Toxicology Exam 1 Flashcards
(223 cards)
1
Q
What is the governing agency that regulates pesticides?
A
EPA - environmental protection agency
2
Q
What are the two major federal pesticide statuses regulated by the EPA?
A
FIFRA (federael insecticide, fungicide, and rodenticide act) - governs the sale and use of pesticide products in the US.
FFDCA (federal food, drug, and cosmetic act) - governs the limit of pesticide residues on food and feeds
3
Q
What does the EPA determine?
A
Whether a “safe” level of pesticide residue, called a “tolerance” can be established before registration
4
Q
The EPA specifies approved uses and conditions of uses, including what?
A
safe methods of handling (personal protection, ventilation, etc), storage, and disposal
must be explained on the product label - material safety data sheet
5
Q
What are some natural sources of organochlorines?
A
through biological, physical, and chemical processes
- include bacteria, fungi, plants, marine organisms, insects, and other animals, to forest fires, volcanoes, and other geothermal events
- major sources include oceans followed by soil
6
Q
what are some synthetic sources of organochlorines?
A
- chlorination modifies the physical properties of hydrocarbons in several ways resulting in a wide structural variety and divergent chemical properties that leads to a broad range of names and applications.
7
Q
what are some chemical properties of organochlorines?
A
- persistent in the environment –> chlorination of the organic compounds reduces reactivity - results in increased size, decreased volatility, increased boiling point - MORE STABLE
- persistent in the environment!
- lipophilic
8
Q
what are the two main groups of organochlorine pesticides?
A
DDT type compounds
chlorinated alicyclics (open and closed chains)
9
Q
What was the effect of DDT on many birds?
A
- biomagnification
- eggshell thinning - estrogen like activity impairs the shell gland’s ability to excrete calcium carbonate to harden the shell
endocrine disruptor
10
Q
what was an unintentional consequence of DDT use?
A
- DDT was used to reduce malaria in Borneo
- observed that thatched roofs were collapsing because DDT killed the wasps that ate thatch eating caterpilars
- dead wasps were eaten by lizards and then eaten by cats
- cats died as a result –> increase in rodents
- increase in rodent related diseases
- stop use of DDT
- CAT DROP to drop an excess of 20 cats in the area
11
Q
Why were organochlorines developed?
A
to replace DDT (methoxychlor)
12
Q
what are the uses of Methoxychlor?
A
used to protect crops, ornamentals, livestock, and pets against fleas, mosquitoes, cockroaches, and other insects
13
Q
what was the problem with organochlorines?
A
Methoxychlor
- acute toxicity
- bioaccumulation
- endocrine disruption
Lindane (lice and scabies)
- banned by the EPA for agricultural use but still used for pharmaceutical use in humans and animals
14
Q
how are animals exposed to organochlorines?
A
- label directions not followed
- concentrations miscalculates for sprays or dips
- contaminated feed or water
- packages or containers unsecured or unlabeled
- lack of appropriate PPE
15
Q
How are organochlorines absorbed?
A
- dermal most common - damaged skin facilitates absorption
- inhalation and oral as well
16
Q
What is the MOA of DDT-type organochlorines?
A
- neuronal membrane permeability or transport of Na and K is altered
- axonal Na channels remain open and K channels don’t open completely –> inhibits repolarization
- continued NT release
- hyperexcitability
17
Q
what is the MOA of chlorinated alicyclic type organochlorines?
A
- binds to but doesn’t activate GABA receptors –> BLOCKS action of GABA (an antagonist)
- inhibits repolarization
- hyperexcitability
18
Q
how are organochlorines metabolized/excreted?
A
- liver enzymes - most are dechlorinated (CP450), conjugated, and excreted in feces and urine
- biliary excretion is major route of decontamination (metabolites can enter enterohepatic recycling, be reabsorbed, and result in toxicity!)
- excreted in milk
19
Q
what are the main clinical signs with organochlorines?
A
- CNS HYPERSTIM
- salivation, vomiting, weakness, incoordination, disorientation
- tremors, spastic gait, chewing, hyperthermia, muscle spasms
- tonic-clonic seizures, opisthotonos, coma, and death
- some mammals may show intermittent or persistent depression instead of CNS excitement
- birds may show depression, abnormal postures, blindness, death
20
Q
how do we diagnose organochlorine toxicosis?
A
- no specific lesions
- secondary changes - trauma from convulsions, congestion/edema of organs
chemical analysis
- can confirm acute toxicosis if chemical in blood, liver,r or brain at high concentrations
21
Q
What are the DDx with organochlorine toxicosis with swine?
A
- dehydration/Na imbalance
- pseudorabies
22
Q
What are the DDx with organochlorine toxicosis with dogs and cats?
A
- strychine
- fluoroacetate
- lead
- organophosphate
- metaldehyde
- rabies
23
Q
What are the DDx with organochlorine toxicosis with cattle?
A
- OP
- lead
- polioencephalomalacia
- infectious thromboembolic meningoencephalitis
- ketosis
- coccidiosis
24
Q
What is the treatment for organochlorine?
A
no specific antidote
decontamination
- soap and water
- induce emesis
- cathartics
- activated charcoal
- IV fat emulsion
symptomatic treatments
- diazepam or barbiturates for seizures
- oxygen, ventilation, fluids
25
when is activated charcoal the most effective?
