toxo final

 MOA blocks the synthesis of vitamin K dependent clotting factors (II, VII, IX, X)
 Clinical 2-5 day lag time since factors don’t immediately deplete
o Hemorrhage, depression, anorexia, icterus, pale mm, sudden death
 TX VITAMIN K 1 orally w/ fatty meal for 30 d. plasma,
o avoid phenothiazines (ACE)
 Brodifacoum – highly toxic, most common sold

 MOA blocks the synthesis of vitamin K dependent clotting factors (II, VII, IX, X)
 Clinical 2-5 day lag time since factors don’t immediately deplete
o Hemorrhage, depression, anorexia, icterus, pale mm, sudden death
 TX VITAMIN K 1 orally w/ fatty meal for 30 d. plasma,
o avoid phenothiazines (ACE)
 Brodifacoum – highly toxic, most common sold

 rodenticides, vitamins, Calcipotriene skin cream
 MOA ↑ Ca & P absorption from GI ↑ osteoclast resorption via PTh & renal retention of Ca via distal tubule resorption  ↑Ca, ↑ P
 Clinical renal tubular damage & necrosis, abnormal soft tissue mineralization
 TX saline diuresis, furosemide, prednisone, calcitonin, PAMIDRONATE

 Rodenticide, pugent garlic odor, decomposes in acid/moist environment (more toxic in animals that just ate)
 MOA blocks ion transport energy deficit in CNS and heart  CNS excitement and seizures
 Clinical  15 minutes to 7 hours – signs are variable
o Bloody vomiting, ataxia, weakness, seizures, hyperesthesia
 Lesions – hepatic fatty change, myocardial and renal tubular damage
 Treatment – supportive, no antidote

 Rodenticide dyed red or green
 MOA antagonizes glycine (inhibitory neurotransmitter) uncontrolled excitation of the spinal reflex (extensor muscles)
 Clinical15 minutes to 2 hours
o muscle tremors, extremely sensitive to external stimuli, tonic to tetanic seizures, rigid limbs, death from anoxia
 Treatment – supportive care, respiratory support, control seizures

 Rodenticide particularly toxic to cats, green pellets
 MOA impairs Na pump fluid accumulation in myelin sheaths and CNS  paralysis
 Clinical signs – dose dependent
o Low dose –ataxia,bladder & hind limb paralysis, depression, coma
o High dose – convulsion, hyperexcitability, running fits, hyperesthesia, seizures
 Treatments Supportive, AC, dexamethasone, mannitol, diazepam

 Snail and slug bait, Cyt P450 inducers
 MOA ↓ brain neuroamidase, serotonin & 5-HIA  ↓seizure threshold
 Clinicalminutes to several hours –
o muscle tremors, continuous spasms, hyperesthesia, opisthotonus (rigid in all 4 limbs), hyperthermia, hyperpnea, acidosis, mydriasis, nystagmus
 Lesions – hepatocellular swelling, neuronal degeneration
 TX supportive care for signs, no antidote

 type 1 – slows open/close of Na/K/Cl channels  extend action potential  muscle tremors and excitement
o permethrin (type 1) is very toxic to cats
 Type 2 – membrane depolarization predominates  affect GABA  weakness and paralysis
 Clinical <1hr – hyperexcitable, tremors, seizures, ataxia, vomiting
o Cats – hypersalivation, vomiting, seizures
 DX ↑ neutrophils, ↓ glucose
 Tx supportive, methocarbamol, GLUCOSE

 MOA inhibit acetylcholinesterase at cholinergic synthesis
 Clinical – minutes to hours – Cats more sensitive to
o SLUD, vomiting, death from respiratory failure
o Muscle tremors, stiffness, paralysis, rarely seizures
 Interactions – phenothiazine tranquilizers, neuromuscular blocking agents, aminoglycoside antibiotics
 Tx ATROPINE or glycopyrrolate, supportive, 2-PAM

 Don’t use on cats
 MOA acts on alpha 2 adrenergic agonist (similar to xylazine)
 Clinical  dose related and onset in 2-4 hours
o small doses – mild GI signs
o High doses – CNS depression/ataxia, ↓ temp, HR, temp, ↑ Glucose
o Fatal in horses
 TX supportive care, yohimbine, atipamezole

