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Toxicology ABT COPY for AeJ > ABT EXAM > Flashcards

ABT EXAM Flashcards

1
Q

LEAD

A 
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
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2
Q

ARSENIC

A 
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
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3
Q

Mercury

A

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

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4
Q

CHROMIUM

A

lung cancer, oxidative injury

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5
Q

BERYLLIUM

A

effects on skin, conjuctivitis, chronic granuloma, carcinogen; zone 2 of liver
genetic polymorphism

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6
Q

LEAD EFFECTS

A 
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
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7
Q

EXCRETED INTO MILK

A

simple diffusion
basic compounds more likely because milk is acidic
lipid soluble
aldrin, chlordane, DDT,PCB, PBB, DBpD, furans

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8
Q

CARBON MONOXIDE

A

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

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9
Q

SALICYLATE

A

Ph1: hyperventilation leading to resp alkalosis
Ph2: paradoxic aciduria, with resp alkalosis
Ph3: dehydration, hypokalemia, metabolic acidosis

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10
Q

ALPHA RADIATION

A

most cannot penetrate skin

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11
Q

BETA RADIATION

A

short range
ejected electron
moderately penetrating
clothing provides some protection

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12
Q

GAMMA and XRay

A

highly penetrating
electromagnetic
dense material needed to shield

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13
Q

chlorophenothane (DDT)

A

estrogen mimetic
acute: motor unrest, tremors
poor absorption through skin
genotoxicity, endocrine disruptor

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14
Q

ACETONE

A

Solvent

very low toxicity

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15
Q

DIELDRIN

A

chlorinated hydrocarbon
persistent
biomagnifies
skin contamination is greatest hazard

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16
Q

NICOTINE

A

agonist at nicotinic acetylcholine receptor

absorbed through skin

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17
Q

PARATHION

A

cholinesterase inhibitor
absorbed through skin
metabolized to paraoxon
Activated by replacement of Sulfur with Oxygen
metabolized to both active and inactive metabolites

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18
Q

Phenacetin

A

Methemoglobin ; hemolytic anemic; renal damage

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19
Q

“ethanol and carbon tetrachloride are chronically absorbed into an organism, the effect on the liver would be _____.”

A

Synergy

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20
Q

PHENOTHIAZINE

A

hypothermia; dry mouth, hypotension

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21
Q

SIACYLATE POISONING

A

direct stimulation of resp center initially
enhanced urinary excretion of sodium or potassium bicarbonate
accumulation of acids
depressed respiration

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22
Q

CARBON MONOXIDE ACUTE EXPOSURE

A

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

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23
Q

STYRENE

A

narcosis
nausea
respiratory irritaiton

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24
Q

MALOXON

A

direct acting cholinesterase inhibitor

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25
Q

Produce Methemoglobinemia

A

para-aminopropiophenone

sodium nitrite

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26
Q

DIETHYLSTILBESTROL

A

endocrine disruptor

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27
Q

Reserpine

A

indole alkaloid, antipsychotic, antihypertensive
depletes catecholamines from peripheral sympathetic nerves
Tox: GI, nasal congestion, breast cancer, passes into breast milk, depression leading to suicide

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28
Q

treatment of acute digitalis glycoside poisoning

A

Phenytoin, cholestyramine

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29
Q

Asbestos

A

water contaminant
air pollutant
cancer risk enhanced by smoking

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30
Q

OLEANDER

A 
GI and Cardiac (cardiac glycoside)
CNS
sap can cause skin irritation, and allergic dermatitis
Induce vomiting
Charcoal to absorb remaining toxins
Digoxin Immune Fab
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31
Q

JIMSON WEED

A 
Datur stramonium
nightshade
all parts are poisonous
HALLUCINIGENIC
toxicity by tropane alkaloids
ATROPINE, scopolamine, hyoscyamine
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32
Q

LILY OF THE VALLEY

A

all parts are poisonous

GI and Heart (cardiac glycoside)

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33
Q

FOXGLOVE

A

DIGOXIN, cardiac glycoside

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34
Q

Produce Pancytopenia

A

chloramphenicol, cyclophosphamide, phenylbutazone, benzene

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35
Q

CHINESE HAMSTER OVARY TEST

A

identify chromosomal aberrations or sister chromatid exchanges
CA only detects structural damage; score metaphase cells
SCE: measure of DNA damage

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36
Q

AMES TEST

A

S. typhimirium - unable to synthesize histidine
back mutation in the presence of mutagenic chemical
restored bacterial growth

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37
Q

MOUSE LYMPHOMA ASSAY

A

ability of cells to acquire resistance to trifluorothymidine (forward mutation at the TK locus)
mutated cells grow

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38
Q

PHILADENDRON

A

contains .7% oxalate

vomiting, diarrhea, colic, drooling

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39
Q

DIEFFENBACHIA

A

cells contain needle-shaped Calcium Oxalate Crytals (Raphides)
pain swelling in mouth, edema
vomiting, diarrhea, drooling

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40
Q

apricot seeds

A

cyanide; nausea, fever, rash headace,

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41
Q

COBALT

A

stimulus for EPO production

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42
Q

CADMIUM

A

kidney, liver, low phosphate, muslce weakness, coma, arthritis,

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43
Q

COBRA VENOM

A

primarily neurotoxin, some cardiotoxic

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44
Q

CORAL SNAKE VENOM

A

Most potent venom of any North American Snake
short fangs
powerful neurotoxin - paralyzes breathing muscles

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45
Q

COPPERHEAD SNAKE VENOM

A

lethal dose = 100 mg
lowest potency of all pit vipers, slightly weaker than cottonmouth
extreme pain, tingling, throbbing, swelling, and severe nausea.