1-3 hours (effective up to 6 if toxicant has delayed release)
26
what is the MOA of organophosphates?
irreversibly inactivate acetylcholinesterase = persistent acetylcholine activity
27
what are the common exposure routes for organophosphates?
- contaminated feed or drinking water
- use of empty pesticide containers for feeding/watering animals
- dusting, spraying of animals or animal grounds or housing
- sheep dip
- flea treatment, meds
- overdose
- intentional poisoning
28
Why are organophosphates more toxic after 1-2 years in storage?
subject to storage activation
29
are organophosphates lipo or hydrophilic?
lipophilic - readily absorbed through the skin and mucus membranes, GIT, and inhalation
30
how are organophosphates normally metabolized?
in liver - excretion/bioactivation
31
Which organophosphate requires lethal synthesis?
thiophosphate
- liver enzymes (CYP450) metabolize or bioactivate
32
what can happen with continued low dose/chronic exposure of OPs?
- can lead to adaptation to decreased acetylcholinesterase - homeostatic response
- enzyme induction or increased acetylcholinesterase production
- receptor down regulation or decrease in acetylcholine receptor
33
thiophosphates are biologically inactive until transformed by?
the liver to -oxon metabolites
34
what is the major route of elimination for thiophosphates?
paraoxonase - a serum bound enzyme --> hydrolysis of paraoxon
35
what is the MOA of OPs? (plus primary - tertiary)
Irreversible inhibition of cholinesterases! (end result = increase in acetylcholine!)
- OP binds to cholinesterase
- aging = conformational change in OP-AChesterase complex that results in increased or irreversible binding of complex over time
primary: muscarinic receptor over stimulation
seconary: nicotinic receptor over stimulation (neuromuscular and CNS stim)
tertiary: nicotinic blockage (neuromuscular blockade, CNS depression)
36
what is the result of high exposure with OPs?
paralysis of diaphragm leading to pulmonary edema, asphyxia, and death due to respiratory failure
37
delayed neurotoxicity is possible with what OP?
thiophosphates
"OP induced delayed polyneuropathy"
38
what are the muscarinic effects of OP toxicity?
DUMBELLS
- diarrhea
- urination
- miosis
- bronchospasm
- emesis
- lacrimation
- salivation
39
what are the nicotinic effects of OP toxicity?
- ACh accumulation at the neuromuscular junction ans preganglionic synapses
- there are initial stimulations and muscle fasciculations followed by paralysis due to nicotinic block
- stimulation of the SNS may produce sweating, hypertension, and tachycardia
40
what are the CNS effects of OP toxicity?
- cross the BBB
- increase sensory and behavioral distrubances, incoordination, depressed motor function, and resp depression
- resp paralysis
- increased pulmonary secretions coupled with resp failure = USUAL CAUSE OF DEATH
41
what is the normal cause of death in a patient with OP toxicity?
- increased pulmonary secretions coupled with respiratory failure
42
what is OP-induced delayed polyneuropathy?
- develops 10-14 days after exposure
- distal degeneration of long/large diameter motor and sensory axons of peripheral nerves and spinal cord
- clinical signs = muscle weakness, ataxia, rear limb paralysis
- chickens most sensitive
43
what is OP-induced intermediate syndrome?
- occurs 204 days after acute cholinergic effect and signs of the acute effects are no longer obvious
- symptoms and signs occur after apparent recovery from acute effects
- NO muscarinic signs or muscle fasciculations
- weakness of resp muscles and accessory muscles
44
what is the pathology of OP toxicity?
- acute death, no specific lesions
non specific lesions
- pulm edema
- congestion
- cyanosis
- hemorrhages
- edema of various organs
- necrosis of skeletal muscle
delayed effects: degeneration and demyelination of peripheral and spinal motor neurons
45
what lab diagnosis can we use for OPs?
- plasma achetylcholinesterase activity level
| - <50% is suspicious, <25% is diagnostic!
46
what test can we run to see if an animal has been exposed to OPs?
atropine response test
- if the test is POS (dry MM, increased HR, dilated pupils) = LOW LIKELY OP poisoning!
- if the test is NEG (no signs seen) = LIKELY OP POISONING
47
how do we generally treat OP poisoning?
1. decontaminate
- if dermal, wash gently
- if ingested and RECENT, induce emesis but NOT if resp is depressed of if there are seizures
- if ingested, give activated charcoal
2. supportive care
- rest, nutrition, ventilation, O2 therapy
3. avoid phenothiazines, aminoglycosides, muscle relaxants, and drugs that depress the respiration (opioids)
48
what DRUG do we use to treat OP poisoning?
Atropine
- specific ACh
antagonist
- repeat with decreasing doses 3-6 hours based on clinical response
49
what is the main goal for atropine therapy with OP poisoning?
to suppress or dry pulmonary secretions
**main concern with OP tox is resp failure from excessive airway secretions**
50
How can we treat OP poisoning with 2-PAM?
- it is a cholinesterase reactivator - "oximes"
| - binds to OP-inactivated acetylcholinesterase and reverses the binding
51
Carbamate pesticides are derived from?
carbamic acid
52
What was the first successful carbamate insecticide?
