Toxicities Flashcards
Lathyrus hirsutus(Caley Pea) Intoxication in a Herd of Horses
Holbrook et al, JVIM 2015
Results: Bermuda grass hay consumed by the horses contained large quantities of mature Lathyrus hirsutus. Acute clinical signs conform to earlier descriptions of Lathyrus hirsutus intoxication in cattle. Residual neurologic signs were characterized by incoordination in the rhythmicity of multiple gaits. Evidence of mild neurogenic muscle atrophy was recognized in 1 of 5 horses biopsied.
Conclusions and Clinical Importance: Caley Pea intoxication may occur within days of seed pod consumption. The neurologic signs are unique and suggest involvement of the upper motor neuron system and regions of the spinal cord influencing voluntary motor movement. Drought conditions during plant growth may increase the risk of toxicosis
Poisonweed
Staggerweed
delphinium
larkspur
delphinium:
toxin and mechanism
NEUROTOXIN
Diterpene alkaloid (methyllyca-conitine)
Mechanism: NMB –> resp paralysis
delphinium: toxic part
it flowers early, so poisonings occur in spring or fall
early growth or dried parts are worse - less bad after flowering happens
delphinium suceptibility
Cattle > horses > sheep
LD50 cattle is 0.5% BW = 17g/kgBW
delphinium CS
NEUROTOXIN
Sudden death
CNS signs, aspiration pneumonia, bloat, constipation, regurg, salivation
Death d/t resp paralysis/bloat animals fall w/ head downhill
Fatalities within 3-4hrs
Lesions: nonspecific; bloat, congestion, pneumonia, GI inflamm
delphinium TX
Prognosis: guarded
(1) AC + SC
(2) Physostigmine (rarely have enough)
(3) Turn head uphill
(4) Relieve bloat
(5) Abx for asp pneumonia
Prevention: move to new pasture, spot spray, revegetate
*An affected animal may be mistaken for a grass tetany case; however, treatment with magnesium exacerbates the effect of larkspur’s toxins at the neuromuscular junction and should be avoided.
Lathyrus hirsutus
sweet pea vetchlings
Osteolathyrism
Neurolathyrism
Lathyrus hirsutus
sweet pea vetchlings
Lathyrus hirsutus / Osteolathyrism
neurotoxin of cattle in the SE US
Lathyrus hirsutus: toxin and mechanism
Aminopropionic acid derivative
Mechanism: interferes with glutamate receptors in the brain, causing influx of Ca2+ into cells = cell death
Heat-labile = cook it to destroy!
Lathyrus hirsutus: clinical signs
NEUROTOXIN
Neurolathyrism: neuronal degeneration; mm rigidity, paralysis, bradycardia; horse: abnormal gait, hopping gait, tying-up, head low, laryngeal hemiplegia
Osteolathyrism: cattle –> lameness after 3-5d; boney Δ
Horses –> skeletal deformities and aortic rupture (defective cartilage/connective tissue)
–>Holbrook case report
poison hemlock
Conium maculatum
Conium maculatum: toxin and mechanism
Piperidine alkaloids (like nicotine): conine EXTREMELY TOXIC; LD50 < 10g/kg
Mechanism: Direct cholinergic effects (antagonist and agonist) – large dose causes skeletal m stimulation followed by neuromuscular blockade and paralysis
Conium maculatum: toxic part
Young plants = LOW alkaloid concentrations
Roots, stem, leaves and fruit = toxic
Conium maculatum: clinical signs
Nicotinic: salivation, bloating, tachycardia progressing to incoordination and colic
2’ cardiac arrhythmias
Teratogen: 1st trimester = cleft palate, brain/face problems, arthrogryposis, hydrocephalus : Seen in cattle that consumed between 40-70 day gestation
Lathyrus hirsutus: TX
Prognosis: full recovery OR chronic
(1) Gastric lavage
(2) AC + SC
(3) Symptomatic + supportive therapy
Conium maculatum: TX
1) Emetics (don’t repeat if vomited)
(2) Gastric lavage
(3) AC + SC
(4) Resp support (IPPV or Dopram)
(5) Diazepam (seizures)
Water hemlock
(Cicuta maculatum or Cicuta douglasii)
Among most poisonous plants in US
also toxic to humans
Water hemlock: toxin and mechanism
Cicutoxin (unsaturated alcohol) seizurigenic
EXTREMELY TOXIC
2oz kill sheep
8-10oz kill cow
Mechanism: Acts directly on CNS as a violent convulsant (GABA antagonist)
water hemlock: toxic part
stem and root
water hemlock: CS
Seizurigenic: rapid onset (15-60min) –> salivation, abdominal pain, tremors, seizures –> death due to respiratory failure
water hemlock: TX
Prognosis: good if survive 2hrs (excrete alcohol)
