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291 Cards in this Set
- Front
- Back
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What is T1/2?
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half life- time required for plasma concentration of a checmical to decrease by 1/2 (time course of toxicants in organisms)
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Biological activities of xenobiotics are graded how?
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based on the toxicant/toxin reaching their sites of action (effectors) in a biological system at a sufficient concentration and duration
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The intensity of a biological effect of a toxin is ____?
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dose related
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What are the four parts of pharmacokinetics?
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absorption
distribution biotransformation excretion |
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What is pharmacodynamics?
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the interaction between effectors (receptor/non-receptor and toxicants
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What is the most common exposure route for small animals/pets?
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oral
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What is the problem with cats when it comes to species sensitivity to a toxin/toxicant?
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they have an inherent weakness in toxin/toxicant metabolism (bioactivation/detoxification)
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What is LD50?
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the dose that causes death in 50% of patients exposed
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T/F: LD50 has no bearing on the severity of the clinical signs of a toxicity
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true
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T/F: LD50 has no relationship to chronic toxicity
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true
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Give 2 examples of toxins/toxicants that cause acute toxicity
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cyanide and carbon monoxide
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Give an example of toxins/toxicants that cause subacute toxicity
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pesticides
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Give an example of toxins/toxicants that cause a chronic toxicity response
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heavy metals
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What is the most important thing to to/remember when treating a toxicity?
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stabilize the patient first!! (tx the patient not the toxin)
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what do you do if there's been ocular exposure to a poison?
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flush eyes with tepid water or saline solution for 20-30 minutes
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What do you do if there's been dermal exposure to a poison?
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repeated baths in warm water with mild liquid dishwashing detergent (Dawn is frequently recommended)
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What do you do if there's been an oral exposure to a poison?
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dilution
induce emesis gastric lavage endoscopic +/- surgical intervention adsorbent +/- cathartics +/- emulcents |
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What do you do if there's been ingestion of a corrosive?
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administer GI protectants and demulscents
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What do you NOT want to do if a corrosive has been ingested?
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do NOT neutralize it with vinegar or sodium bicarb
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What can happen if acids are ingested?
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oral & esophageal irritation
pain on swallowing mucous membrane burns epiglottal edema (dyspnea) esophageal necrosis and stricture |
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What are considered corrosives?
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acids or alkalines
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What are 2 things you DON'T do when an acid has been ingested?
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NO emetics or acid/base neutralization
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T/F: gastric lavage removes 40-60% of stomach contents and is better than emetics for dogs and cats
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false: emetics remove 40-60% of stomach contents and is better than gastric lavage for dogs and cats
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Name some alkalies
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sodium hypoclorite
sodium hydroxide "button batteries" |
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what happens when alkalies are ingested?
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mucous membrane burns
esophageal necrosis/stricture - can occur without any evidence of injury in the oral cavity |
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which is worse in general: ingestion of acids or alkalies?
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alkalies
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What happens with dermal exposure to acids or alkalies?
what do you do? which is worse: acids or alkalies? |
pain & edema
wash with water more penetrating injuries with bases, saponification of skin fat occurs |
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When are emetics used? in what spp specifically?
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early (2-3hrs) post ingestion of toxins (could be later with time-released formulated toxicants)
dogs and cats |
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When are emetics contraindicated?
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acids/alkalies
corrosive toxins petroleum distillates hazardous for animals who've already vomited, exhibiting coma, seizures, or lacking glottis control |
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What is the emetic of choice in dogs?
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apomorphine
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Apomorphine:
-MOA -how long does it take to work and how long does it last? -side effects |
-stimulates dopamine receptors in chemoreceptor trigger zone
-immediate (4-5 minutes); lasts 1-2 minutes -CNS depression and occasional convulsions |
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Examples of emetics
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apomorphine
xylazine- Rompun 3% hydrogen peroxide Syrup of Ipecac Table salt |
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Xylazine (Rompun)
-in what spp is it used as an emetic? -route in administration -how long until it takes effect? -side effects |
-cats (not dogs)
-IV, IM, or SQ -5 minutes -CNS and respiratory depression, bradycardia, possible hypotension |
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Why is 3% hydrogen peroxide th e most suitable emetic?
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it's inexpensive, effective, and available
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3% hydrogen peroxide:
-MOA -route of administration -how long until it takes effect? |
-causes vomiting thru gastric irritation
-PO -vomit w/i 10-15 minutes post-tx |
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Syrup of Ipecac
-how is it given? -how long until it takes effect? -problems? |
-PO followed by 1-3 cups of water
-could have a long latent period (20 minutes or so) -effective only 80% of the time, inactivated when given w/activated charcoal, possibly cardiotoxic |
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When do you use table salt for emesis? why?
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NEVER
ineffective, causes hypernatremia and CNS effects |
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Why not use liquid dishwasher or powdered mustard?
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they're ineffective
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Gastric lavage:
-when do you use it? -what agent is used? -how many times do you repeat it? |
-with unconscious or anesthetized animals
-use activated charcoal -repeat 10-15 times until solution is clear |
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What type of agent is activated charcoal? name some others
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adsorbant
-bentonite (clay) -ion exchange resins -cathartics -mineral oil |
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Activated charcoal
-How is it administered? -what else is used with it? when? why? -when might a dose be repeated? |
-via stomach tube
-follow up 30-40 minutes later w/saline cathartic (Na sulfate) or mineral oil to prevent tx-induced constipation -repeat charcoal in cases where toxicants undergo enterohepatic recirculation |
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what two things are bentonite (clay) used for?
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paraquat poisoning
mycotoxins (aflotoxicosis) |
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How do ion exchange resins work?
