Week 8 Flashcards
Ionophore - Monensin
Uses:
• Anticoccidial in cattle, poultry 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 reduction of rumen acidosis in ruminants
• Prevention of tryptophan‐induced atypical bovine pulmonary emphysema
Properties: include monensin, lasalocid, salinomycin, narasin, semduramicin sodium, and laidlomycin propionate potassium
• Carboxylic acid derivatives antibiotics
• Slightly soluble in water and soluble in organic solvents and oils
• Form lipid‐soluble complexes with polar cations (Na+, K+, Ca2+, Mg2+) that are transported across cellular membranes
Sources: Monensin is most common
• 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
Toxicity:
• All animals are susceptible
• Equines (and Turkeys) are the most sensitive species, cattle are intermediate and poultry are the least sensitive
o Horses that ingest recommended levels for cattle are not poisoned, but slight increases will cause toxicity
o Possibly due to
♣ (1) 100% absorption
♣ (2) Slow Metabolism due to low oxidative demethylases
♣ (3) lack of gall bladder
• Concurrent administration of other drugs increase toxicosis (they are microsomal enzyme inhibitors)
o Tiamulin – anti-microplasma drug, used when tetracycline does not work
o Chloramphenicol // Erythromycin // Sulfonamides
o Cardiac glycosides (digoxin/digitalis that are cardiotoxic)
[tetracyclines are used to treat intracellular microorganisms, followed by fluoroquinolones]
TK of Monensin:
• Ruminants absorb about 50% but monogastric animals (such as horses) absorb most of it
• Distributed throughout the body (highly lipid soluble)
• Blood and tissue levels are relatively small
• Monensin does not accumulate in tissues of animals when given in high doses
• Rapidly metabolized by P‐450 oxidative demethylation enzymes in the liver
o (slow metabolism in equines because they have the lowest oxidative demethylases than other domestic species)
• Excreted mainly in bile (horses do not have gall bladders)
MOA: Disrupt transmembrane electrochemical gradients
•
The main targets are the mitochondria of highly energetic tissues (myocardium, skeletal muscles and the kidney)
• Influx of the sodium‐ionophore complex increasing intracellular sodium accompanied by increasing intracellular calcium
• Sequestering of calcium by mitochondria (to protect cell) and inhibition of mitochondria and decreased ATP and energy
• Increased cytoplasmic Ca
• Cell death due to disrupting homeostatic mechanisms
• Also catecholamine release results in 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
Clinical Signs of Monensin/Ionophores: only acute in onset and death
• Horses: Rapid onset “similar to human suffering heart attack” – most severe
o Anorexia, profuse sweating, colic, depression, incoordination, hyperventilation, tachycardia, tachyarrythmias, prostration, death
• Cattle: Similar but more skeletal muscle, less cardiac
o Anorexia, diarrhea, depression, labored breathing, ataxia, prostration, and death
• Poultry: Similar - Anorexia, diarrhea, ataxia, resting on the knees with wings and leg directed outward, and decreased egg production
• Dogs: Similar - Ataxia, muscle weakness of hind limbs, respiratory paralysis, dysuria, constipation, and depression
Lesions- depends on duration
• Mainly cardiac muscle lesions in horses (pale cardiac muscles, white streaks of necrosis in the myocardium), and 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
Diagnosis: History, CS, Lesions, Lab diagnosis
• Chemical analysis: detect ppb levels – best sample is FEED…. Can also use GI content, liver & feces (excreted in bile)
• Elevated Enzymes (related to muscle damage): CPK, AST, ALP, Lactic dehydrogenase (LDH)
• Decreased serum Ca2+ and K+ (during first 12 hr.. will be corrected later) BUT No change in Na
• Increased PCV – due to dehydration and D
DDx: other myopathy and neuropathy conditions
• Horses- (1) Colic, (2) Blister beetle ingestion (cantharidin toxicosis)- very caustic and irritating (3) Azoturia/ Renal Failure
• Cattle - Vitamin E/selenium deficiency
• Poisonous plants
¥ Skeletal muscle:
Ð Coffee senna (Senna occidentalis)- eat the legumes – causes myoglobinurea (making pee coffee like)
• Used as a Irritant puritive of small and large intestines
Ð Coyotillo (Karwinskia humboldtiana)
Ð White snakeroot (Eupatorium rugosum)
¥ Cardiotoxic
Ð Oleander – MOST COMMON – evergreen with flowers – very toxic (only need a few leaves)
Ð Taxus spp.
