron
moderately penetrating
clothing provides some protection
GAMMA and XRay
highly penetrating
electromagnetic
dense material needed to shield
chlorophenothane (DDT)
estrogen mimetic
acute: motor unrest, tremors
poor absorption through skin
genotoxicity, endocrine disruptor
ACETONE
Solvent
very low toxicity
DIELDRIN
chlorinated hydrocarbon
persistent
biomagnifies
skin contamination is greatest hazard
NICOTINE
agonist at nicotinic acetylcholine receptor
absorbed through skin
FLUORIDE
3.0 ppm chronic moderate fluorosis(mottled teeth)
PARATHION
cholinesterase inhibitor
absorbed through skin
metabolized to paraoxon
Activated by replacement of Sulfur with Oxygen
metabolized to both active and inactive metabolites
Phenacetin
Methemoglobin ; hemolytic anemic; renal damage
“ethanol and carbon tetrachloride are chronically absorbed into an organism, the effect on the liver would be _____.”
Synergy
PHENOTHIAZINE
hypothermia; dry mouth, hypotension
SIACYLATE POISONING
direct stimulation of resp center initially
enhanced urinary excretion of sodium or potassium bicarbonate
accumulation of acids
depressed respiration
CARBON MONOXIDE ACUTE EXPOSURE
increases affinity of unbound hemoglobin sites for oxygen
decreases overall oxygen carry capacity of blood
shifts the dissociation curve for oxyhemoglbin to left
causes blood to become cherry red
STYRENE
narcosis
nausea
respiratory irritaiton
MALOXON
direct acting cholinesterase inhibitor
Produce Methemoglobinemia
para-aminopropiophenone
sodium nitrite
DIETHYLSTILBESTROL
endocrine disruptor
Reserpine
indole alkaloid, antipsychotic, antihypertensive
depletes catecholamines from peripheral sympathetic nerves
Tox: GI, nasal congestion, breast cancer, passes into breast milk, depression leading to suicide
treatment of acute digitalis glycoside poisoning
Phenytoin, cholestyramine
Asbestos
water contaminant
air pollutant
cancer risk enhanced by smoking
OLEANDER
GI and Cardiac (cardiac glycoside) CNS sap can cause skin irritation, and allergic dermatitis Induce vomiting Charcoal to absorb remaining toxins Digoxin Immune Fab
JIMSON WEED
Datur stramonium nightshade all parts are poisonous HALLUCINIGENIC toxicity by tropane alkaloids ATROPINE, scopolamine, hyoscyamine
LILY OF THE VALLEY
all parts are poisonous
GI and Heart (cardiac glycoside)
FOXGLOVE
DIGOXIN, cardiac glycoside
Produce Pancytopenia
chloramphenicol, cyclophosphamide, phenylbutazone, benzene
CHINESE HAMSTER OVARY TEST
identify chromosomal aberrations or sister chromatid exchanges
CA only detects structural damage; score metaphase cells
SCE: measure of DNA damage
AMES TEST
S. typhimirium - unable to synthesize histidine
back mutation in the presence of mutagenic chemical
restored bacterial growth
MOUSE LYMPHOMA ASSAY
ability of cells to acquire resistance to trifluorothymidine (forward mutation at the TK locus)
mutated cells grow
PHILADENDRON
contains .7% oxalate
vomiting, diarrhea, colic, drooling
DIEFFENBACHIA
cells contain needle-shaped Calcium Oxalate Crytals (Raphides)
pain swelling in mouth, edema
vomiting, diarrhea, drooling
apricot seeds
cyanide; nausea, fever, rash headace,
COBALT
stimulus for EPO production
CADMIUM
kidney, liver, low phosphate, muslce weakness, coma, arthritis,
COBRA VENOM
primarily neurotoxin, some cardiotoxic
CORAL SNAKE VENOM
Most potent venom of any North American Snake
short fangs
powerful neurotoxin - paralyzes breathing muscles
COPPERHEAD SNAKE VENOM
lethal dose = 100 mg
lowest potency of all pit vipers, slightly weaker than cottonmouth
extreme pain, tingling, throbbing, swelling, and severe nausea.
