Toxicology Lectures 1 - 3

Front 1

poison definition

Back 1

- a substance that causes dose-related adverse health effects at relatively small doses

Front 2

toxicant = ?

Back 2

poison

Front 3

toxin definition

Back 3

- poison of biological origin

Front 4

toxicity

Back 4

characterization of the potency and toxic effecs associated with a poison

Front 5

toxicosis

Back 5

disease/syndrome caused by a poison

Front 6

how are carcinogens evaluated differently than poisons?

Back 6

- with carcinogens we assume there is no safe level of exposure
- with every exposure there will be potential for mutagenic change
- there is no NOAEL
- evaluated under the linear model

Front 7

what kind of response graph do vitamins and trace elements usually have?

Back 7

- hormesis
- low dose response is opposite of high dose response

Front 8

name an example that would cause a shift to the right

name an example that would cause a shift to the left

Back 8

- right: Inappropriate response
- Usually seen with some type of adaptive process
- ex: increase in enzyme for the metabolism of a toxicant

- left: inability of the animal to deal with the toxicant
- ex: liver damage prevents conjugation of subsequent toxicant

Front 9

mixture effects of chemical reactions

2

Back 9

- precipitation
- chemical reactions forming new compounds

Front 10

mixture effects on PK ixns

Back 10

- changes in rates of absorption
- enzyme induction/suppression

Front 11

mixture effects on PD ixns

Back 11

- cumulative responses
- synergism
- antagonism

Front 12

what is the DOS of treatment stand for?

Back 12

- Decontaminate
- Oppose
- Support

Front 13

venom

Back 13

a poisonous secretion produced in specialized glands and delivered via a specialized parenteral delivery system

Front 14

venin

Back 14

single component of a venom

Front 15

envenomation

Back 15

act of venom delivery

Front 16

3 types of venomous reptiles in North America

Back 16

- pit vipers (rattlesnakes, copperheads, cotton mouth, water moccasins)
- coral snakes
- gila monsters

Front 17

pit viper family

what attribute makes them good envenomators?

Back 17

Crotalinae
- front fangs
- rapid envenomation

Front 18

can venom delivery be controlled?

% breakdown based on severity

Back 18

- yes, can be controlled
- 25% are "dry"
- 35% mild
- 20% moderate
- 10-15% severe

Front 19

viper venom contains how many different venins?

how many different venom protein families?

Back 19

- 50-100 venins
- 10-20 venom protein families

Front 20

major venin classes

name 6

Back 20

- hyaluronidase
- myotoxins
- hemorrhagic toxins
- cardiotoxins
- metalloproteinases
- neurotoxins

Front 21

effect of hyaluronidase venin

Back 21

- spreading factor
- breaks down connective tissue

Front 22

effect of mytoxin venin

Back 22

- muscle necrosis

Front 23

effect of hemorrhagic toxin venin

name 3

Back 23

- hypercoagulation
- hypocoagulation
- fibrinolysis

Front 24

effect of cardio toxins

name 2

Back 24

- myocardial depression
- unresponsive hypotension

Front 25

effect of metalloproteinases venin

Back 25

- general tissue necrosis

Front 26

effect of neurotoxin viper venin

Back 26

- transmitter release stimulation
- transmitter release inhibition
- transmitter blocking

Front 27

venom local manifestations

2

one of these can cause a major problem, name it

Back 27

- tissue swelling
- pain
- severe swelling can obstruct airways/perfusion

Front 28

systemic venom manifestation

3

Back 28

- hypotension
- neurotoxic effects
- coagulopathy

Front 29

clinical pathology of venom bite

4

Back 29

- elevated creatinine
- altered blood clotting parameters
- hematuria, rhabdomyolysis
- echinocytosis

Front 30

are do severe local venom manifestations mean severe systemic effects or vice versa?

Back 30

- no
- bite could have little local effects but be severe systemically

Front 31

treatment of pit viper bite

drug name
ROA
what is dose dependent on?

