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365 Cards in this Set
- Front
- Back
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what is the conversion between ppm and mg/kg?
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1 ppm = 1 mg/kg?
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how do you convert from g to mEq?
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g of compound ÷ mg/mEq = g of compound ÷ (MW/Valence/1000)
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how do you convert % to ppm?
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4 decimal places to the right (with percentage as a decimal)
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how do you convert between g/ton and ppm?
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100 g/ton = 110 ppm
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how do you convert lb/acre to mg/kg exposure in animals?
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1 lb/acre = 7 mg/kg exposure
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how do you convert lb/acre to ppm residue on forage?
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1 lb/acre = 230 ppm on the forage
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1% = how many mg/mL?
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1% = 10 mg/mL
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what are the primary toxicants in chocolate?
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theobromine and caffeine
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what is the mechanism of action of methylxanthine derivatives (e.g. chocolate)
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- increased catecholamine release (i.e. epinephrine, norepinephrine)
- ↓phosphodiesterase → ↑cAMP - blockage of adenosine receptors, leading to bronchodilation and cardiac arrhythmias |
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what systems do methylxanthines affect?
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CNS, cardiac, urinary, GI
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what is the onset and duration of methylxanthine toxicosis?
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- onset: 2-4 hours
- duration: 12-36 hours |
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what are clinical signs of methylxanthine toxicosis? (2 main ones)
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1. bounce like a ball (↑spinal reflexes)
2. "Energizer Bunny on Speed Syndrome" - vomiting - depression - anxiety-hyperactivity - ±seizures - hyperthermia - diarrhea - muscle tremors - cardiac arrhythmias including PCVs |
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how is chocolate/methylxanthine toxicosis diagnosed?
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- history of access
- serum analyzed for theobromine |
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how is chocolate/methylxanthine toxicosis treated?
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- symptomatic: emesis (< 8 hr post ingestion); gastric lavage; activated charcoal (1 g/kg) with saline cathartic.
- for CNS effects: diazepam, methocarbamol (muscle relaxant similar to guaifenesin), or pentobarbital - fluids; metoclopramide for vomiting - if necessary, β-blockers for heart: ESMOLOL, metoprolol, or lidocaine (no lidocaine in cats) |
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what breeds of dogs are predisposed to idiosyncratic hepatic necrosis with administration of carprofen (Rimadyl™)?
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Labs and Goldens
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how do the COX-inhibitor effects manifest in NSAID toxicosis?
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- compromised circulation to stomach and kidneys
- ↓gastric acid and bicarb production; ↑gastrin and HCl secretion |
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describe the onset of NSAID toxicosis
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- **IT IS BIPHASIC:
- GI ≤ 6 hours - renal 12 hr - 5 days |
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what are clinical signs of NSAID toxicosis?
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- vomiting ± blood
- diarrhea - lesions: oral and GI ulcers; nephrosis and papillary necrosis - anorexia - melena - abdominal pain - polydipsia - polyuria, oliguria |
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what systems do NSAIDs affect?
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renal, GI, (liver)
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with severe NSAID toxicosis, what would you see on a PM of a kidney?
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papillary necrosis
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how is NSAID toxicosis diagnosed?
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- HX of access/administration
- ↑renal indices. Establish a baseline and monitor every 24 hours; ulcer anemia - leukocytosis with left shift may indicate GI ulcer with perforation - serum analysis possible - u/s for stomach ulcers, rt. dorsal colon ulcers (horse), and papillary necrosis |
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how is NSAID toxicosis treated?
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- symptomatic; blood transfusion if necessary
- bicarb for metabolic acidosis and ion trapping - sucralfate to coat ulcer post 24 hour ingestion - OMEPRAZOLE or ranitidine to ↓ gastric acid - MISOPROSTOL - MOST BENEFICIAL - Sx for perforated ulcers |
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what are the two most beneficial drugs in treating the GI manifestations of NSAID toxicosis?
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omeprazole and misoprostol
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why is the cat particularly susceptible to acetaminophen toxicosis?
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glucuronidation deficits
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what is a pathognomonic sign of acetaminophen toxicosis in cats?
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peripheral edema, jaw edema, and big paws
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what is the primary site for acetaminophen toxicosis?
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liver
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in which breeds and species of animals has ivermectin toxicity been reported?
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- collies and Aussies
- possible in all dogs - kittens, foals, tortoises |
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if a dog undergoes ivermectin toxicosis, what are three important clinical signs? Other clinical signs?
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1. mydriasis
2. blindness (temporary) 3. muscle tremors - hypersalivation - bradycardia - convulsions; coma (esp. in collies) - ataxia - anaphylactoid response with microfilarial death (- no visible lesions) |
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why are certain dog breeds predisposed to ivermectin toxicosis?
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they have a P-glycoprotein defect in the blood-brain barrier
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what is the mechanism of action of ivermectin toxicosis?
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- ↑GABA: ↑presynaptic GABA release; ↑postsynaptic GABA binding; direct GABA agonist
- GABA → inhibitory via postsynaptic chloride channels → hyperpolarization |
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how is ivermectin toxicosis diagnosed?
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- HX of recent administration/access
- brain ivermectin concentration - test for defective P-glycoprotein susceptibility at Washington State |
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how is ivermectin toxicosis treated?
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- symptomatic
- short-acting barbiturate for convulsions (note, benzos potentiate GABA effects; barbiturates don't bind at the same site) - physostigmine may temporarily wake up animal so it can eat and give owner hope - flumazenil (benzo reversal agent); $$$; untested - lipid infusion to trap (Intralipid™) |
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how does physostigmine temporarily alleviate some of the effects of ivermectin toxicosis?
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it is an acetylcholinesterase inhibitor, which will ↑ACh at the site and compete with GABA inhibition
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which neurotransmitters are most commonly affected by antidepressants?
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norepinephrine, serotonin, dopamine, epinephrine
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which antidepressant will cats eat because of its taste/smell?
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venlafaxine (Effexor™)
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how are tricyclic antidepressants cardiotoxic?
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they inhibit fast sodium channels
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which systems are affected by antidepressant toxicosis?
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CNS, GI, cardiac
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what is the onset and duration of antidepressant toxicosis?
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- onset: 30 min - 12 hours
- duration: 1-3 days |
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what is the name of the toxicosis caused by SSRIs? What are two major clinical signs? What are some other clinical signs?
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- serotonin syndrome
1. hyperreflexia 2. clonus - tachycardia - hypertension - convulsions - muscle tremors |
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what are two major clinical signs of antidepressant toxicosis? What are some others?
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1. hyperreflexia
2. clonus - vomiting - diarrhea - agitation, vocalization - tachycardia, arrhythmia, hypertension - depression, lethargy - convulsions - hyperthermia - possible blindness - bradycardia, hypotension |
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how is antidepressant toxicosis treated?
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- symptomatic: multiple doses of activated charcoal & enemas for long-lasting formulations
- diazepam or methocarbamol for seizures/muscle tremors - ACEPROMAZINE or chlorpromazine for agitation and serotonin antagonism - CYPROHEPTIDINE PO or PR for SSRIs - bicarb for tricyclics; IV fluids for BP, renal function and thermoregulation; cooling baths; propanolol for hypertension & tachycardia |
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what is the mechanism of action of pseudoephedrine toxicity?
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- α- and β-agonists (note phenylephrine is only α)
- endogenous catecholamine release → stimulation of brain, heart, and peripheral vasoconstriction |
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what is the typical syndrome associated with (pseudo)ephedrine/phenylephrine toxicity?
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"fight or flight" response of the epinephrine rush in conjunction with the β effect on HR and α effect on hypertension
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what systems are affected by (pseudo)ephedrine/phenylephrine?
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CNS, cardiac
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what is the onset time and duration of (pseudo)ephedrine/phenylephrine toxicosis?
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- onset: 30 min - 2 hr
- duration: 1-3 days |
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what are some clinical signs of (pseudo)ephedrine/phenylephrine toxicosis?
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- agitation, hyperactivity
- mydriasis - vomiting - head bobbing - arrhythmias - hallucinations (e.g. fly-biting) - tachycardia, hypertension - muscle tremors - hyperthermia with tachypnea |
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how is (pseudo)ephedrine/phenylephrine toxicosis diagnosed?