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46
Q

TCDD

A

contaminant in 2,4,5-T; most toxic chemical; teratogenic and carcinogenic; induces P488 more than P-450

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47
Q

ATROPINE

A

anti-muscarinic; competitively inhibits acetylcholine at post-ganglionic parasympathetic neuroeffector sites
tachycardia, CNS stimulation, dry mouth, dry skin, flushing skin

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48
Q

RHUBARB

A

leaves can be toxic

oxalic acid

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49
Q

CASTOR BEAN

A

Ricin - inhibits protein synthesis in ribosomes
nausea, diarrhea, tachycardia, hypotension seizures persisting for a week
IV administration results in agglutination and hemolysis

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50
Q

ELDERBERRIES

A

cooked berries are edible
uncooked berries and the rest of the plant are poisonous: cyanide-inducing glycoside
Amygdalin

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51
Q

CYANIDE

A

CN- ion halts cellular respiration by inhibiting cytochrome c oxidase (in mitochondria)
antidote: amyl nitrite, followed by sodium nitrite, followed by sodium thiosulfate; hydroxocobalamin

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52
Q

JEQUIRITY BEAN

A

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

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53
Q

SODIUM AZIDE

A

found in automobile airbags
hypotension
interferes with cellular respiration and aerobic metabolism
CNS and CV system most sensitive

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54
Q

PHTHALIC ACID ESTERS

A

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

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55
Q

METHANOL

A

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

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56
Q

BOTULISM

A

toxin taken into neurons via endocytosis; prevents release of acetylcholine at axon endings

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57
Q

Metal Fume Fever

A

ZnO, MgO, chromium, cadmium; flu-like symptoms, 4 days for full recovery

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58
Q

HYDROGEN SULFIDE

A

complex binds with iron in the mitochondrial cytochrome enzymes, preventing cellular respiration
CNS is most affected
occurs naturally in body at low concentrations

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59
Q

ARSINE

A

Toxicity is distinct from other arsenic compounds, exposure via inhalation; attacks hemoglobin, resulting in lysis, hemolytic anemia

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60
Q

Dimercaprol (BAL)

A

treatment of arsenic, mercury, gold, lead, antimony,
competes with thiol groups
narrow therapeutic window
rapidly metabolized

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61
Q

PHOSPHOROUS

A

jaw necrosis, “phossy jaw”; liver and kidney toxicity

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62
Q

PROYLENE GLYCOL

A

toxicity requires extremely high intake

GRAS food additive

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63
Q

TOLUENE DIISOCYANATE

A

acute inhalation: irritation skin eyes, resp, GI CNS
Chronic inhalation: asthma-like
tumors in rodents
dyschromatopsia (alter color vision) - organic solvents

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64
Q

4 manifestations of deviant development

A

death, malformation, growth retardation, functional deficit

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65
Q

Rabbit Gestation

A

31-34 days

blastocyst: d2.6-6
implantation: d6
organogenesis: d6-17

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66
Q

Rat Gestation

A

21-22 days

blastocyst: d3-5
implantation: d5-6
organogenesis: d6-17

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67
Q

Monkey Gestation

A

166 days
Blastocyst: d4-9
implantation: d9
organogenesis:d20-45

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68
Q

Human Gestation

A

267 days

blastocyst: d4-6
implantation: d6-7
organogenesis: d21-56

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69
Q

Pre-implantation exposure to DDT, nicotine, methylmethane sulfonate

A

body and or brain weight deficits, embryo lethality , but NOT malformatino

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70
Q

toxic effects during gastrulation

A

malformations of eye brain and face; indicate damage to anterior neural plate

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71
Q

Fetal Toxicity

A

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

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72
Q

CHLORINE

A

irritates the resp system; accumulates at bottom of poorly ventilated spaces
irritant, inflammation, pulmonary congestion and edema

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73
Q

NITROSAMINE

A

carcinogen; formed from precursors in human stomach acid; reactions of nitrites and secondary amines; smoked food and tobacco;

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74
Q

Specific Locus Test

A

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.