Back 31

- Crotalid Fab antivenom: CroFab
- IV admin w/in 6 hours of bite
- dose dependent on venom load, not patient weight

Front 32

what is the risk of trt with antivenom?

Back 32

- anaphylaxis

Front 33

Elapid snakes are more commonly known as what?

more or less agressive than pit vipers?

are the fangs fixed or hinged?

Back 33

- coral snakes
- less aggressive than vipers
- fixed fangs, snakes

Front 34

most important effect of highly potent coral snake venom

general

Back 34

- neurotoxin

Front 35

MOA of coral snake neurotoxin

Back 35

- blocks postsynaptic acetylcholine receptors

Front 36

onset of symptoms after elapic snake bite?

name 4 symptoms

Back 36

- onset is variable, can be up to 18 hours
- respiratory depression
- CNS abnormalities
- loss of muscular function
- respiratory muscle paralysis

Front 37

trt of elapic snake bite

antivenom?
what supportive care suggested?

Back 37

- no commercially available antivenom
- compression bandage, immobilization of limb
- reduces lymph drainage, delays onset of effects

Front 38

location of venom glands in Gila monster

Back 38

- submandibular venom glands

Front 39

Gila monster
- rate of envenomation?
- CS of bite

Back 39

- slow envenomation, requires long contact time
- swelling and severe pain
- may induce hypotension, nausea, vomiting

Front 40

Gila monster bite treatments

Back 40

- trt the pain
- trt hypotension
- check for retained teeth
- clean/cover wounds

Front 41

name the 2 toads discussed

Back 41

- colorado river toad
- cane toad

Front 42

what gland produces toxin on the skin of toads?

Back 42

- parotid gland

Front 43

- what type of toxins are present in toad secretion?
- 2 cardiac glycosides
- 2 hallucinogens
- 3 others

Back 43

- bufagenins and bufotoxins
- bufotenine and indolealkylamine
- dopamine, EPI, serotonin

Front 44

local signs of toad toxins

Back 44

- mouth and throat
- hypersalivation, vomiting, inflamed mucous membranes

Front 45

systemic effect of toad toxins

Back 45

- cardiac arrhythmias
- ataxia
- seizure

Front 46

trt of toad toxins

7 things to do

Back 46

- flush oral mucous membranes with water
- activated charcoal
- digibind
- trt cardiac arrhythmias
- control seizures
- enhance elimination (IV fluids, furosemide)
- supportive

Front 47

black widow nesting sites

Back 47

- basements, garages, wood piles

Front 48

color for black widows

color of hourglass, is it always brightly colored?

Back 48

- range from black to brown/grey
- red/orange hourglass
- not always brightly colored

Front 49

black widow bite

size?
pain?
skin reaction?

Back 49

- small wound
- initally not painful
- slight swelling and redness at bite site

Front 50

black widow toxins are what kind?

what CS could we see?

duration of CS?

Back 50

- neurotoxins
- sweating, cramping, muscle contractions, cardiac arrhythmias, altered breathing
- most symptoms disappear by 2-3 days

Front 51

trt of black widow bite

Back 51

- antivenin: Lyovac
- slow IV injection
- analgesics

Front 52

brown recluse spiders

do the have nests?

Back 52

- no nests
- actively roams at night in search of prey

Front 53

brown recluse bite local symptoms

4

Back 53

- initial bite not painful
- develops into a necrotic lesion with erythema, scabbing
- affected tissue may slough
- very slow healing

Front 54

brown recluse systemic effects (these are rare)

Back 54

- hemolytic anemia
- but negative with a negative direct antiglobulin (Coombs) test

Front 55

trt for brown recluse bite

Back 55

- open would management
- symptomatic trt
- antibiotics

Front 56

fire ant

home?
aggressive?

Back 56

- build soil mounds
- active foragers
- aggressive

Front 57

mode of attack for fire ants

Back 57

- bite and sting

Front 58

species most affected by fire ants?