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- history of access and appropriate clinical signs
- NOTE: hyperreflexia and clonus NOT seen, versus SSRIs - can measure sympathomimetics in serum or urine - hyperglycemia and hyperinsulinemia, secondary hyperkalemia |
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if a phytochemical ends in "-ine", what is its chemistry and what is one general treatment option?
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if it comes from a plant and ends in "-ine", it is a base and acidifying the urine is a treatment option
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how is pseudoephedrine toxicosis treated?
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- symptomatic: Rx heart arrhythmias (e.g. β-blockers)
- ACEPROMAZINE/CHLORPROMAZINE to control CNS excitement; may need barbiturate or gas anesthesia for seizure control - benzos (e.g. diazepam) contraindicated due to possible disinhibition - cooling baths, α-blocker (prazosin) for BP - acidify the urine except if myoglobinuria present |
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1% equals how many ppm?
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10,000
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what do toxicologists call Margin of Safety?
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standard safety margin/certain safety factor
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what are two typical characteristics of dose-response curves for endogenous compounds versus normal drugs?
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1. inverted
2. biphasic |
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any substance causing a deleterious effect in or on a biological system
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toxicant
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a toxicant derived from a biological source
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toxin
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disease state caused by a toxicant
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toxicosis
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amount of toxicant required to produce detrimental results
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toxicity
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the likelihood of poisoning occurring under specific conditions is called what?
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hazard/risk
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injury to one kind of biological matter without injuring another kind, even if they are in close proximity is called what?
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selective toxicity
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what is the definition of "toxicant?"
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any substance causing a deleterious effect in or on a biological system
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what is the definition of "toxin?"
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a toxicant derived from a biological source
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what is the definition of "toxicosis?"
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disease state caused by a toxicant
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what is the definition of "toxicity?"
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amount of toxicant required to produce detrimental results
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what is the definition of "hazard" or "risk" in the context of toxicology?
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the likelihood of poisoning occurring under specific conditions
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what is the definition of "selective toxicity?"
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injury to one kind of biological matter without injuring another kind, even if they are in close proximity
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what are the five major ways to classify a toxicant?
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1. target organ
2. source 3. use 4. effect 5. chemical composition |
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what is the toxic potential for a toxicant that is
- extremely toxic? - highly toxic? - moderately toxic? - slightly toxic? - practically nontoxic? - relatively harmless? |
- extremely toxic: < 1mg/kg
- highly toxic: 1 - 50 mg/kg - moderately toxic: 50 - 500 mg/kg - slightly toxic: 0.5 - 5 g/kg - practically nontoxic: 5 - 15 g/kg - relatively harmless: > 15 g/kg |
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how my cm in one inch?
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1 inch = 2.54 cm
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how many pounds in one kilogram
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1 kilogram = 2.20 pounds
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how many mL in one fl oz?
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1 fl oz = 30 mL
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how do you calculate the mg/kg of toxicant in the body from the ppm in feed?
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mg/kg bw. = (ppm in feed x kg of feed eaten) ÷ kg body weight
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how do you calculate the ppm in feed required to produce a certain mg/kg body weight?
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ppm in feed = mg/kg body weight exposure ÷ %bw of feed eaten per day (note: % in decimal form)
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what are 8 general supportive procedures that should be considered when treating a toxicosis?
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1. prevent or treat convulsions
2. maintain respiration 3. treat for shock 4. correct/control cardiac dysfunctions 5. correct/control fluid and electrolyte loss 6. maintain body temperature 7. alleviate pain 8. protect skin and mucous membranes |
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how do you prevent further absorption of toxicant from the skin and hair?
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- wash liberally with water
- use a small amount of detergent (too much ↑absorption of lipophilic substances) - rinse well - may need to clip/shave animal |
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how do you prevent further absorption of toxicant from the eyes?
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flush liberally with water several times
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how do you prevent further absorption of toxicant from the GI tract?
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- emesis
- lavage - activated charcoal (1 g/kg) - evacuation of the gut: catharsis, endoscopy, Sx (gastrotomy, rumenotomy) |
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generally, how long after ingestion is vomition useful?
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1-2 hours
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what are four important contraindications for vomition?
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1. unconscious or very depressed animal
2. patient is convulsing 3. corrosive or caustic toxicants 4. petroleum distillates or other volatiles (CNS depression and lipid pneumonia) |
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what are three emetics for use by owners?
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1. 3% hydrogen peroxide - safest
2. 1 tsp. of LIQUID soap in a glass of water 3. ↓syrup of ipecac |
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what are the choice emetics and their corresponding reversal agents for dogs and cats?
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- dogs: apomorphine (DON'T USE IN CATS); reverse with naloxone
- cats: xylazine (reverse with yohimbine if needed) |
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what are the three major mechanisms involved in elimination of absorbed poisons?
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1. excretion
2. biotransformation 3. storage |
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what are two ways to increase renal excretion of a toxicant?
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1. diuresis
2. ion trapping |
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what are the top 5 classes of toxicants in dogs?
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Anticoagulant Rodenticides
Ethylene Glycol Tremorgens Garbage Theobromine (Chocolate) |
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what are the top 5 classes of toxicants in cats?
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Pyrethrins
Ca Oxalate Plants Lilies Acetaminophen (Tylenol) Ethylene Glycol |
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what are the top 5 classes of toxicants in horses?
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Fescue
ELEM (Leukoencephalomalacia) Ionophores Black Walnut Slaframine |
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what are the top 5 classes of toxicants in cattle?
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Vomitoxin
Plants (Yew, Buckeye, Oak, Fescue) Lead Nitrates Inorganic Arsenic |
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what is the safe pH range for
- parenteral solutions - oral solutions |
- parenteral: 5-8
- oral: 2-12 |
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what is the minimum particle size that can get into the alveoli?
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1 μm
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comment on the toxicity of suspensions vs. solutions when administered PO or IV
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- suspensions < solutions orally
- suspensions > solutions IV |
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how does a dilution of a solution that is taken orally affect its toxic effects?
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- for caustic/corrosive, dilution is the solution
- for systemically absorbed compounds, diluting them makes them more toxic because they will have more surface area for absorption |
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list the general order of routes of administration from the most toxic effects to the least from the following list: IM, IP, IV, PO, SC
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IV > IP > IM > SC > PO
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which route of administration has the most variability and why?
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oral, because the 1st pass effect is hard to predict
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what makes the most variability in toxicity when the toxicant is absorbed through the skin?
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the location of the toxicant because the stratum corneum thickness varies
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how does fractionation (splitting doses) affect toxicity?
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- it usually decreases toxicity because of lower peak concentrations if the time interval between doses is >> than the t1/2 of the toxicant
- however, if there is a frequent exposure to compounds with a long t1/2, they may bioaccumulate |
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how does frequent exposures to a toxicant affect its toxicity?
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if liver enzymes are induced, these enzymes make the toxicant more or less toxic, depending on the toxicity of the metabolites
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at what time of day are enzymes most active, and thus may increase the toxic dose of a metabolite?
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night
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what type of toxicants have increased toxicity in
- cold weather? - hot weather? |
- cold: ergot alkaloids
- hot: oxidative uncouplers |
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what species of animals
- cannot vomit? - have the most "denaturable" hemoglobin? - have a low GFR? |
- can't vomit: horse, rat, rabbit
- cats have more SH groups on their hemoglobin that can be oxidized - poultry and birds have a low GFR (recall they don't urinate) |
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if a toxicant is in a feed, why will you often see only some of the animals affected and not all, assuming they are all eating the contaminated feed?
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because there is a Gaussian distribution of log dose versus effect, showing that there is variance in how animals of the same species respond to a toxicant.
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why might you see bi- or multi-modal dose-response curves for a particular toxicant/species?
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- genetic differences (e.g. breed susceptibility)
- environmental influences |
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why does fasting/starvation introduce variability into the effects of a toxicant?
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usually more susceptible because lack of intake decreases protein synthesis and an animal may have a lack of cofactors (vitamins and minerals), so hepatic metabolism may differ. This may work for or against the animal depending or not if the metabolite is more toxic than the toxicant.