TCDD
contaminant in 2,4,5-T; most toxic chemical; teratogenic and carcinogenic; induces P488 more than P-450
ATROPINE
anti-muscarinic; competitively inhibits acetylcholine at post-ganglionic parasympathetic neuroeffector sites
tachycardia, CNS stimulation, dry mouth, dry skin, flushing skin
RHUBARB
leaves can be toxic
oxalic acid
CASTOR BEAN
Ricin - inhibits protein synthesis in ribosomes
nausea, diarrhea, tachycardia, hypotension seizures persisting for a week
IV administration results in agglutination and hemolysis
ELDERBERRIES
cooked berries are edible
uncooked berries and the rest of the plant are poisonous: cyanide-inducing glycoside
Amygdalin
CYANIDE
CN- ion halts cellular respiration by inhibiting cytochrome c oxidase (in mitochondria)
antidote: amyl nitrite, followed by sodium nitrite, followed by sodium thiosulfate; hydroxocobalamin
JEQUIRITY BEAN
contains ABRIN; binds transport proteins on cell membranes, prevents protein synthesis by inactivating 26S subunit of ribosome; symptoms identical to ricin
IV administration results in agglutination and hemolysis
SODIUM AZIDE
found in automobile airbags
hypotension
interferes with cellular respiration and aerobic metabolism
CNS and CV system most sensitive
PHTHALIC ACID ESTERS
endocrine disruptor; mixed with plastics, released into the environment, metabolites present in urine; fatty foods are biggest source; cause birth defects in rodents; interferes chick embryo heart cells
METHANOL
breakdown to formic acid and cause blindness
CNS depressant
metabolism via alcohol dehydrogenase in liver converts to formaldehyde then to formate: inhibits mitochondrial cytochrome c oxidase, metabolic acidosis
BOTULISM
toxin taken into neurons via endocytosis; prevents release of acetylcholine at axon endings
Metal Fume Fever
ZnO, MgO, chromium, cadmium; flu-like symptoms, 4 days for full recovery
HYDROGEN SULFIDE
complex binds with iron in the mitochondrial cytochrome enzymes, preventing cellular respiration
CNS is most affected
occurs naturally in body at low concentrations
ARSINE
Toxicity is distinct from other arsenic compounds, exposure via inhalation; attacks hemoglobin, resulting in lysis, hemolytic anemia
Dimercaprol (BAL)
treatment of arsenic, mercury, gold, lead, antimony,
competes with thiol groups
narrow therapeutic window
rapidly metabolized
PHOSPHOROUS
jaw necrosis, “phossy jaw”; liver and kidney toxicity
PROYLENE GLYCOL
toxicity requires extremely high intake
GRAS food additive
TOLUENE DIISOCYANATE
acute inhalation: irritation skin eyes, resp, GI CNS
Chronic inhalation: asthma-like
tumors in rodents
dyschromatopsia (alter color vision) - organic solvents
4 manifestations of deviant development
death, malformation, growth retardation, functional deficit
Rabbit Gestation
31-34 days
blastocyst: d2.6-6
implantation: d6
organogenesis: d6-17
Rat Gestation
21-22 days
blastocyst: d3-5
implantation: d5-6
organogenesis: d6-17
Monkey Gestation
166 days
Blastocyst: d4-9
implantation: d9
organogenesis:d20-45
Human Gestation
267 days
blastocyst: d4-6
implantation: d6-7
organogenesis: d21-56
Pre-implantation exposure to DDT, nicotine, methylmethane sulfonate
body and or brain weight deficits, embryo lethality , but NOT malformatino
toxic effects during gastrulation
malformations of eye brain and face; indicate damage to anterior neural plate
Fetal Toxicity
Fetus begins at 8 weeks; recognizable human form; tissue differentiation, growth, physiologic maturation
closure of the urethral groove in the male occurs around day 90
CHLORINE
irritates the resp system; accumulates at bottom of poorly ventilated spaces
irritant, inflammation, pulmonary congestion and edema
NITROSAMINE
carcinogen; formed from precursors in human stomach acid; reactions of nitrites and secondary amines; smoked food and tobacco;
Specific Locus Test
detecting recessive mutations in diploids. Normal individuals treated with mutagen are mated to testers that are homozygous for the recessive alleles at a number of specific loci; the progeny are then screened for recessive phenotypes.
