Tox 1a

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mayabug
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74025
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Tox 1a
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2011-03-28 22:07:12
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Tox
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  1. toxicity
    • the quantity of a toxicant, which under specified conditions, will result in detrimental changes to an organism
    • mg/kg, dose
    • not equal to hazard
  2. hazard
    • the likelihood or chance that a toxicant will produce a dz state under the conditions of use
    • or
    • the likelihood or chance of exposure to a particular toxicant under the conditions of use
    • no equal to toxicity
  3. toxicologist
    a health professional interested in and knowledgable of the properties of toxicants and the tx of dz conditions
  4. veterinary toxicologist
    a veterinarian who is an expert in the toxic dz of animals as well as one who is expert in extrapolating from animals to humans and is a diplomate of the American Board of Veterinary Toxicology (ABVT)
  5. toxicosis
    the dz state which may result from exposure to a toxicant or poison
  6. dose
    • mg of chemical/ kg of body wt
    • no equal to ppm
  7. parts per million
    • ppm not equal to dose
    • concentration
    • 1ppm= 0.0001%
    • 10,000ppm= 1%
    • 1 inch in 16 mi
    • 1g needle in a ton of hay
    • 1 drop in 80 fifths
  8. LD50
    • quantity of toxicant required to kill 50% of animals
    • single oral dose
  9. LC50
    conc of toxicant in water or feed that will kill 50% animals
  10. acute vs subacute vs chronic toxicity
    • A: single exposure, 7d
    • S: daily exposure for 90d
    • C: daily exposure >90d
  11. toxicity rating chart
    • highly 1mg/kg
    • non-toxic 15gm/kg
  12. margin of safety
    • ratio btw LD50 and ED50 normally
    • in tox we want therapeutic index so LD01 over ED99
    • want MS 20-40 but anesthetic agents are 1
  13. NOEL or NOAEL
    • no observed (adverse) effect level in the most sensitive species
    • mg/kg/d
    • max dose that does not did not produce any adverse effect
  14. ADI
    • acceptable daily intake
    • mg/kg/d
    • max amt ingested and not expect adverse effect after lifetime of use
    • =NOEL/safety factor
  15. tolerance
    • max quantity that can appear legally in food for human consumption or in animal feeds
    • =(ADI x 60kg)/(food factor x 1.5kg/d)
    • =residue
  16. action level
    • similar to tolerance
    • a guide line and not legally established
  17. delany clause
    n amendment to the federal food drug and cosmetic act whhich states that a carcinogen may not appear in food for human consumption
  18. TLV
    • threshold limit value
    • upper limit of toxicant conc in which an avg healthy person can work an 8hr day, 40hr week, for a lifetime and not be adversely affected
    • ex- breathing limit of iso for anesthesia techs
    • can either be a time weighted avg or ceiling vlue
  19. level of concern
    • FDA-CVM term
    • definition?