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how does pregnancy affect the susceptibility of an animal to a toxicant? Why?
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- more susceptible.
- ↓enzyme activity - ↓albumin (less binding) - ↑in non-metabolizing tissue |
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what are two reasons why younger animals can be more susceptible to a toxicant than mature animals?
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1. deficiency of enzymes (glucur., CYP-450, GSSH)
2. ↑BBB permeability |
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why are fat animals often more susceptible to toxicants? What is an exception to this general rule?
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- because on a dosage by body weight, they have less %age of metabolizing tissues.
- fat soluble compounds are an exception |
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how can non-toxic chemicals in the environment cause variability in an animal's susceptibility to a toxicant?
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although these chemicals may not be toxic, they may induce metabolic enzymes (e.g. cedar chips). This could make the animal more or less susceptible, depending or not if the metabolites are more toxic than the toxicant.
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what is the average application rate of an herbicide in lb/acre and ppm?
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1 lb/acre; 230 ppm
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2,4-D, MCPP, and MCPA are all what chemical class of herbicides?
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phenoxyacetic acids
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what species is most susceptible to phenoxyacetic acid herbicides and why?
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dogs, because they don’t excrete organic acids well through their kidneys
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comment on phenoxyacetic acid herbicides (such as 2,4-D) and cancer?
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there are many conflicting studies as to whether or not this compound actually causes cancer (lymphoma in dogs). It probably doesn't.
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what is the mechanism of action of phenoxyacetic acid herbicides?
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- in the plants to which they are applied, they can ↑cyanide and ↑nitrate accumulation in the plant, making it more toxic
- in dogs, ↑K+ conductance and ↓Cl- conductance, producing an overall irritability of skeletal muscle |
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what are two important clinical signs of phenoxyacetic acid herbicides? What are some others?
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1. myotonia (muscle weakness with rigidity)
2. paresis, especially in hind limb - anorexia - diarrhea ± bloody - vomiting - ataxia - depression, lethargy - convulsions (rare) - lesions: oral ulceration, enteritis, hepatic and renal degradation |
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what is the onset of phenoxyacetic acid herbicide toxicosis?
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< 12 hr
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how is phenoxyacetic acid herbicide toxicosis diagnosed?
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- stomach content analysis; dog serum and urine
- EMG changes - increases in skeletal muscle enzymes possible (CK, AST, LDH) |
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how is phenoxyacetic acid herbicide toxicosis treated?
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- symptomatic
- fluids with bicarb for acidosis and possible ion trapping |
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how is phenoxyacetic acid herbicide toxicosis prevented?
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- keep dogs off of lawn until dry
- keep livestock off of pasture for 1-2 weeks if feasible - some lawn care companies say to put horses back on pasture the next day |
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paraquat and diquat are what chemical class of herbicides?
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dipyridyl
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what is the most common presentation of dipyridyl (e.g. paraquat) toxicity?
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dogs being maliciously poisoned
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what is the mechanism of action of dipyridyl (paraquat and diquat) toxicity?
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- paraquat metabolized to free radical in the body, causing lipid peroxidation and free radical damage/fibrosis of the lung; fibrosis occurs several days after initial exposure after most of the paraquat has been excreted
- diquat does not cause free radical problems in the lung; free radicals formed in other tissues like kidney and liver |
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what is the onset of high dose dipyridyl toxicosis?
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< 2 hr
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what are some clinical signs of high dose dipyridyl toxicosis?
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- convulsions
- hyperexcitability - ataxia |
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what system is most affected by high doses of dipyridyl derivatives?
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CNS
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what systems are most affected my medium doses of dipyridyl derivatives?
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GI, respiratory, renal
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what are some clinical signs of medium dose dipyridyl toxicosis?
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- stomatitis
- vomiting - anorexia - depression, lethargy - diarrhea, colic - dyspnea 2-7 days after exposure from paraquat (not diquat) due to lung fibrosis - lesions: nephrosis; pulmonary congestion, edema, and hemorrhage; fibrosis in lung (paraquat only) |
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what is the onset of medium dose dipyridyl toxicosis?
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1-3 days
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how is dipyridyl toxicosis diagnosed?
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- stomach contents, serum, or urine within 2 days of exposure (before excretion occurs)
- colorimetric test for urine - moderate dose cases: ↑BUN & creatinine; liver enzymes also sometimes increased |
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how is dipyridyl toxicosis treated?
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- symptomatic: Fuller's earth or clays (e.g. kitty litter) may be better than activated charcoal; if no clay available, use activated charcoal
- fluids - diuretics - selenium, Vitamin E, acetylcysteine (GSH), SOD for free radicals/peroxides |
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how long should you keep animals off of pasture after dipyridyl treatment?
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1 week
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what are triazines used for?
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herbicides, especially on farms
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what is the most common presentation of triazine herbicide toxicity?
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cattle getting into bags of stored herbicides
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what is the onset for triazine toxicosis?
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< 24 hours
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what system is most affected by triazine herbicides?
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CNS
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what are some clinical signs of triazine toxicosis?
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- hyperesthesia
- muscle tremors of hind end - prostration - salivation - ataxia - anorexia - no specific lesions |
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how is triazine toxicosis diagnosed?
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- stomach contents or liver for analysis
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how is triazine toxicosis treated?
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- symptomatic
- methocarbamol or acepromazine for hyperesthesia |
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what type of herbicide can turn dogs' coats different colors, such as green or orange? Why does it do this?
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dinitroanaline herbicides. Because they are dyes (note they can be washed off with alcohol sanitizer to dry hair & blot off, followed by shampoo/rinse)
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comment on the toxicity of glyphosate (RoundUp™)
- how toxic is it? - cattle - dogs |
- low toxicity
- not toxic in cattle, but cattle prefer pasture sprayed with RoundUp™. This may ↑ the palatability of toxic plants on the pasture. - concentrate potentially toxic to dogs, probably due to the anionic surfactant in solution |
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what is the onset time and duration for glyphosate (RoundUp™) herbicide toxicosis?
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- onset related to dose
- duration < 24 hours |
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what are some clinical signs for glyphosate (RoundUp™) toxicosis?
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- depression/lethargy
- vomiting - tachycardia - salivation - anorexia |
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which herbicide is a "hit and run" lung toxicant?
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paraquat (a dipyridyl)
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which herbicide causes myotonia in dogs?
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2,4-D (a phenoxyacetic acid derivative)
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which herbicide causes hyperesthesia in cattle and may cause mutations in frogs?
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Atrazine (a triazine)
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what class of herbicides causes convulsions in high doses and is often associated with malicious poisoning of dogs?
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dipyridyl herbicides (paraquat and diquat)
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name two herbicides that are generally regarded to have low toxicity, but cause GI problems when the concentrates are ingested.
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1. glyphosate (RoundUp™)
2. fluazifop (a household grass killer) |
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what is an important fungicide that is sprayed at high concentrations on seeds?
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captan
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what is the most common concern about the toxic effects of fungicides (e.g. Captan) toxicosis?
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teratogenic/carcinogenic effects
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what is an important clinical sign in cattle with Captan fungicide toxicosis? What are some other clinical signs?
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1. dyspnea
- pink-stained mouth/hair - anorexia - depression/lethargy - lesions: hydrothorax, ascites, petechial hemorrhages on gall bladder, enteritis |
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what is the onset time for captan toxicosis?
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delayed days
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if a farmer is determined to feed leftover seed corn to cattle, which contains captan fungicide, what should you recommend?
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- dilute 3:1 with clean corn
- quit 1 month before slaughter to avoid pink face appearance - make sure no chlorinated hydrocarbons have been used as seed protectants in addition |
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what type of fungicides are the most toxic?
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carbamates
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what type of fungicides and herbicides have chemical structures similar to some insecticides, but do not cause acetylcholinesterase inhibition?
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1. carbamate fungicides
2. thiocarbamate herbicides |
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why are cats 3-4x more sensitive to ethylene glycol than dogs?
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because they have more oxalates in their system
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rank the following in order of most susceptible to least susceptible to ethylene glycol (on a mL/kg basis): cat, dog, human primates, poultry
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human primates = cat > dog > poultry
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using "units" of common dinnerware, how much ethylene glycol (pure) does it take to kill a cat? A dog?