 MOA when ↑ level, can’t keep up to reduce to ammonia nitrite absorbed into blood  vasodilation
o oxidizes ferrous iron in hemoglobin to ferric state  forms methemoglobin  hyperemic hypoxia brown blood
 Clinical 30 minutes to hours
o weakness, cyanosis of mucous membranes, ataxia, collapse, death
 TX methylene blue 1% IV (reduces methemoglobin to hemoglobin)

 pitted fruits, trees and shrubs, almonds, grasses – almond odor
 MOA cyanide ion combines w/ferric in the cytochrome oxidase path  blocks electron transport & oxygen transfer  cellular hypoxia
 Clinical excitement, muscle tremors/seizures, polypnea, dyspnea, mucous membranes are bright red
 Diagnosis – sodium nitrate and sodium thiosulfate (excretes in urine)

 Cobras and corals
 MOA neuromuscular blocking, postsynaptic
 Clinicaldelayed up to 12 hours –
o ascending flaccid paralysis, salivation, death via respiratory failure
 TX supportive, antivenin if early enough

 Pit vipers – copperhead, cottonmouth, rattlesnakes –
 MOA—many components pain, thrombolytic which dissolves clots
 Clinicalpain, petechiation, ecchymosis & skin discoloration, hypotension/shock, spherocytes, tissue necrosis & sloughing w/ time
 Lab – hemolysis, hypoproteinemia, thrombocytopenia
 TX supportive, antivenin will reverse coagulopathy, thrombocytopenia and paralysis but not tissue necrosis and renal damage

 Clinical erosions/ ulcers on all mucous membranes, myocardial necrosis, polyuria, hematuria, colic, hyperemic mucous membranes
 Tx symptomatic, mineral oil, analgesics (Flunixin meglumine)

 MOA ↓ RNA polymerase ↓ mRNA ↓ protein synthesis
o Liver, kidneys, and intestines are affected the most
 4 clinical phases
o Initial latent period 6-24 hours
o Gastroenteric phasesharp colicky abdominal pain, nausea, vomiting and watery diarrhea
o Second latent period  apparent recovery
o Organ failure phase 36-48 hours post exposure
 TX – supportive

Bluegreen Algae

 Exposure= ingestion of performed toxin or spores, contamination of wounds with spores
 MOA ↓ release of acetylcholine from presynaptic vesicles
 Clinicalprogressive flaccid paralysis, weakness and ataxia
 TX antitoxin only effective against unbound toxin, penicillin

 horses and lambs
 2 toxins= tetanospasmin (neurotoxin) & tatanolysin (spore formation)
 MOA blocks release of inhibitory neurotransmitters
 Clinical signs – 5-10 days after infection – localized stiffness
 TX penicillin, antitoxin (only prevents unbound toxin)

 Large shrubs to small tress – all parts are toxic
 Toxin =Andromedotoxin blocks inactivation of sodium channels prolonged depolarization and excitation
 Clinical salviation, vomiting, diarrhea, weakness, paralysis, impaired vision, varying degrees of heart block
 Therapy – supportive, ATROPINE

 Toxin – tropane alkaloid anticholinergic effect at muscarinic receptors
 Clinical look like an atropine overdose – ↓ secretions, blindness, mydriasis, paralytic ileus, bloat

 Dogs only, toxin unknown
 Clinical non-fatal, reversible paresis and paralysis (usually hind limbs)
o Vomiting, mild abdominal pain, weakness, lameness, joint pain, recumbency, ataxia, CNS depression, tremors, hyperthermia, pale mucous membranes
 TX recover in 48 hours regardless of therapy

 Toxin – Taxine A and B cardiotoxin ↓ conduction or depolarization, (direct action on cardiac myocyte ion channels)
o not a cardiac glycoside,
 Clinical– bradycardia, dyspnea, fatigue, collapse, coma, v/d
 Tx supportive, none

 MOA↑ free radical formation  direct RBC damage & denatured hemoglobin  Heinz body formation & acute hemolysis
o Also has anti-thrombotic agents, cardiac & smooth muscle relaxants, vasodilators and hypotensives,
 Dogs most often affected
 Clinical acute hemolytic crisis( weakness, tachypnea, icterus, anemia, hemoglobinuria)
 Treatment – supportive, transfusion