Back 58

- ground nesting birds
- turtles
- frogs

Front 59

what to fire ants use to cue others to sting and bite?

Back 59

- pheromone cues

Front 60

is there immediate reaction to fire ant bites/stings?

Back 60

- yes, immediate reaction

Front 61

trt of fire ant bites

Back 61

- symptomatic trt
- antihistamines, topical corticosteroids

Front 62

bee and wasp

what types of toxins are present?

Back 62

- vasoactive amines
- phospholipase

Front 63

effect of massive bee and wasp bites

Back 63

- CV collapse
- coagulopathy (due to phospholipase)

Front 64

what toxin is produced by blister beetles?

how is this transferred b/w beetles?

Back 64

- cantharidin
- produced by males, but transferred to females during copulation

Front 65

please choose the parameter of toxicity that is most reliable as a guide to determining the level of oral exposure that is safe for an individual animal

oral LD50, IV NOAEL, IV LD50, Oral LOAEL, Oral NOAEL

Back 65

- oral NOAEL

Front 66

which one of the following types of toxicants is most likely to follow a linear dose-response model

trace metal (Cu), mutagenic carcinogen (aflatoxin), tumor-promoting carcinogen (phorbol ester), metabolizing enzyme inducer (pentobarbital), toxicant with persistent long term effects (lead)

Back 66

- mutagenic carcinogen

Front 67

what domestic animal species is most susceptible to blister beetle toxicosis?

Back 67

- horses

Front 68

what type of feed to blister beetles tend to congregate on?

Back 68

- alfalfa hay

Front 69

- cantharidin causes blisters mainly on what two surfaces?

Back 69

- contact dependent
- GIT during ingestion
- urinary during excreted

Front 70

CS related to cantharidin toxicosis in horses?

similar to what?
2 groups of CS

Back 70

- similiar to colic
- restlessness, depression, sweating
- mucous membrane congestion, tachycardia

Front 71

what can we test for cantharidin exposure?

2

Back 71

- stomach content
- urine

Front 72

what amount of cantharidin is considered clinically relevent?

Back 72

- any detectable concentration

Front 73

how long does it take for cantharidin to be excreted, why is this important?

Back 73

- renal clearance in 3-4 days
- negative test result after this period is not-diagnostic

Front 74

what can you trt with to help cantharidin toxicosis?

3

Back 74

- enhance elimination
- correct dehydration
- trt colic: pain

Front 75

how can we differentiate cantharidin poisoning from colic

Back 75

- will have frequent and diarrhea

Front 76

synchronous diaphragmatic flutter and muscle fasciculations in a horse are a sign of what type of poisoning?

what would we find on clin path results?

Back 76

- cantharidin
- hypocalcemia
- hypomagnesemia

Front 77

fire flies contain what toxin

this toxin is related to what?

common reptile affected?

Back 77

- fireflies contain lucibufagins
- related to cardiac glycosides
- bearded dragons

Front 78

what is the most hazardous scorpion in north america?

Back 78

- arizona bark scorpion

Front 79

scorpion toxin is what kind?

Back 79

- polypeptide neurotoxin

Front 80

most important effect of AZ bark scorpion toxin

3 others

Back 80

- hyperaeshesia (pain with any stimulus)
- agitation
- tachycardia
- hypertension

Front 81

trt of scorpion toxin

is antivenom available?

2 things

Back 81

- available in Mexico, experimental in US
- control pain
- maintain open airway

Front 82

poisoning with metal usually only occurs only after what?

what metal might be an exception?

