Quiz 1: Principles, Diagnosis, Treatment, Neurotoxicants Flashcards
(122 cards)
1
Q
Paracelsus
A
“Father of Toxicology”
Swiss physician that said “all substances are poisons”
2
Q
Toxicology is concerned with
A
Identification, treatment, and assessing risks of poisons
3
Q
Definition of Toxicant
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Compound that causes toxicity
May be natural or man-made
Xenobiotic = foreign substance
4
Q
Definition of Antidote
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Substance that prevents/relieves effects of a toxicant
No antidote works on all toxins (not even activated charcoal)
5
Q
NOAEL
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“No observed adverse effect level” on dose-response curve
6
Q
LOAEL
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“Lowest observable adverse effect level” on a dose-response curve
7
Q
Classifications of chemical interactions in toxicity
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Additive
Antagonistic
Synergism
8
Q
Factors influencing toxicity
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Factors related to exposure
Factors related to the subject
Factors related to the environment
9
Q
Types of exposure classifications
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Acute
Sub-acute/subchronic
Chronic
10
Q
Acute exposure
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A single exposure or multiple exposures in 24 hours
11
Q
Sub-acute/subchronic exposure
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Exposure over 7 to 90 days
12
Q
Chronic exposure
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Protracted exposure (6 months - lifetime)
13
Q
Most important veterinary toxicants are absorbed by what routes?
A
Oral and dermal
14
Q
What usually detoxifies a compound and increases its elimination?
A
Metabolism
15
Q
When metabolism increases the toxicity of a compound
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Bioactivation
16
Q
Mechanism of Toxicity (4 steps)
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- Delivery from site of exposure to target
- Reaction of the ultimate toxicant with the target molecule
- Cellular dysfunction and resultant toxicities
- Repair or disrepair
17
Q
How do toxicants cause toxicity?
A
Cellular damage
Organ system dysfunction
18
Q
Most common toxicants that cause death
A
Insecticides
Rodenticides
Ethylene Glycol
19
Q
When treating a patient for a toxicosis, what do you do first?
A
Evaluate for immediate life-threatening problems
20
Q
How to prevent aspiration of vomitus in an unconscious patient?
A
Keep head lower than body
21
Q
A patients may need assisted ventilation if:
A
Hypoventilation, hypercapnia
Metabolic acidosis (venous pH 7.35)
Hypoxia, treat with 40% oxygen
22
Q
How to treat CNS hyperactivity (seizures)
A
Diazepam
Phenobarbital
Methocarbamol
23
Q
How to treat CNS depression
A
Analeptics
Doxapram
24
Q
How to treat tachycardia and arrhythmias
A
Lidocaine
Propranolol
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How to treat hypertension
Nitroprusside
| Hydralazine
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How to increase cardiac contractility
Dobutamine
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Priority in animals with severe clinical signs
1. Assess hypo/hyperthermia
| 2. Pull blood for laboratory profile and diagnostic testing (3cc EDTA tube and 2 serum tubes)
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4 major themes of a History
1. Health history
2. Current clinical history
3. Environment
4. Diet
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Two most common methods of decontamination
Emesis
| Activated charcoal
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Contraindications of emesis in decontamination
1. >30 minutes since exposure
2. Chronic exposure
3. Ingestion of caustic materials
4. Recent GI surgery
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Induce emesis if:
1. Toxic dose of substance was ingested
2. No vomiting has yet occurred
3. Activated charcoal is not an option
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Contraindications of using activated charcoal
1. If it will not bind the toxin (inorganic compounds, oils, gasoline, ethylene glycol, cyanide, etc.)
2. If airways are obstructed
3. If patient has altered state of consciousness
4. Chronic exposure
5. If you suspect GI perforation
33
Activated charcoal is most useful for what type of toxins?
Toxic plants
Pesticides
Herbicides
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Give charcoal if:
1. Substance is known to be absorbed by it
2. Ingestion was very recent/undergoes enterohepatic circulation/is sustained release
3. The patient can tolerate it
4. There is no immediate need to administer oral meds
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Effect of cathartics
Decrease GI transit time
Increase movement of toxins/charcoal-toxin complex
Decrease absorption of the toxin
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Example of a cathartic
Mineral Oil
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What to do for corrosive toxins that have been ingested?
Use dilution instead of emesis
Milk water or eggs
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How to treat dermal toxicant exposure?