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75
Q

ETHANOL

A

competitively inhibits ADH

GABA, NMDA and glycine recptors

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76
Q

TOCP

A

GI; peripheral neuropathy; cramps in calves, paresthesia in feet or hands; weak feet, wrist drop, paralysis
Inhibits acetylcholinesterase

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77
Q

ROTENONE

A

mildly toxic to humans, extremely toxic to insects and fish; lipophilic; long half-life in water; parkinson’s disease in rats

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78
Q

PYRETHRINS

A

chrysanthemum; insecticide; neurotoxic

tremors, convulsions,

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79
Q

MMS

A

methyl methanesulfonate; alkylating agent; carcinogen; reproductive toxicant

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80
Q

ACROLEIN

A

smell of burnt fat; unsaturated aldehyde; biocide; high toxicity; respiratory and cutaneous irritant; hemorrhagic cystitis;

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81
Q

ALLYL FORMATE

A

not toxic in the rat liver, converted via allyl alcohol into acrolein; requires alcohol dehydrogenase; localized to zone 1 of liver

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82
Q

CHROMATE

A

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

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83
Q

CARBON MONOXIDE POISONING SYNDROME

A

headache, numbness; cognitive; depression, irritability; blurry or double vision, loss of hearing seizures

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84
Q

TRICHLOROETHYLENE (TCE)

A

CNS depression, tachypnea; cardiac arrhythmias (exacerbated by epinephrine); reacts wit CO2; cranial nerve dysfunction; hepatotoxicity;

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85
Q

DELANEY CLAUSE

A

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

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86
Q

STYRENE

A

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

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87
Q

HAZARD INDEX

A

Sum of hazard quotients that affect the same target organ

substance’s intrinsic toxicity (ie Hazard ) and exposure

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88
Q

HAZARD QUOTIENT

A

ratio between the exposure and a reference concentration (NOAEL)

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89
Q

DISULFURAM

A

anti-buse; blocks the oxidation of ethanol at the acetylaldehyde stage

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90
Q

Bluegill

A

consume daphnids; bioaccumulate selenium

effects on growth and survival of juvenile fish; effects on larvae (skeletal deformities)

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91
Q

ELIMINATION: zero order

A

constant quantity per time unit of the drug

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92
Q

ELIMINATION: first order

A

constant fraction per time unit of the drug; elimination is proportional to drug concentration

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93
Q

CHOLESTYRAMINE

A

bile acid sequestrant; ion exchange resin;

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94
Q

2,4-DINITROPHENOL

A

inhibitor of ATP production; uncouple oxidative phosphorylation; environmental contaminant; from car exhaust

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95
Q

BENZOPYRENE

A

Skin cancer
Epoxide intermediate
Pulmonary tumors in rats

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96
Q

FLUORIDE

A

Adversely affected ameloblasts lay down defective bone matrix

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97
Q

Increased production of methemoglobin is due to decreased activity of

A

NADH cytochrom b5 reductase

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98
Q

Isopropyl alcohol and CCL4 chronic absorption, the effect on the liver…

A

potentiation

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99
Q

Treatment of strychnine with diazepam

A

functional antagonism

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100
Q

Use of antitoxin for snakebites

A

chemical antagonism

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101
Q

known to produce dispositional tolerance

A

Cadmium and CCL4

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102
Q

Margin of Safety

A

TD1/ED99

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103
Q

Reasons for selective toxicity

A

transport differences between cells
biochemical differences between cells
cytology of plant cells versus animal cells

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104
Q

Fertility Index

A

percentage of matings that result in pregnancy

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105
Q

Gestation Index

A

Percentage of pregnancies that results in liver litters

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106
Q

Lactation index in rats

A

percentage of animals alive at 4 days that survive the 21 day lactation period

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107
Q

Assessment of neurotox

A

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

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108
Q

Organogenesis in rats

A

Day 7-17

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109
Q

Emax

A

all receptors are occupied by a toxicant, and there is maximum amount of receptor toxicant complexes

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110
Q

TOCP

A

delayed neurotoxicity

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111
Q

Reason for embryo/fetal toxicity of DES

A

higher concentrations of free DES in embryo/fetus compared to adults

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112
Q

Acyl glucuronides toxicity to liver

A

active transport systems in the hepatocyte and bile duct system can greatly upconcentrate them

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113
Q

Selective Renal Toxicity of Cephaloridine (over cephalothin)

A

selective uptake by the organic anion transporter

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114
Q

Alpha amanitin

A

inhibits, RNA polymerase II
transported into the hepatocyte by a bile acid transporter
mushroom toxin

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115
Q

Paraquat toxicity

A

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

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116
Q

Enzyme induction of of phenobarbital

A

mediated through CAR receptor

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117
Q

CAR is down regulated by

A

proinflammatory cytokines

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118
Q

Pregnane X Receptor

A

cytosolic receptor
involved in induction of cyp 3A4
primarily expressed in skin

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119
Q

Amphipathic xenobiotics that get trapped in lysosomes and cause phospholipidosis

A

amiodarone
amitriptyline
fluoxetine

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120
Q

Bromobenzene (Parent)

A

bromobenzene 3,4 oxide (Electrophilic metabolite)

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121
Q

benzene (Parent)

A

muconic aldehyde (Electrophilic metabolite)

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122
Q

Allyl Alcohol (parent)

A

Acrolein (Electrophilic metabolite)