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they trap toxins by binding toxin to carrier and/or inhibiting systems promoting toxin absorption (cholestyramine or cholestid binding to lipoproteins and/or bile acids) thus limiting GI absorption
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What happens once ion exchange resins bind a carrier to the toxin?
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the carrier-toxin is excreted in the feces (interrupts enterohepatic recirculation)
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When would you use ion exchange resins?
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w/poisonings induced by some pesticides, anticoagulant, E.coli, heat stable enterotoxin, digitalis, etc
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Name two common cathartics:
-how are they given? -which is less effective? -side effects |
sodium sulfate (Glaubers salt)
magnesium sulfate (Epsom salt) -PO -Magnesium sulfate -possible CNS depression and freeing up toxin from activate charcoal |
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Mineral oil (adsorbant)
-contraindicated with ? -careful with what? |
-fat-soluble toxins (organo0chlorine toxicity) and in cases with GI irritation
-careful not to deposit in the lungs (aspiration pneumonia) |
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T/F: Ionized compounds do not readily cross cell membranes
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true
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How does ion trapping work?
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creates a pH difference from blood pH that favors trapping and reabsorption
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Ion trapping
-weak acids are excreted faster in...? -weak bases are excreted faster in...? -how are strong acids and bases excreted? |
-alkaline pH (anion form favored)
-acidic pH (cation form favored) -strong bases and acids tend to be already charged and are excreted by the kidney w/o further modifying the urine pH |
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Ion trapping
-What agent is used to created acid urine? -contraindicated with...? -what can develop and what side effects does it cause? |
-ammonium chloride
-hepatic or renal insufficiency, ammonia toxicity, severe rhabdomyolysis or myoglobinuria (nephrotoxicity effect is enhanced in acid urine) -ammonia toxicity --> CNS depression and coma |
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Ion trapping
-what agent is used to create alkaline urine? -what is this used to treat? -how should it be given? |
-sodium bicarbonate
-ethylene glycol, salicylate, phenobarbital, 2,4-dichlorophenoxyacetic acid (2,4-D herbicide) -slow administration |
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agents that promote diuresis are contraindicated in which animals?
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anuric
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With what conditions do you force diuresis?
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pulmonary edema
cerebral edema metabolic acidosis/alkalosis electrolyte imbalances (hypoNa, hypoK) cardiac arrhythmias |
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Name two commonly used diuretics
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mannitol (IV)
furosemide (IV/IM) |
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When should mannitol NOT be given?
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anuric, cardiac decompensation, pulmonary congestion/edema, dehydrated, or intracranial hemorrhage patients
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Since forced diuresis is contraindicated in anuric animals, what can you do?
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peritoneal dialysis or hemodialysis
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How does ethanol treat ethylene glycol (EG) toxicity?
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it will inhibit EG from getting to alcohol dehydrogenase (AD) and therefore stop the metabolism of EG to the toxic metabolite glycoaldehyde bc AD has a much greater affinity for ethanol
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What is a cathartic?
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an agent that stimulate bowel evacuation
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What is the first thing that's necessary to diagnose a poisoning (excluding c/s)?
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minimum database
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What are antidotes?
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agents w/specific action against the activity or effect of toxicants in the living organism, administered post exposure to a toxicant and, most often, when clinical responses are observed
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COMMON TOXICANTS
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AND ANTIDOTES (and how they work)
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Copper toxicity
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D-Penicillamine (complex formation)
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Iron toxicity
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Desferrioxamine (complex formation)
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Cyanide toxicity
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Na nitrite/Na thiosulfate (functional restoration)
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Opioid toxicity
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Narcan/Naloxone (receptor site competition)
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Xylazine, Amitraz toxicoses
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Yohimbine (alpha2 receptor blocker)
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OP (organophosphate) and Carbamate insecticides
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Atropine (receptor blocking)
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OP (organophosphate) insecticide toxicosis
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Pralidoxime/2-PAM (functional restoration)
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Anti-coagulant rodenticide
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Vitamin K (functional restoration)
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Ethylene glycol/methanol ingestion
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Ethanol and 4-MP (prevent toxic metabolite synthesis)
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Acetominophen toxicosis
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N-Acetylcysteine (supply glutatione inter.)
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methemoglobinemia
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Ascorbic acid (functional restoration)
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Lead toxicosis
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2,3-dimercapto-1-propanol/BAL (complex formation)
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Arsenic toxicosis
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2,3-dimercapto-1-propanol/BAL or Succimer (complex formation)
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Zinc toxicosis
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Succimer ?? (complex formation)
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Lead toxicity
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Calcium EDTA (complex formation)
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What is the point of supportive therapy?
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to maintain normal body temperature (tx hyper/hypothermia)
to control CNS activity (tx depression, hyperactivity) CV and respiratory support |
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List some screening tools used to differentiate/detect chemical compounds
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gas chromatography/mass spectrometry (GC/MS)
inductively coupled argon plasma emission spectroscopy (ICPAES) inductively coupled plasma mass spectrometry (ICP/MS) |
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What is urine used to detect?
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drugs and pesticides
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What is a kidney sample used to detect?
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heavy metals
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What is a liver sample used to detect?
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(best single tissue)
mineral or organic chemical |
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What is a fat sample used to detect?
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fat-soluble chemicals
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What is whole blood or serum used to detect?
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lead (RBCs)
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What are the 3 challenges in interpreting results?
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detection limits
time expired between exposure and sampling the agent you're looking for (parent compound or metabolites) |
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What are pesticides designed for?
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designed to be toxic to some form of life
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list the incidence of pesticide toxicosis (from most to least) between horses, dogs, cats, and livestock
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dog > cat > livestock > horse
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What is one of the most common causes of animals poisoning?
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rodenticides (mainly anti-coagulants)
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Warfarin and 2nd generation rodenticides are considered what?