Bathe in liquid dish soap
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Lipid infusion
Relatively new treatment for toxicant ingestion
| Off label-use of IV fluids
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Emetic agent for dog, pigs
Apomorphine
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Emetic agent for cats
Xylazine
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Good agent for at-home emesis induction
Salt water
| Hydrogen peroxide
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Treatment for sustained-release toxicants
Gastric lavage or whole bowel irrigation
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Common antidotes to know
Vitamin K for rodenticide toxicities
| Digoxin for plant toxicities
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Analytic testing
Testing for toxicants
Not one test that will screen for all toxicants
Can be costly
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Ancillary support includes
Managing any hepatic or renal injury
Maintain body temperature (hyperthermia- cold baths, ice; hypothermia- blankets, circulating warm water pads, NO HEAT LAMPS)
Ensure adequate urine output
Prevent irritation of skin/membranes with demulcents, milk, sucralfate
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How to prevent future toxicant exposures
Change pasture, feed, water, etc.
Remove baits, pesticides, etc.
Bathe or flush cutaneous or ocular exposures
Educate clients
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Types of Neurotoxicants
```
Pesticides
Pharmaceuticals
Mycotoxins
Ammoniated feed toxicosis
Strychnine
Salt
```
49
Largest class of chemicals inducing toxicosis
Neurotoxicants
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Pesticide usage
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Billions of pounds made each year in US
300 types of pesticides in US
>50% use is non-commercial
Improper use and storage
Many benefits (higher crop yields, better health)
```
51
Organophosphate Pesticides
Agricultural and residential use has increased
Used in flea collars, dips, fly, ant, roach bait
Parathion, malathion, chlorpyrifos
Highly water soluble and acute toxicity
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Mechanism of action of Organophosphates
Irreversible inhibition of Acetylcholinesterase activity (anti-cholinesterase)
Leads to cholinergic overstimulation within minutes to hours
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Clinical signs of anti-cholinesterase toxicity
Clinical signs may last 1-5 days
Muscarinic: SLUDGE-M
Nicotinic: Muscle fasciculations, tremors, weakness, paralysis
CNS: Respiratory depression, ataxia, nervousness, clinic-tonic seizures
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Atropine Challenge
Used to diagnose anti-cholinesterase toxicity
Administer pre-anesthetic dose of atropine and see if patient responds normally
If normal, toxicity is NOT due to anti-cholinesterase toxicant
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Treatment of anti-cholinesterase toxicity
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GI decontamination
Bathe if dermal exposure
Atropine sulfate for muscarinic signs
Oxides (protopam, 2-PAM) to reactivate AChE
Diazepam or barbiturates for seizures
Time
```
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Histopathology of patient following OP toxicity
Vacuolization of brain
| Degeneration of neurons
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Organophosphate-induced Delayed Neurotoxicity
Axonal degeneration of long motor neurons
Hindlimb weakness, paralysis
No treatment
Poor prognosis
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What is Ivermectin?
Antihelminthic
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What breeds are susceptible to Ivermectin toxicosis?
Border Collies
Australian Shepherds
Shelties
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Mechanism of action of ivermectin toxicosis
GABA receptor agonist
Increased inhibitory input = DEPRESSIVE effect
Can see cumulative toxicity with repeat doses
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Clinical signs of ivermectin toxicosis
Ataxia, lethargy, mydriasis, coma, blindness, bradycardia, recumbency, disorientation, seizures, respiratory distress, anaphylactic reactions
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Diagnosis of ivermectin toxicosis
History of administration
Brain concentration >100 ppb
Can also measure in GI content, fat, liver, and feces
No visible lesions, no diagnostic bloodwork
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Treatment for ivermectin toxicosis
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Recent exposure: multiple doses of activated charcoal
Supportive care
Electrolyte therapy
Epinephrine
Barbiturates for seizures
```
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How to prevent ivermectin toxicosis
Test dogs prior to administering higher doses
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What are pyrethroid pesticides?
Pesticides made from pyrethrins of chrysanthemum flowers
Considered "safer" than organophosphates
Used in dog flea/tick topical prevention
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Mechanism of action of pyrethroid pesticides
Lipophilic, absorbed by all routes
Binds voltage-gated sodium channels
Causes repetitive nerve discharges -> hyperactivity and overstimulation
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Why are cats more susceptible to pyrethroid toxicity than dogs?