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123
Q

Can accept electrons from reductases and form radicals

A

paraquat, doxorubicin, nitrofurantoin

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124
Q

ASO4 (-3) to ASO3 (-2)

A

example of formation of electrophilic toxicant from inorganic chemical

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125
Q

most common nucleophilic detox reaction that amines undergo

A

acetylation

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126
Q

hydroxyl radical formation

A

interaction of ionizing radiation and water
reductive homolytic fission of hydrogen peroxide
interaction of silica with surface iron ions in lung

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127
Q

detoxication reaction

A

electrophile is covalently bound to protein that does not play a critical function

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128
Q

peroxisome proliferator activated receptor

A

clofibrate

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129
Q

estrogen receptor

A

zeralenone

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130
Q

kainate

A

glutamate receptor

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131
Q

muscimol

A

GABA A receptor

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132
Q

meperidine

A

opioid receptor

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133
Q

adrenergic beta I receptor

A

metoprolol

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134
Q

serotonin(2) receptor

A

ketanserin

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135
Q

glutamate receptor

A

ketamine

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136
Q

Inhibitors of citric acid cycle

A

flroroacetate, DCVC, malonate

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137
Q

Inhibitors of ADP phosphorylation

A

oligomycin, DDT, N-ethylmaleimide

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138
Q

Cause calcium influx into cytoplasm

A

capsaicin, domoate, amphotericin B

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139
Q

Inhibit Calcium export

A

vanadate, bromobenzene, CCL4

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140
Q

Blockade of Potassium Channels (voltage gated)

A

cisapride, terfenadine, grepafloxacin

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141
Q

Diazoxide

A

acts on potassium channels in pancreatic beta cells to impair insulin secretion

142
Q

Cytochrome oxidase inhibitors

A

phosphine, azide, hydrogen sulfide

143
Q

Inhibitors of NADH coenzyme Q reductase

A

rotenone, paraquat, amytal

144
Q

overexpression of divalent metal transporter I in iron deficiency will lead to

A

increased intestinal absorption of cadmium and lead

145
Q

AMPK

A

increases ATP production and decreases ATP consumption

146
Q

Repair misfolded proteins

A

heat-shock response and ER stress response

147
Q

Produce free radicals in inflammed tissue

A

NADPH oxidase, nitric oxide synthase, myeloperoxidase

148
Q

Hypoxia response

A

production of HIF-1alpha, EPO, angiogenic factors

149
Q

Strychnine target

A

glycine receptor

150
Q

phorbol ester target

A

protein kinase C

151
Q

warfarin

A

vitamin K2,3 epoxide reductase

152
Q

Toxins that act by enzymatic action

A

ricin, anthrax, botulinum

153
Q

Oxidative DNA Damage

A

8-hydroxy-deoxyguanosine in urine is a marker
can lead to base pair transversions
can lead to point mutation

154
Q

PPAR alpha receptor

A

involved in fatty acid beta oxidation

155
Q

Proteins in brown fat act mechanistically like

A

pentachlorophenol

156
Q

Glutathione

A

can act nonenzymatically as radical scavenger
upregulated in response to a need
sustrate for glutathione peroxidase

157
Q

Apoptosis signal transduction pathways

A

ras/ERK - suppression
JNK mediates
p38 production of inflamamtory cytokines

158
Q

Paclitaxel

A

disrupts mitosis

159
Q

Galacosamine

A

focal liver necrosis

160
Q

Practolol Withdrawn because…

A

occulomucutaneous syndrome

161
Q

Inhibits opening of mitochondrial permeability transition pore

A

cyclosporin A
L-deprenyl
bongkrekic acid

162
Q

Microcystins target

A

protein phophatase

163
Q

Molecular Chaperones

A

repair denatured proteins

164
Q

Nephrotoxic effect of mercury

A

dicysteinyl-mercury complex mimicking endogenous cystine

165
Q

Soft Neutrophile

A

Sulfur in glutathione

166
Q

Fenton Reaction

A

produces hydroxyl radical and hydroxyl ions from hydrogen peroxide

167
Q

Muscimol

A

direct GABA A agonist

168
Q

Benzodiazepines

A

indirect GABA A agonist

169
Q

Clonidine

A

alpha-2 adrenoceptor agonist

170
Q

Baclofen

A

direct GABA B agonist

171
Q

Bicuculline

A

direct GABA A Antogonist

172
Q

Theophylline

A

adenosine antagonist

173
Q

Nicotine

A

agonist at neuromuscular junction

174
Q

Clozapine

A

direct serotonin antagonist/glycine uptake inhibitor

175
Q

tecadenoson

A

direct adenosine agonist

176
Q

Yohimbine

A

alpha-2 adrenoceptor antagonist

177
Q

Cocaine

A

inhibits norepinephrine uptake

178
Q

alpha-bungarotoxin

A

direct nicotine antagonist

179
Q

bromocriptine

A

direct dopamine agonist

180
Q

haloperidol

A

dopamine antagonist

181
Q

amount of volatile liquid excreted by lungs

A

directly proportional to its vapor pressure

182
Q

Absorbed in the colon

A

water, sodium ions, hydrogen ions

183
Q

methylmercury crosses BBB

A

by combining with cysteine and forming a molecule similar to methionine

184
Q

Efflux transporters on enterocytes

A

P-gp, MRP2, BCRP

185
Q

Substrates for P-gp

A

cyclosporin, paclitaxel, colchicine

186
Q

Fick’s Law

A

transfer of toxicants by simple diffusion from areas of high conc. to areas of low conc

