Toxicology 1 Flashcards
Sodium toxicosis /water deprivation
Combo of water volume depletion (LA) and ingestion of excess salt (SA)
Excess could be play dough, road salt/melt run off, frozen over water sources
acute toxicity - sodium toxicosis
Salt ingestion or activated charcoal overuse
Passive movement of Na+ across BBB due to increased Na+ levels. Inhibition of energy production (glycosis) necessary for active transport to excrete Na from CNS - water replacement - primary effect is cerebral edema
Chronic toxicity - water deprivation
Water deprivation ≥ 3 days
Generation of idiogeneic, organic & inorganic osmoses in CSF to compensate for increased osmalolity in blood
Rapid water replacement = dilution of Na+ concentration in blood = movement of water into CNS = cerebral edema
Diagnosing sodium toxicosis /water deprivation
> 170 mEa/L Na in serum or CSF
1800 ppm Na in brain
Laminar necrosis in brain in all animals - eosinophilic cuffing in swine only
Clinical signs of water deprivation in cattle
GIT irritation, anorexia, nasal discharge, thirst polyuria, rumen stasis, diarrhea, mucus covered feces, paresis/rear leg knuckling, blindness, nystagmus, belligerent, seizures
NaCL toxicity
Cattle, swine & horses -
Dogs
Poultry
Clinical signs in swine
Onset time ≥ 3 days
Dog sitting, wandering, pivoting around foot
Blind, deaf, nose twitching, seizures, coma, anorexia, constipation
*star gazing, *jaw champing, head pressing, pruritus
Eosinophilic perivascular cuffing in brain with laminar necrosis
Clinical signs in poultry
Takes 1-2 days no water = sodium toxicosis
Depression, lethargy, anorexia, thirst, diarrhea, nasal discharge, dyspnea, nervousness, paresis, serisures
Lesions in poultry sodium toxicosis
Enteritis, ascites, generalized edema, hydro-pericardium
Clinical signs in dogs
<4 hours from acute ingestion
Treating swine or cattle with Na toxicosis
Give access to small amounts of water in 1 hour intervals
Prognosis is very poor
Treatment for dogs with Na toxicosis
Replace free water deficit
Consider use of furosemide - loop diuretic for Na excretion
Difficult therapy bc of intracellular dehydration combined w hypervolemia, monitor Na levels, monitor pulmonary edema
Ionophores
Indirect neurotoxic feed additive (muscular toxicosis)
- monensin, salinmycin, iasalocid - coccidiostatic feed antiviral & growth promotants
Ionophore toxicity
Primarily a problem in horses, sheep & turkeys
Horses & turkeys have lower LD50 for monensin than cattle & chickens - death can be sudden
Mechanism of Ionophore toxicity
Toxic action related to influx of ions across mitochondrial membranes of heart & skeletal muscle - intracellular Ca2+ accumulation - opening of MPTP (mitochondrial permeability transition pore) - decrease ATP formation & cell necrosis = cell death
Organ failure in horses & cats
Heart > skeletal muscle
Organ failure for cattle & rabbits
Heart = skeletal muscle
Organ failure for sheep, pigs, dogs
Skeletal muscle > heart
diagnosing Ionophore toxicity
Anorexia, GIT problems, death following use of new concentrate or minerals
- Se deficiency, cardiac infarct, cardio toxic plants
Lesions for Ionophore toxicity
Pale, flabby heart & skeletal muscles, hydrothorax, ascites necrosis / white streaking of skeletal &/or heart muscles
Treatment for Ionophore toxicity
Change feed immediately
There’s no treatment for horses
Prognosis is guarded to poor
Yellow buckeye toxicity
Aesuculus flava
All parts are toxic but fruiting /nut are most toxic
Toxic principle - aesculin
Clinical signs for buckeye toxicity