ETHANOL
competitively inhibits ADH
GABA, NMDA and glycine recptors
TOCP
GI; peripheral neuropathy; cramps in calves, paresthesia in feet or hands; weak feet, wrist drop, paralysis
Inhibits acetylcholinesterase
ROTENONE
mildly toxic to humans, extremely toxic to insects and fish; lipophilic; long half-life in water; parkinson’s disease in rats
PYRETHRINS
chrysanthemum; insecticide; neurotoxic
tremors, convulsions,
MMS
methyl methanesulfonate; alkylating agent; carcinogen; reproductive toxicant
ACROLEIN
smell of burnt fat; unsaturated aldehyde; biocide; high toxicity; respiratory and cutaneous irritant; hemorrhagic cystitis;
ALLYL FORMATE
not toxic in the rat liver, converted via allyl alcohol into acrolein; requires alcohol dehydrogenase; localized to zone 1 of liver
CHROMATE
high concentratoins of chromium III can lead to DNA damage. Chromium III is excreted, and chromate ion is trsferred ino cell; oxidative damage to kidney, liver, blood cells, hemolysis, reanl and liver failure; dialysis useful for treatment; chromates cause allergic reactions; bronchogenic carcinoma when inhaled chronically
CARBON MONOXIDE POISONING SYNDROME
headache, numbness; cognitive; depression, irritability; blurry or double vision, loss of hearing seizures
TRICHLOROETHYLENE (TCE)
CNS depression, tachypnea; cardiac arrhythmias (exacerbated by epinephrine); reacts wit CO2; cranial nerve dysfunction; hepatotoxicity;
DELANEY CLAUSE
shall not approve for use in food any chemical additive found to induce cancer in man, or, after tests, found to induce cancer in animals
STYRENE
hazardous chemica; metabolized to styrene oxide then to styrene glycol; by P450; mutagenic, possible carcinogen;
Acute effects: eye and throat irritation
subchronic: neurotoxicant in humans - decreased cns function
HAZARD INDEX
Sum of hazard quotients that affect the same target organ
substance’s intrinsic toxicity (ie Hazard ) and exposure
HAZARD QUOTIENT
ratio between the exposure and a reference concentration (NOAEL)
DISULFURAM
anti-buse; blocks the oxidation of ethanol at the acetylaldehyde stage
Bluegill
consume daphnids; bioaccumulate selenium
effects on growth and survival of juvenile fish; effects on larvae (skeletal deformities)
ELIMINATION: zero order
constant quantity per time unit of the drug
ELIMINATION: first order
constant fraction per time unit of the drug; elimination is proportional to drug concentration
CHOLESTYRAMINE
bile acid sequestrant; ion exchange resin;
2,4-DINITROPHENOL
inhibitor of ATP production; uncouple oxidative phosphorylation; environmental contaminant; from car exhaust
BENZOPYRENE
Skin cancer
Epoxide intermediate
Pulmonary tumors in rats
FLUORIDE
Adversely affected ameloblasts lay down defective bone matrix
Increased production of methemoglobin is due to decreased activity of
NADH cytochrom b5 reductase
Isopropyl alcohol and CCL4 chronic absorption, the effect on the liver…
potentiation
Treatment of strychnine with diazepam
functional antagonism
Use of antitoxin for snakebites
chemical antagonism
known to produce dispositional tolerance
Cadmium and CCL4
Margin of Safety
TD1/ED99
Reasons for selective toxicity
transport differences between cells
biochemical differences between cells
cytology of plant cells versus animal cells
Fertility Index
percentage of matings that result in pregnancy
Gestation Index
Percentage of pregnancies that results in liver litters
Lactation index in rats
percentage of animals alive at 4 days that survive the 21 day lactation period
Assessment of neurotox
good concordance between human and animal neurotxicity assessment
monkeys can be used to test low level effect of neurotoxicants
in vitro cell cultures canbe used in neurotox assessment
Organogenesis in rats
Day 7-17
Emax
all receptors are occupied by a toxicant, and there is maximum amount of receptor toxicant complexes
TOCP
delayed neurotoxicity
Reason for embryo/fetal toxicity of DES
higher concentrations of free DES in embryo/fetus compared to adults