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anti-coagulants
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Main affect of Bromethalin
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neurotoxic
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cholecalciferol is what?
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an analog of vitamin D3
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FOR THE NEXT 4 SLIDES, LIST WHICH SIGNS YOU WILL SEE IN THE TOXICOSIS OF EACH AGENT OUT OF THE FOLLOWING:
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Seizures
Hypercalcemia Hemorrhage Coagulopathy Paralysis Onset (delayed or acute) |
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Anticoagulants
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Seizures (rare)
Hemorrhage Coagulopathy Paralysis (rare) Delayed onset |
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Cholecalciferol
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Seizures (rare)
Hypercalcemia Hemorrhage Delayed onset |
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Bromethalin
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Seizures
Paralysis Delayed onset |
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Strychnine
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Seizures
Acute onset |
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FOR THE NEXT 4 SLIDES, LIST WHICH SIGNS YOU WILL SEE IN THE TOXICOSIS OF EACH AGENT OUT OF THE FOLLOWING:
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SeizuresPulmonary Edema
Skin lesions Liver +/- kidney involvement Onset (delayed or acute) |
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1080 (Rodenticide)
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Seizures
Liver +/- kidney involvement Acute onset |
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Thallium (Rodenticide)
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Seizures (rare)
Skin lesions Liver +/- kidney involvement Chronic to acute onset |
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ANTU (Rodenticide specifically for brown rats)
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Pulmonary edema
Acute onset |
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Zinc phosphate
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Seizures
Pulmonary edema Liver +/- kidney involvement Acute onset |
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List 3 common rodenticides used today
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Warfarin
Bromethalin Cholecalciferol |
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List 5 uncommon rodenticides
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Strychnine
1080 Thallium ANTU Zine phosphide |
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How are anti-coagulant rodenticides classified?
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classified into 1st or 2nd generation by their ability to kill warfarin-resistant rodents
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Which anti-coagulant rodenticides are 1st generation?
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warfarin
Rodex, Rid-a-Rat, Eagles |
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**What is the plasma t1/2 (halflife) of first generation anti-coagulant rodenticides in dogs?
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14 hours
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Which generation of anti-coagulant rodenticides can kill warfarin resistant rodents?
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2nd
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list some 2nd generation anti-coagulant rodenticides
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brodifacum
D-con, Havoc, Enforcer bromedialone difethialone pindone diphacinone assassin, Tomcat |
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Which animals can handle the highest dose of warfarin without it being toxic: dog, cat, or pig?
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dog or cat
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Which animals can handle the highest dose of diphacinone (2nd generation) without it being toxic: dog, cat, or pig?
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pig (cat being second)
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Which animals can handle the highest dose of bradifacum without it being toxic: dog, cat, or pig?
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cat
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T/F: all anti-coagulant rodenticides share a common MOA
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true
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What is the MOA of anti-coagulant rodenticides?
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Vitamin K reductase inhibition
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Anti-coagulant rodenticides
1. GI absorption - high or low 2. plasma protein binding - high or low 3. where is it metabolized 4. where is it excreted? 5. can they cause relay activity? which ones? |
1. high
2. high (albumin) 3. liver 4. kidney 5. second generation |
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t1/2 of warfarin in a dog
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20-24hrs (and yes, I know this contradicts what was said before about 1st generations - his notes suck)
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What animals are more susceptible to the development of anti-coagulant rodenticide toxicosis?
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-hypo-prothombinemic juveniles
-patients with deficient clotting factor prod'n due to liver failure or GI malabsorption syndrome -concurrent administration of highly protein-bound drugs -other disease states |
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What does Vitamin K reductase do?
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it is required for the re-conversion of inactive vitamin K to its active quinone form
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What is the MOA of anti-coagulant rodenticide toxicity?
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interferes with the vit K epoxide reductase enzyme, which ultimately results in decr levels of vitamin K-dependent flotting factors (II, VII, IX, X) and Vitamin K1
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Severity and duration of the coagulopathy caused by anti-coagulant rodenticide toxicity primarily depends on what?
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the specific anti-coag ingested
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For how long does warfarin depress the amount of vit. K dependent clotting factors?
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7-10 days
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For how long does Chlorofacinone depress the amt of vit. K dependent clotting factors?
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3-4 weeks
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Anti-coagulant rodenticide toxicity slows which pathways?
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all 3: intrinsic, extrinsic, and common
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With anti-coagulant rodenticide toxicity, animals are asymptomatic until when?
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the depletion of active clotting factors (approx 1-2 days after ingestion)
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Possible c/s of anti-coagulant rodenticide toxicity
-if subacute |
depression, v/d, anorexia, ataxia, melena, weakness, dyspnea, hemorrhage (may cause sudden death if in pericardium, thorax, mediastinum, abdomen, or cranium)
-pale mm, anemia, dyspnea, weakness, hematemesis, epistaxis, bloody feces |
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Half life of:
1. clotting factor II 2. clotting factor VII 3. clotting factor IX 4. clotting factor X |
1. 41 hrs
2. 6.2 hrs 3. 13.9 hrs 4. 16.5 hrs |
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What needs to be monitored when you have a potential anti-coagulant rodenticide toxicity? When?
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PT bc factor VII has the shortest half life (6.2 hrs) and is monitored by PT
Needs to be monitored 1 and 3 days after exposure |
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What will you find on bloodwork with an anti-coagulant rodenticide toxicity?
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decr PCV
incr ACT inct PT incr OSPT/PTT normal or marginally decr PLT count normal fibrin degredation products elevated levels of carboxylated forms of the Vitamin K dependent coag factors |
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What is the specimen of choice when testing for anti-coagulant rodenticide toxicity?
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unclotted blood (can also test liver, stomach contents, and kidney)
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What is the most potent rodenticide available for commensal rodents?