Carbaryl
- broad spectrum of insect control
- very low mammalian, oral, and dermal toxicity
- outdoors - used as a lawn and garden insecticide
- indoors - used in sprays or baits in the control of pests
53
what is the MOA of Aldicarb?
- mimics the structure of acetylcholine
| - MOST TOXIC Carbamate
54
do carbamates undergo storage activation?
NO
55
what are the toxicokinetics of carbamates?
- do not penetrate the CNS - effects are mostly resp
- do NOT require hepatic bioactivation (most toxic than some OPs in very young patients)
- faster onset and shorter duration than OPs
56
what is the MOA of carbamates?
- REVERSIBLE inhibition of acetylcholinesterase (competitive inhibition)
57
what are the clinical signs associated with Carbamate poisoning?
- similar to OP toxicity
- SLUD (salivation, lacrimation, urination, diarrhea)
- death results from resp failure and hypoxia due to bronchoconstriction leading to tracheobronchial secretion and pulmonary edema
58
what is the main drug treatment for carbamate poisoning?
atropine!
59
are oximes or 2PAM effective against carbamates?
no - reversible binding reduces benefit
60
Naphthalene is the toxic component of what household item?
mothballs
61
how many mothballs can cause a toxic reaction in dogs/cats?
just one can be highly toxic!
- 400 mg/kg lowest canine lethal dose
62
how are animals exposed to naphthalene?
- absorbed through inhalation, orally, dermally, vapor (eye irritation)
- won't really be absorbed until it hits the intestine if eaten
- people keep moth balls in closet
63
how does pH affect the absorption of naphthalene?
- acids delay
- bases enhance
**it is lipid soluble so the oils increase skin and GI tract absorption**
64
where can we find high concentrations of naphthalene in the body?
- fat, kidneys, liver, lungs
65
why is naphthalene a risk for fetuses and neonates?
- crosses the placenta
| - excreted in milk
66
how is naphthalene metabolized?
1. metabolized in the liver by hepatic enzymes (CYP450)
- metabolites can for epoxides or quinones - reabsorption may cause cellular damage
- metabolites can be conjugated with glutathione to non-toxic substances
- metabolites can be conjugated with sulfate, glucoronic, or mercapturic acid for excretion
67
how is naphthalene excreted?
primarily through urine but also bile
68
what is the MOA of naphthalene?
- the oxidative metabolites (oxides) in the circulation can cause hemolysis and methemoglobinemia
- effect is cellular/tissue hypoxia
69
what are the main clinical signs with naphthalene?
- salivation
- vomiting
- mothball scented breath
- pale or brown gums
- methemoglobinemia, hemolytic anemia, hemoglobinuria
- weakness or lethargy
- labored breathing
- tremors and seizures
70
what are some changes we can see in the blood with naphthalene toxicity?
- hemolysis, heinz bodies
- methemoglobinemia (blood is chocolate brown)
- hemoglobinuria
71
what can we use to treat severe cases of naphthalene poisoning?
methylene blue 1%
- reduces methemoglobin to hemoglobin
- make sure to use correct dose
- controversial in CATS - can case hemolysis
72
how is nicotine absorbed?
- readily through MM and resp tract - caustic
| - absorption in GIT --> acids delay/bases enhance absorption
73
what dose of nicotine are clinical signs reported?
1mg/kg
*cigars have 45-150mg
74
how is nicotine metabolized/excreted?
- liver readily extracts nicotine from circulation
- two principal oxidative metabolites (cotinine and nicotine oxide)
- metabolites are inactive and extracted by the kidneys and excreted in urine
- -> renal excretion is decreased in alkaline or high pH - increased reabsorption
- -> renal excretion increased in acidic or low urine pH
75
what is the MOA of nicotine?
- potent PSNS stimulation
- cholinergic receptor agonist
- at low doses -> mimics acetylcholine and stimulates post synaptic nicotinic receptors
- at high doses --> stimulation will be followed by blockage
- stimulates CRTZ --> vomiting
76
what are the clinical signs associated with nicotine?
1. early stimulation (ganglionic and neuromuscular)
- ataxia
- lethargy
- bradycardia
- tremors
2. later (or with high doses) nicotinic blockade
- CNS depression
- tachycardia
- vasodilation
- paralysis of resp muscles = RESP FAILURE
77
how do we treat nicotine poisoning?
1. decontamination
- induce emesis/lavage
- activated charcoal
- AVOID antacids, which increase pH and DECREASE excretion/INCREASE GI absorption
2. enhance excretion
- diuretics/IV fluids
- lower pH of urine
3. atropine for parasympathetic effects
4. diazepam to control seizures
78
what are some properties of neonicotinoids?
- water soluble
- degrades slowly in the environment
- degraded by direct light
- charged nitrogen metabolites (toxic to non target species)
79
what are the toxicokinetics of neonicotinoids?
- poorly absorbed
- metabolized in liver
- excreted in bile and urine
80
what is the MOA of neonicotinoids?
- ACh receptor agonist - binds to nicotinic receptor
- bind ACh-esterase (binding is irreversible - OPs too)
- high levels of ACh agonist and neonic-induced inhibition of cholinesterase results in overstimulation, paralysis, DEATH
81
neonicotinoids cannot cross the BBB in what animals?
mammals!
can cross in insects
82
what is rotenone only approved for as a use?
piscicide
- used by fish managers to kill unwanted fish in rivers and lakes - NOT SPECIES SPECIFIC - repopulation needed!
