4-Musculoskeletal Toxicity

Question 1

Muscle toxicants

Answer 1

Phenoxyacetic acid herbicides

Ergot alkaloids

Ionophores

DDX: tetanus

Question 2

Muscle toxicant Signs

Myopathy

Lameness

Answer 2

Myopathy

• Gossypol
• Strychnine

Lameness

• Ergot/fescue
• Selenium
• Vitamin D overdose

Question 3

Phenoxyacetic acid herbicies

Answer 3

Types (causes weed overgrowth then death)

• 2,4-D (Scott’s weed and feed)
• 2,4,5-T
• Silvex

Low tox most animals (won’t see very much)

• Cattle >200mg/kg for mult days
• dogs > 20mg/kg for mult days
• LD50 pigs and chickens > 500 mg/kg

Silvex: very toxic

Susceptible animals predisposed, kidney or genetic dysfunction

MOA: unknown

*ubiquitous and widely used

Question 4

Phenoxyacetic acid tox

Clin signs

Answer 4

GI effects (dogs)

Muscle effects

• myotonia with serious toxicosis
• rumen atony
• rigid skeletal muscles, hesistation to move
• atakia, weakness, posterior weakness

Renal tubular degeneration

Hepatic necrosis

Question 5

Phenoxyacetic acid tox

Diagnosis

Answer 5

Chemical analysis of serum, urine

Clin path (not many signs….liver)

Hyperemia of lymph nodes

Congestion of kidney/liver

Enteritis, rumen stasis

Oral and GI ulcers

Question 6

Phenoxyacetic acid tox

TX

Answer 6

GI

• emesis, lavage

Dermal

• bath, decontamination

Activated charcoal/cathartic

Ion-trapping to enhance excretion

• 1-2 mEq/kg NaHCO₃ if kidneys normal
• BW: BUN creatinine, N u output

Prognosis good for treated animals

Question 7

Ergot alkaloids

Answer 7

Produced in small grains by claviceps purpurea

• barley, rye, wheat, oat

Tall fescue (doesn’t always produce the ergot stuffs)

• endophytic fungus

In infected grains, seeds are replaced by sclerotia

• look like mouse droppings

Fescue infection not detectable by naked eye

At least 40 alkaloids have been identified

• ergovaline
• ergonovine
• ergotamine
• LSD

Question 8

Salam Witch Trials

Answer 8

Ergot poisoning hypothesis

-rye was contaminated with claviceps purpurea and causing hallucinations

St. Anthony’s fire

-gangrenous fingers

Question 9

Ergot toxicities

Answer 9

Hallucinations

• dopamine serotonin agonism of alkaloids

Decreased prolactin secretion

• activity at dopamine receptors in pituitary
• affects fertility and reproduction

Smooth muscle contraction causes abortion and eschemia

• uterus
• peripheral vasculature
  
  • alpha-adrenergic antagonist activity

Question 10

Ergot alkaloid tox

Clinial signs in cattle

Answer 10

Reduced feed intake

weight gain,

heat intolerance

Summer slump: retain winter coat

Necrotizing ergotism

• lameness
• gangrene of extremities
  
  • ‘Fescue foot’: sloughing of feet, ears, tail

Fat necrosis

Poor reproductive performance

Question 11

Ergotism in horses

Clinical signs

Answer 11

abortions

weak foals

prolonged gestatino

Question 12

Ergotism in pigs

Clinical signs

Answer 12

Infertility

Early parturition

Decreased milk production

Question 13

Ergotism and treating Ergotism

Answer 13

Evidence of sclerotia in feed

Fescue in forage matter

Chemical analysis of feed and forage for ergot metabolites

Treatment

• remove source
• prevent secondary infections
• Metoclopromide and domperidone
  
  • inc prolactin secretion and normalize gestation in mares

Question 14

Ionophores

Answer 14

Compounds that form lipid soluble complexes with cations

• facilitate specific ionic transport across membranes

Used as antibiotic (monensin, salinomycin)

• Monensin: beef and dairy to prevent coccidiosis and prevent bloat
• Imp efficiency of milk production

Several other marketed and off-label uses

*horses most susceptible

Question 15

Ionophores

MOA

Answer 15

Inc intracellular Na and Ca

• mitochondrial swelling
• cell death
• muschle probs (Ca)

Feed mixing errors

Horses most susceptible (LD50 1-2 mg/kg)

• consumption of ionophore containing poultry or cattle feed

Poultry least sensitive

Question 16

ionophore tox

clinical signs

Answer 16

Usually 12-72 hours after ingestion

Anorexia

• common in all animals

Horses

• anorexia
• colic
• profuse sweating on flanks
• ataxia, weakness
• cattle (similar to horses, plus diarrhea and respiratory diff)

dogs: posterior paresis, paralysis with lasalocid

Cats: polyneuropathy from salinomycin

Question 17

Ionophore tox

DX

Answer 17

Increased muscle enzymes and myoglobinuria

Elevated AST, CK, LDH, Alkaline phosphatease, BUN, Bilirubin

Hypokalemia, Hypocalcemia (horses)

Chemical analysis of feeds, liver (NOT BLOOD)

Differentiate from other colics

• vit E, selenium deficiency
• white snakeroot
• blister beetle
• gossypol
• botulism

Question 18

Ionophore tox

Necropsy

Answer 18

WHite muscles

Wide striations

infiltration with leukocytes

Question 19

Ionophore tox

TX

Answer 19

Stop feeding ionophores

Supportive therapy

Recovered animals may die from exercise intolerance

Question 20

Tetanus

(Clostridium tetani)

Answer 20

Mostly affects cattle

Usually caused by spores in puncture wounds, can be ingested

Toxics block release of GABA and glycine (block inhibition)

• inhibitory neurotransmitters

Overstimulation of muscles leading to stiffness and tetany

*Strychnine is a ddx

Question 21

Tetanus tox

Clinical signs

Answer 21

Stiffness, reluctance to move

Twitching and tremors of the muscles

Lockjaw

Unsteady gait with stiff tail

Bloat (ruminants)

Later

• collapse
• spasm
• death

Question 22

Tetanus tox

TX

Answer 22

Antitoxin

• effective at very early stage

Supportive therapy

Prognosis poor

Question 23

Pulmonary toxicants

Ventilatory muscle paralysis

Answer 23

Botulism, tetanus, snake venom

OP insecticides

Strychnine

Question 24

Common respiratory toxins

Respiratory center depression

Answer 24

Barbiturates, opiates/opiodes

Ethylene glycol

Hypnotics, sedatives

Trycyclic antidepressants

Crude oil: no emesis, dilute, avoid aspiration

Paraquat and diquat: herbicides