Quiz 1: Principles, Diagnosis, Treatment, Neurotoxicants Flashcards
Paracelsus
“Father of Toxicology”
Swiss physician that said “all substances are poisons”
Toxicology is concerned with
Identification, treatment, and assessing risks of poisons
Definition of Toxicant
Compound that causes toxicity
May be natural or man-made
Xenobiotic = foreign substance
Definition of Antidote
Substance that prevents/relieves effects of a toxicant
No antidote works on all toxins (not even activated charcoal)
NOAEL
“No observed adverse effect level” on dose-response curve
LOAEL
“Lowest observable adverse effect level” on a dose-response curve
Classifications of chemical interactions in toxicity
Additive
Antagonistic
Synergism
Factors influencing toxicity
Factors related to exposure
Factors related to the subject
Factors related to the environment
Types of exposure classifications
Acute
Sub-acute/subchronic
Chronic
Acute exposure
A single exposure or multiple exposures in 24 hours
Sub-acute/subchronic exposure
Exposure over 7 to 90 days
Chronic exposure
Protracted exposure (6 months - lifetime)
Most important veterinary toxicants are absorbed by what routes?
Oral and dermal
What usually detoxifies a compound and increases its elimination?
Metabolism
When metabolism increases the toxicity of a compound
Bioactivation
Mechanism of Toxicity (4 steps)
- Delivery from site of exposure to target
- Reaction of the ultimate toxicant with the target molecule
- Cellular dysfunction and resultant toxicities
- Repair or disrepair
How do toxicants cause toxicity?
Cellular damage
Organ system dysfunction
Most common toxicants that cause death
Insecticides
Rodenticides
Ethylene Glycol
When treating a patient for a toxicosis, what do you do first?
Evaluate for immediate life-threatening problems
How to prevent aspiration of vomitus in an unconscious patient?
Keep head lower than body
A patients may need assisted ventilation if:
Hypoventilation, hypercapnia
Metabolic acidosis (venous pH 7.35)
Hypoxia, treat with 40% oxygen
How to treat CNS hyperactivity (seizures)
Diazepam
Phenobarbital
Methocarbamol
How to treat CNS depression
Analeptics
Doxapram
How to treat tachycardia and arrhythmias
Lidocaine
Propranolol
How to treat hypertension
Nitroprusside
Hydralazine
How to increase cardiac contractility
Dobutamine
Priority in animals with severe clinical signs
- Assess hypo/hyperthermia
2. Pull blood for laboratory profile and diagnostic testing (3cc EDTA tube and 2 serum tubes)
4 major themes of a History
- Health history
- Current clinical history
- Environment
- Diet
Two most common methods of decontamination
Emesis
Activated charcoal
Contraindications of emesis in decontamination
- > 30 minutes since exposure
- Chronic exposure
- Ingestion of caustic materials
- Recent GI surgery
Induce emesis if:
- Toxic dose of substance was ingested
- No vomiting has yet occurred
- Activated charcoal is not an option
Contraindications of using activated charcoal
- If it will not bind the toxin (inorganic compounds, oils, gasoline, ethylene glycol, cyanide, etc.)
- If airways are obstructed
- If patient has altered state of consciousness
- Chronic exposure
- If you suspect GI perforation
Activated charcoal is most useful for what type of toxins?
Toxic plants
Pesticides
Herbicides
Give charcoal if:
- Substance is known to be absorbed by it
- Ingestion was very recent/undergoes enterohepatic circulation/is sustained release
- The patient can tolerate it
- There is no immediate need to administer oral meds
Effect of cathartics
Decrease GI transit time
Increase movement of toxins/charcoal-toxin complex
Decrease absorption of the toxin
Example of a cathartic
Mineral Oil
What to do for corrosive toxins that have been ingested?
Use dilution instead of emesis
Milk water or eggs
How to treat dermal toxicant exposure?