Ataxia, muscle tremors, lateral recumbency, paralysis, in coordination w hypermetria (high stepping) hyperesthsia, nystagmus/strabismus, prostration, seizures, coma
Lesions and treatment for buckeye toxicity
No lesions just presence of Buckeyes in rumen
Sedatives until symptoms resolves
Decontamination
Indole alkaloids - claviceps ergot
Structures formed from group of fungi in genus claviceps
Fungi infect flowering plants
Sclerotia - dark purple, brown or black & resemble seed heads
Toxicity of claviceps
Produce mixture of ergot peptide alkaloids (ergotamine, ergo sine, ergocyptine, ergocristine, ergonovine) similar structure to LSD
Mechanism of action of ergotamine
CNS properties similarly to LSD, vasoconstriction - burning sensation with subsequent gangrene
Decreased production of prolactin in reproductive females
Clinical signs for acute ergotism
Onset 1-5 days (course 1-7 days)
Ataxia, hyperexcitable, muscle tremors, seizures, opisthotonus (clin signs will subside if leave animal alone)
Syndrome is inseparable from Bermuda grass staggers & perineal ryegrass staggers
Chronic clinical signs for ergotism
Onset 1 week
Anxious, lame, rising temp/pulse/resp rate (TRP)
Swelling above coronary band, ataxic, feed refusal
Sloughing of hooves, ears, tail, skin, teats
- necrosis on tip of tongue in sheep
- potential abortion
Clinical signs for swine - claviceps
(Reproductive)
Onset in late gestation (last 2-4 wks)
Chronic effect, similar to fescue in mares (decreased prolactin)
Feed refusal, agalactia, gestation shorted by 3-5 days, abortion is rare
Fescue, source & toxicity
Lolium arundinaceu, >95% infested with endophytic fungus
All parts of plants infected with endophyte & ergot alkaloids
Primary toxin - Ergovaline
Toxicosis primarily in cattle & mares
Mechanism of action for fescue
Ergot alkaloids have multiple physiologic effects
D2 dopaminergic (decreased prolactin) and alpha 1 agonist (vasoconstriction)
4 primary syndromes
- reproductive dysfunction
- summer slump: intolerance to heat
- fescue foot - peripheral vasoconstriction w gangrenous necrosis
- fat necrosis - abdominal
Bromethalin rodenticide
Rodenticide - often contain 0.01% bromethalin
LD50 for cats
0.54mg/kg
MLD - 0.45mg/kg
MTD - 0.3mg/kg
LD50 for dogs
3.7mg/kg
MLD - 2.5 mg/kg
MTD - 1.67mg/kg
Mechanism of action for bromethalin toxicity
Metabolized in the body, metabolite uncouples oxidative phosphorylation esp in brain
Lack of ATP production = weak Na/K gradient pump in brain = fluid accumulates in myelin sheaths = inference of axon transmission = respiratory arrest/paralysis
Myelin edema appears like spongiosis
Clinical signs for bromethalin toxicity - acute
Acute/convulsant syndrome
Dose ≥. LD50
Can appear 10-24 hr post ingestion
Mortality rate ~ 100%
Agitation, muscle tremors, hyperesthsia, hyperthermia, unequal pupil size, focal, generalized seizures, death
Lesion: spongiosis
Clinical signs for chronic brothemalin toxicity
Paralytic syndrome
Delay in signs usually occur 2 to 5 days post ingestion
Tremors, ataxia, CNS depression, recumbancy, anisocoria, lateral recumbency
Hind limb paresis, loss of deep pain
Lesions: white matter spongiosis
Diagnosing bromethalin toxicity
Diagnosing possible exposure rate
Clinical signs
Ante-mortem fat biopsy
Post-mortem analysis of fat, liver, kidney
Treating & prognosis bromethalin toxicosis
Decontamination - Emesis & repeated doses of activated charcoal (which undergoes enterohepatic recirculation 48hrs)
Treat seizures/supportive care
Prognosis varies on signs, amt ingested and reaction from treatment
Mycotoxins