Inefficient glucuronide conjugation
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Clinical signs of pyrethroid toxicosis in cats
Drooling, paresthesia, muscle tremors, seizures, excessive muscle activity, hyperthermia
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Clinical signs of pyrethroid toxicosis in dogs
Paresthesia, shaking of legs, muscle fasciculation, rubbing of application site, agitation, nervousness
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Diagnosis of pyrethroid toxicosis
Difficult
Look at clinical signs, history of exposure
Chemical analysis for pyrethrin/pyrethroid
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Treatment of pyrethrin toxicity
Stabilize: treat seizures (methocarbamol)
WASH IT OFF
IV fluids, furosemide
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Bromethalin
Single-dose rodenticide
| Kills in 3-5 days -> delayed toxicosis
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Mode of action of bromethalin toxicosis
Parent and metabolite uncouple oxidative phosphorylation in CNS
Loss of ion gradients in leads to fluid accumulation in myelin sheaths
Causes decreased nerve conduction, respiratory arrest, and edema
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Clinical signs of bromethalin toxicosis
Ataxia, hindlimb paralysis, hyper-excitability, severe muscle tremors, running fits, grand mal seizures
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Diagnosis of bromethalin toxicosis
1. Cerebral edema and cerebellar degeneration
| 2. Histological evidence of neuronal vacuolization and edema
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Treatment of bromethalin toxicosis
```
Emesis if recent exposure
Give activated charcoal/sorbitol
Maintain hydration and electrolytes
Furosemide for edema
Treat seizures
```
77
Primary cause of pharmaceutical toxicosis
Careless storage
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Top prescribed pharmaceuticals that cause toxicoses in animals
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Vicodin
Synthyroid
Zocor
Lipitor
Lisinopril
```
79
Mechanism of action for alprazolam toxicosis
Acts at limbic, thalamic, and hypothalamic levels of CNS
| Depressive effects
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Clinical signs of alprazolam toxicosis
Ataxia, vomiting, depression, tremors, tachycardia, diarrhea, ptyalism, hypothermia
Usually occurs within 30 minutes of ingestion
Some animals may initially show CNS excitation
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Diagnosis of alprazolam toxicosis
Based on clinical signs and history of exposure
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Treatment of alprazolam toxicosis
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Emesis with apomorphine if recent ingestion
Activated charcoal
Flumazenil for severe CNS depression
Close monitoring
Fluids
```
83
Zolpidem
Ambien
Sleep aid
Non-benzodiazepine hypnotic drug
84
Mechanism of action of zolpidem toxicosis
Inhibits neuronal excitation by binding to the benzodiazepine site of GABA receptors
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Clinical signs of zolpidem toxicosis
Ataxia, vomiting, lethargy, disorientation, hyper-salivation, hyperactivity and panting
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Diagnosis of zolapidem toxicosis
Based on clinical signs and history of exposure
87
Treatment of zolpidem toxicosis
Supportive
Keep patient in a quiet place
Treat clinical signs if needed
88
What are mycotoxins?
Fungal metabolites that cause pathological, physiological, and/or biochemical alterations usually on several organ systems
Can affect all species
Includes aflatoxins, slaframine, and fumonisin
89
What is Slaframine?
Produced by "black patch" fungus on red clover
Rain, high humidity, cool weather triggers growth
Occurs in central, SE, SW USA
90
Mechanism of action of Slaframine
ACh mimic, partially acts as a muscarinic cholinergic agonist, especially in exocrine glands
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Slaframine toxicity is most common in what species?
Horses and cattle
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Clinical signs of slaframine toxicosis
Copious salvation (the "slobbers")
Bloat, diarrhea, frequent urination
Feed refusal
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Diagnosis of slaframine toxicosis
Consumption of clovers with "black patch"
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Treatment of slaframine toxicosis
Remove source
Maintain hydration and electrolytes
Atropine
Rarely fatal
95
What is fumonisin?
Metabolite of Fusarium spp.
Found almost exclusively on corn
Usually occurs in years of drought followed by wet weather
Presence of Fusarium spp. Is not indicative of fumonisin
96
Mechanism of action of fumonisin toxicosis
Inhibition of sphingosine-N-acetyltransferase causing increased levels of sphingosine, which is cytotoxic
Affects vascular epithelial cells, which can lead to stroke, hepatic injury, and pulmonary edema
97
Which species are susceptible to fumonisin toxicosis?