Control seizures
Alcohol molecule size too small for AC
Tx with barbituates to control seizures
jimson weed
Belladonna alkaloids: Jimson weed (Datura stramonium)
Belladonna alkaloids exposure:
seed contamination of grain, plant contamination of forage
all plant parts are toxic
Belladonna alkaloids : toxin and mechanism
Belladonna alkaloids = antimuscarinic:
Belladonna (Atropa) –> atropine
Mechanism: competitive antagonism at muscarinic receptors preventing acetylcholine binding
Belladonna alkaloids: CS
mostly toxic to ruminants
Antimuscarinic: tachycardia, tachypnea dry skin, ↓salivation, mydriasis (can be topical), blurred vision, hyperthermia, ↓feed, tremors, bloat, recumbancy
Belladonna alkaloids: TX
(1) Physostigmine
(2) Emetic/AC
CS resolve within 24hrs – death is rare
Yellow Star Thistle
(Centauria solstitialis)
Russian Napweed
Yellow Star Thistle: toxin and mechanism
Unknown
NOT HIGHLY TOXIC
**only toxic to horses
signs after grazing 30-90d (hundreds of ##)
Contains a neurotoxin destroys dopaminergic nigrostriatal pathway – inhibiting effects on cerebral cortex pathways that control prehension and chewing (CN’s V, VII, IX)
Yellow Star Thistle: CS
Mixed CNS: hypertonic facial/lip mm, tongue lolling, head tossing, dysphagia, immerse head in water to drink death 2’ starvation
Lesions: pathognomonic bilaterally symmetric nigropallido-encephalomalacia – liquefactive necrosis in globus pallidus and substantia nigra
“Sardonic grin” is class term used to describe facial lesions
Yellow Star Thistle: TX
Irreversible once symptomatic euthanize
Locoweeds
(Astragalus spp, Oxytropis sericea)
Most destructive to livestock of all poisonous plants
locoweed
whole plant is toxic
Locoism: toxin and mechanism
Locoism:alkaloid swainsonine inhibits mannosidase brain accumulation of oligosaccharides (generalized lysosomal storage disease of CNS)
Locoism: CS
Methemoglobinemia fetlock knuckling (cracker heels), dyspnea, cyanosis, death (24hrs); abortion (fetal Hgb sensitive); brown blood
Locoism: CNS dep, dullness, emaciation, ataxia, then excitement;
reduced fertility (cattle); abortion
Teratogen: skeletal problems
Locoism: TX
Selenosis: no tx; allow to excrete; soft bedding; change diet
Locoism: improve feed; horses = euthanize
Cardiac Glycoside Mechanism
Inhibit membrane sodium-Potassium-ATPase pumps – intracellular sodium increases and potassium decreases – changes in ions flux decreases electrical conductivity = arrhythmias
Used therapeutically to increase myocardial contractility (by decrease intracellular sodium, increases intracellular calcium through Na:Ca Exchanger – more calcium available to actin-myosin apparatus
Nerium oleander
Oleander
Toxin = cardiac glycoside
Oleander suceptibility
ruminants on ionophores are MORE susceptible
CARDIAC GLYCOSIDE CS
Early (GI) = projectile vomiting, diarrhea; bloating, salivation
Later (CV): hypotension, bradycardia,Vtach, SVT, conduction probs
Even later: sudden death
Death hrs or days after ingestion
Lesion: cardiac mm necrosis
CARDIAC GLYCOSIDE TX
MEDICAL EMERGENCY
(1) Emetics
(2) AC + SC
(3) AVOID K+ in tx
(4) Manage cardiac effects for 1-3d (drugs designed for animals w/ pre-existing cardiomyopathy) = unless lethal arrhythmia, don’t be too aggressive w/ heart
Treating arrhythmias: Bradycardia: atropine
Heart block: phenytoin
Tachyarrhythmia: propranolol
Digitalis Abs (FAD antibody): Digibind (works well but $$$)
Milkweed
Asclepias spp
Toxin = Cardenolides (Cardiac glycoside)
AFFECTS SHEEP
Nerium Oleander
Asclepias / Milkweed
Taxus cuspidate / Japanese Yew
Zigadenus / Black Snakeroot / Death Camas
Cardio toxins
Taxus cuspidate
Japanese yew
Toxin = Taxine A and B
cardio toxic
Zigadenus spp
Black snakeroot
Death camas
Toxin = steroidal alkaloids
cardio toxic
Veratrum spp
teratogen in sheep
toxin = cyclopamine, veratramine
Lantana, Crotalaria, and Ragwort and Groundsel are all
hepatotoxins
Crotalaria / Senecio: toxin and mechanism
Pyrrolizidine alkaloids –> pyrrole derivatives (must be bioactivated) –> irreversible liver damage (hepatocyte DNA alkylation, megalocytosis)
Crotalaria / Senecio: CS
Hepatic veno-occlusive dz –> icterus, ascites, edema–> fibrosis