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Brodifacum/Talon (comes in pellet or wax blocks)
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Problem with warfarin
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some rodents are resistant
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Name the first generation anti-coagulant rodenticides
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Warfarin
Pindone/Pival Chlorophacinone/Mouse Out Diaphacinone/RoKill |
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T/F: Chlorophacinone and Diphacinone are more toxic than the anti-coagulant rodenticides
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true
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What is the treatment for anti-coagulant rodenticide toxicity? Preferred route? How long until it takes effect?
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Vitamin K (phytonadione)
-PO (can also be given IV, IM, SC) -6-12 hours transfusion of whole blood (if not anemic) PT 2-3 days after vitamin K tx stopped |
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What are 3 trade names for Bromethalin rodenticides?
**What is the chemical name? |
Vengeance, Assult, or Trounce
N-methyl-2,4-dinitro-N(2,4,6-tribromophenyl)-6-(fluromethyl)-benzenamine |
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What does Bromethalin rodenticide toxicity cause?
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CNS depression and paralysis --> death in 2-4 days
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What does Bromethalin rodenticide look like?
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tan, pelleted, comes in paper ("place pack" envelope)
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Bromethalin rodenticide toxcity
1. where is it absorbed 2. where is it metabolized to the active form 3. what is the toxic form 4. how is it excreted 5. circulation? **6. halflife |
1. GI (rapid)
2. liver 3. desmethyl-bromethalin form **4. biliary (slow!) 5. enterohepatic recirculation 6. 5.6 days |
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When might relay or secondary toxicity occur with Bromethalin rodenticide toxicity?
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at peak plasma concentration (4 hours)
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MOA of Bromethalin rodenticide toxicity
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absorbed in GI --> metabolized in liver to desmethyl-bromethalin --> mitochondria --> incouples oxidative phosphorylation --> decr ATP --> altered homeostasis bc Na/K pump doesn't have enough ATP to work --> myelin injury --> cerebral edema
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What are the main c/s you will see with bromethalin rodenticide toxicity?
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"acute signs of cerebral edema or posterior paralysis or paresis"
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Onset of bromethalin rodenticide toxicity
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delayed (10-72 hours)
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What c/s will you see with a high oral dose (above LD50) with bromethalin rodenticide toxicity? What is this called?
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local/generalized seizures
hyperreflexia of limbs tremors hyperthermia Acute Syndrome |
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What c/s will you see with a lower dose of bromethalin rodenticide toxicity? What is this called?
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CNS depression --> coma
localized/general seizures miosis/mydriasis hindlimb ataxia paralysis extensor rigidity tremors opisthotonos anisocoria Toxic Syndrome |
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How long until you see c/s w/bromethalin rodenticide toxicity?
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seen w/i 24 hrs
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How do you dx bromethalin rodenticide toxicity?
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history of exposure
c/s **white matter edema detection of bromethalin or its metabolites in fat, brain, or liver |
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Tx for bromethalin rodenticide toxicity
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-decontamination therapy (emetics, activate charcoal, saline or osmostic cathartics)
-control of cerebral edema (mannitol, dexamethasone, furosemide) |
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**MOA of cholecalciferol rodenticide toxicity
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cholecalciferol metabolized in the liver --> 25-OH-D3 (25-hydroxycholecalciferol) --> metabolized in kidney --> calcitriol (1,25-(OH)2-D3) --> enhances bone resorption, intestinal Ca transport (incr absorption), and kidney Ca resorption
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Who is more susceptible to cholecalciferol rodenticide toxicity?
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cat may be more susceptible than dogs
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Which animals are predisposed to cholecalciferol rodenticide toxicity?
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animals with preexisting kidney dz
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How long until c/s are seen in cholecalciferol rodenticide toxicity?
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12-36 hours after ingestion
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Most common c/s of cholecalciferol rodenticide toxicity
-other c/s |
diarrhea
PU/PD -anorexia -depression -abdominal pain -vomiting -dehydration -muscle weakness -constipation |
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All of the c/s with cholecalciferol rodenticide toxicity are related to what?
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development of hypercalcemia
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What will you find with bloodwork when you have cholecalciferol rodenticide toxicity?
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BW:
hypercalcemia hyperphosphatemia azotemia hyperproteinemia elevated serum levels of 25-hydroxy and 1,25dihydroxycholecalciferol metabolic acidosis |
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What will you find with a urinalysis when you have cholecalciferol rodenticide toxicity?
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proteinuria
glycosuria hypostenuria (USG 1.002-1.006) WBCs, RBCs, casts |
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Gross lesions and histopath with cholecalciferol rodenticide toxicity
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**hemorrhagic gastroenteritis (most prominent)
nephrosis myocardial degeneration diffuse mineralizations (incl lung, kidney, atria, stomach, myocardium, arterial intima) |
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How do you tx cholecalciferol rodenticide toxicity?
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decontaminate (emetic, charcoal, saline cathartic)
decr serum Ca address organ dysfunction (may need peritoneal dialysis for renal issues, cardiac arrhythmias, seizure control) |
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How would you gauge the effectiveness of therapy when treating cholecalciferol rodenticide toxicity?
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monitor serum Ca
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How could you decr serum Ca when treating cholecalciferol rodenticide toxicity?
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Incr Calciuresis - normal saline and furosemide diuresis
Incr urine Ca elimination - corticosteroid therapy Decr absorption low Ca diet Keep out of sunlight |
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What needs to be checked post-exposure to cholecalciferol rodenticide toxicity? How often?
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serum Ca and BUN at 1, 2, and 3 days post-exposure
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How could you inhibit the GI reabsorption when treating cholecalciferol rodenticide toxicity?
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Calcitonin (half life = 2-3hr, so give every 2-3 hrs)
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how could you inhibit bone reabsorption when treating cholecalciferol rodenticide toxicity? In which spp is it used?