Acyl glucuronides toxicity to liver
active transport systems in the hepatocyte and bile duct system can greatly upconcentrate them
Selective Renal Toxicity of Cephaloridine (over cephalothin)
selective uptake by the organic anion transporter
Alpha amanitin
inhibits, RNA polymerase II
transported into the hepatocyte by a bile acid transporter
mushroom toxin
Paraquat toxicity
lungs accumulate paraquat in an energy dependent matter
enters lung via polyamine transport system
similar molecules with smaller distances between nitrogen atoms do not enter the lungs as readily
Enzyme induction of of phenobarbital
mediated through CAR receptor
CAR is down regulated by
proinflammatory cytokines
Pregnane X Receptor
cytosolic receptor
involved in induction of cyp 3A4
primarily expressed in skin
Amphipathic xenobiotics that get trapped in lysosomes and cause phospholipidosis
amiodarone
amitriptyline
fluoxetine
Bromobenzene (Parent)
bromobenzene 3,4 oxide (Electrophilic metabolite)
benzene (Parent)
muconic aldehyde (Electrophilic metabolite)
Allyl Alcohol (parent)
Acrolein (Electrophilic metabolite)
Can accept electrons from reductases and form radicals
paraquat, doxorubicin, nitrofurantoin
ASO4 (-3) to ASO3 (-2)
example of formation of electrophilic toxicant from inorganic chemical
most common nucleophilic detox reaction that amines undergo
acetylation
hydroxyl radical formation
interaction of ionizing radiation and water
reductive homolytic fission of hydrogen peroxide
interaction of silica with surface iron ions in lung
detoxication reaction
electrophile is covalently bound to protein that does not play a critical function
peroxisome proliferator activated receptor
clofibrate
estrogen receptor
zeralenone
kainate
glutamate receptor
muscimol
GABA A receptor
meperidine
opioid receptor
adrenergic beta I receptor
metoprolol
serotonin(2) receptor
ketanserin
glutamate receptor
ketamine
Inhibitors of citric acid cycle
flroroacetate, DCVC, malonate
Inhibitors of ADP phosphorylation
oligomycin, DDT, N-ethylmaleimide
Cause calcium influx into cytoplasm
capsaicin, domoate, amphotericin B
Inhibit Calcium export
vanadate, bromobenzene, CCL4
Blockade of Potassium Channels (voltage gated)
cisapride, terfenadine, grepafloxacin
Diazoxide
acts on potassium channels in pancreatic beta cells to impair insulin secretion
Cytochrome oxidase inhibitors
phosphine, azide, hydrogen sulfide
Inhibitors of NADH coenzyme Q reductase
rotenone, paraquat, amytal
overexpression of divalent metal transporter I in iron deficiency will lead to
increased intestinal absorption of cadmium and lead
AMPK
increases ATP production and decreases ATP consumption
Repair misfolded proteins
heat-shock response and ER stress response
Produce free radicals in inflammed tissue
NADPH oxidase, nitric oxide synthase, myeloperoxidase
Hypoxia response
production of HIF-1alpha, EPO, angiogenic factors
Strychnine target
glycine receptor
phorbol ester target
protein kinase C
warfarin
vitamin K2,3 epoxide reductase
Toxins that act by enzymatic action
ricin, anthrax, botulinum
Oxidative DNA Damage
8-hydroxy-deoxyguanosine in urine is a marker
can lead to base pair transversions
can lead to point mutation
PPAR alpha receptor
involved in fatty acid beta oxidation
Proteins in brown fat act mechanistically like
pentachlorophenol
Glutathione
can act nonenzymatically as radical scavenger
upregulated in response to a need
sustrate for glutathione peroxidase
Apoptosis signal transduction pathways
ras/ERK - suppression
JNK mediates
p38 production of inflamamtory cytokines
Paclitaxel
disrupts mitosis
Galacosamine
focal liver necrosis
Practolol Withdrawn because…
occulomucutaneous syndrome
Inhibits opening of mitochondrial permeability transition pore
cyclosporin A
L-deprenyl
bongkrekic acid
Microcystins target
protein phophatase
Molecular Chaperones
repair denatured proteins
Nephrotoxic effect of mercury
dicysteinyl-mercury complex mimicking endogenous cystine
Soft Neutrophile
Sulfur in glutathione
Fenton Reaction