Back 82

- high and persistent exposure
- lead

Front 83

name 4 essential biological functions that metals are needed for

Back 83

- electron transfer
- redox rxns
- electrochemistry and signaling
- structure

Front 84

toxicity mechanisms for metals

4, and give an example

Back 84

- oxidative damage: Zince
- altered electrophysiology and osmotic states: Na
- competition with "normal" elements for absorption: Mo, Cu
- incorporation into proteins in place of normal constituents: Pb/ Ca

Front 85

name the 6 most important veterinary metals

Back 85

- lead
- copper
- zinc
- sodium
- iron
- arsenic (metalloid)

Front 86

primary target for lead poisoning

Back 86

- nervous system

Front 87

effects of lead

2

Back 87

- mildly irritant to GI mucosa
- anemia due to interference with RBC maturation

Front 88

is there any safe exposure level of lead in humans?

Back 88

- no

Front 89

common sources of lead poisoning

4

Back 89

- lead carbonate from old paint
- lead acid batteries
- industrial/mining pollution
- lead shot, fishing weights, toys

Front 90

what % of pit viper bites are associated with envenomations leading to severe poisoning
- 10-15
- 20
-25
- 35
- 50

Back 90

10-15 %

Front 91

what is the effect/function of hyaluronidase in pit viper venom

fibrinolysis, tissue necoris, neurotransmitter blocking, venom spreading, myocardial depression

Back 91

- spreading factor

Front 92

a dog was bitten by a coral snake. how long should it be monitored for neurotoxic effects
- 4 hrs
12 hrs
18 hrs
36 hrs
72 hrs

Back 92

18 hours

Front 93

what sample should be submitted for detecing cantharidin exposure in a horse?

whole blood, serum, urine, liver, kidney

Back 93

- urine

Front 94

what 3 factors will increase the absorption of lead?

Back 94

- more surface area (GIT mucosal area)
- acidic environment (low pH leads to ionization)
- more time (lead particles may be trapped in reticulum

Front 95

tissue half lifes of lead

blood
liver/kidney
brain
bone

Back 95

- few days
- weeks
- months
- 1000 days, but essentially a lifetime

Front 96

CNS effects of lead

name 3

Back 96

- NT disruption
- endothelial damage/ pinpoint hemorrhage
- moderate brain swelling, necrosis of gyri tips

Front 97

effect of lead on RBCs

2

Back 97

- elevated numbers of nucleated RBCs
- variable degrees of anemia

Front 98

2 other effects of lead

Back 98

- GIT irritation, more pronounced in monogastrics
- reduced production and fertility

Front 99

what is the most common CS seen with lead poisoning?

Back 99

neurological

Front 100

what presentation of lead poisoning is seen most commonly in dogs?

Back 100

- GIT effects
- vomiting
- diarrhea

Front 101

diagnosis of blood toxicosis needs what sample?

live animal
dead animal

Back 101

- live
- whole blood
- Pb binds to RBC membranes

- dead
- liver/kidney

Front 102

what method is used by EPA to determine impact of lead in wildlife?

Back 102

- aminolevulinic acid dehydratase (ALAD) suppression

Front 103

what are the 4 trt methods for lead poisoning

Back 103

- remove the source
- counter brain edema with corticosteriods and diuretics
- supportive trt: fluids, electrolytes, anti-seizures
- sulfate salts to reduce absorption
---sodium sulfate, magnesium sulfate

Front 104

chelating agents for trt of lead poisoning

cattle
small animals

Back 104

- Ca- EDTA for cattle
- Succimer (DMSA) for small animals

Front 105

what species are most at risk for copper poisoning

2

Back 105

- sheep and goats

Front 106

what appearence do kidneys have with copper poisoning?

Back 106

- gun-metal black kidneys

Front 107

what is the most common source of copper poisoning?

Back 107

- excessive copper in the feed
- copper in cattle feed can be too much for sheep

Front 108

name 3 other sources of copper causing poisoning

Back 108

orchard sprays

algaecides

industrial pollution

Front 109

how is copper [ ] regulated in the body? name 3

which are sheep deficient in?