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Pamidronate disodium (Aredia)
dogs |
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how long should therapy for cholecalciferol rodenticide toxicity be continued?
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until serum Ca levels return to and stay w/i normal limits for 72 hours after discontinuation of therapy
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What is the most common cause of small animal poisonings?
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insecticides
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Which insecticides cause acute syndrome?
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cholinesterase inhibitors
arsenic pyrethrins/pyrethroids organophosphates (OP)/carbamates organochlorine |
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What insecticide causes chronic toxicosis? What is the chronic problem?
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OP
delayed neuropathy (OPIDN) |
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Which insecticide leaves residues?
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organochlorines
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Which insecticides are acetylcholinesterase inhibitors?
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OP (parathion, chlorpyrifos "Dursban")
Carbamates (Carbaryl, physostigmine) |
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Poisonings with ACHE inhibitors are usually from what?
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deliberate dermal application or accidental ingestion
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T/F: OP insecticides are much more persistent than organochlorines
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false: OP insecticides are much LESS persistent than organochlorines
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What is the MOA of carbamates? Is it reversible or irreversible?
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enzyme carbamylation
reversible |
|
|
What is the MOA of OPs? Is it reversible or irreversible?
|
enzyme phosphorylation ("aging")
irreversible |
|
|
T/F: carbamates cause little concern in environmental contamination
|
true, though aldicarb is a problem in water
|
|
|
What does ACHE (acetylcholinesterare) do?
|
it is the mediator at pre and post ganglionic neurons in both the sympathetic and parasympathetic nervous systems
it effects smooth muscle or glands, motor nerves and skeletal muscle, and some neuron to neuron junctions in the CNS |
|
|
Which ACHE inhibitor is not approved for use in cats? What is the exception?
|
chlorpyrifos
except for flea collars |
|
|
ACHE is found where? pseudocholinesterase is found where?
|
ACHE in RBCs
pseudocholinesterase in plasma |
|
|
The "aging" that occurs with OP toxicosis occurs in what time period?
|
12-24 hrs
|
|
|
T/F: carbamate and OP groups both contain agents of only high toxicity
|
false: carmabate and PO groups both contain agents with high and low toxicity
|
|
|
T/F: ACHE inhibitors all have a low LD50
|
false: the LD50 of ACHE inhibitors varies greatly, from >100mg/kg to <5mg/kg
|
|
|
What is the minimal lethal dose of chlorpyrifos in a cat? when else would they show severe signs?
|
10-40mg/kg
show severe signs at lower dose if they are chronically exposed |
|
|
ACHE inhibitors
1. how are they absorbed 2. where are they metabolized 3. when do signs appear? 4. some OPs require ___ before inhibiting ACHE |
1. rapidly from skin and GI tract (bc lipophilic)
2. liver (do not bio-accumulate) 3. rapid (minutes to hours after exposure) 4. requrie metabolic activation |
|
|
What are the 3 major effects produced by ACHE inhibitor toxicosis?
|
1. muscarinic (salivation, lacrimation, bronchial secretion, v/d, bronchospasm, bronchial secretions)
2. nicotinic (tremors, respiratory paralysis) 3. CNS (seizures, miosis, hyperactivity) |
|
|
What is the classical syndrome of OP poisoning? When is this generally not seen?
|
SLUD (salivation, lacrimation, urination, defecation)
not seen in cats or bulls except following oral exposure |
|
|
How long after dermal exposure would c/s appear with ACHE toxicosis?
|
1-5 days
|
|
|
Inhibitions of >50% ACHE is indicative of what?
|
poisoning
|
|
|
Inhibition of >75% ACHE is considered what?
|
diagnostic when coupled with c/s
|
|
|
To diagnose ACHE inhibitor toxicosis, where can we evaluate ACHE activity?
|
brain, retina, blood/plasma/serum
|
|
|
What is different about diagnosing cats?
|
cats are prone to develop reduced whole blood ACHE activity following exposure, higher in pseudocholinesterase, therefore is it less prognostic than in other spp
|
|
|
In carbamate toxicity, what can a long incubation result in?
|
reversal of activity
|
|
|
What are the c/s of ACHE inhibitor toxicity in cats?
|
depression, ataxia, tremors, behavior change (agression), hyperactivity, hyperesthesia, miosis/mydriasis, tachypnea/dyspnea
|
|
|
In cats, what si the tachypnea/dyspnea caused by?
|
excessive bronchoconstriction and hypersecretion --> life-threatening to over-stressed cats
|
|
|
What can c/s that last for several weeks in bulls and cats after they are exposed topically to ACHE inhibitors cause and why?
|
hypokalemia bc of the prolonged cholinesterase inhibition
|
|
|
With ACHE inhibitor toxicity, where will an EMG (electromyograph) find the most severe changes?
|
in the rear limbs
|
|
|
What is a negative result for the Atropine test to diagnose ACHE inhibitor toxicity?
|
if the muscarinic signs that are observed in the animal diminish (normal atropine rxn) with the pre-anesthetic dose (means it is unlikely to be either OP or carbamate toxicity)
|
|
|
What is the best organ/tissue to analyze to dx ACHE inhibitor toxicity after oral exposure?
|
stomach or rumen (the other tissues have little residue)
|
|
|
What is a rare condition that can occur with OP toxicoses? how does it work? When do the c/s occur?
|
OP induced delayed neuropathy (OPIDN) --> causes central-peripheral distal axonopathy ("Dying back polyneuropathy")
|
|
|
What causes the c/s of OPIDN? what are they? when do they occur?
|
phosphorylation and aging ot NTE (neuropathy target esterase)
ataxia/waddling, hindlimb, hypermetria, depressed CP, weakness, ascending paralysis 2-3 weeks |
|
|
How do you tx ACHE inhibitor toxicity?
|
-GI decontamination (charcoal, gastric/rumen lavage)
-Bathe animal (mild detergent shampoo) -Antagonists -Antidotes |
|
|
What antagonist can you use to tx ACHE inhibitor toxicity?