produces hydroxyl radical and hydroxyl ions from hydrogen peroxide
Muscimol
direct GABA A agonist
Benzodiazepines
indirect GABA A agonist
Clonidine
alpha-2 adrenoceptor agonist
Baclofen
direct GABA B agonist
Bicuculline
direct GABA A Antogonist
Theophylline
adenosine antagonist
Nicotine
agonist at neuromuscular junction
Clozapine
direct serotonin antagonist/glycine uptake inhibitor
tecadenoson
direct adenosine agonist
Yohimbine
alpha-2 adrenoceptor antagonist
Cocaine
inhibits norepinephrine uptake
alpha-bungarotoxin
direct nicotine antagonist
bromocriptine
direct dopamine agonist
haloperidol
dopamine antagonist
amount of volatile liquid excreted by lungs
directly proportional to its vapor pressure
Absorbed in the colon
water, sodium ions, hydrogen ions
methylmercury crosses BBB
by combining with cysteine and forming a molecule similar to methionine
Efflux transporters on enterocytes
P-gp, MRP2, BCRP
Substrates for P-gp
cyclosporin, paclitaxel, colchicine
Fick’s Law
transfer of toxicants by simple diffusion from areas of high conc. to areas of low conc
TCDD
large octanel/water partitition coefficient
Protect fetus from toxicant exposure
multiple tissue layers of placenta
biotransformation ability of the placenta
presence of transporter systems in placenta
Why infants more susceptible to methemoglobinemia
higher pH of GI tract
Grapefruit juice effects
activity of CYP3A4
function of P-gp
absorption of lovastatin
Most characterized transplacental carcinogen
diethylstilbestrol
Gut microflora enzyme conjugates
UDP-glucuronic acid
Sulfate
Enterohepatic Cycling
hydrolysis of organic conjugate in gut and reabsorption of liberated parent compound
Arsenic
highest bile to plasma concentration ratio
Biliary Excretion Transporters
P-gp, Mrp2, Bcrp
Captopril
covalent binding to plasma protein
ABC family of transporters
all require ATP, can bind 1 or 2 substrates P-gp is an example
Metal Transporter Systems
Thallium can be absorbed by the iron transporter
Lead can be absorbed by the calcium transporter
Lithium can compete with Sodium transporter
Mephenytoin
probe drug for human CYP2C19 activity
CYP2D6
converts codeine to morphine
Is polymorphic
poor metabolizers have a lower risk of lung cancer
Aryl Hydrocarbon Receptor Agonists
TCDD, benzopyrene, benzene
Osteomalacia
associated with enzyme induction
Metabolism Dependent Inhibition of Cytochrome P450
metabolite is a potent inhibitor
Gemfibrozil
conjugated with glucuronic acid before it is oxidized by cytochrome P450
UDP Glucuronyltranferases conjugate these endogenouse molecules
thyroid hormone, bilirubin, steroid hormones
Codeine give to a 2D6 ultrametabolizer
higher than normal levels of morphine at 2 hours post-dose
Victim Drug
drug whose clearance is determined mostly by a single route of elimination
Victim drug and perpetrator
terfenadine and ketoconazole
PARAQUAT
Ingested; lung damage by all routes of exposure; selectively concentrates in lungs, progressive fibrosis; NADPH depletion, FR damage, parkinson’s like
CHLORINATED DIBENZO P DIOXIN
photochemically degraded,
METHYLENE CHLORIDE
after absorption methylene chloride is metabolized in the liver to carbon monoxide
Micronucleus Test
Clastogenesis
Chromosome damage
Ames Test
Reverse Mutation
OZONE
deep lung irritant; minimal change in resistance and increase frequency of breathing
Mast Cells Release
serine proteases, tryptase, histamine, serotonin, heparin, eicosanoids (thromboxane, prostaglandin D2, leuotriene C4, Platelet activating factor), cytokines (eosinophil chemotactic factor)
Organophoshates & Carbamates target
ACETYLCHOLINESTERASE Inhibition
Pyrethroids (I and II) and DDT target
Sodium Channels activation
Dihydropyrazoles target
Sodium Channels Inhibition
NICOTINE & NEONICOTINOIDS target
nicotinic acetylcholine receptors - activation
CYCLODIENES, PHYENYLPYRAZOLES, TYPE II PYRETHROIDS target
GABA receptors-gated chloride channels inhibition
AVERMECTINS
glutamate-gated chloride channels activation (found only in insects). In mammals (GABAa receptors)