83
explain the exposure routes and metabolism of rotenone
- it is readily degraded upon exposure to warm air and light
- more LIPOphilic than hydrophilic
- GIT and dermal absorption is LOW and incomplete UNLESS mixed with fats/oils
- inhalation is more toxic - direct pathway to circulatory system
- metabolized in liver and excreted in feces/urine within 24 hours
84
rotenone is highly neurotoxic to what animals?
- fish and arthropods
85
what is the route of exposure with rotenone?
through the gills or trachea
- resp mechanism of fish directly linked to water
- rotenone passes directly into the bloodstream through the gills and is converted to highly toxic metabolites in the LIVER
86
why isn't rotenone highly toxic to mammals and birds?
- route of exposure is normally through the gut
| - rotenone is readily broken down to less toxic metabolites before toxic quantities can enter the blood stream
87
what is the MOA of rotenone?
- blocks oxidative phosphorylation in the citric acid cycle
- interferes with the electron transport chain/ATP production in mitochondria
- cellular oxygen is reduced, resulting in reactive oxygen species (ROS)
- ROS can result in oxidative stress, damaging DNA and organelles resulting in neuronal death --> NEUROTOXICITY
88
What are the clinical signs with rotenone toxicity?
1. dermal exposure
- local irritation such as conjunctivitis, congestion, dermatitis
2. oral exposure
- GIT irritation, convulsions, muscle tremors, lethargy, incontinence, and resp stimulation followed by resp depression
3. resp exposure
- severe pulmonary irritation and asyphyxia
*Generally as a neurotoxin, depression and convulsions are the main CS*
89
what lab results might we see antemortem with rotenone toxicity?
- hypoglycemia
- liver enzyme changes
- hypoxemia/hypercapnia
90
what is the treatment for rotenone toxicity?
- no specific treatment (rapid metabolism - 24hr)
- detox if appropriate
- supportive treatment for seizures/hypoglycemia
91
How are pyrethrin/pyrethroids used?
- home and farm insecticide
- farm animals
- companion animals (fleas/ticks)
**most cannot be used on cats**
92
what is the relationship between pyrethrins and pyrethroids?
pyrethroids are synthetic analogs of pyrethrins
- pyrethroids now make up the majority of commercial household insecticides (like BOP)
93
are pyrethrins water or lipid soluble?
lipid
94
so synthetic pyrethroids or natural pyrethrins have higher risk for acute toxicity?
natural pyrethrins
95
how does an animal get a chronic toxicity to pyrethrins?
respiration mainly, less by dermal
96
in what animals do pyrethrins cause high toxicity?
- high toxicity in bees
- high acute toxicity in fish and aquatic invertebrates
- high acute toxicity in cats
97
which generation of pyrethroids are more toxic?
second generation (type 2) - do not contain alpha-cyano moiety which increases insecticidal potency and decreases metabolism
98
what are the toxicokinetics of pyrethroids?
- more lipophilic
- dermal exposure isn't common --> ingestion and inhalation are rare but possible
- rapid metabolism through hydrolysis and oxidation
- conjugated metabolites are excreted in urine within 24hrs after exposure
- cats are MORE sensitive than dogs (reduced rate of metabolism becauuse of their shitty liver)
- presence of the alpha-moiety in pyrethroid type 2 decrease metabolism by decreasing hydrolysis
- doesn't accumulate in tissues
99
what are pyrethroids commonly formulated with for a synergistic effect?
piperonyl butoxide or MGK-264
| - both increase toxicity in insects and non-targeted species by delayed metabolism
100
what is the MOA of pyrethrins/pyrethroids?
1. are axonic excitotoxins
2. similar to organochlorine DDT-type MOA
- neuronal membrane permeability of Na is altered
- continued NT release
- hyperexcitability of the nerve --> depolarization --> paralysis
3. type 2 pyrethroids have a greater effect on Na channels
- similar to organochlorine alicyclic MOA at high concentrations - GABA antagonist
- inhibit neuronal Ca, Mg ATPase activity --> hyperexcitability
101
what endocrine organ might pyrethrins/pyrethroids stimulate?
adrenal glands
| - increased cortisol resulting in hyperglycemia
102
True/False:
insect metabolism of pyrethrins is much faster than that of mammals
FALSE
it's SLOWER - especially with piperonyl butoxide
103
what are the main clinical signs with acute pyrethrin toxicity?
- generalized muscle tremors, depression, blindness (reversible), ataxia, lethargy
- salivation, vomiting, diarrhea, hyperexcitability, drooling
- may progress to seizures, death
***many cats DIE or need to be euthanized because of the severity***
104
how do we diagnose pyrethrin toxicity?
- no specific lesions
- generally low tissue levels
- brain and liver in post mortem are best
- tissue levels don't correlate well
*diagnosis is generally made with history and appropriate clinical signs*
105
how do we treat pyrethrin toxicity?
- no specific antidote
- decontaminate --> wash with soap/water
- activated charcoal is NOT used (rapid metabolism)
- avoid exacerbating the toxicity (monitor and control temp, treat hyperthermia and prevent hypothermia)
- symptomatic treatment ( methocarbamol for more severe tremors or diazepam/barbs/propofol)
106
what is the prognosis for pyrethrin tox?
good except for cats
107
what is the chemistry of DEET?