  20. zero order kinetics
    a fixed quantity is excreted during a given time
  21. first order kinetics
    a constant fraction is excreted per unit time
  22. specific diagnosis of intoxication
    • clinical signs
    • history
  23. phases of biotransformation of toxicants
    • phase I- non synthetic chemical rxns (oxidation, reduction, hydrolysis)
    • phase II- synthetic rxns (amino acids, sugars, fatty acids, sulfates, acetates)
  24. if owner insists tx animal with intoxication
    • only if time delay and animal not depressed
    • wash with soap and water
    • 5ml hydrogen peroxide
    • 1tbs ipecac
    • milk with egg white
    • activated charcoal
    • water
    • transport animal, bring suspect materials, bring vomitus
  25. delay absorption
    • remove external contaminants
    • induce emesis
    • gastric lavage
    • absorbants
    • cathartics
  26. induce emesis
    • syrup of ipecac
    • table salt
    • hydrogen peroxide
    • apomorphine
  27. contraindications for induction of emesis
    • unconscious or CNS depression
    • intox with petroleum
    • caustic materials
    • >2-4 hr post ingestion
  28. gastric lavage
    • light anesthesia
    • cuffed ET tube
    • lower head and thorax
    • measure oral-gastric tube nose to xiphoid cartilage
    • flush with water and aspirate, repeat
  29. activated charcoal
    • absorbent
    • ex- toxiban, superchar
    • then give cathartic
  30. cathartic
    saline, sodium sulfate, Mg sulfate, mineral oil
  31. pKa
    • high is strong base
    • low is strong acid
  32. ion trapping
    • used in GIT and kidney
    • compounds non-ionized at physiologic pH
  33. chelating agent
    • donor molecule that forms a bond with a metal or metalloid
    • higher Km means tighter bond in vitro
    • organic material donate both electrons and contain N, O, or S
    • induce histamine release with toxic amts
    • tox has low incidence of adverse effects
    • only BAL causes neuro dz in toxic amts
  34. metals
    • MOA: bind with active site of enzymes
    • bind sulf-hydrial groups
    • mealleable when pure
  35. metalloid
    • not malleable when pure
    • bind sulf-hydrial groups on enzyme
  36. arsenic forms
    • arsenite (As+3) more toxic than arsenate (As+5)
    • once there, always there
  37. arsenic uses
    • hematinics
    • fowlers solution
    • wood preservative
    • syphilis and HW tx
    • growth promotant
    • tx swine dysentery
    • fever tick dip
  38. inorganic arsenicals and trivalent organics
    • effect GIT and capillaries
    • ex- arsenic trioxide, sodium arsenite/arsenate, chromated copper arsenate, lead arsenate, paris green, smelters
  39. pentavalent organic arsenical
    • effect neuro
    • ex- MSMA, DMSA
  40. phenylarsenic
    • demyelination
    • arsenic should not be found
    • no tx
  41. growth promotant arsenic source
    • arsanilic acid
    • roxarsone
  42. medicinal arsenic sources
    • arsenamide
    • fowlers solution- K arsenite
    • sodium cacodylate
    • tryparsamide
    • melarsoprol
    • neoarsphenamine
  43. MOA arsenic (AS+3)
    • react with -SH of proteins and inhibit enzymes by blocking active groups
    • inhibits alpha-keto oxidases which contain dithiol groups and are involved in oxidation of pyruvate
    • inhibit lipoic acid, an essential co-enzyme for pyruvic acid oxidase
    • BAL will reverse
  44. MOA arsenic (AS+5)
    • uncouple oxidative phosphorylation
    • may interfere with B6 and B1= demyelination
  45. arsenic absorption
    • small amt via skin
    • best via GIT
    • accumulates in liver
    • cros placenta
    • stored in bones, skin, hair, hooves
  46. arsenic excretion
    • urine
    • feces
    • sweat
  47. arsenic toxicity
    inorganic As3 (arsenite)> inorganic As5 (arsenate)> trivalent organics (As+3)> pentavalent organics (As+5)
  48. arsenic causes of poisoning
    • soil around old dipping vats
    • improper disposal of containers
    • around smelters
    • human carelessness
    • feeding gin trash instead of cotton seed hulls
    • HUMAN MISTAKES!
