Ionophore toxicosis Flashcards
5 uses of ionophores?
- Anticoccidial in poultry, cattle, and goats
- Growth promoter feed additive in cattle
- Monensin is approved to improve efficiency of milk production in dairy cattle in the US
- Reduction of bloat and rumen acidosis in ruminants
- Prevention of tryptophan-induced atypical bovine pulmonary emphysema
Examples of ionophores?
- Monensin
- Lasalocid
- Salinomycin
- Narasin
- Semduramicin sodium
- Laidlomycin propionate potassium
- Carboxylic acid derivatives antibiotics
Solubility?
Slightly soluble in water, soluble in organic solvents and oils
Form lipid-soluble complexes with what?
With polar cations (Na, Ca, K Mg) that are transported across cellular membranes
What is the most common source of ionophore toxicosis?
Monensin
What are 3 other sources of ionophore toxicosis?
- Eating feeds that contain more than the recommended levels in chickens, cattle and swine
- Eating feeds with added ionophores, accidentally or intentionally, in horses, sheep and dogs
- Malicious poisoning in horses
Which animals are susceptible to ionophore toxicosis? Which species are the least, intermediate, and most sensitive?
- All animals susceptible
- Equine are the most sensitive, cattle are intermediate, and poultry are the least sensitive
T/F: Horses that ingest recommended ionophore levels for cattle are poisoned
FALSE–they are not poisoned
Concurrent administration of which drugs increases toxicosis?
- Tiamulin
- Chloramphenicol
- Erythromycin
- Sulfonamides
- Cardiac glycosides
Toxicokinetics of monensin
Absorbence: ruminants vs. monogastrics?
- Ruminants absorb about 50%
- Monogastric animals absorb most of it
Toxicokinetics of monensin
Where is it distributed?
Throughout the body
Toxicokinetics of monensin
T/F: Blood and tissue levels are relatively small, but monensin accumulates in tissues of animals when given in high doses
FALSE–monensin does not accumulate in tissues when given in high doses (the rest is true)
Toxicokinetics of monensin
Metabolization and excretion?
Rapidly metabolized by P-450 oxidative demethylation enzymes in the liver (slow metabolism in equines because they have the lowest oxidative demethylases) and excreted mainly in bile
Mechanism of action
What does ionophore toxicosis disrupt?
Disrupts transmembrane electrochemical gradients
Mechanism of action
What are the main targets?
The mitochondria of highly energetic tissues (myocardium, skeletal muscles, and the kidney)
Mechanism of action
Ionophore toxicosis causes an influx of what?
Influx of the sodium-ionophore complex increasing intracellular Na accompanied by increasing intracellular Ca
Mechanism of action
Ionophore toxicosis causes sequestering of, inhibition of, and decreased what? What does this lead to?
Sequestering of Ca by mitochondria and inhibition of mitochondria and decreased ATP and energy–> increased cytoplasmic Ca
Mechanism of action
What is the cell death due to?
Disrupting homeostatic mechanisms
Mechanism of action
Ionophore toxicosis also causes catecholamine release, which results in what?
Oxidation products and free radicals causing sarcolemmal membrane damage
Disruption of ion concentrations in excitable cells (neurons, myocardium, skeletal muscles, smooth muscles) alters their functions
Pretty chart explaining mechanism of action
(actually it’s pretty ugly/boring)
Clinical signs in horses?
- Rapid onset
- Anorexia, profuse sweating, colic, depression, incoordination, hyperventilation, tachycardia, tachyarrhythmias, prostration, and death
Clinical signs in cattle?
Anorexia, diarrhea, depression, labored breathing, ataxia, prostration, and death
Clinical signs in poultry?
Anorexia, diarrhea, ataxia, resting on the knees with wings and legs directed outward, decreased egg production
Clinical signs in dogs?
Ataxia, muscle weakness of hind limbs, respiratory paralysis, dysuria, constipation, and depression
Lesions?
- Mainly cardiac muscle lesions in horses (pale cardiac muscles, white streaks of necrosis in the myocardium), and also skeletal muscle lesions
- Mainly skeletal muscle lesions in sheep, swine, and dogs (pale skeletal muscles)
- Both skeletal and cardiac muscle lesions in cattle and poultry
Chemical analysis for ionophores (detection, best samples, other samples)?
- Methods detect ppb levels
- Best sample is feed
- Other samples are GI contents, liver, and feces
Which enzymes are elevated following ionophore toxicosis?
- Creatinine phosphokinase (CPK)
- Aspartate transaminase (AST)
- Lactic dehydrogenase (LDH)
- Alkaline phosphatase (ALP)
What is decreased on the clinical pathology? What remains unchanged? What is increased (besides enzymes)?
- Decreased serum Ca and K (during first 12hrs)
- No change in Na
- Increased PCV
Diagnosis?
- History of feed-related problem
- Clinical signs
- Lesions
- Lab diagnosis
DDx
General (all species)?
Include other myopathy and neuropathy conditions
DDx
Horses
- Colic
- Blister beetle ingestion (cantharidin toxicosis)
- Azoturia
DDx
Cattle?
Vitamin E/selenium deficiency
DDx: poisonous plants
Plants affecting skeletal muscle?
- Coffee senna (Senna occidentalis)
- Coyotillo (Karwinskia humboldtiana)
- White snakeroot (Eupatorium rugosum)
DDx: poisonous plants
Plants that are cardiotoxic?
- Oleander
- Taxus spp.
- Milkweed
- Vetch
DDx
Poultry
- Nutritional myopathy
- Coffee senna toxicosis
- Botulism
- Na-water deprivation toxicosis
- Mycotoxicosis (moniliformin cyclopiazonic acid)
- Round-heart disease
- Downer syndrome (viral arthritis)
Is there a specific antidote for ionophore toxicosis?
Nope, that’d be too easy
Treatment
- Remove medicated feed
- Decreasing absorption
- Activated charcoal
- Mineral oil
- Saline cathartics
Symptomatic treatment
- IV fluids and electrolyte therapy (to correct hypovolemia and support cardiovascular and renal functions)
- Potassium to correct hypokalemia (<2 mEq/L)
- Monitor cardiac function for several months
- Horses should not be ridden or stressed for several months
- Vitamin E and selenium may decrease muscle damage especially in cattle and swine
Prognosis?
- Horses that survive may suffer myocardial scarring and necrosis
- Horses may not reach previous performance
