Ionophores & B-agonist Flashcards
Why were ionophores originally created?
- To enhance growth and feed conversion
- Monensin and Iasalocid have secondary label as a coccidiostat
- Increase milk production efficiency
What are the ionophores available today
- Monensin (RumensinTM) - most common
- Narasin
- Salinomycin
- Lasalocid
- Laidlomycin proprionate
- Semduramicin
- Maduramicin
What is the dosage for monensin?
- Dose: 0.14 - 0.42 mg/lb BW
- up to 480 mg/hd/day beef
- up to 660 mg/hd/day dairy
- Monensin 90 = 90.7 gm/lb
What can Monensin be fed with?
- decoquinate
- Tyolsin
- MGA
- ractopamine
- zilpaterol
- tilmicosin
What is the MOA of ionophores?
- “ion Mover”
- assists in membrane exchange of sodium, calcium, hydrogen, and other ions
- Shifts microbial fermentation to produce mor propionic acid (rather than acetic and butyric)
- more efficient energy production ⇢ increase rate of gain / feed efficiency
- Interferes with transmembrane ion balance in muscle
- Intracellular calcium build-up ⇢ decrease in ATP production ⇢ apoptosis
- Myocardial degeneration and necrosis
What are the microbial shift effects of Ionophores?
- Propionate synthesized at the expense of acetate and butyrate
- Reduced levels of ketone bodies in early lactation cows
- reduced ketosis
- Sparing effect on AA normally used for gluconeogenesis
- Protein-sparing effects in the rumen by decreasing rumen proteolysis and AA deamination
- Increased ruminal escape of dietary protein
- Decrease rumen ammonia production
- Milk fat depression with little effect on lactose or protein content
What are the kinetics of Ionophores?
- Rapidly absorbed, widely distributed
- Metabolized in liver - CYP450
- Parent compound and metabolites excreted in bile
What species is most and least affected by monensin?
- Horses (LD50 2-3 mg/kg)
- Trout (>1000ppm)
What are the risks of ionophores?
- OD
- cattle 10x dose
- Unintended species
- Repeat exposure
- cattle: LD50 26.4 mg/kg ⇢ 7mg/kg
- Synergisms - macrolide antibiotics
What increases and animal’s sensitivity to ionophores?
- Repeat exposure
- Low quality diet
- Poor body condition
- compromised metabolism
- Synergism - macrolide antibiotics
What is the clinical picture associated with ionophore toxicosis?
- Initial 24-48 hours:
- Off feed and diarrhea
- Depression, colic, ataxia, weakness, knuckling, recumbency
- Sudden death especially with stress, forced exercise or elevated ambient temperatures
- Progressive disease as muscle lesions worsen
- Signs of congestive heart failure
- weakness, collapse, recumbency, dyspnea, death
- Signs of congestive heart failure
What is the clinical pathology associated with ionophore toxicosis?
- Clinical Pathology:
- Elevations in:
- CPK
- ALP
- LDH
- AST
- BUN
- bilirubin
- hematocrit
- Cardiac troponins can be used for a few days post-exposure to evaluate heart damage
- Elevations in:
How is Ionophore toxicosis diagnosed?
- Chem 10
- Gross lesions
- Histopathology
What are the gross lesions associated with ionophore toxicosis?
- Pale, streaky heart
- epicardial & endocardial hemorrhage
- Fluid accumulation in body cavities
- Pulmonary congestion and Edema
What is the histopathology results common with ionophore toxicosis?
- Myocardial degeneration and necrosis
- skeletal muscle lesions
- occasional necrosis in liver and kidney
What does monensin do to horses?
- Myocardial necrosis
- muscle fibers are hyalinized, fragmented and have a loss of cross striations. They are infiltrated and separated by neutrophils, macrophages, and serocellular debris
What is Lasalocid used for in Baby calves?
- Off-label use as anti-cryptosporidial
- drench or added to milk replacer
What is the toxic dose of Lasalocid in baby calves? what happens?
- >4mg/kg BW lethal
- Heart failure with high death loss
What affects does monensin have in sheep?
- Looks like white muscle disease
- Predominately affects skeletal muscle
- Myocardial lesions variable and minor
What are the differential diagnosis for white muscle disease?
- Ionophores
- VIt E/Selenium deficiency
- Gossypol
What affect does Lasalocid have in dogs
- Predominately skeletal muscle lesions
- Often no myocardial damage
- Ascending flaccid paralysis of hind limbs
- Looks like tick paralysis or botulism
- death due to respiratory paralysis
What is the lethal does of Lasalocid in dogs?
10-15 mg/kg
What affect does Monensin have in Poultry?
- Similar in most bird species:
- anorexia, diarrhea, depression first 1 - 3 days
- Weak, ataxia, sternal recumbence, paralysis
- skeletal, cardiac, liver, GI lesions
- Cardiac hypertrophy, asites
- Infertile eggs, early embryonic death, weak at hatching
when does fertility return to poultry exposed to monensin?
3-4 weeks post exposure
What affect does Narasin have in swine?
- Mainly skeletal muscle necrosis at similar dosage to cattle
- Synergism with tiamulin (denagard)
- probably due to tiamulin suppression of narasin metaobolism
- Acute, necrotizing, myositis
- Myoglobinuria
What are the clinical signs of ionophore toxicosis in swine?
- reduced feed intake
- neurological signs (dog sitting, incoordination, recumbency, etc)
- diarrhea
- death
What are the lesions associated with ionophore toxicosis in swine?
- Macro:
- focal degenerative cardiomyopathy
- necrosis of skeletal muscle
- congestive heart failure
- Micro:
- diffuse
- extensive myodegeneration
What are the differentials for swine (FIX)
- Ionophore toxicosis
- Selenium toxicosis
- Strep suis septicemia
How is ionophore toxicosis treated?
- Remove ionophore from feed
- Avoid stress and excitement
- Activated charcoal & cathartics - may be to stressful
- IV diuresis - Ca correction if you can monitor
- Injectable Vit E & Selenium
What are Beta- Agonists?
- Adrenergic compounds used for growth promotion
- Clenbuterol - not legal to feed in US
- Ractopaine-Paylean, Optaflexx, Topmax
- Zilpaterol-Zilpaterol hydrochloride
What are the affects of Ractopamine (Paylean)?
- Beta-adrenergic agonists
- Enhances growth by repartitioning nutrients ⇢ lean tissue over fat
- 18 g/ton improves feed efficiency 13%
- increases in “downer pigs” near finishing or at packing plants
What is the dose for Ractopamine - (Optaflexx) in cattle?
- 8.8 - 24.6 g/ton
- provides 70-430 mg/hd/day
- Last 24-48 days on feed
What is the dose of Ractopamine (Topmax 9) for turkeys?
- 5 - 13 ppm x 1.1 = 5.5 - 14.3 gm/ton
- last 7-14 days prior to slaughter
What affect does Zilpaterol have on horses?
- within hours:
- restlessness
- muscle tremors
- tachycardia
- after 2nd dose next day:
- restlessness, muscle tremors, profuse sweating 20-25 minutes after dose
- Tachycardia developed w/n 40 min
- took up to 2 weeks to resolve
What is Zilpaterol?
- B-agonist used for cattle
- 6.8 g/ton = 60-90 mg/hd/day
- fed last 20-40 days on feed
- Can be fed with MGA, monensin, and tylosin
- ‘Recently’ associated with lameness problems
- hoof sloughing