  49. acute arsenic tox
    • abdominal pain
    • staggering gait
    • incoordination
    • diarrhea
    • sudden death
  50. sub-acute arsenic tox
    • depression
    • anorexia
    • convulsions
    • fluid, dark feces
    • hematuria
  51. chronic arsenic tox
    • easily fatigued
    • intense thirst
    • dry hair coat
    • brick red MM
    • looks like vit A def
  52. phenylarsonic clinical signs
    • neuro
    • blind
    • erythema
    • BAL will not help
  53. arsenic tox lesions
    • soft, yellow liver
    • hemorrhagic gastroenteritis
    • rumen mucosal necrosis
    • intestinal ulcers
  54. phenylarsonic lesions
    • downer pig
    • demyelination of optic nerve
  55. arsenic tx
    • early- emetics, gastric lavage, milk, cathartic, Na thiosulfate
    • late- BAL (will reverse lipoic acid inhibition)
    • no tx for phenyllarsenic
  56. arsine (AH3) intox
    • hot acid interacts with metal
    • most toxic arsenical
    • causes hemolysis
    • abnormal ECG and pulm edema
    • BAL is tx if chronic
  57. sources of lead tox
    • old paint
    • glazed pottery
    • lined feed troughs, buckets, pipes
    • batteries
    • smelters
    • vegetation sprayed with lead arsenate
    • white lotion
    • leaded gas on forages
    • lead shot
  58. lead absorption
    GI or resp
  59. lead distribution
    • bound to RBC
    • soft tissue
    • bone, teeth, hair
  60. lead excretion
    • urine- adults
    • feces- infants, animals
    • milk
  61. organ systems affected by lead
    • nervous
    • GI
    • blood and bone marrow
    • renal
  62. MOA lead tox
    • inhibits -SH groups on enzymes
    • interfere with hemoglobin synthesis
  63. acute lead tox
    • death
    • GI signs
    • CNS
  64. chronic lead tox
    • roaring in equine
    • lead line in gums
    • lead lines in metaphysis of long bones of immature dog
    • inhibit hematopoiesis
  65. lead tox lesion
    • agonal hemorrhages
    • pale muscles
    • hemorrhagic thymus
  66. lead tox diagnosis
    • renal cortex
    • blood- high in acute and chronic
    • liver
    • feces - high if 2 to 4 wk, normal if more than 4 wks
  67. lead tox tx
    • CaNa EDTA
    • thiamine (combo with EDTA to reduce neuro)
    • BAL+EDTA if severe neuro
    • succimer
    • must tx for 3-5 days
  68. copper:molybdenum in ruminants
    • 6:1
    • if adequate SO4 then will excrete opposite
  69. copper tox in ruminants
    • mostly sheep
    • 10:1
    • never feed cattle feed to sheep bc high in Cu
    • chronic accumulation in liver- hepatic necrosis, hemolysis
  70. molybdenum tox in ruminants
    • mostly cattle
    • 2:1, excess sulfate
    • chronic dz- poor doers, hypoproteinemia, repro prob, jt prob
    • achromotrichia- hair color black to grey or red to tan
    • sheep- wool slipping, swayback lamb
  71. copper tox lesion in ruminants
    • icterus
    • gun metal kidney
    • yellow friable liver
    • blackberry jam spleen
    • hemoglobinuria
  72. copper tox tx in ruminants
    penicillamine
  73. Cu and Mo in non-ruminants
    • interactions not as marked
    • dec Cu tx with Zn
    • no hemolysis with Cu tox
    • achromotrichia, aortic rupture with Mo tox
  74. elemental liquid Hg
    • ingestion
    • nontoxic
  75. elemental vapor Hg
    • inhalation
    • oxidized to Hg++
    • in blood- renal prob
    • in CNS- neuro (primary)
    • BAL to tx renal
    • no tx for CNS
  76. mercuric (Hg++)
    • ingestion
    • charged so does not cross BBB
    • GI, renal (primary)
    • CNS
    • tx with BAL
    • most toxic
  77. mercurous (Hg+)
    • ingestion
    • not metabolized to Hg++
    • BAL gor renal prob
  78. alkyl Hg++(CH3)2
    • ingestion
    • dealkylated to HG++
    • in blood- renal prob
    • in CNS- neuro (primary)