Back 109

- modulated uptake
- storage in the liver
- excretion in the bile

- sheep are deficient in excretion from the liver, and copper accumulates

Front 110

what effect does copper have on RBCs

2

Back 110

- oxidative damage to RBCs
- hemolysis

Front 111

what initiates release of high liver copper to the blood?

Back 111

stress

Front 112

clinical presentation of copper poisoning usually occurs after what 2 occurences?

Back 112

- chronic exposure
- acute stress

Front 113

name 4 clin path signs of copper poisoning

Back 113

- methemoglobinemia
- anemia
- hemoglobinuria
- signs of liver and renal failure (elevated liver enzymes, creatinine, BUN)

Front 114

necropsy lesions for copper poisoning

4

Back 114

- icterus
- brown colored blood
- hepatosis
- gun metal kidneys

Front 115

what is the relationship of Mo to Cu when ingested

Back 115

- Mo will decrease Cu absorption and vice versa

Front 116

what copper [ ] should not be exceeded in sheep feed?

what about cattle feed?

Back 116

- 20 ppm for sheep
- 50 ppm for cattle

Front 117

besides Mo, what other minerals will reduce uptake of copper?

3

Back 117

- Fe
- Zn
- S

Front 118

trt of copper poisoning

3

Back 118

- remove source
- limit stress
- chelation

Front 119

what should the Cu:Mo ratio be in order to prevent copper poisoning?

Back 119

- maintain ratio at 6:1 to 10:1

Front 120

what effect can excessive molybdenum cause?

name the mineral and effect

Back 120

- copper deficiency

Front 121

what effects does molybdenum poisoning have?

5

Back 121

- poor growth and production
- lightening of coat color
- diarrhea
- immune deficiency
- glucose intolerance (type 2 diabetes?)

Front 122

what effect does zinc poisoning have in dogs?

what about other species?

Back 122

- hemolytic anemia in dogs
- pancreatitis in other species

Front 123

what are some common sources of zinc that cause problems?

Back 123

- post 1982 pennies
- galvanized metal
- zinc oxide ointments
- shampoos
- dietary formulation errors

Front 124

what is the MOA of zinc poisoning in dogs?

what other effect does this zinc have?

Back 124

- oxidative damage
- GIT irritation

Front 125

what effect does zinc poisoning have in other species besides dogs?

Back 125

- zince accumulates in the pancreas
- it has cytotoxic effects causing pacreatitis

Front 126

what type of tubes are used for diagnosing Zinc poisoning, why?

Back 126

- collect serum in tubes with royal blue tops
- rubber tops of normal tubes contain Zn

Front 127

name the 4 methods for trt of zinc poisoning

Back 127

- give antacids to increase gastric pH: reduces Zn dissolution
- remove source: endoscopy, surgery
- chelation: Ca- EDTA, Succimer
- supportive: fluids, diuretics, etc

Front 128

which element has the most significant effect on the toxic potential of copper?

Back 128

MO

Front 129

Which chelating agent is most appropriate for treating copper poisoning in sheep?

Ca- EDTA, Dimercaperol (BAL), Succimer (DMSA), Ammonium tetrathiomollybdate, Penicillamine

Back 129

penicillamine

Front 130

What is the half life of lead in the skeletal system of cattle

1-3 days, 10-14 days, 60-90 days, 120-280 days, >1000 days

Back 130

>1000 days

Front 131

what sample should be submitted for detecting acute lead poisoning in a live animal?

serum, kidney, whole blood, hair, plasma

Back 131

- whole blood for live animal

- kidney, liver for dead animal

Front 132

sodium toxicity is usually the result of what?

Back 132

- water deprivation

Front 133

name two lesion found with sodium toxicity, or water deprivation

Back 133

- brain edema
- eosinophillic meningoencephalitis

Front 134

name 3 scenarios where sodium toxicity can occur

Back 134

- water deprivation with moderately high salt intake
- ingestion of large doses of salt
- sudden ingestion of large water volumes

Front 135

what species is sodium toxicity most common in

Back 135

pigs

Front 136

common CS for sodium toxicosis in pigs

Back 136

- restlessness, circling, ataxia, muscle tremors, head pressing

Front 137

how would you treat a case of sodium toxicosis?