Liver necrosis and death: bipsy – triad of fibrosis, bile duct proliferation and megalocytosis
Ragwort mechanism
Pyrroles crosslink DNA – antimitotic effect and hepatocytes can’t divide = replaced by connective tissue = megalocytosis
Perilla frutescens
Perilla mint
Perilla mint: toxin and mechanism
Perilla ketone (similar to 4-ipomeanol from moldy sweet potatoes) –> reactive metabolite in Clara cells –> lung damage (especially alveolar Type I cells; proliferation of type II pneumocytes = interstial pneumonia)
perilla mint: CS
Acute bovine pulmonary emphysema & edema (ABPE) Respiratory distress (grunt on exhale), nasal discharge, cyanosis, hypersalivation
Lesions: pulmonary fibrosis, emphysema, edema, congestion
perilla mint: TX
No specific antidote
Hard to reverse once CS
Supportive: steroids, antihistamines, abx
Prevention: eliminate
Ddx for ABPE: moldy sweet potatoes, lush pasture (3-methylindole)
Pteridium aquilinum
bracken fern
bracken fern: toxin and mechanism
Ptaquiloside – primary carinogen
Causes bone marrow supp ↓neut/plt/anemia
SE: thiaminase thiamine deficiency (horses and pigs = NOT cattle)
bracken fern: CS
Bone marrow: hemorrhage on mucus membranes, hyphema, melena, anemia
Thiamine deficiency: anorexia, wt loss, weakness, ataxia, crouching stance, arched neck in horses
polioencephalomalacia (ruminants)
Bladder neoplasia = Red water disease (cattle/sheep)
Veratrum tenuipetalum; V. californicum”
Hellebore
Over 50 alkaloids – some are teratogenic
Sheep: if consumed on 14th day of gestation = CYCLOPS LAMP (Boards ?) and monkey faced facial deformities
After 30-35 days, shortened limbs
bracken fern exposure
Common in South East US
Exposure: fresh plant or dried in hay (young fronds palatable)
More likely in dry years
bracken fern tx
give thiamine
Organophosphates and carbamates
Both are acetylcholinesterase (AChE) inhibitors w similar chemical effects
Carbamates are esters of carbamic acid
OPs are esters of phosphoric acid
Organophosphates and carbamates: mechanism of action
Can enter body through oral, dermal or resp route
Bind and inhibit the AChE (and other cholinesterases) within the nervous system, the neuromuscular junctions and blood, causing an accumulation of the acetyl choline neurotransmitter at postsynaptic receptors
OP’s considered irreversible inhibitors of the enzymes, whereas carbamates are reversible inhibitors of AChE
Muscarinic signs of AChE inhibition
vomiting, dyspnoea, colic, salivation, lacrimation, urination, diarrhoea, miosis, tracheobronchial secretion, lung oedema, cyanosis
Nicotinic signs of AChE inhibition
twitching of muscles, tremors, followed by convulsions, and seizures which can finally progress to paresis and even paralysis
Organophosphates and carbamates: diagnosis
atropine test dose – preanaesthetic dose of 0.02 mg/kg IV à if HR decreases and mydriasis occurs, it is not an OP or carbamate poisoning
antidote tx for OP: atropine sulphate and pyridine 2-aldoxime methochloride (2-PAM)
- -atropine will control muscarinic R associated signs. 0.22 mg/kg (1/4 dose given IV, remainder IM or SC)
- -2-PAM will control the nicotinic signs. 2-aldoxime methochloride reactivates the AChE enzyme and can control nicotinic and CNS associated signs. Has to be administered within 24 h of exposure. Dose in horses is 20 mg/kg slow IV, repeated q 4-6 h. Not recommended for carbamate toxicosis because this drug has less affinity for carbamates and the AChE inhibition is usu rapidly reversible
metalaldehyde toxicity
Cyclic tetramer of acetaldehyde
Toxicity characterised by CNS signs, metabolic acidosis and resp alkalosis
Exact mechanisms unknown, but decrease in the conc of the inhibitory NT GABA, noradrenaline and serotonin (5-hydroxytryptamine, 5-HT) as well as increased monoamine oxidase activity may be involved
CS usu within 15 min to a few hours: agitation, ataxia, hypersalivation, hyperaesthesia, muscle spasms, profuse sweating, convulsions, tachycardia and hyperpnoea. Signs of severe and unrelenting colic also reported.
Death, usu dt resp failure, can occur within a few hours of ingestion and oft preceded by violent convulsions