Fumoisin, slaframine, penitrem A & roquefortine
Molds or fungi developed in feed or silage during storage
≤13.5% moisture
Fumonisin
Moldy corn poisoning
Fusarium fungi especially back in horses
Most cases appear between December-January
Toxicity of fumonisin
B1 & B2 - interfere with formation of sphingolipids, cell membrane and lipid rich structure formations
Low morbidity, high case mortality
Fumonisin mechanism of action
Interferes with sphingolipid biosynthesis - increased sphingosine - inhibition of L-type calcium channels - decrease of Ca2+ release from myocardial sarcoplasmic reticulum - decreased contractility - left sided heart failure
Clinical signs in horses w fumonisin toxicity
Onset 1-4 wks
Acute/rapid CNS clinical signs, death 4-12 hours following onset. Liver/cardiac disease 3-8 days
CNS: depression, ataxia, blindness, facial paralysis, head pressing, maniacal behavior, hypersensitivity, convulsions
Liver tox: mastication problems, yawning, icterus, head edema, petechial hemorrhage
Diagnosing and treating fumonisin toxicity
Presence of contaminated feed & clinical signs
Necropsy - lesion: malacia /necrosis of white matter of brain + hemorrhage
Treatment: remove corn from diet
Slaframine
Slobber syndrome - grown on legumes or clover/alfalfa
Common in horses, goats, cattle, sheep
High morbidity / low mortality
Mechanisms of action for slaframine
Metabolized in liver to ketoimine (active metabolite)
The amine structure in ketoimine has quarternary amine structure similar to acetylcholine and is a parasympathetic alkaloid that works on cholinergic receptors
Does not cross BBB
Clinical signs of slaframine toxicity
SLUD: hypersalavation, lacrimation, urination, diarrhea, dyspnea, feed refusal, piloerection, bloat
- rare abortions/death
Treatment /prevention of slaframine toxicity
Usually none
Antihistamines
Avoid buying legume hay after second cutting or in a wet growing year
Avoid atropine in horses
Tremorgenic mycotoxins
(Aspergillus & penicillium)
Produce molds that grow in organic, decaying matter (milk, moldy English & black walnuts) commonly found in garbage, compost piles, road-kill
Harbor endotoxins/enterotoxins
Toxicity of tremorgenic
Dogs -
Penitrem A & roquefortine are lipophilic, preformed (no metabolizing) = rapid onset & enteroheptic recirculation
*toxic to all species of animals
Mechanism of action of tremorgenic toxins
Suspected they affect transmission of impulses across motor end plates
± inhibits inhibitory neurotransmitters
± increases release of excitatory neurotransmitters
Acute clinical signs of tremorgenic toxins
Onset 10min-4hrs, course 2-3 days
Vomiting, decontamination, salivation, ataxia, muscle tremors, hyperesthesia, facial twitching, clonic-tonic seizures, paralysis, nystagmus
Diagnosing /treating tremorgenic toxins
Stomach contents analysis
Differentiate from strychnine or ethylene glycol toxicity**
Treat: diazepam ± effective, activated charcoal
Toxins causing toxicity with tremorgenic toxins
Lolitrems A & B in perennial rye grass
Paspalitrems in Bermuda & Dallis grass
Fumitremorgens in ergot sclerotia
Chronic clinical signs of tremorgenic toxins
Onset 7-10 days - moderate morbidity, low mortality
Muscle tremors, paralysis, nystagmus/anisocoria, hypersalavation, vomiting, ataxia, hypermetria, hyperesthesia
Diagnosing /treating tremorgenic toxins
Feed analysis, field assessment, ergot sclerotia in hay assessment
Change feed/remove toxins
Sedate animals as needed to protect from CNS signs
Endotoxins cause
Inflammatory reaction
Enterotoxins cause
Fluid and electrolyte loss