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- cat: teaspoon
- dog: teacup (8 oz.) |
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what is the biochemical pathway from ethylene glycol to calcium oxalate? Comment on the toxicity of intermediates
|
ethylene glycol → glycoaldehyde (more toxic; CNS toxicant) → glycolic acid (primary cause of severe acidosis) → glyoxylic acid (most toxic, but shortest t1/2) → oxalic acid (chelates calcium) → calcium oxalate
|
|
|
what is the rate-limiting step in ethylene glycol toxicosis?
|
the first step, the conversion of ethylene glycol to glycoaldehyde via alcohol dehydrogenase
|
|
|
which ethylene glycol metabolite is most important in causing CNS toxicity? What is its effect? Duration?
|
- glycoaldehyde
- decreased respiration - rapidly metabolized to glycolic acid |
|
|
what is considered to be the primary toxicant in ethylene glycol toxicosis? What are its effects?
|
glycolic acid; causes profound acidosis
|
|
|
what is the normal pH range of the body?
|
7.38 - 7.43
|
|
|
in ethylene glycol toxicosis, what happens to oxalic acid?
|
- forms Ca Ox crystals in the urine
- deposits in renal tubules, vessel walls of arteries, and the brain |
|
|
comment on the onset time of ethylene glycol toxicosis
- early stage - mid stage - late stage |
- early: 30 min - 12 hours
- mid: 12 - 24 hours - late: 24 - 72 hours |
|
|
what are the systems affected by ethylene glycol in the
- early stage? - mid stage? - late stage? |
- early: CNS
- mid: CNS, GI - late: renal |
|
|
what are clinical signs during the early stages (30 min - 12 hours) of ethylene glycol toxicosis?
|
- mostly CNS due to ethylene glycol itself
- ataxia, incoordination, knuckling - muscle fasciculations, ↓ withdrawal reflex - GI irritation, PU/PD - polypnea, tachycardia |
|
|
what are clinical signs during the mid stages (12 - 24 hours) of ethylene glycol toxicosis?
|
- anorexia, nausea, vomiting
- hypothermia and miosis - CNS depression that increases with time - decreased respiration; coma; death |
|
|
what are clinical signs during the late stages (24 - 72 hours) of ethylene glycol toxicosis?
|
- oliguria or anuric renal failure
- salivation, anorexia, vomiting, oral ulcers - oliguria with isosthenuria - severe depression; coma or seizures |
|
|
comment on the differences between dogs and cats in ethylene glycol toxicosis
|
- clinical signs similar to dogs
- depression is greater, starts earlier, and lasts longer - no polydipsia - oliguric renal failure in cats occurs about 12-24 hours (earlier than dogs) |
|
|
what is a normal value for an anion gap? What is typical of ethylene glycol poisoning?
|
normal: 10-15 mEq/L
- EG poisoning: 40-50 mEq or more |
|
|
when does ethylene glycol concentration peak in the
- serum? - urine? |
- serum: 1-4 hours
- urine: 6-8 hours |
|
|
comment on ethylene glycol commercial bench tests:
- sensitivity - specificity |
- will detect down to about 50 mg/dL (500 ppm), but may bit be sensitive enough for cats
- false positives from other compounds such as propylene glycol (commonly added as a softener to pet foods) |
|
|
how does glycolic acid from ethylene glycol toxicosis affect
- blood pH - plasma [bicarb] |
- severe acidosis (pH < 7.3)
- severely low bicarb (< 15 mEq/L; normal ≈ 25) |
|
|
comment on canine urine with ethylene glycol toxicosis
|
- often isosthenuric
- SG low-normal and fixed - pH < 6 (normal 6.5 - 6.8) - Ca oxalate crystalluria |
|
|
what are the two forms of Ca oxalate urine crystals?
|
1. monohydrate: prisms
2. dihydrate: maltese crosses (under polarized light) |
|
|
what are some blood chemistry indicators for ethylene glycol toxicosis?
|
- ↑BUN, creatinine, phosphate, K+, glucose
- ↓ Ca2+ (in 50% of cases) |
|
|
what is a typical CBC for ethylene glycol toxicosis?
|
- ↑CBC and TP due to dehydration
- stress leukogram |
|
|
what are some gross pathological lesions found in ethylene glycol toxicosis?
|
- gastric and pulmonary hyperemia
- kidneys often pale, swollen, and tan with grey streaks; may have hemorrhage at the corticomedullary junction |
|
|
what is a common histopathological finding of ethylene glycol toxicosis?
|
- pale, yellow crystals that are birefringent in polarized light in the renal tubules, vessel walls, and brain
|
|
|
what are three useful diagnostics for ethylene glycol toxicosis?
|
1. serum or urine test kits
2. osmolal and anion gap 3. UA |
|
|
what are three clinical signs that should lead you to be suspicious of ethylene glycol toxicosis?
|
1. azotemia
2. fixed USG 3. acute onset of clinical signs |
|
|
what are seven differential diagnoses for ethylene glycol toxicosis?
|
1. ARF
2. decompensated CRF 3. acute gastroenteritis 4. DKA 5. pancreatitis 6. alcohol intoxication 7. metaldehyde |
|
|
what is the best specific therapy to treat ethylene glycol toxicosis?
|
- block alcohol dehydrogenase with 4-methylpyrazole (4-MP)
|
|
|
what are some advantages of using 4-MP to treat acute ethylene glycol toxicosis?
|
- good success up to 8 hours post-ingestion (but don't stop at 8 hours)
- does not increase osmolality (dehydration) - drug is stable for years in the refrigerator - very specific for alcohol dehydrogenase and does not cause CNS depression, like ethanol |
|
|
why do cats need more 4-MP when treating them for ethylene glycol toxicosis?
|
because their alcohol dehydrogenase enzyme is less sensitive
|
|
|
what is the maximum percentage ethanol that you should use IV for ethylene glycol toxicosis?
|
20%
|
|
|
comment on supportive therapy for ethylene glycol toxicosis:
- if there is poor kidney function - if there are seizures due to hypocalcemia - to remove metabolites if olig/anuric - diet |
- poor kidney function: use diuretics such as mannitol or furosemide (Lasix™)
- seizures with hypocalcemia: calcium borogluconate - olig/anuria: use peritoneal dialysis to remove EG and metabolites faster - patient should be on a bland, low-protein diet for 1 month because of liver and kidney damage |
|
|
comment on the prognosis of ethylene glycol toxicosis:
- in dogs - in cats - in azotemic animals |
- dogs: excellent if Rx with 4-MP within 5--8 hours
- cats: good if Rx with 4-MP within 3 hours - azotemic animals: poor or grave prognosis |
|
|
with short chain alcohols, how does toxicity relate to molecular weight?
|
toxicity increases with increasing MW up to 7 carbons
|
|
|
why is methanol more toxic in primates than in other animals?
|
- primates do not metabolize formate well
- formic acid stays in body longer - leads to acidosis and ocular damage (cataracts) - due to the fact that primates have less folates, which are important in metabolizing compounds with only one carbon |
|
|
what is the mechanism of action of alcohol toxicosis?
|
- disrupt normal membrane structure: affect Na+ conductance and block formation/propagation of action potentials
- affects GABA-mediated Cl- uptake |
|
|
what is the onset and duration of alcohol toxicosis in non-primates?
|
- onset within 1 hour
- lasts up to 12 hours |
|
|
how is alcohol toxicosis diagnosed?
|
- increased osmolal and anion gaps
- blood [EtOH] |
|
|
how is alcohol toxicosis treated in non-primates?
|
- CNS: treat symptomatically
- respiratory problems: ET tube, ventilator; monitor HR, BP, ECG - fluids and electrolytes: LRS or bicarb - ACTIVATED CHARCOAL: 2 g/kg (limited binding) |
|
|
what are the two basic types of anticoagulant rodenticides? Give two specific examples of each.
|
1. coumarins - warfarin, brodifacoum
2. indanediones - pindone, diphacinone |
|
|
what is an example of a human medication that behaves like an anticoagulant rodenticide?