187
Q

TCDD

A

large octanel/water partitition coefficient

188
Q

Protect fetus from toxicant exposure

A

multiple tissue layers of placenta
biotransformation ability of the placenta
presence of transporter systems in placenta

189
Q

Why infants more susceptible to methemoglobinemia

A

higher pH of GI tract

190
Q

Grapefruit juice effects

A

activity of CYP3A4
function of P-gp
absorption of lovastatin

191
Q

Most characterized transplacental carcinogen

A

diethylstilbestrol

192
Q

Gut microflora enzyme conjugates

A

UDP-glucuronic acid

Sulfate

193
Q

Enterohepatic Cycling

A

hydrolysis of organic conjugate in gut and reabsorption of liberated parent compound

194
Q

Arsenic

A

highest bile to plasma concentration ratio

195
Q

Biliary Excretion Transporters

A

P-gp, Mrp2, Bcrp

196
Q

Captopril

A

covalent binding to plasma protein

197
Q

ABC family of transporters

A

all require ATP, can bind 1 or 2 substrates P-gp is an example

198
Q

Metal Transporter Systems

A

Thallium can be absorbed by the iron transporter
Lead can be absorbed by the calcium transporter
Lithium can compete with Sodium transporter

199
Q

Mephenytoin

A

probe drug for human CYP2C19 activity

200
Q

CYP2D6

A

converts codeine to morphine
Is polymorphic
poor metabolizers have a lower risk of lung cancer

201
Q

Aryl Hydrocarbon Receptor Agonists

A

TCDD, benzopyrene, benzene

202
Q

Osteomalacia

A

associated with enzyme induction

203
Q

Metabolism Dependent Inhibition of Cytochrome P450

A

metabolite is a potent inhibitor

204
Q

Gemfibrozil

A

conjugated with glucuronic acid before it is oxidized by cytochrome P450

205
Q

UDP Glucuronyltranferases conjugate these endogenouse molecules

A

thyroid hormone, bilirubin, steroid hormones

206
Q

Codeine give to a 2D6 ultrametabolizer

A

higher than normal levels of morphine at 2 hours post-dose

207
Q

Victim Drug

A

drug whose clearance is determined mostly by a single route of elimination

208
Q

Victim drug and perpetrator

A

terfenadine and ketoconazole

209
Q

PARAQUAT

A

Ingested; lung damage by all routes of exposure; selectively concentrates in lungs, progressive fibrosis; NADPH depletion, FR damage, parkinson’s like

210
Q

CHLORINATED DIBENZO P DIOXIN

A

photochemically degraded,

211
Q

METHYLENE CHLORIDE

A

after absorption methylene chloride is metabolized in the liver to carbon monoxide

212
Q

Micronucleus Test

A

Clastogenesis

Chromosome damage

213
Q

Ames Test

A

Reverse Mutation

214
Q

OZONE

A

deep lung irritant; minimal change in resistance and increase frequency of breathing

215
Q

Mast Cells Release

A

serine proteases, tryptase, histamine, serotonin, heparin, eicosanoids (thromboxane, prostaglandin D2, leuotriene C4, Platelet activating factor), cytokines (eosinophil chemotactic factor)

216
Q

Organophoshates & Carbamates target

A

ACETYLCHOLINESTERASE Inhibition

217
Q

Pyrethroids (I and II) and DDT target

A

Sodium Channels activation

218
Q

Dihydropyrazoles target

A

Sodium Channels Inhibition

219
Q

NICOTINE & NEONICOTINOIDS target

A

nicotinic acetylcholine receptors - activation

220
Q

CYCLODIENES, PHYENYLPYRAZOLES, TYPE II PYRETHROIDS target

A

GABA receptors-gated chloride channels inhibition

221
Q

AVERMECTINS

A

glutamate-gated chloride channels activation (found only in insects). In mammals (GABAa receptors)

222
Q

FORMAMIDINES

A

Octopamine receptors activation (in mammals, Alpha2 adrenoceptors)

223
Q

ROTENOIDS

A

mitochondrial complex I inhibition

224
Q

RENAL EXCRETION TRANSPORTERS

A 
Bcrp, Bsep
Cnt
Dmt
Ent
Ibat
Mate1, Mdr, Mrp, 
Npc1L1, Npt, Ntcp
Oat, Oct, Oatp
Pept
Urat
225
Q

Stinging Nettle

A

Contact urticaria

226
Q

Mistletoe

A

GI , bradycardia; phoratoxin

227
Q

Bagassosis

A

interstitial lung disease; hypersensitivity pneumonitis attributed to moldy molasses (sugar cane dust)