What will this do? What does it NOT do? |
Atropine (1/4 dose IV, 3/4 SQ or IM)
reverses muscarinic signs (miosis, bradycardia, dyspnea) won't control muscle tremors (nicotinic signs) |
|
|
Suppression of which of these two is more indicative of exposure/toxicosis to ACHE inhibitors: cholinesterase or pseudocholinesterase? why? What's the exception?
|
cholinesterase bc whole blood cholinesterase is less sensitive than plasma pseudocholinesterase, making it a more accurate indicator
exception: felines bc whole blood cholinesterase is VERY sensitive in cats |
|
|
What is the antidote that can be used to tx ACHE inhibitor toxicity? How does it work? When is it not effective?
|
Pralidoximine chloride (2-PAM)
regenerates ACHE by allowing its release from OPs (relieve tremors and nicotinic signs) |
|
|
When is 2-PAM not effective?
When should it be discontinued? |
not effective if: 1. aging has already occurred and 2. with carbamate insecticides
discontinue if no benefits observed after 36 hrs |
|
|
What can cause a false negative when measuring blood cholinesterase?
|
blood cholinesterase activity may not represent CNS cholinesterase activity in a symptomatic animal
|
|
|
What will you see in bloodwork on a cat with chlorpyrifos toxicity?
|
hypokalemia and incr serum creatine kinase
|
|
|
List d/dx for agents that cause CNS depression
|
OP
carbamates pyrethrins pyrethroids cirtic oil derivates |
|
|
List d/dx for agents that cause muscle tremors and CNS stimulation
|
OP
carbamates pyrethrins pyrethroids rotenone organochlorine |
|
|
What is the prognosis for ACHE inhibitor toxicity?
|
depends on the agent
OP: long-term recovery is dependent on re-synthesis of ACHE Chlopyrifos: assoc w/longterm effects aggressive therapy needed in many cases |
|
|
What are the safest insecticides available?
|
pyrethrins/pyrethroids
|
|
|
Classification of pyrethrins/pyrethroids are based on what 3 things?
|
neurophysiology effect
toxicologic effect chemical structure |
|
|
Pyrethrins are derived from what?
|
naturally derived from chrysanthemums (pyrethrin flowers)
|
|
|
What are pyrethroids?
|
synthetic insecticides
|
|
|
Which are more persistent and chemically stable: pyrethrins or pyrethroids?
|
pyrethroids
|
|
|
T/F: pyrethrins/pyrethroids are generally low in toxicity
|
true
|
|
|
what can be combined with pyrethrins/pyrethroids to enhance insecticidal activities and potentially make them more toxic?
|
synergists
|
|
|
What are synergists?
|
microsomal enzyme inhibitors (piperonyl butoxide, N-octyl-bicycloheptane dicarboximide/MGK 264)
|
|
|
T/F: pyrethrins/pyrethroids are highly lipophilic and undergo rapid absorption and distribution following oral administration
|
false: pyrethrins/pyrethroids are highly lipophilic and undergo rapid absorption and distribution following TOPICAL administration
|
|
|
Pyrethrins/pyrethroids
1. where are they metabolized? 2. rapid hydrolysis happens where? 3. oral administration of which one leads to enterohepatic recirculation? |
1. liver
2. GI tract 3. pyrethrins and some pyrethroids |
|
|
T/F: different pyrethrins/pyrethroids have many different MOAs
|
true
|
|
|
What are the MOAs of pyrethrins/pyrethroids?
|
-interference with sidium channels
-enhanced sodium ion conductance -post-synaptic GABA receptor-chloride ionophore complex blockade |
|
|
What substance is found in some pyrethroids that makes it more toxic?
|
alpha cyano moiety
|
|
|
Pyrethrins/pyrethroids
1. where are they metabolized? 2. where does hydrolysis take place? 3. onset of signs: delayed or rapid? When can it be different? |
1. liver
2. stomach 3. rapid (within several hours after exposure) - can be somewhat delayed after dermal exposure |
|
|
What are the two different types of syndromes and what c/s are associated with each?
|
Type I: tremors/T syndrome- tremors, prostration, altered startle reflexes
Type II: choreoathetosis/CS syndrome- incr salivation, vomiting, ataxia, dyspnea, hypo/hyperthermia |
|
|
All of the pyrethrins/pyrethroids with alpha cyano moiety produce which type?
|
Type II (choreoathetosis syndrome)
|
|
|
What is the problem with the c/s of pyrethrin/pyrethroid toxicity?
|
you canNOT distinguish it from OP or carbamate toxicity based on the c/s alone
|
|
|
T/F: development and severity of c/s is proportional to concentration of pyrethroid in nervous tissues
|
true
|
|
|
What test can be done to dx pyrethrin/pyrethroid toxicity? What does a negative result mean? a positive?
|
Atropine test (same as for OP and carbamates)
if it is a positive result (muscarinic signs diminish) then its post likely pyrethrin/pyrethroid tox - if it's a negative result, could be OP or carbamate tox |
|
|
How do you tx pyrethrin/pyrethroid toxicity?
|
GI decontamination (charcoal)
bathe animals Atropine (reduces some signs) seizure control - most severe sign (diazepam/valium preferres - phenothiazine contraindicated) |
|
|
T/F: most pyrethrin/pyrethroid toxicity cases will resolve without tx w/i 48-72 horus
|
true (aggressive therapy is rarely needed)
|
|
|
Which are most sensitive to pyrethrin/pyrethroid toxicosis?