|
coumadin
|
|
|
list the following species in order of the most to least susceptible to brodifacoum: cat, dog, mouse, pig, rabbit, rat, sheep
|
rabbit = mouse = rat ≥ dog ≥ pig >>> cat ≥ sheep
|
|
|
what is the mechanism of action of anticoagulant rodenticides?
|
blocks the action of Vitamin K epoxide reductase. The PIVKA proteins are unable to be carboxylated by Vitamin K, so they can't bind to Ca2+, and therefore, blood can't clot
|
|
|
anticoagulants:
- peak plasma time - protein binding - half-life |
- peaks at around 12 hours
- 90-95% protein bound, so long time for excretion - long half-life |
|
|
why is relay toxicity rare with anticoagulant rodenticides?
|
because the LD50 required for a dog (and especially a cat) is higher than a typical rodent would have in its system
|
|
|
what are PIVKA proteins?
|
- "proteins inhibited by vitamin K antagonists"
- they are inactivated (non-carboxylated) factors 2, 7, 9, 10 |
|
|
why must you handle patients with anticoagulant toxicosis very carefully?
|
because ruptured capillaries will not stop bleeding
|
|
|
what is the onset time for bleeding with anticoagulants?
|
2-5 days
|
|
|
what are eight common presentations of hemorrhage and lesions associated with anticoagulant toxicosis?
|
1. petechiation
2. epistaxis; hematemesis; melena 3. intrapulmonary hemorrhage (tachypnea, dyspnea) 4. intrathoracic and intra-abdominal 5. intraarticular (lameness) 6. HYPOVOLEMIA: pale MM, anemia 7. weakness, dyspnea, ataxia, cyanosis 8. shock and irregular pulse |
|
|
which coagulation systems are affected by anticoagulant rodenticides?
|
extrinsic, intrinsic, and common
|
|
|
what is the most sensitive test, which is seen first with anticoagulant toxicosis?
|
PT (aka APT) - tests the extrinsic system (factor 7)
|
|
|
how does anticoagulant toxicosis affect:
- PCV? - FDP? - platelets? |
- PCV may or may not be lowered
- FDP normal until bleeding occurs - platelets normal or slightly lowered |
|
|
what are 5 differential diagnoses for anticoagulant toxicosis?
|
1. DIC
2. congenital factor deficiency 3. von Willebrand's disease 4. canine ehrlichiosis 5. platelet deficiency |
|
|
what are three symptomatic treatments for anticoagulant toxicosis?
|
1. fresh whole blood or plasma
2. fluids for hypovolemia 3. supplemental O2 |
|
|
which vitamin K derivative is contraindicated in anticoagulant toxicosis and why?
|
Vitamin K3 - it is not effective and can cause instant death due to severe hemolytic anemia
|
|
|
what specific drug is given for anticoagulant toxicosis. Explain the regimen.
|
- Vitamin K1 PO or SC for 3-4 weeks or longer
- avoid IV due to anaphylaxis - if given orally, give with food containing fat |
|
|
if a lactating bitch has anticoagulant toxicosis, what do you do with her pups?
|
- test bitch for coagulopathy
- wean pups ASAP - oral vitamin K1 for pups for 1-3 weeks |
|
|
compare the toxicity of strychnine in dogs versus cats
|
6x more potent in dogs versus cats
|
|
|
strychnine:
- absorption - distribution - metabolism - excretion, t1/2 |
- absorption: rapid and complete from GIT
- distribution: throughout the body; larger amounts in liver and kidney - metabolism: readily metabolized by CYP-450 - excretion: urine; t1/2 ≈ 10-12 hours |
|
|
what is the mechanism of action of strychnine?
|
- antagonizes inhibitory Gly in the medulla and SC
- interneurons - competitive and reversible - OVERSTIMULATION of the CNS - extensor rigidity - respiratory muscles → suffocation |
|
|
what is the onset time of strychnine toxicosis?
|
15 min - 2 hours
|
|
|
strychnine toxicosis clinical signs:
- premonitory signs - CNS - muscle |
- premonitory signs: nervous, apprehensive, restless
- CNS: hyperesthesia; sound, light, and touch can send them into a convulsive seizure - muscle stiffness: stiff gait and neck; rigid spine - "facial grin"; ears erect (to the point of touching or laid back); blepharospasm |
|
What is the likely toxicosis, given the clinical signs?
|
Meatwad is a cartoon ball of raw ground beef and can't be poisoned. Trick question.
|
|
|
characterize the seizures caused by strychnine toxicosis
|
- tetanic, bilateral, symmetrical
- set off by external stimuli - opisthotonus and extensor rigidity |
|
|
how do the eyes appear in strychnine poisoning
|
pupils are widely dilated
|
|
|
how does an animal usually die from strychnine poisoning?
|
tetany of the inspiratory/expiratory muscles leads to asphyxiation
|
|
|
how is strychnine toxicosis diagnosed?
|
- history
- **type of seizures - chemical analysis: stomach contents, liver, bait, vomitus - often no pathological findings, but may see rapid rigor mortis |
|
|
what are 9 differentials for strychnine toxicosis?
|
1. OP/carbamate insecticides
2. chlorinated hydrocarbons 3. metaldehyde 4. lead toxicosis 5. tetanus 6. Penitrem A (a mycotoxin) 7. Roquefortine (a mycotoxin) 8. Cocaine 9. Amphetamines |
|
|
how do you treat strychnine toxicosis in its early stages?
|
- emesis only if no clinical signs due to risk of aspiration pneumonia
- gavage with activated charcoal 1-2 g/kg - diuretics: furosemide (Lasix™) - acidify the urine with ammonium chloride or ascorbic acid |
|
|
what supportive therapies are indicated for strychnine toxicosis?
|
- control/prevent seizures with benzodiazepines (diazepam) or barbiturates (pentobarb) and/or methocarbamol (a muscle relaxant similar to guaifenesin)
- artificial respiration |
|
|
what are three drugs contraindicated for strychnine toxicosis?
|
1. acepromazine
2. ketamine 3. morphine |
|
|
what is metaldehyde?
|
a polymer of acetaldehyde, used as slug and snail bait.
|
|
|
what body systems do metaldehyde target?
|
CNS and GI
|
|
|
metaldehyde:
- absorption - metabolism/excretion - distribution |
- readily absorbed by the GIT
- metabolized by aldehyde dehydrogenase to acetic acid, which is excreted in the urine - readily crosses the BBB |
|
|
what is the mechanism of action of metaldehyde toxicosis?
|
- aldehydes in general are severe CNS toxicants that cause vasomotor and respiratory depression
- ↑CNS serotonin - ↓CNS GABA |
|
|
which rodenticide causes "shake and bake" syndrome?
|
metaldehyde
|
|
|
which rodenticide causes bilateral, symmetrical tetanic seizures?
|
strychnine
|
|
|
what are some early signs of strychnine toxicosis?
|
- anxiety, restlessness leading to depression
- salivation, vomition, diarrhea - mydriasis, ataxia, incoordination - hyperesthesia |
|
|
what are three important clinical signs of metaldehyde poisoning that has progressed beyond the early stages? What are some other clinical signs?
|
- "SHAKE AND BAKE"
1. Shake: muscle tremors, polypnea, tachycardia 2. Bake: hyperthermia 3. severe acidosis - opisthotonus, frequent convulsions - nystagmus (especially in cats) |
|
|
how is metaldehyde toxicosis diagnosed?
|
- HX and clinical signs: especially convulsions and hyperthermia; "shake and bake"
- necropsy: congestion of GI, lungs, liver, kidney; odor of aldehydes |
|
|
what are five differential diagnoses for metaldehyde toxicosis?
|
1. ethylene glycol
2. strychnine 3. organochlorines 4. urea toxicosis 5. lead toxicosis |
|
|
how is metaldehyde toxicosis treated?
|
- aggressive detoxification
- emesis and lavage - activated charcoal and saline cathartic/sorbitol - sedation & seizure control (very important): diazepam, pentobarb, methocarbamol - artificial respiration - fluid therapy: correct acidosis - cold water baths or ice packs for hyperthermia |
|
|
why is vitamin D3 (cholecalciferol) such an effective rodenticide?
|
because it takes 2-5 days to kill them, so there is no bait shyness
|
|
|
besides rodenticides, where else might a dog eat something that exhibits a toxicosis similar to cholecalciferol?
