Tox-1 Flashcards
Xenobiotic
Foreign substance
Antidote
Any substance that prevents/relieves the effects of a toxicant (no antidote works on all toxicants)
NOAEL
No Observed Adverse Effect Level; the highest experimental point that is without adverse effect
LOAEL
Lowest Observed Adverse Effect Level; the lowest concentration or amount of a substance that causes an adverse effect experimentally
Additive
The sum of the effects of the chemicals involved in the reaction
Antagonistic
When the net effect of the chemical reaction is zero (antidotes for poisons)
Synergism
When the sum of the effects is more than each chemical individually
Cats are deficient in this type of metabolism
Glucuronidation
Dogs are deficient in this type of metabolism
Acetylation
Pigs are deficient in this type of metabolism
Sulfation
Bioactivation
When metabolism increases the toxicity of a compound
These three conditions make patients candidates for intubation
Unconscious, paralyzed, and severe respiratory distress
Ventilation may be needed if there is…
Hypoventilation and hypercapnia, metabolic acidosis, or hypoxia
At what concentration of oxygen do you treat hypoxia?
40%
What are three cardiovascular signs of toxicity?
Tachycardia, arrhythmias, and hypertension
What two drugs were mentioned that can be used to treat toxicity-associated tachycardia and arrhythmias?
Lidocaine and propranolol
What two drugs were mentioned that can be used to treat toxicity-associated hypertension?
Nitroprusside and Hydralazine
What are two CNS signs of toxicity?
Hyperactivity (seizures) and depression
What three drugs were mentioned that can be used to treat toxicity-associated CNS hyperactivity (seizures)?
Diazepam (GABA modulator), Phenobarbital, and Methocarbamol
What drug was mentioned that can be used to treat toxicity-associated CNS depression (decreased respiratory rate)?
Doxapram
What are the four major themes of the complete history for a patient presenting with a potential toxicity?
Health history, current clinical, environment, diet
What are the two most common methods of GI decontamination?
Emesis and activated charcoal
What is the goal of inducing emesis after a suspected toxic exposure?
Prevent toxicant absorption
Within how much time is inducing emesis successful in preventing toxicant absorption?
60 minutes
What are the contraindications of inducing emesis?
Too long, chronic exposure, caustic material, recent gastric sx, some species, oils/gasoline
What is the rule of thumb for when to induce emesis?
Toxic dose of the substance was ingested, no vomiting has yet occurred, and activated charcoal is not an option
What is the goal of using activated charcoal after a suspected toxic exposure?
Prevent toxicant absorption
What are the contraindications of activated charcoal?
Corrosive agents (acids, alkaloids), oil/gas, cyanide, obstructed airway/altered state, ruptured intestinal wall, chronic exposures
What is the rule of thumb for when to use activated charcoal?
Substance is known/thought to be adsorbed by it, ingestion was very recent/undergoes enterohepatic circulation/is sustained released, can tolerate it, and there is no immediate need to administer oral meds
What substances are not adsorbed by activated charcoal?
Acids, alkalis, alcohols/glycols, metals, oils, petroleum distillates, detergents
What is the goal of administering cathartics after a suspected toxic ingestion?
Facilitate toxicant removal
What are examples of cathartics?
Mineral oil, saline cathartics (milk of magnesia)
For corrosives, strong acids or bases, use ___ instead of emesis
Dilution with milk, water, or eggs
Lipid infusion is a relatively new treatment and is specifically used in _____ toxicosis
Ivermectin
What are the common names of organophosphate pesticides?
Parathion, malathion, chlorpyrifos
What is the mechanism of activity of organophosphate pesticides?
Irreversible inhibition of acetylcholine esterase (AChE) activity (anticholinesterase)
What are the clinical signs of organophosphate pesticide toxicity?
Muscarinic (SLUDGE-M), nicotinic (muscle fasciculations beginning with the face, generalized tremors, weakness, paralysis), CNS (depression, ataxia, nervousness, seizures)
How do you diagnose organophosphate pesticide toxicity?
Atropine challenge
If you observe dry mouth, mydriasis, and increased heart rate after an atropine challenge during a suspected organophosphate pesticide toxicity, what do you conclude?