228
Q

Tricyclic Antidepressant Overdose

A

cardiovascular and neurologic
tachycardia, drowsiness, dry mouth, nausea, vomiting, urinary retention, confusion, agitation, headache; prolonged QRS and PR/QT; Seizures, apnea

229
Q

TCA (tricyclic antidepressant) MOA

A

anticholinergic, excessive blockade of NE reuptake, direct alpha adrenergic blockade, block Na membrane channels - quinidine like effects on myocardium

230
Q

FLUORIDE TOXICITY

A

GI Distress, convulsions, weakness, hypocalcemia, hyperkalemia, hypotension, coma, within hours; Tx: induce vomiting; calcium chloride/gluconate orally; give milk

231
Q

Legal Antioxidants

A

Butylated hydroxyanisole
Propyl gallate
butylated hydroxytoluene

232
Q

POKEWEED

A

Phytolacca

contains a mitogen

233
Q

Photochemical Smog

A

Ozone, hydrocarbons, oxides of nitrogen

234
Q

ETHANOL

A

depression of reticular activating system
dilation of cutaneous vessles
stimulation of gastric secretion
increased NADH/NAD ratio in lkiver

235
Q

ERGOT

A

fungus: Claviceps; moldy grains
alkaloid: burning sensation in limbs; vasoconstriction; gangrene
neurotropic: hallucinations, uterine contractions, nausea, seizures; induce abortions

236
Q

Organic TIN

A

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

237
Q

SPIRONOLACTONE

A

steroidal antimineralocorticoid, anti-androgen, weak progestogen, indirect estrogen and glucocorticoid
diuretic and antihypertensive; potassium sparing diuretic

238
Q

Thiazide

A

diuretics; inhibit reabsorption of Na and Cl from distal convoluted tubules; increase Ca reabsorption
Tox: hypokalemia, hyperglycemia, adversely effects fetus

239
Q

Done Nomogram

A

describes toxicity resulting from salicylate overdose based on blood levels sampled at fixed timepoint postingestion

240
Q

NUX VOMICA

A

Strychnine

241
Q

METHYL PARATHION

A

detoxification by glutathione dependent dealkylation

242
Q

CARBON DISULFIDE

A

Enhances excretion of zinc and interferes with thiamine utilization

243
Q

RED SQUILL

A

EMETIC - causes vomiting in humans; toxic to rats because they can’t vomit

244
Q

Solution

A

most potentially dangerous formulation of an insecticide

245
Q

DIBROMOCHLOROPROPANE (DBCP) & ETHYLENE DIBROMIDE

A

malignant gastric squamous cell tumor in rodents

Altered spermatogenesis

246
Q

CCL4 treatment

A

magnesium salts and large volumes of water

247
Q

CO2 overdose symptoms

A

dyspnea, nausea, increased chest movt; increased abdominal movt

248
Q

Causes pulmonary edema

A

phosgene, perchloroethylene, hydrogen fluoride

249
Q

Niacin Overdose

A

flushing, itching, increased peristalsis, vasodilation

250
Q

Byssinosis

A

respiratory disease associated with inhalation of dust from cotton flax or hemp

251
Q

COBALT

A

cross reaction sensitization because of haptene similarities among chromium, cobalt and nickel

252
Q

methotrexate antidote

A

thymidine

253
Q

heparin antidote

A

protamine

254
Q

RADON daughters

A

alpha particles

mining, in some dwellings, assoc with SCLC in miners

255
Q

organic phosphate antidote

A

pralidoxime

256
Q

CYANIDE INTOXICATION

A

respiratory alkalosis; sodium thiosulfate for conversion of CN to thioCN; sodium itrite to produce metHb, which binds CN

257
Q

RADON daughters

A

mining, in some dwellings, assoc with SCLC in miners

258
Q

methyl ethyl ketone and methyl n-butyl ketone

A

neurotoxic because of a common metabolite: 2,5-hexanedione

259
Q

Tumor promotion

A

reversible
exhibits threshold leveles
modulated by environmental factors

260
Q

PHENOTHIAZINE blurry vision

A

from storage of phenothiazine on melanin pigments in ciliary body

261
Q

Mouse Organogenesis

A

Days 6-15

262
Q

biotransformation of parent compound to liver toxicant

A

halothane, bromobenzene, CCL4, acetaminophen

263
Q

Male Rat Hydrocarbon Nephropathy

A

exacerbation of hyaline droplet formation; granular casts , chronic nephrosis ultrastructurally, increase in size and incidence of crystalloid change of proximal tubular cell phagolysosomes