Horses, ponies, swine, rabbits
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Two diseases cause by fumonisin toxicosis
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Equine leukoencephalomalacia (ELEM)
Porcine pulmonary edema (PPE)
```
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Porcine pulmonary edema
Lethal pulmonary edema that occurs 4-7 days after consuming fumonisin contaminated feed
Manifests as respiratory distress
Necropsy shoes pulmonary pathology and edema, hepatic lesions, tissue necrosis
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Most specific biochemical changes for PPE
Increase in tissue and serum sphingoid bases
| Increased liver enzymes
101
Equine Leukoencephalomalacia (ELEM)
Fumonisin toxicosis of horses
Most common in late fall/early winter
Target organs: brain and liver
CNS toxicity: hysteria that gets progressively worse
Liver toxicity: jaundice, hepatic encephalopathy
Necropsy: CNS liquefaction
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Treating fumonisin toxicosis
No treatment.
"Ultrasorb S": newly created mycotoxin deactivator
Isolate infected animals, change feed
Pigs usually recover in 48 hours after removing contaminated feed
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Ammoniated feed toxicosis is caused by
Over consumption of
Non-protein nitrogen sources (ammonium, salts) that are added to cattle feed
Mineral licks
104
"Bovine bonkers"
Hyperexcitability state caused by ammoniated feed toxicosis
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Onset of clinical signs or death in ammoniated feed toxicosis
15 minutes - several hours
Death within 24 hours when blood ammonia >2mg/dL
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Normal blood ammonia concentration
<0.5mg/dL
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Diagnosis of ammoniated feed toxicosis
Check blood ammonia levels (>0.5 mg/dL)
Increased glucose, BUN
Decreased blood pH
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Treatment of ammoniated feed toxicosis
No specific treatment
Remove feed
Sedation may help prevent self-mutilation
Milking out affected cows
Give 5 gallons cold water and 1 gal vinegar
109
What is Strychnine?
Compound from seeds of Indian tree
Used as poison for pocket gophers
Often used as malicious poison
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Mechanism of action of strychnine toxicosis
Strychnine is a competitive agonist at post-synaptic spinal cord and medulla glycine receptors
Glycine is an inhibitory transmitter
Causes overstimulation of muscles
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Clinical signs of strychnine toxicosis
Anxiety, restlessness, stiff neck and gait, "grinning" as facial muscles stiffen, ears twitch
Proceeds to violent titanic seizures and respiratory distress
"Sawhorse stance": rigid extension of all 4 limbs
Death from respiratory failure, exhaustion
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Diagnosis of strychnine toxicosis
Hyperthermia
Elevated CPK and LDH in serum
Lactic acidosis, hyperkalemia, leukocytosis
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Treatment of strychnine toxicosis
Aggressive decontamination (e.g. Gastric lavage)
Control seizures with phenobarbital/methocarbamol to prevent asphyxiation
Ion trapping with ammonium chloride
114
What is salt toxicosis?
Too much salt in blood caused by dehydration or consumption of large amounts of salt
Most common in pigs
115
Mechanism of action in salt toxicosis
Na moves passively into CNS which causes:
1. Inhibition of glycolysis and ATP
2. Attraction of water to maintain osmotic balance-> increased volume and pressure
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Clinical signs of salt toxicosis
```
Salivation
Increased thirst
Abdominal pain
Circling, wandering
Head pressing
Blindness
Seizures
Partial paralysis
```
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Threshold of blood salt levels in salt toxicosis
2.2 g/kg
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Diagnosis of salt toxicosis
Na levels >160 meq/L
| Brain Na >2000ppm
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Treatment of salt toxicosis
SLOW rehydration over 2-3 days
Lower serum sodium levels at 0.5-1 mEq/L/hr by IV
Give loop diuretic (furosemide) to prevent pulmonary edema
120
What pharmaceutical would be most useful for treating salt toxicosis in a pig?
Furosemide
121
True or False:
| Ivermectin is a GABA receptor blocker, causing clinical signs such as depression and respiratory distress in animals
False
It's a GABA receptor agonist
122
True or False:
| Hyperthermia following Strychnine toxicosis often happens in dogs
True