Bathe in liquid dish soap
Lipid infusion
Relatively new treatment for toxicant ingestion
Off label-use of IV fluids
Emetic agent for dog, pigs
Apomorphine
Emetic agent for cats
Xylazine
Good agent for at-home emesis induction
Salt water
Hydrogen peroxide
Treatment for sustained-release toxicants
Gastric lavage or whole bowel irrigation
Common antidotes to know
Vitamin K for rodenticide toxicities
Digoxin for plant toxicities
Analytic testing
Testing for toxicants
Not one test that will screen for all toxicants
Can be costly
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
How to prevent future toxicant exposures
Change pasture, feed, water, etc.
Remove baits, pesticides, etc.
Bathe or flush cutaneous or ocular exposures
Educate clients
Types of Neurotoxicants
Pesticides Pharmaceuticals Mycotoxins Ammoniated feed toxicosis Strychnine Salt
Largest class of chemicals inducing toxicosis
Neurotoxicants
Pesticide usage
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)
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
Mechanism of action of Organophosphates
Irreversible inhibition of Acetylcholinesterase activity (anti-cholinesterase)
Leads to cholinergic overstimulation within minutes to hours
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
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
Treatment of anti-cholinesterase toxicity
GI decontamination Bathe if dermal exposure Atropine sulfate for muscarinic signs Oxides (protopam, 2-PAM) to reactivate AChE Diazepam or barbiturates for seizures Time
Histopathology of patient following OP toxicity
Vacuolization of brain
Degeneration of neurons
Organophosphate-induced Delayed Neurotoxicity
Axonal degeneration of long motor neurons
Hindlimb weakness, paralysis
No treatment
Poor prognosis
What is Ivermectin?
Antihelminthic
What breeds are susceptible to Ivermectin toxicosis?
Border Collies
Australian Shepherds
Shelties
Mechanism of action of ivermectin toxicosis
GABA receptor agonist
Increased inhibitory input = DEPRESSIVE effect
Can see cumulative toxicity with repeat doses
Clinical signs of ivermectin toxicosis
Ataxia, lethargy, mydriasis, coma, blindness, bradycardia, recumbency, disorientation, seizures, respiratory distress, anaphylactic reactions
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
Treatment for ivermectin toxicosis
Recent exposure: multiple doses of activated charcoal Supportive care Electrolyte therapy Epinephrine Barbiturates for seizures
How to prevent ivermectin toxicosis
Test dogs prior to administering higher doses
What are pyrethroid pesticides?
Pesticides made from pyrethrins of chrysanthemum flowers
Considered “safer” than organophosphates
Used in dog flea/tick topical prevention
Mechanism of action of pyrethroid pesticides
Lipophilic, absorbed by all routes
Binds voltage-gated sodium channels
Causes repetitive nerve discharges -> hyperactivity and overstimulation
Why are cats more susceptible to pyrethroid toxicity than dogs?
Inefficient glucuronide conjugation
Clinical signs of pyrethroid toxicosis in cats
Drooling, paresthesia, muscle tremors, seizures, excessive muscle activity, hyperthermia
Clinical signs of pyrethroid toxicosis in dogs
Paresthesia, shaking of legs, muscle fasciculation, rubbing of application site, agitation, nervousness
Diagnosis of pyrethroid toxicosis
Difficult
Look at clinical signs, history of exposure
Chemical analysis for pyrethrin/pyrethroid
Treatment of pyrethrin toxicity
Stabilize: treat seizures (methocarbamol)
WASH IT OFF
IV fluids, furosemide
Bromethalin
Single-dose rodenticide
Kills in 3-5 days -> delayed toxicosis
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
Clinical signs of bromethalin toxicosis
Ataxia, hindlimb paralysis, hyper-excitability, severe muscle tremors, running fits, grand mal seizures
Diagnosis of bromethalin toxicosis
- Cerebral edema and cerebellar degeneration
2. Histological evidence of neuronal vacuolization and edema
Treatment of bromethalin toxicosis
Emesis if recent exposure Give activated charcoal/sorbitol Maintain hydration and electrolytes Furosemide for edema Treat seizures
Primary cause of pharmaceutical toxicosis
Careless storage
Top prescribed pharmaceuticals that cause toxicoses in animals
Vicodin Synthyroid Zocor Lipitor Lisinopril
Mechanism of action for alprazolam toxicosis
Acts at limbic, thalamic, and hypothalamic levels of CNS
Depressive effects
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
Diagnosis of alprazolam toxicosis
Based on clinical signs and history of exposure
Treatment of alprazolam toxicosis
Emesis with apomorphine if recent ingestion Activated charcoal Flumazenil for severe CNS depression Close monitoring Fluids
Zolpidem
Ambien
Sleep aid
Non-benzodiazepine hypnotic drug
Mechanism of action of zolpidem toxicosis
Inhibits neuronal excitation by binding to the benzodiazepine site of GABA receptors
Clinical signs of zolpidem toxicosis
Ataxia, vomiting, lethargy, disorientation, hyper-salivation, hyperactivity and panting
Diagnosis of zolapidem toxicosis
Based on clinical signs and history of exposure
Treatment of zolpidem toxicosis
Supportive
Keep patient in a quiet place
Treat clinical signs if needed
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
What is Slaframine?