 Toxin – calcium oxalate crystals damage cells in the mouth, local reactions are from kinins
 Clinical immediate pain & irritation upon chewing, headshaking, intense salivation, swelling of mucous membranes of pharynx and tongue, vomiting, diarrhea, secondary dehydration
 TX rinse mouth, oral calcium may help precipitation of soluble oxalates, supportive

 Toxin = Toxalbumin/lectin – affinity for sugar molecules
 MOA B chain binds to galactoside-containing proteins on cell surface facilitating internalization  A chain enters the ER and depurinates 28S rRNA  inhibition of protein synthesis
 Clinical  few hours to days –
o Bloody vomit, bloody diarrhea, tenesemus and abdominal pain
 Lesions – catarrhal to hemorrhagic gastroenteritis, petechial hemorrhages on serosa, necrotizing enteritis, edematous mesenteric LN
 Therapy – no specific antidote, supportive

 Cats are uniquely sensitive
 Clinical both renal and GI – vomiting, salivation, depression, anorexia, polyuria (12-24 hours), dehydration around (48hours), weakness, recumbence and death in 3-7 days
 Lab results – proteinuria, glucosuria, isosthenuria, casts
 Lesions – pulmonary & hepatic congestion, perirenal edema & swollen kidneys
o Microscopic – diffuse acute renal tubular necrosis (proximal tubules usually), intact basement membranes, granular and hyaline casts
 Tx GI decontamination, fluid therapy prior to anuria

 Toxin – Diterpenoid phorbol esters – directly irritant/blistering cmpds
 Clinical severe irritation of the mouth and GI tract, blistering, periocular and perioral swelling, salivation
 TX supportive, dilute toxins water or milk

 Only see in dogs (but not all)—MOA is unknown
 Clinical V/D within a few hours of ingestion, anorexia, lethargy & weakness, abdominal pain, polydipsia, tremors, reduced to no urine production (advanced cases) – looks like hypercalcemia
 Lesions – no gross lesions, degeneration & necrosis of PCT epithelium,
 Treatment – supportive, dieresis, mannitol and furosemide

Horses only


 Toxin – lactones – solstitialin, cynaropicrin
o High intake over 30+ d. required for toxicosis
 Clinical involuntary chewing, twitching of the lips, open mouth, can’t eat
 Lesions – selective necrosis of globus pallidus and substantia nigra, nigopallidal encephalomalacia
 Treatment – none, euthanasia recommended

 Toxins – quinolizidine alkaloids
o Lupanine – bind nicotinic and muscarinic receptors
o Anagyrine – teratogenic alkaloid in cattle but not sheep
 Clinical
o Sheep 1-3 hours post ingestion – labored breathing, depression, salivation, ataxia, clonic spasms, head pressing, tremors, seizures
o cattle  ingestion at 40-70 days gestation – “crooked calf dz” malformed calves alive at term, misaligned joints, twisted bones

 Toxin – Cicutoxin
 Clinical signs – violent seizures, resembles strychnine
 Treatment – GI detoxicification, seizure control

 Toxin tremetone – toxic when dried, secreted in the milk, effects are cumulative induces myonecrosis
 Clinical  slow to develop due to cumulative nature –
o reluctance to move, muscle tremors, acetone odor to breath, sweating, jugular pulses, arrhythmias, dark urine, CRT > 3 sec
 Therapy – supportive

 Only affects horses
 Toxin – unknown – but present in wilted or dried leaves
 MOA toxin induces Heinz body formation, methemoglobinemia, intravascular hemolysis
 Clinical weakness, ↑ RR & HR, icterus, cyanosis, hemoglobinuria
 Treatment – IV fluids, oxygen, blood transfusion

 Toxin – Dimethyl disulfide – only if use is excessive
 MOA oxidizes hemoglobin Heinz body formation hemolytic anemia
 Clinical signs/diagnosis/treatment – same as for red maple or onion

 Toxin – Coumarin glycoside (melilotoside) – requires conversion to coumarin in plant fungi in the stems then converts to dicoumarol
 MOA-- acts as a vitamin K antagonist  ↓ clotting factors
 Clinical hemorrhage, large hematomas, anemia, weakness, pallor
 TX fresh blood or plasma restores clotting factors, VITAMIN K1