264
Q

Cause Testicular Atrophy

A

diethylhexyphthalate
cadmium
manganese
dibromochloropropane

265
Q

Ozone syndrome

A

duplicated by the injection of the ozonide of linoleic acid

266
Q

Cause Interstitial pneumonia

A

Q fever, influenza, cytomegalic inclusion dz, berylliosis

267
Q

2-Naphthylamine

A

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

268
Q

Chronic Toluene diisocyanate

A

asthma

269
Q

Aromatic Amines

A

bladder cancer; dog is susceptible species

2-naphthylamine and benzidine; Chlornaphazine

270
Q

ANILINE

A

aromatic amine; industrial chemical - dyes; methemoglobinemia, heinz body anemia

271
Q

VINYL CHLORIDE

A

liver damage and angiosarcoma of the liver

272
Q

Aromatic Amines

A

bladder cancer; dog is susceptible species

273
Q

VACOR

A

Rodenticide; selectively destroys insulin-producing beta cells of pancreas causing diabetes; hypotension and hypoglycemia; impotence; peanut odor to breath; onset hrs to days

274
Q

PHOTOCHEMICAL AIR POLLUTION

A

O3, NO2, NO, SO2

275
Q

CARBON MONOXIDE

A

reversibly binds Hb; 200-250x >O2; eliminated by lungs, fetus more sensitive
Tx: O2

276
Q

VACOR

A

Rodenticide; selectively destroys insulin-producing beta cells of pancrease causing diabetes; hyptension and hypoglycemia; imppotence; peanut odor to breath; onset hrs to days

277
Q

Pyridoxine

A

nutrtional supplement; antidote for Isoniazide; hydrazine, ethylene glycol
Vitamin B6

278
Q

Isoniazide

A

antibiotic for TB; depletes pyridoxine; hepatotoxic; CYP2E1c1 are more susceptible; slow acetylators more susceptible too; induces seizures -depletes GABA

279
Q

ISONIAZIDE drug interactions

A

phenytoin, carbamazepine, warfarin, rifampin

280
Q

HYDRAZINE

A

chemical intermediate for explosives; caustic; functional pyroxidine deficiency; hepatic necrosis

281
Q

BENZOATE

A

food preservative; bacteriostatic fungistatic in acid environment

282
Q

HYDROGEN SULFIDE

A

petroleum, volcanos, decaying organic matter

death within minutes; inhibits mitochondrial respriration; binds cytochrome aa and cytochrome oxidase

283
Q

STRYCHNINE

A

muscle spasms; lactic acidosis, hyperthermia, rhabdomyolysis; metallic taste
Treat: charcoal, diazepam, phenobarb

284
Q

STRYCHNINE metabolism

A

liver microsomal enzymes: NADPH and O2; competes with glycine

285
Q

FLUOROACETATE (1080)

A

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

286
Q

CYCLODIENE

A

Organochlorine; persistent pollutant

287
Q

GLUTETHIMIDE

A

sedative, addictive; CYP2D6 enzyme inducer with codeine converts to morphine

288
Q

PARALDEHYDE

A

CNS depressant; excreted via lungs, unpleasant odor; anti-seizure

289
Q

ZINC MOA

A

mimics Cd, Cu, Ni

290
Q

MERCURY AND CADMIUM moa

A

attach to SH

291
Q

POTASSIUM moa

A

mimics Thallium

292
Q

IRON moa

A

mimics manganese

293
Q

PHOSPHATE moa

A

mimics arsenate and vanadate

294
Q

SULFATE moa

A

mimics selenate; molydate, chromate

295
Q

Metals that cause oxidate injury

A

Iron, Nickle, Chromium

296
Q

Hexavalent Chromium

A

forms DNA adducts

297
Q

Organic LEAD tox treatment

A

Calcium Sodium EDTA

BAL

298
Q

DEFEROXAMINE

A

removes iron ; binds free iron in blood and enhances urinary elimination

299
Q

MERCURY inorganic

A

concentrates in kidneys; excreted feces/bile

300
Q

MERCURY organic

A

concentrates in RBC more than plasma; uptake by neutral animo acid carrier in enothelial cells due to structural similarity to methionine

301
Q

MERCURY Tx

A

BAL - protects kidneys
Penicillamine - best for vapors
Polythiol resins - for methyl; bind mercury in GI tract; prevents absorption

302
Q

ARSINE

A

As3; binds SH groups of enzymes, pyruvate dehydrogenase; Krebs cycle TCA

303
Q

Chronic ARSENIC

A

rice and water stools, skin pigmentation, hyperkaeratosis; edema, Garlic breath; profressive: dermatitis, liver, kidney injury, peripheral nueritis, encephalopathy, aplastic anemia

304
Q

CADMIUM

A

yellow pigment; ITal-Ital: breaking ribs
Chronic - Kidney tox
Emphysema, hypertension, bone, testes

305
Q

ALUMINUM

A

low tox; SHaver’s dz - inhalation, fibrosis
Neurotox - neurofibrillary tangles
Dialysis dementia - historic

306
Q

Barium

A

low tox; GI and cardiovascular

307
Q

BERRYLIUM

A

conjunctivitis, dermatitis, granulomatous (DTH)

308
Q

CHROMIUM

A

chronic - lung cancer

309
Q

COBALT

A

polycythemia, Goiter, Cardiomyopathy (Beer); inhibits ferrochelatase(required for heme synth)

310
Q

Wilson’s disease

A

SNP in Cu tranporter gene; loss of function

Tx: Penicillamine

311
Q

MANGANESE

A

in some pesticides; pneunomia (inhalation)