Ð Milkweed
Ð Vetch
• Poultry-
¥ Nutritional myopathy
¥ Coffee senna (Senna occidentalis) toxicosis
¥ Botulism
¥ Na+‐water deprivation toxicosis
¥ mycotoxicosis (moniliformin cyclopiazonic acid)
¥ Round‐heart disease
¥ Downer syndrome (viral arthritis)
Treatment: Remove feed, Decrease absorptions (activated charcoal, mineral oil, saline cathartics)
• Symptomatic:
o IV fluids and electrolyte therapy – to correct hypovolemia and support heart and renal function
o Potassium (
Water Deprivation / Sodium Ion (Na) Toxicosis
Sources: Feeding brine, whey, or garbage (high in salt). Ingestion of salt licks or ice‐melts. Drinking water may contain salt
• Factors that cause excess sodium and water deprivation: • Overcrowding • Frozen water • Unpalatable (medicated) water • Lack of water
Properties: Salt taste goods. Salt has a mild irritant effect on mucous membranes (can induce vomiting)
Toxicity: Pigs, cattle and poultry are the most susceptible (intensive raising, crowding). Dogs are less susceptible (sporadic due to ice melts)
• NaCl is normally present at 0.5-1% in feed
• The acute orsal LD 50 ~ 2.2 g/kg in horses, cattle, and swine; 6 g/kg in sheep; and 4 g/kg in dogs (depending on water intake)
• Animals can tolerate more than 10% salt in feed if they have free access to water
• [Aldosterone is needed to conserve Na, in Addison’s disease the animal cannot conserve Na and the animal dies of hypovolemia, shock]
TK:
• Salt is rapidly absorbed from the GI tract and distributed all over the body
• Sodium enters the brain by passive diffusion and is removed by active transport
• The excess of absorbed sodium following large dietary intake is rapidly excreted in urine as long as there is enough water
• Excess sodium (and water deprivation) results in hypertonicity of the blood and toxicosis
MOA: High Na in the brain inhibits anaerobic glycolysis resulting in lack of energy necessary for active transport of sodium out of the brain
• Sodium trapped in the brain attracts water because of the osmotic gradient, resulting in cerebral edema
• Restricted water intake and dehydration increases plasma sodium to 150‐190 mEq/L and cerebrospinal fluid to 145‐185 mEq/L
o Normal sodium levels in plasma are 135‐145 mEq/L and in cerebrospinal fluid are 130‐140 mEq/L
CS: seizures
• Early constipation and thirst (may not be seen) Vomiting, polyuria and metabolic acidosis
• Intermittent convulsive seizures- Last from 0.5 to 2‐3 minutes (Interrupted by other signs). Seizures are Not elicited by external stimuli
• Circling, pivoting, and head‐pressing
• Blindness and deafness
• Inability to eat or drink or even recognize the feed or water
• Poultry only show depression, ascites and collapse
Lesions: eosinophilic meningoencephalitis (only pigs within the first 24 hours), edema, fluid, pinpoint ulcers, gastric congestion/inflammation
• Gastric congestion or inflammation with pinpoint ulcers
• Fluid in body cavities and organ edema
• Prominent cerebral edema
• Histopathologically, eosinophilic meningoencephalitis (filling of cerebral and meningeal perivascular spaces with eosinophils) is pathognomonic in pigs only, if the animal dies early
Diagnosis: History, encephalitic signs, lesions and laboratory diagnosis
• Serum and CSF (or ocular fluid) sodium concentrations are 160 mEq/L or more
• Brain sodium concentrations above 2000 ppm support diagnosis
• Salt in feed
DDx: Encephalitic diseases (Trauma, Tumor, Heat stroke, Viral encephalomyelitic conditions), Chlorinated hydrocarbon insecticides, Roxarsone, Pseudorabies, Urea.