- nearly colorless liquid with faint odor
- lipophilic
- relatively stable but sensitive to light
108
what is the MOA of DEET?
- mosquito attraction to a host is thought to involve long-range (visual) and short range (olfactory) stimuli
- lactic acid on the skin may be an essential olfactory stimulant to attract mosquito to land
- effectiveness may be due to its ability to mask sensory perception
109
what is the general toxicity of DEET?
- slightly toxic to some fresh water fish
- dogs are more susceptible, care more sensitive
- young animals more sensitive
- caustic
110
what are the toxicokinetics of DEET?
- dermal absorption (can accumulate and persist in fat)
- guinea pigs - 19-48% of a topical dose absorbed
- can increase dermal absorption of other products
- GI absorption
- metabolized in the liver and excreted in urine
111
what is the MOA of DEET?
- undetermined!
- known to affect the olfactory and nervous system in insects
- when DEET is combined with carbamates the effects are potentiated
112
what are the CS with DEET toxicity?
- rabbits/rats: depression, excitation, ataxia, tremors, seizures, and coma
- dogs/cats: hypersalivation, vomiting, hyperexcitability, tremors, ataxia, seizures, skin and MM irritation
113
how do we diagnose DEET toxicity?
- history, presentation +/- chem analysis
- no specific lesions
- chem analysis can be performed (blood, urine, skin, stomach contents, bile, kidney)
- 20ppm is diagnostic
- must differentiate between other CNS excitatory toxins (strychnine, metaldehyde, organochlorine, OP/carbamate)
114
how do we treat DEET toxicity?
- no specific antidote
- decontaminate
- if dermal: wash with soap and water
- emesis if not contraindicated
- activated charcoal may be given (avoid magnesium cathartics as this may cause CNS depression)
115
the active ingredient of which pesticide might be used to treat the effects of myasthenia gravis?
carbamates and OPs
116
which is correctly matched with its MOA?
pyrethrin: monoamine oxidase inhibitor
ivermectin: octapomine receptor antagonist
amitraz: alpha adrenergic receptor agonist
DEET: uncoupling of oxidative phosphoylation
amitraz - alpha adrenergic receptor agonist
117
what is the MOA of pyrethrin?
Na channel agonist
118
what is the MOA of ivermectin?
GABA agonist
119
what is the MOA of rotenone?
uncoupling of oxidative phosphorylation
120
what is the MOA of OPs and carbamates?
ACh-esterase inhibitors
121
what is the MOA of nicotine and neonics?
nicotinic adrenergic receptor agonists
122
what is the MOA of naphthalene?
toxic oxides --> hemolysis, methemoglobinemia
123
what drug can increase dermal absorption of DEET?
pyrethroids
124
what are the main reasons we use amitraz?
- rapid action against ectoparasites such as ticks and mites
- can control all life stages
- used in beekeeping to control Varroa mite
125
what is the MOA of amitraz?
- kills by interfering with nervous system
- octopamine receptor antagonist
- works as repellent (detachment effect)
126
what are the main CS with amitraz toxicity?
- hyperexcitability, paralysis, death
127
in what species is amitraz contraindicated in?
cats and horse
128
what are some uses of amitraz?
- used in flea and tick collars
- topical liquid
- generalized demodicosis in dogs
- ascaricide/tickicide for swine and cattle
129
does amitraz bioaccululate in the fat?
no
130
what are the toxicokinetics of amitraz?
- dermal absorption is low (less than 10% in dogs and pigs)
- not readily absorbed into tissues, but quickly distributed throughout the body including the brain
- GIT absorption is moderate - most is quickly excreted unchanged
- rapidly metabolized in liver and excreted in urine
131
what are the 3 MOAs for amitraz in mammals/vertebrates?
1. alpha adrenergic receptor agonist
- alpha 2 agonist in CNS
- alpha 1 and alpha 2 agonist in PNS
- increase in epinephrine, NE, and dopamine
- neurotoxic and preconvulsant effects
2. inhibition of monoamine oxidases
- can lead to suppression of insulin in dogs
- also increases NTs
3. inhibits synthesis of PGs
- inhibits synthesis from arachidonic acid
132
what is the MOA of amitraz with arthropods?
interaction with octopamine receptors
- toxic effects on arthropods, less so on vertebrates
- this receptor is less sensitive in vertebrates
- kills by interfering with nervous system
- tick's sharp barbed mouth becomes paralyzed and cannot pierce skins so it falls off
133
what are the main CS seen with amitraz toxicity?
- hyperglycemia
- hypothermia
- PU
- anorexia
- vomiting
- diarrhea
- depression
- tremors
- bradycardia
**ultimately can lead to CV collapse and rep failure**
134
how do we treat amitraz toxicity?
- decontaminate
- if collar ingested: induce emesis and/or remove, activated charcoal, cathartics, gastric lavage
- supportive care
- ANTIDOTE: alpha2 antagonists = yohimbine or atipamezole
135
what is the MOA of ivermectin?
gaba agonist
- induces neurological damage by binding to glutamate gates chloride ion channels in nerve and muscle cells of invertebrates that results in paralysi and death
136
what is the main use of ivermectin?
broad spectrum antiparasitic agent
- kills a wide range of internal and external parasites in commercial livestock and companion animals
- GI roundworms, lungworms, heartworms, mites, lice, and horn flies
137
how are animals exposed to ivermectin?