FORMAMIDINES
Octopamine receptors activation (in mammals, Alpha2 adrenoceptors)
ROTENOIDS
mitochondrial complex I inhibition
RENAL EXCRETION TRANSPORTERS
Bcrp, Bsep Cnt Dmt Ent Ibat Mate1, Mdr, Mrp, Npc1L1, Npt, Ntcp Oat, Oct, Oatp Pept Urat
Stinging Nettle
Contact urticaria
Mistletoe
GI , bradycardia; phoratoxin
Bagassosis
interstitial lung disease; hypersensitivity pneumonitis attributed to moldy molasses (sugar cane dust)
Tricyclic Antidepressant Overdose
cardiovascular and neurologic
tachycardia, drowsiness, dry mouth, nausea, vomiting, urinary retention, confusion, agitation, headache; prolonged QRS and PR/QT; Seizures, apnea
TCA (tricyclic antidepressant) MOA
anticholinergic, excessive blockade of NE reuptake, direct alpha adrenergic blockade, block Na membrane channels - quinidine like effects on myocardium
FLUORIDE TOXICITY
GI Distress, convulsions, weakness, hypocalcemia, hyperkalemia, hypotension, coma, within hours; Tx: induce vomiting; calcium chloride/gluconate orally; give milk
Legal Antioxidants
Butylated hydroxyanisole
Propyl gallate
butylated hydroxytoluene
POKEWEED
Phytolacca
contains a mitogen
Photochemical Smog
Ozone, hydrocarbons, oxides of nitrogen
ETHANOL
depression of reticular activating system
dilation of cutaneous vessles
stimulation of gastric secretion
increased NADH/NAD ratio in lkiver
ERGOT
fungus: Claviceps; moldy grains
alkaloid: burning sensation in limbs; vasoconstriction; gangrene
neurotropic: hallucinations, uterine contractions, nausea, seizures; induce abortions
Organic TIN
tetraethyl has delayed reaction; triethyl causes cerebral edema (animals); headaches, EEG changes, visual in workers; Dialkyl salts are severe skin irritants and inflammatory to bile ducts
organic more toxic than inorganic
SPIRONOLACTONE
steroidal antimineralocorticoid, anti-androgen, weak progestogen, indirect estrogen and glucocorticoid
diuretic and antihypertensive; potassium sparing diuretic
Thiazide
diuretics; inhibit reabsorption of Na and Cl from distal convoluted tubules; increase Ca reabsorption
Tox: hypokalemia, hyperglycemia, adversely effects fetus
Done Nomogram
describes toxicity resulting from salicylate overdose based on blood levels sampled at fixed timepoint postingestion
NUX VOMICA
Strychnine
METHYL PARATHION
detoxification by glutathione dependent dealkylation
CARBON DISULFIDE
Enhances excretion of zinc and interferes with thiamine utilization
RED SQUILL
EMETIC - causes vomiting in humans; toxic to rats because they can’t vomit
Solution
most potentially dangerous formulation of an insecticide
Solution
most potentially dangerous formulation of an insecticide
DIBROMOCHLOROPROPANE (DBCP) & ETHYLENE DIBROMIDE
malignant gastric squamous cell tumor in rodents
Altered spermatogenesis
DIBROMOCHLOROPROPANE (DBCP) & ETHYLENE DIBROMIDE
malignant gastric squamous cell tumor in rodents
Altered spermatogenesis
CCL4 treatment
magnesium salts and large volumes of water
CCL4 treatment
magnesium salts and large volumes of water
CO2 overdose symptoms
dyspnea, nausea, increased chest movt; increased abdominal movt
Causes pulmonary edema
phosgene, perchloroethylene, hydrogen fluoride
Niacin Overdose
flushing, itching, increased peristalsis, vasodilation
Byssinosis
respiratory disease associated with inhalation of dust from cotton flax or hemp
COBALT
cross reaction sensitization because of haptene similarities among chromium, cobalt and nickel
methotrexate antidote
thymidine
heparin antidote
protamine
RADON daughters
alpha particles
mining, in some dwellings, assoc with SCLC in miners
organic phosphate antidote
pralidoxime
CYANIDE INTOXICATION
respiratory alkalosis; sodium thiosulfate for conversion of CN to thioCN; sodium itrite to produce metHb, which binds CN
RADON daughters
mining, in some dwellings, assoc with SCLC in miners
methyl ethyl ketone and methyl n-butyl ketone
neurotoxic because of a common metabolite: 2,5-hexanedione
Tumor promotion
reversible
exhibits threshold leveles
modulated by environmental factors