|
a very potent analog of vitamin D3 used to treat psoriasis is available as a cream (calcipotriene, Dovonex™, Taclonex™)
|
|
|
what is the mechanism of cation of cholecalciferol toxicosis?
|
- cholecalciferol and its active metabolites ↑Ca absorption from the gut, stimulate bone resorption, and promote Ca reabsorption in the renal tubules
- cholecalciferol → 25-hydroxycholecalciferol in the liver → 1,25-dihydroxyxholecalciferol (rate limiting step) in the kidney - metabolic and dystrophic calcification - toxicosis is caused by tissues responding to the elevated levels of 25-hydroxycholecalficerol, which has a t1/2 of 15 days |
|
|
what is the most important metabolite in Vitamin D toxicosis?
|
25-hydroxycholecalciferol
|
|
|
what are the systems affected by vitamin D toxicosis?
|
GI, renal, cardiac
|
|
|
what is the onset time for vitamin D toxicosis?
|
18-36 hours
|
|
|
what are some clinical signs of vitamin D toxicosis?
|
- multisystemic calcification
- anorexia - depression, lethargy - vomiting - diarrhea - PU/PD - ECG abnormalities |
|
|
given they both produce calcium deposits in tissues, how would you differentiate vitamin D toxicosis from late-stage ethylene glycol toxicosis?
|
- with cholecalciferol, ↑[Ca]
- with ethylene glycol, 50% of the time ↓[Ca] |
|
|
what would an abdominal radiograph look like with vitamin D toxicosis?
|
plaques on the serosa, sometimes on the mucosa, and mineralization throughout the kidney
|
|
|
in a necropsy, how do the kidneys present when the animal died from vitamin D toxicosis?
|
enlarged and pitted when the capsule is removed
|
|
|
how is vitamin D toxicosis diagnosed?
|
- serum P elevated at 12 hours post-exposure
- serum Ca elevated at 24 hours post-exposure (note that puppies naturally have higher [Ca]) - ↑BUN and creatinine, hyposthenuria (from ↓ADH) - radiopaque kidneys - serum 25-OH increased - decreased serum PTH |
|
|
how is vitamin D toxicosis treated?
|
- symptomatic: establish baseline Ca values
- calciuresis with normal saline and furosemide (Lasix™) - prednisolone may be required for several weeks (↓GI absorption, bone resorption, and ↑renal loss of Ca) due to long t1/2 - calcitonin or human-label osteoporosis drugs (pamidronate or clodronate) - low Ca diets - may need to treat for 2-4 weeks |
|
|
what is bromethalin?
|
rodenticide used to kill moles, gophers, and other rodents
|
|
|
what is the mechanism of action of bromethalin toxicosis?
|
- bromethalin → desmethyl bromethalin; oxidative uncouplers
- uncouplers ↓ATP production → weakened Na/K pump in brain → fluid accumulation in myelin sheaths → interference with axon transmission → respiratory arrest and paralysis |
|
|
***how does a histopath section of the brain look with bromethalin toxicosis?
|
myelin edema, which looks like spongiosis
|
|
|
what are two important clinical signs of high-dose bromethalin toxicosis in the dog, what are some others?
|
1. anisocoria (pupils ≠ size), miosis
2. loss of bark (early clinical sign) - muscle tremors - hyperthermia (CNS and from Ox uncoupling) - hyperexcitability - anorexia - miosis - convulsions/circling - depression - hind limb hyperreflexia - forelimb paralysis with extensor rigidity |
|
|
what is an important clinical sign of low-dose bromethalin toxicosis in the dog and cat? What are some others?
|
1. hind limb ataxia and paresis/paralysis
-bladder/intestinal stasis & vocalization (cats) - muscle tremors - depression/lethargy - lateral recumbency - vomiting - respiratory depression - decerebrate posture (rear leg extensor rigidity and forelimb flexion) - coma |
|
|
how is bromethalin toxicosis diagnosed?
|
- EEG showing voltage depression and/or excessive slow wave activity; ↑CSF pressure (neither test usually done)
- no distinctive pathological changes - analysis of fat > liver > kidney in dead animal; fat biopsy in live animal? |
|
|
how is bromethalin toxicosis treated?
|
- symptomatic
- mannitol ± furosemide for brain edema; not really efficacious; keep head raised 15-30° - multiple doses of activated charcoal to prevent enterohepatic circulation: caught early, use with cathartic; subsequent, don't use with cathartic (dehydration) |
|
|
***why are dogs and cats so eager to eat zinc phosphide rodenticide pellets?
|
because they have a fishy or garlic-like odor
|
|
|
name three rodenticides in which relay toxicosis is possible.
|
1. zinc phosphide
2. avitrol 3. bromethalin (rare, but possible in cats) |
|
|
how does having eaten a previous meal affect zinc phosphide toxicity?
|
previous meal makes ingestion more toxic because of acid hydrolysis producing phosphine
|
|
|
zinc phosphide is really two poisons in one. Describe their effects. Which is the more toxic of the two?
|
1. phosphine gas liberated with GI acid: lung edema, CNS (most toxic)
2. zinc: GI irritant, liver, kidney |
|
|
what is the mechanism of action of phosphine gas produced from ingesting zinc phosphide?
|
free radical production with lipid peroxidation and blockage of mitochondrial cytochrome oxidase, especially in brain and lungs
|
|
|
what is the onset and duration of high-dose bromethalin toxicosis in the dog?
|
- onset: 4-36 hours
- duration: 15-63 hours |
|
|
what is the onset and duration of low-dose bromethalin toxicosis in the dog and cat?
|
- onset: 1-5 days
- duration: several weeks |
|
|
what is the onset and duration of zinc phosphide toxicosis?
|
- onset: 15 min - 4 hours
- duration: 4 - 48 hours |
|
|
what are the systems affected by zinc phosphide toxicosis?
|
CNS, respiratory, GI
|
|
|
what are some clinical signs of zinc phosphide toxicosis?
|
- anorexia
- vomiting (Zn) - depression/lethargy - ataxia - cardiac arrhythmias - dyspnea, wheezy (pulmonary edema) - hyperesthesia - convulsions - muscle tremors - lesions: garlic/fishy stomach contents; gastritis; pulmonary edema; kidney/liver degeneration |
|
|
how is zinc phosphide toxicosis diagnosed?
|
- phosphine gas from frozen stomach contents
- elevated [Zn] in stomach contents |
|
|
how is zinc phosphide toxicosis treated?
|
- Maalox™ (Al & Mg hydroxides) to neutralize stomach acids and decrease hydrolysis
- emetic or gastric lavage - activated charcoal ± cathartic - methocarbamol/propofol for seizures - fluids with bicarb - pain medication (butorphanol) |
|
|
what is avitrol
|
an avicide sprayed onto corn bait (non-colored); 4-aminopyridine; used more in the Midwest than in VA and MD
|
|
|
what is the mechanism of action of avitrol?
|
- ↑cholinergic transmission with ↑release of ACh and other stimulatory neurotransmitters
- blocks K current of repolarization following action potential; efflux of K following action potential is blocked |
|
|
what is the onset time and duration of avitrol in mammals? Birds?
|
- onset: 10-15 minutes
- duration: < 4 hours; < 15 min in birds |
|
|
what are some clinical signs of avitrol toxicosis?
|
- hyperexcitability
- salivation - muscle tremors - birds squawk and crash - ataxia - convulsions - cardiac arrhythmias - lesions: none; corn in stomach |
|
|
how is avitrol toxicosis diagnosed?
|
- analysis of corn in stomach contents
- rapid rigor mortis |
|
|
how is avitrol toxicosis treated?
|
- symptomatic
- diazepam for convulsions in dogs - xylazine for horses - propanolol for arrhythmias |
|
|
what system is affected by soap and shampoo?
|
GI
|
|
|
what is the onset time for toxicosis associated with soap and shampoo?
|
< 2 hours
|
|
|
what are the major clinical signs for soap and shampoo toxicosis?
|
vomiting and diarrhea
|
|
|
how is soap and shampoo toxicosis treated?