- extra label use for parasites in dogs/cats
- formulation errors are most common
- excessive licking after a pour on
138
what is the gene mutation resulting in multi-drug resistance?
- ABCB1/MDR1 gene codes for P-glycoprotein
- dogs will have a dysfunctional BBB
- don't treat
139
true/false: cats have a higher bioavailability to ivermectin
false - lower
give them a higher dose
140
what is the MOA of selamectin?
- binds to glutamate gated Cl channels in parasite NS --> blocks berve transmission
- no effect in mammal NS
*selamectin is revolution*
141
what are the main CS with ivermectin toxicity?
- CNS DEPRESSION!!
| - mydriasis, blindness, vomiting, drooling, weakness, ataxia, coma
142
how do we diagnose ivermectin toxicity?
- history, clinical presentation
- no specific lesions
- chemical analysis possible but not usually necessary
143
how do we treat ivermectin toxicity?
- no specific antidote
- decontaminate
- activated charcoal is more useful than emesis
- supportive care
144
what are the CS associated with EO overexposure?
- unsteadiness
- depression
- low body temp (in severe cases)
- vomiting
- diarrhea
145
what are the characteristics of D-Limonene?
- cyclic monoterpene hydrocarbon
- clear, colorless
- volatile
- lipophilic
146
what are the sources of exposure for D-Limonene?
1. botanical insecticide
- 5% d-limonene - controls lice, fleas, ticks
2. botanical herbicide
- 70% d-limonene - broad spectrum weed killer
3. biodegradeable cleaning agents and solvents
- up to 100% d-limonene defatting and degreasing
147
what percentage of D-limonene is considered safe in a product?
1-5%
148
what are the toxicokinetics of D-limonene?
- lipid soluble
- readily absorbed through skin and GIT
- maximal blood concentrations 10 mins after dermal exposure
- metabolized by liver and excreted in urine
149
what is the MOA of D-limonene?
- unknown
150
what CS do we see with d-limonene toxicity?
- ataxia
- weakness
- recumbency
- paralysis
- CNS depression
- hypothermia
- hypotension
- skin reaction
- smells like lemons
151
how do we treat D-limonene toxicity?
- decontaminate with shampoo and mild dish soap
- monitor temp
- other supportive care
152
what is the most common type of molluscicide used?
metaldehyde
- other types are ACh-esterase inhibitors (OPs), metal salts, and methiocarb (banned in 2014)
153
when using a molluscicide what is mollusk death due to?
- excessive mucus, dehydration, cell damage
154
what are the main properties of metaldehyde?
- restricted use
- polymer of acetylaldehyde
- highly flammable
- hydrophobic
- short soil half life
155
how are animals exposed to metaldehyde?
- ingestion of bait most common
- brightly colored and flavored --> dogs want to eat it
- sometimes malicious poisoning
- snail baits often mixed with tasty items that would attract other species by accident
156
what are the common routes of exposure for metaldehyde?
- inhalation = most toxic
- dermal = least toxic
- ingestion = most common and intermediate toxic
157
what are the toxicokinetics of metaldehyde?
- once ingested, undergoes GIT acid hydrolysis to acetaldehyde
- readily absorbed as wither metaldehyde or acetaldehyde
- both cross BBB (neurotox)
- rapidly metabolozed by liver by P450
- undergo enterohepatic recirculation (prolongs tox)
- enzyme inducers may decrease tox
- excreted in urine
158
what is the MOA of metaldehyde?
- decreased brain GABA -> neuro stimulation
- increased monoamine oxidase - decreased brain serotonin and NE --> reduced seizure threshold
- increased neuromuscular activity and production of metaldehyde metabolites --> metabolic acidosis, hyperthermia
- death from resp failure (acute) or liver failure (chronic)
159
what are the main CS with metaldehyde toxicity?
- acute neuro manifestations within 1-3hr after ingestion
- initial onset: severe muscle tremors, salivation, ataxia, tachycardia, hyperthermia
- progression into acidosis: V, D, depression, tonic convulsions that are unresponsive to ext stimuli
- seizures eventually lead to CNS depression, resp failure, and death within 4-24hrs
160
what are the lesions associated with metaldehyde poisoning?
- acute: nothing specific
- stomach contents will have a specific apple cider odor
- petechiae/ecchymoses in GIT
- congestion, edema, hemorrhage in lungs, liver, kidneys
- longer survival may result in degenerative changes in liver and brain (ganglion cells)
161
how do we treat metaldehyde poisoning?
- no specific antidote
- decontaminate
- emetics
- gastric lavage
- activated charcoal
- enemas
- fluids to address metabolic acidosis
- treat seizures
- muscle relaxants
162
what is the problem with some barbiturates when treating metaldehyde?
- some barbs (pento) can interfere with metabolism of acealdehyde and cause displacement from protein binding sites
- BUT phenobarb can help accelerate elimination of the toxin!
163
what is the LEAST accurate answer following acute exposure to metaldehyde?