Produced by “black patch” fungus on red clover
Rain, high humidity, cool weather triggers growth
Occurs in central, SE, SW USA
Mechanism of action of Slaframine
ACh mimic, partially acts as a muscarinic cholinergic agonist, especially in exocrine glands
Slaframine toxicity is most common in what species?
Horses and cattle
Clinical signs of slaframine toxicosis
Copious salvation (the “slobbers”)
Bloat, diarrhea, frequent urination
Feed refusal
Diagnosis of slaframine toxicosis
Consumption of clovers with “black patch”
Treatment of slaframine toxicosis
Remove source
Maintain hydration and electrolytes
Atropine
Rarely fatal
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
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
Which species are susceptible to fumonisin toxicosis?
Horses, ponies, swine, rabbits
Two diseases cause by fumonisin toxicosis
Equine leukoencephalomalacia (ELEM) Porcine pulmonary edema (PPE)
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
Most specific biochemical changes for PPE
Increase in tissue and serum sphingoid bases
Increased liver enzymes
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
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
Ammoniated feed toxicosis is caused by
Over consumption of
Non-protein nitrogen sources (ammonium, salts) that are added to cattle feed
Mineral licks
“Bovine bonkers”
Hyperexcitability state caused by ammoniated feed toxicosis
Onset of clinical signs or death in ammoniated feed toxicosis
15 minutes - several hours
Death within 24 hours when blood ammonia >2mg/dL
Normal blood ammonia concentration
<0.5mg/dL
Diagnosis of ammoniated feed toxicosis
Check blood ammonia levels (>0.5 mg/dL)
Increased glucose, BUN
Decreased blood pH
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
What is Strychnine?
Compound from seeds of Indian tree
Used as poison for pocket gophers
Often used as malicious poison
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
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
Diagnosis of strychnine toxicosis
Hyperthermia
Elevated CPK and LDH in serum
Lactic acidosis, hyperkalemia, leukocytosis
Treatment of strychnine toxicosis
Aggressive decontamination (e.g. Gastric lavage)
Control seizures with phenobarbital/methocarbamol to prevent asphyxiation
Ion trapping with ammonium chloride
What is salt toxicosis?
Too much salt in blood caused by dehydration or consumption of large amounts of salt
Most common in pigs
Mechanism of action in salt toxicosis
Na moves passively into CNS which causes:
- Inhibition of glycolysis and ATP
- Attraction of water to maintain osmotic balance-> increased volume and pressure
Clinical signs of salt toxicosis
Salivation Increased thirst Abdominal pain Circling, wandering Head pressing Blindness Seizures Partial paralysis
Threshold of blood salt levels in salt toxicosis
2.2 g/kg
Diagnosis of salt toxicosis
Na levels >160 meq/L
Brain Na >2000ppm
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
What pharmaceutical would be most useful for treating salt toxicosis in a pig?
Furosemide
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
True or False:
Hyperthermia following Strychnine toxicosis often happens in dogs
True