    • BAL to tx renal
    • no tx for CNS
  79. aryl Hg++
    • ingestion
    • does not enter CNS as readily as alkyl
    • renal prob (primary)
    • BAL to tx
  80. Fluoride
    • in tap water, supplements, soil
    • max water level= 2ppm
  81. fluoride MOA
    • affects enamel
    • damages ameloblasts, ondontoblasts, and osteoblasts
    • faulty calcification
  82. acute fluoride tox
    • GI irritation
    • neuro
  83. chronic fluoride tox
    • brown mottled teeth
    • no cavities
    • excess wear and crumbling of teeth
    • bones affected
    • mature animals- no teeth color change, hyperostosis, economic loss from exostosis
  84. fluoride tox tx
    Al salts
  85. iron tx sources
    • inj (piglets)
    • cast iron skillet
    • oral prep (vit)
  86. iron MOA
    • PO- injure GI
    • hepatic necrosis
    • no means of excretion
  87. acute iron tox
    • CV collapse
    • death in 1-3hr
    • anaphylactic syndrome
  88. chronic iron tox
    hemosiderosis in heart, liver, bone marrow
  89. iron tox lesions
    • yellow-brown discoloration of tissues
    • hepatic necrosis
    • renal lesions
    • GI ulcers
  90. iron tox tx
    • MgO
    • Deferoxamine- chelating agent
  91. cadmium sources
    • galvenized metals
    • smelters
    • NiCad batteries
  92. cadmium tox
    • stored as metallothionine in kidney
    • renal dz like Hg with secondary hypertension
  93. acute cadmium tox
    • GI irritant
    • fume fever when inhaled- pulm edema, resp prob
  94. chronic cadmium tox
    • renal prob
    • stunted growth
    • chronic pain- itah, itah
  95. cadmium tox tx
    • chelating agents may inc tox (Cd-BAL)
    • vit D and Ca
    • EDTA
  96. cobalt tox
    • old foaming agent in beer
    • bone marrow stimulant
    • beer drinkers cardiomyopathy
  97. chromium tox
    • hexavalent toxic
    • chronic ulcers in nasal septum
    • ddx: snorting cocaine
  98. barium tox
    • barium carbonate used as rodenticide
    • do not confuse with barium sulfate used as radiopaque dye
    • stimulates all mm
    • tx by giving Na or Mg to form barium sulfate
  99. Magnesium tox
    • cathartic and equine euth
    • acts at NMJ and competes with Ca
    • CNS dep
  100. iodine general
    • used to tx foot rot in cattle
    • iodized salt to prevent goiter
    • excess may mimic hyperthyroidism
  101. iodism
    • mimic vit A def
    • crusty skin around eyes
    • ddx: arsenic
    • scruffy hair coat
    • bug-eyed (exopthalmus)
  102. silver general
    • disinfectant
    • used in babies eyes to tx syphillus
  103. silver tox
    • gastroenteritis
    • chronic- agyria (slate black discoloration of skin)
    • not usually a problem
  104. selenium general
    • deficiency= white mm dz
    • only FDA regulated nutrient
    • accumulates in plants
  105. selenium tox
    • >5ppm
    • substitute for S in amino acids
    • peri acute- CV collapse, GIT
    • acute- misformulated feed or eat Se accumulating plant
    • chronic- hair loss, liver prob, hoof sloughing
    • calves with garlic odor breath
    • porcine focal symmetrical poliomyelomalacia- posterior ataxia
    • looks like arsenic tox
  106. selenium tox tx
    arsanilic acid to promote excretion
  107. sulfur general
    • purgative
    • >2500 ppm tox
  108. sulfate tox
    • cause polioencephalomalacia in ruminant
    • GI irritation
    • sulfate to sulfide gas in rumen, smells like rotten egg
  109. zinc general
    • industrial pollution
    • galvanized material
    • relatively nontoxic
    • nuts, bolts, pennies
  110. zinc tox
    • puppies- poor growth, renal prob, bouts of syncope
    • horses- arthritis due to cartilage erosion
  111. zinc tox tx
    • dog- EDTA
    • foals- EDTA, Ca, Cu

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