- increase GABA
- increased monoamine oxidase
- decreased serotonin
- decreased NE
increased GABA
164
what happens when ammonia comes in contact with MM?
- forms ammonium hydroxide which is irritating and caustic
165
how does an animal become exposed to ammonia?
- inhalation***
- environmental conditions
- decomposing manure in confined animal houses
- burning plastics
- used in agricultural fertilizer
166
at what level of NH3 will eyes burn?
25-35ppm
167
what exposure of NH3 can cause acute death?
5000ppm
168
what are the toxicokinetics of NH3?
- converted to a strong base irritant (ammonium hydroxide) on MM
- primarily absorbed by inhalation and is distributed to tissue cells
169
what is the MOA of NH3?
1. direct irritation of MM
2. causes pulmonary edema and lung congestion
3 alkalosis and compensatory acidosis
4. inhibit TCA cycle
5. increased susceptibility can lead to resp infections due to continuous exposure - irritation - inflammation - secondary infections
- 50-75ppm: decreased ability to clear bacteria from the lungs --> resp dysfunction
6. decreased growth of young animals
- 100ppm: decreased growth rate by 32% in swine
170
what are the CS with acute NH3 toxicity?
red MM, lacrimation, coughing, sneezing, nasal discharge, keep eyes shut
171
what are the CS with chronic NH3 toxicity?
- decreased growth rate and production
| - dyspnea - fluid in the lungs caused by pulmonary edema/congestion
172
what are the CS with terminal NH3 toxicity?
CNS stimulation, clonic convulsions, cyanosis
173
how do we diagnose NH3 toxicity?
- history
- odor of ammonia
- CS
- lesions (blisters on MM)
174
how do we treat NH3 toxicity?
- remove source
- fresh air
- soothing ointments for eyes
- antibiotics may prevent secondary infections
- diuretics for pulm edema
- treat any secondary infections
175
what are the main properties of hydrogen sulfide gas (H2S?)
- colorless
- odor of rotten eggs
- heavier than air
- flammable
- water soluble
- irritant because converted to sulfuric acid
- forms black or dark colored compounds in GIT and tissues
176
what are the main routes of exposure for H2S?
- INHALATION
- by product or waste material from industry ****
- may be liberated in coal pits, gas wells, or sulfur springs
- also associated with natural gas and crude oil production
177
humans can detect H2S at what level?
0.025ppm
178
at what level does H2S cause eye irritation?
20ppm
179
at what level is H2S possibly fatal?
400ppm
180
what does 1000ppm H2S cause?
rapid unconsciousness and death in about 1 hour
181
>2000ppm H2S cause what?
resp paralysis after 1-2 breaths
182
what are the toxicokinetics of H2S?
- readily absorbed through the lungs and GIT
- converted to alkali sulfides in the blood
- hydrosulfide radical is normally oxidized to sulfate and is excreted in urine
- some sulfide is excreted in feces
183
what is the MOA of H2S?
- direct irritation of MM
- inhibition of cellular respiration
- decreased cytochrome oxidase
- stimulation of the chemoreceptorsof the carotid body - depressed resp drive
- DIE FROM ASPHYXIATION
184
what are the CS from acute H2S exposure?
- sudden collapse
- cyanosis
- dyspnea
- convulsions
- rapid death
185
what are the CS from chronic H2S exposure?
- eye, resp, and lung irritation
186
what are the lesions associated with H2S poisoning?
- blood is dark and may not clot
- tissues may be dark or greenish purple
- carcass may have sewage odor
- if ingested, the GI contents may be black or dark gray and smel of sewage
187
how do we treat H2S toxicity?
- removal of source
- sodiun nitrite IV may be partly effective by forming methemoglobin - binds sulfide radicals and reactivates cytochrome oxidase
- oxygen therapy, ventilation
- educate about prevention (get H2S monitors!)
188
what are the properties of carbon monoxide (CO)?
odorless, colorless, not water soluble
189
what are common exposure routes for CO?
- accidental exposure with fires (incomplete combustion of carbon containing products - wood, paper, petroleum products)
- propane powered equipment, space heaters, portable cookers, de-icers
- automobile exhaust in confined spaces
190
what is the MOA of CO?
- CO combines with hemoglobin to form carboxyhemoglobin and reduced the level of O2 (hemoglobin has a 240x higher affinity for CO)
- carboxyhemoglobin interferes with release and availability of O2 carried by hemoglobin
- some intereference with cellular resp
- also competes with O2 for binding sites on myoglobin
191
what is death due to from CO poisoning?
hypoxia
192
what are the main CS with CO poisoning?
- sudden death at 60-70% COHb
| - in low exposure (30-60% COHb) signs = hypoxia, drowsiness, incoordination, dyspnea, lethargy, coma
193
what are the lesions associated with CO toxicity?
- blood is bright red and the MM are pink
- no significant lesions in acute cases
- in chronic cases there may be brain edema, hemorrhage, and ecrosis which may cause deafness in dogs/cats
194
what lab diagnostics can we run to confirm CO toxicity?
- measuring CO in air
| - percentage of COHb in the blood (correlation to CS is poor)
195
how do we treat CO toxicity?
- oxygen or 5% CO2 in oxygen administered with positive pressure
- blood transfusion
- fluid for acidosis but bicarb use is controversial
196
what are the common sources of Nitrogen Oxide gases?
