Lecture 10 - Ionophores

Toxicosis with ionophores is considered ___ incidence, but as a toxicologist see ___ and is a ___ ___ ____.

low, it a lot, really big deal

What are ionophores?

mono(di)valent polyether “antibiotics” used in oral feed additives for ruminants and poultry

What are the most common ionophores in feed?

monensin, lasalocid

Why are ionophores used in feed?

alters gut microflora to increase feed effiency and rate of weight gain, decrease incidence of bloat, lactic acidosis, bovine pulmonary emphysema and edema (fog fever), coccidiostat

Where are ionophores added?

premixes, complete feeds, mineral blocks, grain, salt mix, liquid, boluses, intraruminal controlled release capsules

Ionophore toxicitity is affected by ___, ___, ___.

specific ionophore, species, dose

How do ionophore poisonings occur?

• unintentional/intentional access by non-target/susceptible species (e.g. horse, dog) that are therapeutic in target animals, acute

• mixing, math errors, exposure to premix in target species, acute to subacute

In contrast to gossypol toxicity, ionophore toxicity almost always see a history of ____ within the past ____.

recent feed change

12-72 hours

Concurrent use of ____ with ionophores will decrease ___ by___fold and increase ____ by __ fold

antibiotics (e.g. oleandomycin, chloramphenicol, sulfonamides)

therapeutic effect, 10

toxicity, 8

Describe the mechanism of action of ionophores

absorbed and rapidly metabolized by liver in 1st pass effect, metabolites excreted in bile/feces, small amount enters systemic and little to no tissue accumulation

Ionohores do what to striated muscle?

complexes in mitochondria and transports Na+ in, K+ out, Ca++ in, decreases oxidative phosphorylation leading to myofiber necrosis

What is the primary target tissue of ionophores?

striated muscle, cardiac vs skeletal depending on species

Cardiac muscle is the ionophore target tissue of what species?

cow, horse, poultry-camelids-goats

Skeletal muscle is the ionophore target tissue of what species?

swine, sheep, dog, cat, poultry-camelid-goats

Describe the clinical signs of ionophore toxicity

GIT - within 12-72h, partial to complete feed aversion within 24 hours, diarrhea, weakness/ataxia/lethargy 3d later

Heart - sudden death, left and right heart failure

Skeletal - paresis/paralysis, dyspnea, respiratory failure

Neurologic - lethargy, peripheral nerves/spinal cord 3d or later with some ionophores

What are the ionophores that could affect the nervous system?

salinomycin, lasalocoid

Clinical pathology related to ionophores are ___ or ___. Can have what lab abnormalities?

non-specific, non-consistent

increased bilirubin, increased CK, LDH, increased troponin, myoglobinemia/uria rarely

Similar to gossypol, may need to do what kind of sampling to find gross and histologic lesions?

intense sampling, multiple necropsies

What gross lesions are seen with ionophore toxicity?

may see none or subtle due the acute, left and right heart failure, centrilobular necoriss, kidney damage, pale streaking in skeletal muscle

What histological lesions are seen with ionophore toxicity?

multifocal degeneration and necrosis of heart and skeletal muscle, acute tubular necrosis, centrilobular necrosis and fibrosis, peripheral nerves and spinal cord axonal degeneration, destruction of myelin sheath

SEND LOTS OF ___ and ___ samples for ionophore toxicity

heart, skeletal muscle

What is the diagnostic criteria for ionophore toxicity?

• feed additive use/recent change in feed in past 2-3d

• initial feed refusal

• GIT, cardiac, skeletal, both, CNS,PNS clinical signs

• feed analysis

• biological tissue anlaysis is time dependent

What is important with regards to feed or biological analysis?

more significant results with a non-target animal than target animal

What is the treatment for ionophore toxicity? Asymptomatic vs symptomatic patients?

remove source

Asymptomatic SA - DECONTAMINATE emesis, anti-emetic, repeated AC+ sorbitol cathartic, cholesytramine(?), gastric lavage, Vitamin E and selenium? IV lipid therapy

Asymptomatic LA - DECONTAMINATE gastric lavage, mineral oil or AC, Vitamin E and selenium? IV lipid therapy?

Symptomatic - treat for heart failure, remove feed

Symptomatic - skeletal damage, remove feed

With ionophore toxicity, what should you monitor daily and for how many days?

CK, troponin, LDH, AST, ALT, ECGs, echocardiograms

5-7 days minimum

What should you expect if animal lives 48-72 hours following ionophore toxicity?

expect survival, but a reduction in production and performance

True or False. Gossypol toxicities are typically chronic exposures while ionophore toxicities are acute

True