1. cats vs dogs 2. young vs old |
1. cats
2. very young |
|
|
Why do you have to be careful about the disposal of unused portions of pyrethrins/pyrethroids?
|
reptiles and fish are very sensitive!
|
|
|
Hartz Blockade is what type of product? What agent(s) does it contain?
|
is it a topical insecticide
have Fenvalerate (pyrethroid) and DEET (insect repellent) |
|
|
What are pyrethroids metabolized by?
|
plasma esterases
|
|
|
T/F: many OPs have been banned in the US
|
false: many organoCHLORINES have been banned in the US
|
|
|
Organochlorine insecticide:
1. is oral toxicity low or high? 2. rapidly absorbed from where? 3. where is it stored and why? 4. metabolized where? |
1. variable (some LD50 can be as low as 2mg/kg)
2. GI (some are well absorbed from skin as well) 3. fat bc they are extremely lipophilic 4. liver |
|
|
What does organochlorine insecticide toxicity cause?
|
serious neurotoxicosis
|
|
|
What is the chemical name for Lindane?
|
hexachlorocyclohexane
|
|
|
What can cause Lindane poisoning?
|
accidental ingestion (rare)
misapplication of topical products |
|
|
In what spp can lindane not be used?
|
cats
|
|
|
What is lindane used for and in what spp?
|
flea control for small animals
treatment for head live in humans |
|
|
Some lindane agents are what?
|
hepatocarcinogenic
|
|
|
Lindane:
1. is onset of c/s acute or delayed? 2. what are the c/s? |
1. acute onset (1-6 hrs)
2. muscle tremors, mixed CNS signs (CNS excitation, seizures), incr salivation, vomiting, ataxia, hyperthermia |
|
|
What is the problem w/lindane toxicity?
|
it can't be distinguished from OP, carbamate, pyrethrin, or pyrethroid toxicity based c/s alone
|
|
|
MOA of lindane toxicity
|
interference w/sodium channels (induce CNS excitation)
|
|
|
What are some other effects of lindane?
|
ACHE activity is UNaffected
some are human carcinogens many are endocrine active (estrogenic, anti-androgenic, concern with eggshell thinning in birds (DDT)) |
|
|
How do you tx lindane toxicosis?
|
GI contamination (charcoal & gastric lavage)
Bathe animal (mild detergent shampoo) seizure control (barbituates) |
|
|
For tx of which toxicity is phenothiazine contraindicated and why?
|
pyrethrin/pyrethroid toxicity bc pyrethrins/pyrethroids are assumed to cause extrapyramidal stimulation
|
|
|
The newer insecticides are characterized by what?
|
low mammalian toxicity
|
|
|
1. What do the newer insecticides target?
2. What do they use as a neurotransmitter? 3. How come they are less toxic to mammals? |
1. insect peripheral nervous system and affect chitin formation (growth regulators)
2. use nicotine as a neurotransmitter 3. Nicotine analogs are modified to have low brain delivery in mammals |
|
|
List some of the newer insecticides (brand names and agents)
|
Nitenpyram (Capstar)
Imidacloprid (Advantage) Fipronil (Frontline) Selamectin (Revolution) Lufenuron (Program) |
|
|
Fipronil
1. product name **2. chemical name 3. spp its meant for 4. used to control what? 5. toxicity (both oral and dermal) |
1. Frontline
2. N-phenylpyrazole 3. cats and dogs 4. ticks and fleas 5. low dermal and oral toxicity |
|
|
What happens when Fipronil is applied?
|
it is NOT absorbed in the skin, but instead is stored int he sweat glands
|
|
|
Fipronil
1. metabolized where? 2. excreted where? **3. plasma halflife 4. What is the MOA |
1. liver
2. renal 3. ~140hrs 4. disrupts normal nerve function by blocking GABA-gated chloride channeld (moreso in insects than mammals) |
|
|
What are the clinical effects of Fipronil toxicosis and how is it treated?
|
usually mild and self-limiting (vomiting, salivation)
Treat the symptoms and support therapy |
|
|
T/F: Fipronil sensitizes the skin
|
false
|
|
|
T/F: tx of Fipronil toxicosis is the same whether it's animal-used products or technical grade products (agricultural applications)
|
false: tx for technical grade products needs to be more aggressive
|
|
|
How do you tx technical grade Fipronil toxicosis?
|
GI decontamination (gastric lavage, charcoal, cathartic/emetic)
symptomatic and supportive therapy (seizures can occur) |
|
|
Imidacloprid
1. product name **2. chemical name 3. spp its meant for 4. used to control what? |
1. Advantage Topical Soln
2. chloronicotinyl nitroguanide compound 3. dogs and cats 4. fleas and ticks |
|
|
Imidacloprid
1. toxicity 2. What happens after it's applied? 3. where is it absorbed? 4. where is it metabolized? 5. where is it excreted? |
1. low dermal and oral tox
2. not absorbed in skin, stored in the sweat glands 3. rapid GI absorption 4. liver (glycine conjugates formed) 5. renal (70%) and fecal (30%) |
|
|
MOA of imidacloprid toxicosis
|
competitive nicotinic receptor antagonist (disrupts normal nerve transmission)
|
|
|
What are the clinical effects of imidacloprid toxicosis and how is it treated?
|
generally mild and self-limiting (vomiting, salivation)
tx symptomatically and supportive |
|
|
How do you tx technical grade imidacloprid toxicosis?
|
needs to be more aggressive
GI decontamination (gastric lavage, charcoal, cathartic) symptomatic and supportive therapy (tx tremors, dyspnea, taxia) |
|
|
What is the different between animal grade and technical grade imidacloprid toxicosis?