1. farm
- NO2 and N2O4 gases are produced by incomplete reduction of nitrates during fermentation process in silo's
- nitrogen oxide poisoning = Silo filler's disease
2. industry
- NO2 is a major pollutant (burning of fossil fuels)
197
what are the major properties of Nitrogen Oxide gases?
- NO2 gas is reddish brown
- N2O4 is colorless
- NO2 is heavier than air but the gases are about as dense as air - forms layers on top of silage and settles down on the chute
- gas mixture has an irritating chlorine-like odor
- low solubility in water
198
which nitrogen oxide gas exposure is more toxic - acute or chronic?
acute
199
what are the toxicokinetics of nitrogen oxide gases?
- animal quarters that develop the irritant odor or yellow haze in the air must not be entered
- nitrogen dioxide and tetraoxide gases form nitric acid upon contact with mucus membranes
- cross resp mucosa and cause cellular damage in the lungs - pulmonary edema
200
what is the MOA of nitrogen oxide gases?
- direct irritation of the MM by nitric acid
- low water solubility - passes from upper to lower resp tract and causes damage in the lungs
- lung damage - due to caustic reaction with the PFAs at cellular membrane - pulmonary edema, hemorrhage
- death is from hypoxia -resp failure
201
what are the CS associated with nitrogen oxide gas toxicity?
- resp signs - generally similar to ammonia poisoning (irritation of MM, effects on respiration)
202
what lesions are associated with nitrogen gas toxicity?
- pulmonary edema
- hemorrhage
- emphysema
- cyanosis
- methemoglobinemia
- necrosis of skeletal muscle
203
how do we treat nitrogen oxide gas toxicity?
- supportive treatment
- diuretics if pulmonary edema
- methylene blue IV for methemoglobinemia
- antibiotic ointment for MM
204
at what percentage of methemoglobinemia do we normally start seeing toxic signs?
15% (normal is 1%)
205
what are the common sources of exposure with sulfure oxide gases?
- sulfur dioxide SO2 and sulfur trroxide (SO3) are industrial pollutants
- fossil fuel combustion at power plants
206
what are the main properties of sulfur oxide gases?
- highly soluble in water
- sharply irritant to MM because the form sulfurous and sulfuric acids on contact with water
- odor causes coughing, choking, and suffocation
207
SO2 at ___ppm is fatal to cats within 30-60mins
500
208
SO2 at 500ppm for __ hour(s) is dangerous to grazing animals
1
209
SO2 at ___ppm for 8 days causes poisoning in pigs
5-40
210
what is the MOA of sulfur oxide gases?
- direct irritation of the MM - primarily upper resp tract
- reflex bronchoconstriction - lung damage
- death due to hypoxia
211
what are the CS and lesions associated with sulfur oxide gas toxicity?
- similar to other toxic gases (irritation to MM, effects on respiration)
212
what all does "smoke" include?
vapors, gases, fumes, heated air and particulate matter, liquid and solid aerosols
213
why is there no LD50 for smoke?
it is a heterogenous mixture of gases - too many variable
214
inhalation of super-heated air and steam can cause?
thermal burns to resp tract and enhance absorption of gases
**burns in the resp tract enhances toxicity**
215
what are the MOAs of smoke inhalation?
1. simple asphyxiants - inert (CO2) gases or vapors displace O2
- low concentration, generally have little if any physiological effect
2. chemical asphyxiant - prevent uptake of O2
- produce toxic local (lungs) and systemic effects
- carbon monoxide --> COHb
3. irritants
- chemically reactive on contact with MM to cause local effects
- sulfur dioxide --> sulfuric acid
- particle - ash and soot
216
what are the CS associated with chemical asphyxiants?
1. resp
- cough, dyspnea, tachypnea
- wheezing, decreased breath sounds, crackles
2. CV
- tachycardia, hypoxemia
- hypotension, dysrhythmias
3. signs of irritation
- conjunctivitis, pharyngitis, rhinitis, drooling, hoarseness
- edema, mucosal ulcerations
- corneal abrasions common from ash/soot
4. CNS
- agitation, confusion, ataxia, abnormal posture, seizure
5. surface burns
217
what kind of lesions might we see with smoke inhalation (chemical asphyxiants?)
- burns
- pulmonary changes
- cerebral edema
218
how do we treat smoke inhalation (chem asphyxiants)?
- prompt removal from the smoke environment + O2 support
- B2 adrenergic agonists may benefit for bronchoconstriction
- NO STEROIDS
- remove soot from skin
- avoid cough suppressants and opioids
- maintain airway patency, ventilation, etc
219
____ of the toxin (gas, chemical) is the most importany determinant of resp injury
solubility
220
highly soluble particles (smoke inhalation) end up where in the resp tract?
upper airway
| - injury to the mucosa, inflammatory mediators, free radicals --> increased permeability --> edema
221
low water soluble particles (smoke inhalation) end up where in the resp tract?
- lung, bronchiole, alveoli
| - slower reaction, delayed effect
222
ammonia and sulfur dioxide have high or low water solubility?
high - end up in upper airway
| - chemically reactive on contact with mucus
223
nitrogen oxides have high or low water solubility?
- low - end up in pulmonary parenchymal injury in the alveoli, alveolar ducts