PHENOTHIAZINE blurry vision
from storage of phenothiazine on melanin pigments in ciliary body
Mouse Organogenesis
Days 6-15
biotransformation of parent compound to liver toxicant
halothane, bromobenzene, CCL4, acetaminophen
Male Rat Hydrocarbon Nephropathy
exacerbation of hyaline droplet formation; granular casts , chronic nephrosis ultrastructurally, increase in size and incidence of crystalloid change of proximal tubular cell phagolysosomes
Cause Testicular Atrophy
diethylhexyphthalate
cadmium
manganese
dibromochloropropane
Ozone syndrome
duplicated by the injection of the ozonide of linoleic acid
Cause Interstitial pneumonia
Q fever, influenza, cytomegalic inclusion dz, berylliosis
2-Naphthylamine
human carcinogen - urinary bladder
cancer in hamsters, dogs, rhesus, rat
benign tumors in mice
req’s metabolism; dna adducts found in bladder and liver of exposed dogs
Chronic Toluene diisocyanate
asthma
Aromatic Amines
bladder cancer; dog is susceptible species
2-naphthylamine and benzidine; Chlornaphazine
ANILINE
aromatic amine; industrial chemical - dyes; methemoglobinemia, heinz body anemia
VINYL CHLORIDE
liver damage and angiosarcoma of the liver
Aromatic Amines
bladder cancer; dog is susceptible species
VACOR
Rodenticide; selectively destroys insulin-producing beta cells of pancreas causing diabetes; hypotension and hypoglycemia; impotence; peanut odor to breath; onset hrs to days
PHOTOCHEMICAL AIR POLLUTION
O3, NO2, NO, SO2
CARBON MONOXIDE
reversibly binds Hb; 200-250x >O2; eliminated by lungs, fetus more sensitive
Tx: O2
VACOR
Rodenticide; selectively destroys insulin-producing beta cells of pancrease causing diabetes; hyptension and hypoglycemia; imppotence; peanut odor to breath; onset hrs to days
Pyridoxine
nutrtional supplement; antidote for Isoniazide; hydrazine, ethylene glycol
Vitamin B6
Isoniazide
antibiotic for TB; depletes pyridoxine; hepatotoxic; CYP2E1c1 are more susceptible; slow acetylators more susceptible too; induces seizures -depletes GABA
ISONIAZIDE drug interactions
phenytoin, carbamazepine, warfarin, rifampin
HYDRAZINE
chemical intermediate for explosives; caustic; functional pyroxidine deficiency; hepatic necrosis
BENZOATE
food preservative; bacteriostatic fungistatic in acid environment
HYDROGEN SULFIDE
petroleum, volcanos, decaying organic matter
death within minutes; inhibits mitochondrial respriration; binds cytochrome aa and cytochrome oxidase
STRYCHNINE
muscle spasms; lactic acidosis, hyperthermia, rhabdomyolysis; metallic taste
Treat: charcoal, diazepam, phenobarb
STRYCHNINE metabolism
liver microsomal enzymes: NADPH and O2; competes with glycine
FLUOROACETATE (1080)
pesticide organofluorine; disrupts citric acid cycle (Krebs); combines with coenzymes A; symptoms in 30 minutes; nausea, vomiting, sweating, agitation, cardiac, seizures; accumulate citrate in blood
CYCLODIENE
Organochlorine; persistent pollutant
GLUTETHIMIDE
sedative, addictive; CYP2D6 enzyme inducer with codeine converts to morphine
PARALDEHYDE
CNS depressant; excreted via lungs, unpleasant odor; anti-seizure
ZINC MOA
mimics Cd, Cu, Ni
MERCURY AND CADMIUM moa
attach to SH
POTASSIUM moa
mimics Thallium
IRON moa
mimics manganese
PHOSPHATE moa
mimics arsenate and vanadate
SULFATE moa
mimics selenate; molydate, chromate
Metals that cause oxidate injury
Iron, Nickle, Chromium
Hexavalent Chromium
forms DNA adducts
Organic LEAD tox treatment
Calcium Sodium EDTA
BAL
DEFEROXAMINE
removes iron ; binds free iron in blood and enhances urinary elimination
MERCURY inorganic
concentrates in kidneys; excreted feces/bile
MERCURY organic
concentrates in RBC more than plasma; uptake by neutral animo acid carrier in enothelial cells due to structural similarity to methionine
MERCURY Tx
BAL - protects kidneys
Penicillamine - best for vapors
Polythiol resins - for methyl; bind mercury in GI tract; prevents absorption
ARSINE
As3; binds SH groups of enzymes, pyruvate dehydrogenase; Krebs cycle TCA
Chronic ARSENIC