4 things

Back 137

- SLOW oral rehydration
- SLOW IV rehydration with furosemide
- rehydration by enema
- mannitol diuresis to reduce brain edema

Front 138

what are the 2 most common causes of iron poisoning?

Back 138

- dose miscalculation for piglets
- accidental ingestion by pets

Front 139

MOA for iron poisoning

Back 139

- elemental iron is corrosive to the GI mucosa
- cause rapid fluid loss and shock
- ulceration and perforation

Front 140

iron is usually bound to what protein in the blood?

excess iron leads to what? What 2 tissues are most susceptible?

Back 140

- transferrin
- unbound iron leads to free-radical mediated oxidative tissue damage: liver, myocardium

Front 141

CS of iron poisoning after ingestion

Early 1-6 hrs

After latent period 6-24 hrs

After 2 or more wks

Back 141

early: vomiting, diarrhea
after latent: heart and liver failure, acidosis, lethargy, seizures, coma
after 2 weeks: GI scarring, strictures

Front 142

name some necropsy lesions found after iron poisoning

5

Back 142

- gastroenteritis, gastric ulceration
- yellow-brown discoloration around injection site
- swollen liver, discolored
- icterus
- kidneys dark in color

Front 143

confirming the diagnosis of iron poisoning can be done by what 3 methods

Back 143

- HISTORY is usually very important
- radiographs
- serum iron or total iron binding capacity

Front 144

what are some ways to treat iron poisoning?

Back 144

- emesis/ gastric lavage
- laxatives
- GI protectorants (sulcralfate)
- iron chelation

Front 145

inorganic arsenic affects what tissue most commonly

Back 145

- GIT

Front 146

organic arsenic affects what tissue most commonly?

Back 146

- many tissues affected

Front 147

common sources for inorganic arsenic include

Back 147

- herbicides
- insecticide baits
- paint pigments

Front 148

lesions of inorganic arsenic poisoning

name 4 GIT lesions due to irritation and contact necrosis

Back 148

- tissue sloughing
- ulceration
- hemorrhage
- increased fluid secretion

Front 149

4 CS of inorganic arsenic poisoning

Back 149

- vomiting
- diarrhea
- dehydration
- shock

Front 150

inorganic arsinic confirmatory test

live animal

dead animal

other sample?

Back 150

- live: urine, GI content
- dead: liver/ kidney
- hair can be useful in chronic exposure

Front 151

treatment of inorganic arsenic poisoning

2 general ways

Back 151

- chelation: BAL (demercaprol) most effective
--- also DMSA (succimer)

- supportive care: fluids/electrolytes, bicarb, blood

Front 152

which arsenic is more easily absorbed from the GIT?

Back 152

- organic arsenic

Front 153

does organic arsenic cause oxidative damage?

Back 153

no

Front 154

use of organic arsenic in feed

3 reasons

Back 154

- growth promotion
- coccidiostats
- bacteriostats

Front 155

how is arsenic used in dogs?

Back 155

- trt of HW

Front 156

what is the effect of organic arsenic on the CNS

Back 156

- causes axonal demyelinating neuropathy
- most severe in sciatic and optic nerves

Front 157

CS of organic arsenic poisoning in pigs

Back 157

- ataxia, goose stepping
- blindness

Front 158

what is the general consideration for use of arsenicals in feed?

Back 158

- arsenicals should be reduced after 2 wks of trt

Front 159

how can you detect high circulating excess iron levels by looking at urine?

Back 159

trt with deferoxamine and look for red color

Front 160

what is the best sample for detecting aresenic

pancreas
hair
muscle
muscle
liver
kidney

Back 160

hair

Front 161

what nerves are most susceptible to organic arsenic poisoning?

Back 161

sciatic

usually longest nerves