|
products used on animals contains approx 0.29 to 9.1% imidacloprid while products used for agricultural applications contain up to 94% imidacloprid
|
|
|
Selamectin
1. brand name 2. what is it? 3, what is it used to control? |
1. Revolution
2. semi-synthetic avermectin 3. broad-spectrum control- fleas, ear mites, hookworms, roundworms, ticks |
|
|
Selamectin
**1. how is it absorbed and where? **2. half life **3. MOA |
1. rapid and near complete GI absorption; **ABSORBED by intact skin (unlike Fipronil and Imidacloprid)
2. 8-11 days 3. competitive GABA receptor antagonist |
|
|
What are the clinical effects of selamectin and how are they treated?
|
generally mild and self limiting (vomiting, salivation, CNS depression, anorexia, muscle tremors, **skin irritation, **transient alopecia)
tx symptomatically and supportive |
|
|
Lufenuron
1. brand name **2. what is it? 3. what spp is it used in? 4. what does it control? |
1. Program
2. benzoylphenol urea insect development inhibitor 3. dogs and cats 4. fleas |
|
|
Lufenuron
**1. halflife **2. MOA 3. Clinical effects and how they're treated |
1. ~60 days
2. chitin synthetase inhibitor (insect growth inhibitor) 3. generally mild and self limiting, so treat symptoms and supportive care |
|
|
Nitenpyram
1. brand name **2. what is it? 3. what spp is it used for? 4. what does it control? |
1. Capstar
2. neonictinoid compound (systemically active insecticide) 3. dogs and cats 4. fleas |
|
|
Nitenpyram
1. how and where is it absorbed **2. halflife 3. where is it excreted 4. MOA |
1. rapidly in the GI (high bioavailability)
2. dog: 2.8hrs; cat: 7.7hrs 3. renal (~90%) 4. competitive nicotinic receptor antagonist |
|
|
What are the clinical effects of nitenpyram and how are they treated?
|
generally mild and self-limiting (vomiting, salivation, tachypnea, tremors)
tx symptomatically and with supportive care |
|
|
Many insecticides use what as a vehicle?
|
petroleum distillates
|
|
|
Where are the c/s found in petroleum distillate toxicity?
|
pulmonary
CNS GI hepatotoxicity renal toxicity heart |
|
|
What are the pulmonary c/s for petroleum distillate toxicity?
|
aspiration pneumonia (can be seen radiographically)
dyspnea w/i minutes of aspiration alveolar collapse and cyanosis those that remain asymptomatic for 12 hrs are unlikely to develop pneumonitis |
|
|
What are the GI c/s of petroleum distillate toxicity?
|
v/d
possible hydrocarbon odor |
|
|
What are the cardiac c/s of petroleum distillate toxicity?
|
arrhythmias
|
|
|
How do you tx alveolar collapse and cyanosis in petroleum distillate toxicosis?
|
oxygen or positive end-expiratory pressure therapy
|
|
|
How do you treat dermal exposure to petroleum distillates?
What is contraindicated? |
mild detergents
clip fur vegetable oils to soften tar material prior to removal solvents or other hydrocarbons are contraindicated (prophylactic Abs and steroids not generally needed) |
|
|
What is hte primary concern with petroleum distillate toxicosis?
|
aspiration pneumonia
|
|
|
How do you tx petroleum distillate toxicosis?
|
rely on gastric lavage
(emetics are generally contraindicated) |
|
|
Paraquat
1. aka 2. what is it 3. where is it absorbed 4. what spp is most frequently affected? |
1. Gramoxone
2. a non-selective contact herbicide (pulmonary toxicant) 3. GI (5-10%) 4. dogs |
|
|
c/s of paraquat poisoning
|
anorexia
depression diarrhea respiratory distress death in weeks following exposure |
|
|
Explain the MOA of paraquat poisoning
|
absorption --> transported to alveolar cells --> metabolic activation in presence of oxygen --> free radical intermediates and hydrogen peroxide formation --> lipid peroxidation --> damaged alveolar cells --> impaired lung fn --> cell (fibrotic) proliferation --> death from hypoxia
|
|
|
How do you diagnose paraquat poisoning?
|
-GI and pulmonary signs suggestive of exposure to hydrocarbon solvents
**-absence of neurological effects (R/O for hydrocarbon solvents) respiratory signs (slow and progressive) |
|
|
What specimen(s) do you test for paraquat poisonings?
|
blood plasma is preferred
blood serum can be used but there are limitations urine is useful to confirm the poisoning involves paraquat |
|
|
In every urine test for paraquat, what means positive?
|
it turns blue
|
|
|
if a pre-screen test (which detects high concentrations of paraquat in plasma and urine) comes out negative, what is next?
|
the more sensitive blue band test is used (detects paraquat down to 0.1microgram/mL
|
|
|
What is the limit of detection of paraquat in plasma and urine?
|
approx 2-3microg/mL
|
|
|
T/F: paraquat concentrations in plasma and serum are not equivalent
|
true (serum concentrations are about 3xs lower than plasma concentrations)
|
|
|
Proudfoot and Syngenta survival curves are based on what concentration of paraquat?
|
plasma
|
|
|
If urine is collected w/i 24 hrs of exposure to paraquat, which test will be prognostic? How are the results of this test interpreted?
|
dithionite test
no color to light blue (means concentration <1mg/L ) = survival navy blue to dark blue (means concentration >1mg/L) = fatal outcome |
|
|
What is the treatment for paraquat poisoning? What is the one thing that is contraindicated
|
treat symptomatically and supportively bc there is NO KNOWN SPECIFIC ANTIDOTE
Oxygen is contraindicated!! early intervention is a must |
|
|
What is the prognosis for paraquat poisoning? What can potentially reduce mortality?
|
poor --> death
longterm corticosteroids in addition to cyclophosphamide |