rice and water stools, skin pigmentation, hyperkaeratosis; edema, Garlic breath; profressive: dermatitis, liver, kidney injury, peripheral nueritis, encephalopathy, aplastic anemia
CADMIUM
yellow pigment; ITal-Ital: breaking ribs
Chronic - Kidney tox
Emphysema, hypertension, bone, testes
ALUMINUM
low tox; SHaver’s dz - inhalation, fibrosis
Neurotox - neurofibrillary tangles
Dialysis dementia - historic
Barium
low tox; GI and cardiovascular
BERRYLIUM
conjunctivitis, dermatitis, granulomatous (DTH)
CHROMIUM
chronic - lung cancer
COBALT
polycythemia, Goiter, Cardiomyopathy (Beer); inhibits ferrochelatase(required for heme synth)
Wilson’s disease
SNP in Cu tranporter gene; loss of function
Tx: Penicillamine
MANGANESE
in some pesticides; pneunomia (inhalation)
PARKISONS (decreased DOPA neurons)
Nickle
pneumonitis (inhalation)
Leukocytosis, delirium, carcinogen (lung)
PHOSPHOROUS
rat poison, fireworks
GI - phosphorescent Vomit
SELENIUM
blind staggers in cattle;
Human - discolored teeth; skin eruptions, GI, loss of hair and nails; liver injury
SILVER
blue skin due to silver sulfide via sun exposure
THALLIUM
rodenticide (historically); destributes like potassium; GI irritation; alopecia
Tx: Prussian blue - breaks enterhepatic circulation
URANIUM
kidney injury
ZINC
vomiting, diarrhea, pyrexia; inhalation fever
ORGANOPHOSPHATE
readily biodegraded; low species selectivity
parathion, gluthion, chloropyrifos, diazinon, malathion, dichlorvos, sarin, metamidophos
PON1
detoxifies OPs; genetic polymorphism
OP delayed polyneuropathcy
2-3 weeks later; dying back axonopathy; tingly weakness, ataxia; young are resistant, Hen for testing
PYRETHROIDS
Cis isomer more toxic than Trans
interact with sodium channel
Tx: Vitamin E
ORGANOCHLORINES
Lindane, Chlordane, Aldrin, Dieldrin, Endrin, Heptachlor, DDT
ORGANOCHLORINE Tox
convulsions, bind GABAa; inhibit Chloride channel; induce hepatic microsomal enzymes; tumor promoter; extremely persistent in environment
Estrogen mimetic
ROTENONE
toxic to fish; inhibits cplxI in mitochondrial resp chain; model for PARKINSONs
CHLOROPHENOXY Cpds
TCDD is a contaminant!
2,4-D, Chronic: sarcomas, nonhodgkins lymphoma
vomiting, abdominal pain, diarrhoea, GI haemorrhage; coma, hypertonia, hyperreflexia, ataxia, nystagmus, miosis, hallucinations and convulsions.
Tx: urinary alkalinization
PARAQUAT moa
electron reduction; Free radical;super oxide anions; lipid peroxidation, NADPH
destruction of aveolar cells
Dithiocarbamate Fungicides
alter thyroid hormone levels - hypertrophy
metabolized to ETU - thyroid/liver cx
Developmental neural tox
Some assoc with PARKINSONS
FLUOROACETATE
target organ: Brain, Heart
Co-enzyme A - fluorocitrate - inhibits Krebs cycle
mouse LLNA
Type IV reactions, prefered over G Pig, detects in situ hyperproliferation; no Freud’s adjuvant
P450
on ER (microsome)
biotransformatoin
Cytochrome P450, cytochrome C reductase, NADPH, Oxygen, magnesium
P450 Oxidation Reactions
aromatic hydroxylation; aliphatic hydroxylation; N,O,S dealkylation; epoxidation, desulfuration, sulfoxidation, n-hydroxylation
ACYL GLUCURONIDES
active transport systems in the hepatocyte and bile duct upconcentrate them
CAR
phenobarb receptor, downregulated by proinflammatory cytokines
PREGNANE X receptor
indcution of CYP3A4
Cause Phospholipidosis
amiodaroneamitriptyline, fluoxetine
Detox of electrophiles
conjugation with Glutathione
Amines - nucleophilic detox
acetylation
CLOFIBRATE receptor
PPAR
Citric Acid Cycle Inhibitors
fluoroacetate, DCVC, malonate
ADP Phosphorylation Inhibitors
Oligomycin, DDT, N-ethylmaleimide
Cause Calcium influx
capsaicin, domoate, amphoterecin B
Inhibit Calcium eflux
vanadate, bromobenzene, CCL4
Inhibitors of Cytochrome Oxidase
Phosphine, Azide, Hydrogen Sulfide
Inhibitors of NADH coenzyme Q reductase
rotenone, paraquat, amytal
Produce Free Radicals in inflammed tissue
NADPH oxidase, nitric oxide synthase, myeloperoxidase
Noncovalent Binding
Strychnine to glycine
Phorbol ester to Protein Kinase C
Warfarin to vit K 2,3 epoxide reductase