Toxicity is NOT due to AChE (not OP toxicity)
What drugs can you use to treat organophosphate pesticide toxicity?
Oximes (protopam, 2-PAM) - reactivates AChE unless it has been too long since the ingestion; diazepam or barbiturates for seizures, GI decontamination, Atropine sulfate for muscarinic signs
What syndrome is characterized by axonal degeneration of long motor neurons (hindlimb weakness, paralysis)?
OPIDN: Organophosphate-Induced Delayed Neurotoxicity
What breeds are the most susceptible to Ivermectin toxicosis?
Border collies, australian shepherds, and shelties
Why are certain breeds susceptible to Ivermectin toxicosis?
Blood Brain Barrier
What is the mechanism of action of Ivermectin?
GABA receptor agonist
Is the half-life of Ivermectin short or long?
Long (2-3 days); can see cumulative toxicity with repeat doses
What are the clinical signs associated with an Ivermectin toxicosis?
Increased inhibition! Ataxia, lethargy, mydriasis, coma, blindness, bradycardia; recumbency, disorientation, and seizures in collies; respiratory distress; anaphylactic reactions
How do you diagnosis Ivermectin toxicity>
History of administration
What organ systems can one use to diagnose Ivermectin toxicity?
Brain, GI content, liver, fat, and feces (no visible lesions, no diagnostic blood work)
What is the appropriate treatment plan for Ivermectin toxicosis?
GI decontamination for recent exposures (multiple doses of activated charcoal), supportive care (fluid and lyte therapy, epinephrine, short acting barbiturates)
What is the prognosis for non-susceptible breeds of dogs if exposed to <5 mg/kg of Ivermectin?
Good
What is the prognosis for any breed at dosages > 5 mg/kg of Ivermectin?
Guarded
What is the cardinal rule of pyrethroid pesticides?
DO NOT USE ON CATS
What is the mechanism of action of pyrethroid pesticides?
Binds voltage-gated sodium channel (causes hyperactivity)
What makes pyrethroid pesticides so toxic in cats?
Cats are not efficient at glucuronide conjugation
What are the clinical signs of pyrethroid pesticide toxicity?
In cats: drooling, paresthesia , muscle tremors and seizures, excessive muscle activity, and hyperthermia
How do you diagnose pyrethroid pesticide toxicity?
Difficult! Clinical values normal, nonspecific lesions, history of exposure, chemical analysis for pyrethrum/pyrethroid
What drug can be used to control the muscle tremors associated with pyrethroid pesticide toxicity?
Methocarbamol
What is the treatment plan for pyrethroid pesticide toxicity?
Stabilize tremors/seizures, bathe multiple times, IV fluids
What is the mechanism of action of bromethalin?
Damages mitochondrial function (uncouple oxidative phosphorylation in CNS -> loss of ion gradient -> fluid accumulation in myelin sheaths -> decreased nerve conduction and respiratory arrest)
What are the clinical signs of bromethalin toxicity?
Ataxia, hindlimb paralysis, hyper-excitability, severe muscle tremors, running fits, grand mal seizures
How do you diagnose bromethalin toxicity?
Cerebral edema and cerebellar degeneration; histological evidence of neuronal vacuolization and edema
How do you treat bromethalin toxicity?
Emesis (if recent exposure), repeated administration of activated charcoal, furosemide, treat seizures
What is the primary cause of pharmaceutical toxicosis?
Careless storage
What is the mechanism of action of Alprazolam (Xanax)?
GABAa receptor modulator that acts at the limbic, thalamic, and hypothalamic level of the CNS
What are the clinical signs of an Alprazolam toxicity?
Ataxia, depression, vomiting, tremors, tachycardia, diarrhea, and ptyalism (Depressive effect); some may initially show excitation at a high dose
What drug can be used as an antidote to Alprazolam toxicity?
Flumazenil (GABAa antagonist)
Can you use GI decontamination with Alprazolam toxicity?
Yes; emesis if recent, activated charcoal if toxic dose ingested
What is the mechanism of action of Zolpidem (Ambien)?