|
- symptomatic
- dilution with milk or water is usually enough - not a systemic problem, so activated charcoal is not needed |
|
|
list the four different surfactant types (type of ion) in order of most to least toxic
|
cationic > amphoteric > anionic > nonionic
|
|
|
what is the mechanism of action of surfactant toxicosis (anionic & cationic)?
|
- anionic surfactants change the surface tension of RBCs, causing them to lyse
- cationic surfactants cause NM and ganglionic blockade; also capable of causing dermal, corneal, and GI mucosal damage/ulcer formation; seizures possible |
|
|
what common household chemical may cause facial edema in dogs?
|
cationic surfactant
|
|
|
how is toxicosis caused by ingestion of granular detergent treated?
|
- symptomatic
- huge dose of anionic may require the use of activated charcoal (N.B. there may be perforating ulcers) - cationic: if no ulcer, can try activated charcoal; not much else you can do except wait |
|
|
why are dishwasher detergents so toxic?
|
because they are strong bases
|
|
|
how do you treat toxicosis associated with dishwasher detergent ingestion?
|
- strong base: dilution with water or milk
- possible use of steroids for ulcers that have not perforated - radiograph thorax and abdomen to rule out perforation - analgesics |
|
|
comment on the toxicity of liquid laundry detergents such as Tide
|
- liquid usually less toxic than granular
- usually GI effects (vomiting and diarrhea), so dilute |
|
|
what are the 3 major types of disinfectant cleaners?
|
1. phenolic compounds (e.g. Lysol)
2. pine oil based products 3. Cationic surfactants |
|
|
why are cats particularly susceptible to phenolic and pine oil disinfectants?
|
- note that pine oils are metabolized to phenols in the body because they are anisole derivatives
- cats have trouble oxidizing the benzene ring |
|
|
what organ systems are affected by the following classes of disinfectant cleaners:
- cationic surfactants - phenol - pine oil |
- cationic surfactants: GI, CNS
- phenol: GI, hepatic - pine oil: GI, hepatic |
|
|
which type of surfactants cause convulsions?
|
cationic
|
|
|
which type of disinfectant cleaners can cause Heinz bodies?
|
phenolic (e.g. Lysol)
|
|
|
which type of disinfectant cleaners can cause icterus and renal damage?
|
pine oil and phenolic
|
|
|
how is toxicosis caused by disinfectant cleaners treated?
|
- dilution with milk/egg whites (precipitates protein) or water
- emesis only if < 5% concentration; ulcers possible > 5% - activated charcoal ± saline cathartic if no ulcer formation expected - sucralfate for ulcers - acetylcysteine (GSH) for pine oils/phenols to ↑ conjugation; SAM (S-adenosylmethionine) for liver sparing action |
|
|
what is the difference in the necrosis caused by strong bases versus strong acids?
|
- strong bases cause liquefactive necrosis and will penetrate deeper into the tissue until neutralized
- strong acids will cause coagulative necrosis and do not penetrate as much |
|
|
what is the big contraindication when treating toxicosis caused by ammonia, oven cleaners, drain cleaners, etc.?
|
- do not induce vomiting
- do not give charcoal or cathartics |
|
|
what is the mechanism of action of hydrocarbon toxicosis?
|
- unknown; CNS depression
- volatile fumes may sensitize heart to endogenous catecholamines and can cause sudden death (± pulmonary edema) - possible aspiration of volatile products |
|
|
how is hydrocarbon toxicosis diagnosed?
|
- HX of exposure with compatible clinical signs
- aspiration pneumonia denoted by chest radiograph, leukocytosis, and fever - animals that have no clinical signs 6-12 hr after exposure are unlikely to develop a toxicosis - if > 1 hour post-exposure, unlikely to develop aspiration pneumonia |
|
|
how do you treat for hydrocarbon exposure?
|
- depends on volatility and amount ingested
- furniture polishes, don't use emetics - if > 1 mL/kg ingested, risk emesis; if < 1 mL/kg, give activated charcoal - oxygen cage for aspiration pneumonia - detergents or hand degreasers for dermal exposures |
|
|
what system is most affected by N-P-K fertilizers in dogs and cats?
|
GI (possible cardio with too much potassium)
|
|
|
how is N-P-K fertilizer poisoning treated?
|
- symptomatic
- dilution (versus charcoal) - demulcent may be needed to soothe irritated mucous membranes |
|
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why are rose fertilizers dangerous
|
they contain a significant amount of iron
|
|
|
what can cause iron syndrome in dogs? Describe the clinical signs.
|
- rose fertilizer (contains 5% iron)
- GI initially with vomiting & diarrhea - CV shock and collapse - liver necrosis after 24-48 hours |
|
|
which four major types of household chemicals is administration of activated charcoal useful?
|
1. huge amount of anionic surfactants
2. cationic surfactants 3. disinfectants (phenol, pine oil, cationic surfactants) 4. hydrocarbons |
|
|
what are three ways which administration of activated charcoal can be useless or harmful?
|
1. doesn't bind acids or alkaline products; damage done already
2. complicates endoscopy; may go through ulcer/peritoneum 3. doesn't bind inorganics (e.g. fertilizers, iron) |
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what are three reasons why emetics are contraindicated with caustics and corrosives?
|
1. stomach wall weakened and may burst
2. re-exposure on the way up 3. aspiration |
|
|
what type of household chemical has the worst prognosis?
|
hydroxide-based drain cleaners (with a Danger label)
|
|
|
what are the three basic types of insecticides that increase acetylcholine effects?
|
1. AChE inhibiting OPs
2. AChE inhibiting carbamates 3. acetylcholine agonists at nicotinic sites (neonicotinoids) |
|
|
what are the three basic types of ion channel targeting insecticides?
|
1. GABA receptor (Cl- channel), e.g. fipronil
2. sodium channel - pyrethrins and pyrethroids 3. both Na+ and Cl- channels: organochlorines |
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what are four types of insecticides that don't work on acetylcholine or ion channels?
|
1. nervous system α2 agonists
2. irritators of skin and/or GI tract 3. repellants 4. insect-specific targeting products |
|
|
what are three examples of OP insecticides?
|
1. malathion
2. diazinon 3. chlorpyrifos |
|
|
what type of OP insecticides are pro-toxicants?
|
those that have a =S instead of a =O
|
|
|
which type of enzyme do birds not have, which makes them more susceptible to OP toxicosis?
|
A-esterases
|
|
|
what are two important enzymes for inactivation for organophosphates. Compare the toxicodynamics.
|
- A-esterases (N.B. birds do not have these!): they hydrolyse OPs, but are not inhibited by Ops
- B-esterases: they hydrolyze OPs, are irreversibly bound by them; therefore, they can be depleted (e.g. in birds, which have no A-esterases) |
|
|
what is the average time of "aging" in OP exposure?
|
≤ 60 minutes
|
|
|
what are the two binding sites on AChE and which site do OP insecticides bind?
|
anionic and esteratic. OPs bind to the esteratic site.
|
|
|
where in the mammalian body does "true" AChE exist?
|
- nervous system
- RBCs |
|
|
what are the withdrawal times for OP exposure?
|
- 7-10 days post-oral
- 20-40 days post-dermal |
|
|
what is a convenient mnemonic for overt clinical signs of (e.g. insecticide) toxicants that cause acetylcholinesterase inhibition?
|
- SLUD
- Salivation - Lacrimation - Urination - Defecation |
|
|
how do AChE inhibiting insecticides affect the
- heart? - GI tract - mucous membranes? - pupils? |
- heart: ↓HR
- GI tract: ↑peristalsis - mucous membranes: ↑secretions - pupils: ↓pupil size (miosis) |
|
|
what is the effect of AChE inhibiting insecticides at the nicotinic receptors? CNS?
|
- NMJ and autonomic ganglia: stimulation (ANS effects & tremors), then block
- CNS: stimulation then block |
|
|
what is usually the cause of death in OP toxicosis?
|
respiratory failure
|
|
|
treatment for AChE inhibition:
- muscarinic signs - for regeneration of AChE - other treatments |
- muscarinic signs: atropine (1/4 given IV and 3/4 given SC)
- for AChE regeneration: 2-PAM - ↓absorption with activated charcoal - symptomatic (e.g. diazepam for convulsions) - TIME |
|
|
what drugs are contraindicated for AChE inhibition?