 Toxins
o Cevanine alkaloid-- neurotoxin, bind open voltage-selective Na channel
o Jervanine alkaloid-- teratogenic – cyclopamine, cycloposine, & jervine
 Cyclopamine – most important since highest concentration– interferes with intracellular signaling and patterning during embryogenesis and organogenesis
 Clinical acute poisoning – ↑ salivation, emesis, ataxia, collapse, death
 Teratogenesis – ewes are exposed from day 12-30 of gestation – cleft lip and palate, syndactylism
o Craniofacial defects (Cyclops) – consumption on day 14
o Limb and tracheal defects – consumption from day 28-33 (shortening of metacarpals/tarsals

 Toxic principle – pyrrolizidine alkaloid
 MOA converted by mixed function oxidases to toxic pyrroles  activated &remain in the liver  react with cellular proteins & nucleic acids  hepatocyte necrosis
o Lower doses – prevent mitosis in hepatocytes  hepatocytomegaly  chronic hepatopathy ensues
 Clinical signs
o acute – hepatic insufficiency, icterus
o Chronic (2-8 mo after)– ↓ weight/ emaciation, icterus, photosensitivity
o CNS – hepatoencephalopathy – head pressing, aimless walking, coma
 Gross lesions – liver failure – anorexia, depression, icterus, edema
o Chronic – firm nodular liver (cirrhosis), icterus, photosensitivity
 Microscopic – hepatocytomegaly (atypical nuclei/karyomegaly), bridging periportal fibrosis
 Treatment – none

 Swine are most affected, but cattle and sheep are susceptible
 Toxin – carboxyatracytloside – found only in the seeds and cotyledons
 MOA competitively inhibits oxidative phosphorylation in mitochondria  block ATP transport  cellular damage  hepatocytes and PCTs highly susceptible to damge
 Clinicaldepression, abdominal pain, convulsions, opisthotonus
 Lesions pale liver w/ lobular pattern, centrilobular hemorrhages
 Histopathhepatic & renal tubule necrosis & hemorrhage
 Treatment – supportive care

 Mainly affects cattle and calves in the fall due to acorns
 Toxin – metabolites of tannic acid
 Three pathways
o Direct toxicity to GI epithelium  ulceration
o Hydrolyzed tannins are absorbed damage endothelia
o Metabolites of ingested tannins are toxic to proximal tubular epithelium  acute tubular necrosis
 Clinical signs – anorexia, dullness, rumen atony, constipation, melena, weak, prostrate, icterus, hematuria
 Gross lesions – ascites, hydrothorax, perirenal blood tinged edema, hemorrhagic and ulcerative gastroenteritis
 Treatment – calcium hydroxide in feed, supportive

 Affects mainly pigs
 Toxin – Unknown – causes acute renal tubular necrosis
 Clinical signs – 5-10 days after ingestion - posterior weakness, incoordination, sternal recumbency
 Histologic lesions – acute tubular necrosis affecting both proximal and distal tubules

 Sheep sometimes cattle
 Toxin – soluble oxalates (sodium and potassium)
 MOA: soluble oxalates complex with serum Ca+  forms crystal in tubular epithelium  functional hypocalcemia
 Clinical signs - 2-6 hours –
o dull, depressed, abdom pain, rumen atony, twitching, bruxism,
 Gross lesions – ascites, hydrothorax
 Microscopic lesions – oxalate nephrosis – crystals are birefringent rosettes under polarized light

 horses – walnut shavings are used for bedding
 Toxin – unknown – juglone is toxin in the leaves but not in hardwood
o causes vasoactive effect with ischemia, reperfusion
 Clinical reluctance to move, depression, ↑ temp, HR, RR, digital pulse, hoof temp lower limb edema, severe laminitis (P3 rotation & separation)
 Treatment – remove bedding, oral detox, treat limb edema & laminitis

 cattle, horses
 Toxin – ergot alkaloid – toxin found in leaves and seeds
 MOA –peripheral vasoconstriction  vascular stasis, inadequate heat dissipation & dry gangrene
 Clinical signs – three syndromes-
o Fescue foot – due to peripheral vasoconstriction, symptomatic tx
 Dry gangrene/sloughing of the extremities
o Bovine fat necrosis – heavily fertilized, endophyteo-infected fescue
 hardened fat in the abdomen, necrotic fat is mineralized
o Summer syndrome Intolerance to heat, ↓ milk & fertility
 Treatment – remove fesicue from diet, reduce seed head production (cut hay early), add legume
 Equine fescue toxicosis – ↓ prolactin and progesterone late term abortions, prolonged gestation, dystocia