Treatment: Giving small amounts of fresh water (0.5% of body weight) gradually over 2‐3 days, if the animal is able to drink (recovery is 50%)
• Intravenous fluids (5% dextrose) and furosemide in small animals
• Anticonvulsants in small animals to control clinical signs
• DO NOT GIVE water in large amounts may kill the animal by aggravating cerebral edema
Prognosis: Poor. Mortality 50%
Video: Just showed CS of mostly seizures, as well as the necropsy & histology signs
Heavy Metals: Inorganic Arsenic
Sources: use is declining
• Ant and roach baits, Wood preservative (arsenic pentaoxide), Insecticides, herbicides, fungicides and rodenticides
• Milk from poisoned cows may be toxic to calves (despite being poor penetrations of membranes)
• Pastures near smelters may be contaminated
• Found in paint, pigments, detergents, and building materials (uncommon)
Properties
• Exists in 3 oxidative states: Elemental, trivalent (arsenite = most toxic), and pentavalent (arsenate)
o makes a different with absorption, CS, irritant
• Reacts with ‐SH group enzyme inhibition (if excess) [part of normal enzyme function at physiological levels]
Toxicity: lethal oral dose in most species is 1‐25 mg/kg (highly potent & toxic)
• Types: Peracute (seconds), acute, or subacute [Chronic toxicosis has not been documented in animals, has been seen in humans]
• Species: Herbivores are most susceptible
o Dogs can get poisoned by ant and roach baits
o Swine, chickens are rarely poisoned
• Form
o Inorganic trivalent is more toxic than pentavalent which is more toxic than organic
o Pentavalent is converted to trivalent in‐vivo
TK:
• Absorbed from the GI tract ( acute > subacute) and hind limb paralysis in subacute
• Peracute: Sudden death or severe colic, collapse and death
• Acute: Rapid onset, severe colic, staggering, salivation, vomiting, thirst, watery diarrhea which may be hemorrhagic, possible hematuria, and death in 1‐3 days
• Subacute: Colic, anorexia, depression, diarrhea with blood or mucosal shreds, dehydration, partial paralysis of hind limbs, and death in several days
Lesions:
• GI mucosal edema and hemorrhage (due to irritation and capillary damage) with sloughing and perforation, liver and kidney damage
• Microscopically, capillary degeneration
• Skin exposure causes skin lesions and blistering in addition to systemic lesions
Arsenic Diagnosis: history, sudden onset of blood D or watery D with mucosal shreds, lesions and lab diagnosis
• Chemical analysis- URINE is best antemortem, LIVER and KIDNEY are best postmortem specimens
o Other specimens are GI contents, vomitus, feces, milk, and suspected source (feed, plant, soil)
o Normal tissue residues is 0.5 ppm……..More than 7‐10 ppm in liver or kidney is a strong indication
o Increased PCV & Increased BUN (blood urea nitrogen) – due to dehydration and kidney damage
DDx: Caustics/corrosive agents, irritant plants, urea, pesticides, severe acute heavy metal toxicosis, monensin, blister beetles in horses, OP, hypomagnesemia, and enteric bacterial and viral diseases
Treatment: ASAP to save animal! Chelation= antidote.
• #1 Supportive (fluids, electrolytes, blood transfusion, treat acidosis, vitamins, antibiotics, pain relief, dopamine, acetylcysteine)
o Control systemic acidosis via IV Na Bicarb (fast onset, short duration) –or- Na Lactate (slower onset, longer- due to metabolism)
♣ Should give Na Bicarb first, then once stable can give LRS with Na Lactate
• Decontamination- gastric lavage (only early), mineral oil, activated charcoal (not very effective for organic metals- better for big plants)
o EMETICS AND STRONG CATHARTICS ARE CONTRAINDICATED
• Demulcents to coat the GI mucosa such as kaolin‐pectin
o Do not use aspirin due to anti-platelet effects
• Chelation therapy: chemical that binds the metal AFTER absorption. Only used after confirmation of toxicosis, due to side effects.
o Dimercaprol (BAL, British antilewisite) – Is the chelator of choice for inorganic arsenic
♣ Not 100% effective
♣ May increase toxicity by mobilization of arsenic (they move the metal around)
♣ Following the dosage and dosage regimen is important to avoid toxicity
♣ Toxic side effects include vomiting, tremors, convulsions, hypotension, shock, coma, and death
o Dimercaptosuccinic acid (DMSA, Succimer)(Chemet)
♣ Given orally or IM
♣ Water soluble analog of BAL
♣ Safer but may be less effective than BAL in severe toxicosis because of its hydrophilicity and poor tissue distribution
Prognosis: Grave if not treated early