|
drugs that cause respiratory depression, such as anesthetics, opioids, antihistamines
|
|
|
what are the three syndromes of OP toxicosis?
|
1. acute toxicosis
2. Intermediate Myotoxicity 3. (delayed) Organophosphate-induced delayed neuropathy |
|
|
what are the top 5 classes of toxicants in sheep?
|
1. copper (chronic)
2. ionophores 3. Rhododendron, mountain laurel 4. selenium injections 5. fescue ergot |
|
|
what are the top 5 classes of toxicants in swine?
|
1. vomitoxin
2. arsanillic acid 3. Na ion/water deprivation 4. iron injection (primary Se deficiency) 5. fumonisin |
|
|
which OP can show more nicotinic signs than muscarinic signs in cats?
|
chlorpyrifos
|
|
|
comment on the intermediate syndrome caused by OPs.
|
- this is a myotoxicity caused by AChE inhibition of the neuromuscular junctions (nicotinic receptors)
- may appear after progression of muscarinic signs - can appear after very slow absorption (i.e. muscarinic receptors have been desensitized) - reverses with time, so no antidote |
|
|
what is OPIDN? What causes it and how long do clinical signs take to appear?
|
- organophosphate induced delayed neuropathy
- caused by inhibition of NTE (neurotoxic esterase), a B-esterase - inhibition of NTE takes hours, but OPIDN takes weeks (1 week - 2 mo.) to appear |
|
|
which type of OPs more typically cause OPIDN?
|
usually not insecticides; more common in other sources, such as fuel additives
|
|
|
OPIDN:
- clinical signs - age predilection - lesions - prognosis |
- irreversible neuropathy: progressive ataxia
- younger are less susceptible and older are more susceptible - lesions: peripheral nerve and spinal cord lesions - poor prognosis |
|
|
comment on the age predilection of the three syndromes associated with organophosphate toxicosis?
|
- acute toxicosis: young more susceptible than old
- intermediate myotoxicity: nothing mentioned - OPIDN: old more susceptible than young |
|
|
comment on the differences (specific or general) in organophosphate toxicity in
- mammals versus insects - mammals versus birds - cats versus other mammals - breed/sex - age |
- mammals versus insects: absorption and metabolism differ
- mammals versus birds: birds more susceptible because they are A-esterase deficient - cats versus other mammals: in cats, dermal = po (from grooming); also, chlorpyrifos causes more nicotinic than muscarinic signs due to receptor tolerance - breed/sex: exotic bulls especially susceptible to chlorpyrifos - age: young more susceptible to ↓AChE; less susceptible to OPIDN |
|
|
how does serial exposures of the same or different OP insecticides affect susceptibility?
|
- depletes B-esterases, so ↑ susceptibility to AChE on subsequent exposure
|
|
|
comment on the interactions between OP insecticides and ester/amide drugs, such as local anesthetics
|
↑ susceptibility because they use the same degradative enzymes
|
|
|
comment on the interactions between OP insecticides and NM blockers & antibiotics
|
NM blockers and some antibiotics also act at nicotinic receptors
|
|
|
comment on the susceptibility with OP insecticides with repeated, sub-clinical, low-dose exposures?
|
tolerance possible. Muscarinic tolerance > nicotinic
|
|
|
what are four important uses for carbamates?
|
1. insecticides
2. herbicides (thiocarbamates) 3. fungicides 4. parasympathomimetic drugs (e.g. neostigmine, physostigmine) |
|
|
name four carbamate insecticides
|
1. carbaryl
2. methomyl 3. carbofuran 4. aldicarb |
|
|
what is the main toxicodynamic difference between OP insecticides and carbamates?
|
carbamates do not form irreversible, covalent bonds with AChE and other esterases; they are all reversible (i.e. no "aging")
|
|
|
what is the main treatment for carbamate toxicosis?
|
atropine + time
|
|
|
what type of insecticides increase the effects of acetylcholine?
|
nicotine / neonicotinoids
|
|
|
what is the mechanism of action of nicotinic receptor agonists?
|
stimulate, then block ANS ganglia, NMJ, CNS receptor sites
|
|
|
what is the preferred antidote for nicotinic receptor agonist toxicosis?
|
there is no antidote
|
|
|
what is an important example of a neonicotinoid insecticide?
|
Imidacloprid (Advantage™, Merit™, Premise™)
|
|
|
for ion channel-targeting insecticide toxicosis, what drugs might you use to control convulsions?
|
- GABA agonists: diazepam, pentobarb
- methocarbamol as a CNS depressant/muscle relaxer |
|
|
what is an important example of a GABA chloride channel ion channel targeting insecticide? What class of chemical is it?
|
fipronil (Frontline™), a phenylpyrazole
|
|
|
what is the mechanism of action of fipronil?
|
a GABA receptor (chloride channel) blocker, which has the most effect on invertebrates
|
|
|
what are some clinical signs of fipronil overdose (GABA Cl- channel blocker)?
|
- muscle fasciculations
- tremors, convulsions - lethargy, ataxia |
|
|
what is the onset and duration of fipronil (GABA Cl- blocker) toxicosis?
|
- onset < 7 hours
- duration 12 - 24 hours |
|
|
what is the mechanism of action of pyrethrins/pyrethroids?
|
they are sodium ion channel blocking insecticides
|
|
|
what are the two types of pyrethrin/pyrethroids in chemical composition and their toxic effects?
|
- Type I: no cyano functional group; "T syndrome", which consists of muscle tremors and hyperexcitation
- Type II: has a cyano functional group: "CS Syndrome"; causes tonic-clonic seizures |
|
|
what species is especially susceptible to pyrethrins/pyrethroids?
|
cats
|
|
|
how can pyrethrins/pyrethroids cause drug interactions?
|
- they are Na+ channel blockers
- they compete for esterases, oxidases, and glucuronidation |
|
|
what is an important example of an insecticide that blocks both Na+ and Cl- channels?
|
DDT
|
|
|
what is the most common toxic effect seen with insecticides, such as DDT, which block both Na+ and Cl- ion channels?
|
- acute toxicosis is rare, but could be NMJ blockers
- chronic is more common: ↑↑↑microsomal enzyme activity and ↓ androgen production |
|
|
comment on the toxicokinetics of DDT:
- absorption - distribution - metabolism - excretion |
- absorbed by all routes
- distributed to all tissues; stored in fat; and gets into milk - toxic metabolites, which occurs in 2 steps - excretion takes a long time (t1/2 1 week - 2 months): kidney, milk, feces |
|
|
what is the main class of compounds that block both Na+ and Cl- channels?
|
organochlorines
|
|
|
what are three mechanisms for chronic exposure to OC insecticides?
|
1. accumulation
2. continuous exposure 3. bio magnification |
|
|
what is an important α2 agonist insecticide, its chemical class, and what is its antidote?
|
amitraz (a formamide); yohimbine is the antidote (or tolazoline)
|
|
|
where is amitraz used agriculturally?
|
on crops to kill caterpillars
|
|
|
what are some signs of amitraz toxicosis?
|
- CNS and respiratory depression
- bradycardia - hypotension - vomiting/intestinal stasis |
|
|
what is the mechanism of action of amitraz?
|
α2 agonist
|
|
|
what are three important insecticides that cause irritation of the GI tract or skin?
|
1. d-limonene
2. Amdro™ (hydromethylnon) 3. boric acid |
|
|
who usually gets poisoned by d-limonene?
|
cats
|
|
|
who usually gets poisoned by Amdro™(hydromethylnon)?
|
dogs
|
|
|
what is Amdro™ used for and what are clinical signs of toxicosis from it?
|
- used to kill fire ants
- salivation, tremors, GI disturbances |
|
|
what is an important example of an insect repellant?
|
DEET
|
|
|
what are some clinical signs of DEET toxicosis?
|
- usually topical: dermatitis, ocular
- if absorbed: encephalopathy (ataxia, confusion, tremors) |
|
|
what are two important examples of insect growth regulators?
|
1. lufenuron (Program™)
2. methoprene |
|
|
what is the dosage of atropine for OP/carbamate toxicosis?
|
0.1 - 0.5 mg/kg
|