 MOA 1-4 hours – metabolized by liver enzyme alcohol dehydrogenase  toxic organic acids cause severe acidosis  bind to form calcium oxalate crystals in kidney tubules
 Clinical signs – 3 stages
o Acute  30 min -12 h, vomiting, ataxis, depression, PU/PD
o Renal stage – 12-72 hours – severe depression (acidosis), V/D, ↓ urine production, miosis, coma, seizures due to hypocalcemia
o 3rd stage – oliguric renal failure, acidosis Calcium oxalate nephrosis
 Laboratory – serum hyperosmolality, large anion gap, hypocalcemia, calcium oxalate crystalluria
 Tx supportive, sodium bicarb, 4-methyl pyrazole or ethanol to block alcohol dehydrogenase, FOMEPIZOL (diethylene glycol)

 Caffeine, theobromine ( chocolate, cocoa mulch), theophylline
o Clinical strong cardiac stimulant, premature ventricular contractions, arrhythmias, CNS excitement, hyperreflexia, seizures, vomiting and urinary incontinence
 Tx supportive, lidocaine for PVCs, beta blockers (PROPRANOLOL)
o Don’t use corticosteroids or erythromycin

 No dose is safe in cats – cats unable to conjugate the drug
 MOA-- metabolite of ACM conjugates to glutathione  binds to liver proteins  liver necrosis and Heinz body anemia
 Cats – predominant blood and metabolic
o Methemoglobin & anemia  cyanosis, hematuria, hemoglobinuria, edema of face and paws, lacrimation, pruritus, anorexia depression
 Dogs – mainly GI (vomiting, diarrhea) and liver
o Icterus and hemolysis, ↑ serum ACM & blood GSH depleted
 Treatment – acetylcystein (Mucomyst), supportive, SAMe, ascorbic acid, cimetidine, methylene blue
o Steroids and anithistamines are contraindicated

 Beta-adrenergic agonist – stimulates cAMP  relaxes bronchial & vascular smooth muscle  arrhythmias, bradycardia, tachycardia, heart block, tachypea and hypertension
 Therapy – beta-adrenergic antagonist (PROPRANOLOL)

 Products – naproxen, ketoprofen, carprofen (rimadyl), deramaxx, metacam (meloxicam) *bold= COX-2 only, others are both COX1 & 2
 Clinical dose dependent
 anorexia, abdominal pain, blood loss anemia, PU/PD, acidosis, ataxia, coma, acute renal failure
 TXsupportive, sucralfate & cimetidine for gastric ulcers, misoprostol inhibits GI effects

 MOA ↓ uptake of serotonin at presynaptic membrane  ↑serotonin  CNS stimulation
 Dogs are more susceptible than other species
 Clinical signs – agitation, vocalization, vomiting, tremors, hyperthermia, transient blindness, seizures, ataxia, GI effects
 Treatment – supportive, CYPROHEPATIDINE (serotonin antagonist), chlorpromazine, beta-blockers

 MOA inhibit uptake of norepinephrine and serotonin in CNS
o Parasympatholytic
 Clinical sedation, anorexia, seizures, cardiac arrhythmias, CV collapse
o Anticholinergic effects – mydriasis, blurred visions, dry mouth, tachycardia, urinary retention
 Tx – supportive, sodium bicarb, physostigmine

 MOA in dog stimulates insulin secretion
o Produces reactive O2 ↓ hepatic cellular ADP, ATP, Pi severe hepatic necrosis
 Clinical hypoglycemia 10-60 minutes post-ingestion, acute hepatic necrosis, ↑ liver enzymes, icterus, melena, hepatic encephalopathy, vomiting, diarrhea, weakness, ataxia, secondary DIC
 Therapy – supportive, IV fluids with dextrose, SAMe, silymarin, N-ACETYLCYSTEIN