Inhibits neuronal excitation by binding to the benzodiazepine site of GABA receptors
What are the clinical signs of Zolpidem toxicity?
Ataxia, vomiting, lethargy, disorientation, hyper-salivation, hyperactivity, and panting
What is the recommended treatment for a pet showing mild signs of Zolpidem toxicity?
Keep quiet in a safe place; CS typically resolve in 12 hours
What mycotoxin is regularly screened for in peanut butter and is linked to liver cancer?
Aflatoxin
What mycotoxin is produced by “black patch” fungus on red clover?
Slaframine
What is the mechanism of action of slaframine?
Muscarinic cholinergic agonist (ACh mimic), especially in exocrine glands
What is the hallmark clinical sign in horses with slaframine toxicity?
the “slobbers”
What other toxicities do you have to differentiate between when there is a suspected slaframine toxicity?
OPs, botulism
How do you treat a slaframine toxicity?
Remove source, maintain hydration and lytes, Atropine if severe CSs
What mycotoxin is a metabolite of Fusarium spp?
Fumonisin
What mycotoxin is found almost exclusively on corn?
Fumonisin
What is the mechanism of action of fumonisin?
Inhibits sphingosine-N-acetyltransferase causing increased levels of sphinganine which is cytotoxic
What are two diseases linked to fumonisin toxicity?
Porcine pulmonary edema and equine leukoencephalomalacia (ELEM)
What are the clinical signs of porcine pulmonary edema caused by fumonisin toxicity?
Inactivity, increased respiratory rate, decreased heart rate -> respiratory distress
What are the two main target organs affected in equine leukoencephalomalacia (ELEM) caused by fumonisin toxicity?
Brain and liver
During necrosis of a horse that died of ELEM caused by fumonisin toxicity, what would you find?
CNS necrosis and liquefaction
What is the treatment of choice for fumonisin toxicity?
None available (isolate, change feed, ultrasorb S?)
What syndrome is associated with ammoniated feed toxicosis in cows?
“Bovine bonkers”
What is the hallmark sign of ammoniated feed toxicosis in cows caused by imidazoles?
Alternating between hyperexcitability and “normal” behavior
Ammonia is at what level in blood when death occurs in cows?
> 2 mg/dL
What are the specific clinical signs of ammoniated feed toxicosis?
Hyperexcitability: nervousness, rapid blinking, dilated pupils, trembling, ataxia, rapid respiration, SLUD, tonic convulsions induced by stimuli
What other differentials must you consider in a suspected ammoniated feed toxicosis?
OPs, cyanide, grain overload, meningitis, and encephalitis
What is the treatment for imidazole toxicosis?
No treatment, just feed removal (sedation PRN, milking out); prognosis good
What is the treatment for NPN overdose toxicosis?
No specific treatment; cold water + vinegar by stomach tube? Time; prognosis poor for recumbent animals
What is the mechanism of action of strychnine?
Competitive antagonist at postsynaptic spinal cord and medulla glycine receptors; glycine is an inhibitor transmitter, therefore evokes an overstimulation
What are the clinical signs of strychnine toxicity?
Anxiety, restlessness, stiff neck and gait, “grinning” as facial muscles stiffen, ears twitch, proceeds to violent seizures and respiratory distress, sawhorse stance; death from respiratory failure (asphyxiation during seizures), exhaustion
What PE and lab findings are typical in strychnine toxicosis?
Hyperthermia, elevated CPK and LDH, lactic acidosis, hyperkalemia, and leukocytosis
How do you treat strychnine toxicity?
Aggressive decontamination, control seizures (phenobarb or methocarbamol), ion trapping with ammonium chloride if not acidotic
What is the most common cause of salt toxicity?
Water deprivation
What is the mechanism of salt toxicity?
Diffusion of sodium into CSF when plasma Na levels are high leading to inhibition of glycolysis and ATP and attraction of water
What are the clinical signs of salt toxicity?
Salivation, increased thirst, abdominal pain; circling, wobbling, aimless wandering, head pressing, blindness, seizures, and partial paralysis
How do you diagnose salt toxicity?
Na levels > 160 mEq/L