PARKISONS (decreased DOPA neurons)

312
Q

Nickle

A

pneumonitis (inhalation)

Leukocytosis, delirium, carcinogen (lung)

313
Q

PHOSPHOROUS

A

rat poison, fireworks

GI - phosphorescent Vomit

314
Q

SELENIUM

A

blind staggers in cattle;

Human - discolored teeth; skin eruptions, GI, loss of hair and nails; liver injury

315
Q

SILVER

A

blue skin due to silver sulfide via sun exposure

316
Q

THALLIUM

A

rodenticide (historically); destributes like potassium; GI irritation; alopecia
Tx: Prussian blue - breaks enterhepatic circulation

317
Q

URANIUM

A

kidney injury

318
Q

ZINC

A

vomiting, diarrhea, pyrexia; inhalation fever

319
Q

ORGANOPHOSPHATE

A

readily biodegraded; low species selectivity

parathion, gluthion, chloropyrifos, diazinon, malathion, dichlorvos, sarin, metamidophos

320
Q

PON1

A

detoxifies OPs; genetic polymorphism

321
Q

OP delayed polyneuropathcy

A

2-3 weeks later; dying back axonopathy; tingly weakness, ataxia; young are resistant, Hen for testing

322
Q

PYRETHROIDS

A

Cis isomer more toxic than Trans
interact with sodium channel
Tx: Vitamin E

323
Q

ORGANOCHLORINES

A

Lindane, Chlordane, Aldrin, Dieldrin, Endrin, Heptachlor, DDT

324
Q

ORGANOCHLORINE Tox

A

convulsions, bind GABAa; inhibit Chloride channel; induce hepatic microsomal enzymes; tumor promoter; extremely persistent in environment
Estrogen mimetic

325
Q

ROTENONE

A

toxic to fish; inhibits cplxI in mitochondrial resp chain; model for PARKINSONs

326
Q

CHLOROPHENOXY Cpds

A

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

327
Q

PARAQUAT moa

A

electron reduction; Free radical;super oxide anions; lipid peroxidation, NADPH
destruction of aveolar cells

328
Q

Dithiocarbamate Fungicides

A

alter thyroid hormone levels - hypertrophy
metabolized to ETU - thyroid/liver cx
Developmental neural tox
Some assoc with PARKINSONS

329
Q

FLUOROACETATE

A

target organ: Brain, Heart

Co-enzyme A - fluorocitrate - inhibits Krebs cycle

330
Q

mouse LLNA

A

Type IV reactions, prefered over G Pig, detects in situ hyperproliferation; no Freud’s adjuvant

331
Q

P450

A

on ER (microsome)

332
Q

biotransformatoin

A

Cytochrome P450, cytochrome C reductase, NADPH, Oxygen, magnesium

333
Q

P450 Oxidation Reactions

A

aromatic hydroxylation; aliphatic hydroxylation; N,O,S dealkylation; epoxidation, desulfuration, sulfoxidation, n-hydroxylation

334
Q

ACYL GLUCURONIDES

A

active transport systems in the hepatocyte and bile duct upconcentrate them

335
Q

CAR

A

phenobarb receptor, downregulated by proinflammatory cytokines

336
Q

PREGNANE X receptor

A

indcution of CYP3A4

337
Q

Cause Phospholipidosis

A

amiodaroneamitriptyline, fluoxetine

338
Q

Detox of electrophiles

A

conjugation with Glutathione

339
Q

Amines - nucleophilic detox

A

acetylation

340
Q

CLOFIBRATE receptor

A

PPAR

341
Q

Citric Acid Cycle Inhibitors

A

fluoroacetate, DCVC, malonate

342
Q

ADP Phosphorylation Inhibitors

A

Oligomycin, DDT, N-ethylmaleimide

343
Q

Cause Calcium influx

A

capsaicin, domoate, amphoterecin B

344
Q

Inhibit Calcium eflux

A

vanadate, bromobenzene, CCL4

345
Q

Inhibitors of Cytochrome Oxidase

A

Phosphine, Azide, Hydrogen Sulfide

346
Q

Inhibitors of NADH coenzyme Q reductase

A

rotenone, paraquat, amytal

347
Q

Produce Free Radicals in inflammed tissue

A

NADPH oxidase, nitric oxide synthase, myeloperoxidase

348
Q

Noncovalent Binding

A

Strychnine to glycine
Phorbol ester to Protein Kinase C
Warfarin to vit K 2,3 epoxide reductase

349
Q

CCL4 treatment

A

magnesium salts and large volumes of water

350
Q

DIBROMOCHLOROPROPANE (DBCP) & ETHYLENE DIBROMIDE

A

malignant gastric squamous cell tumor in rodents

Altered spermatogenesis

351
Q

Solution

A

most potentially dangerous formulation of an insecticide

352
Q

FLUORIDE

A

3.0 ppm chronic moderate fluorosis(mottled teeth)

Toxicology ABT COPY for AeJ (1 decks)

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