Toxicology > Lecture 9 > Flashcards

Lecture 9 Flashcards

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1
Q

The site of action of NM toxicants/toxins is the ______. At this site _____ is the neurotransmitter and it acts on ________ receptors on the
motor endplate.
However, impact of some toxicants/toxins in the CNS can lead to ______
muscle dysfunction via impulses transmitted via the somatic motor nerves.

A

NMJ, ACh, nicotinic, skeletal

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2
Q

Upon the arrival of an action potential at the axon terminal, _______ ions flow from the _____ into the motor neuron’s ______ and bind to particular intracellular proteins. These _____-bound proteins cause neurotransmitter-containing vesicles to attach to the motor neuron’s cell
membrane and thus release _________ into the synaptic cleft which then binds to the ________ _______ receptors on the motor end plate. These receptors are ion channels and, when bound by ____, allow _____ and ______ ions to flow in and out of the cytosol of muscle cells, respectively. What is produced as a result?

A

calcium, ECF, cytosol, calcium, acetylcholine, nicotinic acetylcholine, ACh, sodium, potassium
Because of the differences in electrochemical gradients across the plasma membrane, more sodium moves in than potassium out, producing a local depolarization of the motor
end plate. This depolarization spreads across the surface of the muscle
fiber into transverse tubules, eliciting the release of calcium from the sarcoplasmic reticulum, thus initiating muscle contraction. The acetylcholine is thereafter degraded by acetylcholinesterase to
terminate its effect and stop the contraction.

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3
Q

General Mechanisms of Neuromuscular Toxicosis
* Functional: Impairment of neuromuscular ______
* Structural: peripheral motor ?

What is axonal dieback?

A

transmission, neuronopathy, axonopathy, and myelinopathy

Axonal die back: This is when, after (toxic) injury of a nerve, the tip of the
proximal axon retracts or moves away from the site of injury towards the cell
body. It is basically the degeneration/death of the axon from the distal end that
progresses to the proximal end (towards the nerve cell body/nucleus).

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4
Q

Clinical Signs of Neuromuscular
Toxicosis

A
  • Atony
  • Tetany
  • Tremors
  • Myotonia
  • Paresis/paralysis
  • Myasthenia
  • Cramps, spasms, twitching
  • Convulsions, seizures, ataxia
  • Respiratory signs & recumbency
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5
Q

Name the categories of Neuromusuclar Toxicants

A

Neuromuscular Toxicants
* Biotoxins
* Food-related
* Plants
* Pesticides
* Mycotoxins

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6
Q
  1. What arachnid is pictured below?
  2. Where in the world can it be found?
  3. Females are __________, males are ______. What do females do following mating?
  4. Where in the environment can they be found?
  5. What is a distinct physical feature unique to Black Widows?
A
  1. Black Widow Spider (Lactrodectus Spp.)
  2. Found in continental US
  3. Females are offensive, males are not
  4. Often found on woodpiles and garages
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7
Q
  1. Why toxin do Black Widows possess?
  2. What is this toxin’s MOT?
  3. Explain the MOA of the Ca-independent and dependent mechanism.
A
  1. Toxic principle : alpha-latrotoxin (120-130kD protein)
  2. MOT: alpha-latrotoxin binds to two neuronal receptors, neurexins and CIRL causing release of neurotransmitters via two mechanisms:
    i. Ca-independent: ACh, GABA, glutamate
    ii. Ca-dependent: catecholamines
    * Inhibits presynaptic neurotransmitter reuptake
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8
Q
  1. Which species are most susceptible to Black Widow spiders? What other species are affected? Prevalence is?
  2. Clinical signs of toxicity? What is specifically seen in cats?
  3. Local tissue changes are typically?
A
  1. Susceptible species: cats (very sensitive),
    dogs, horses, camels. Prevalence is unknown.
    * Toxicity: LD50 ranges from 0.43-1.39mg/kg
  2. Clinical signs: CNS & muscular
    – Muscle fasciculation and rigidity, abdominal pain (–>howling in cats), paresthesia, ataxia, cramps,
    seizures, flaccid paralysis –> ascending paralysis
    – Involvement of respiratory muscles causes dyspnea
    – Local tissue changes are typically absent
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9
Q
  1. How would you best describe treating Black Widow Spider toxicosis?
  2. – __________ and ___________ support
    – Pain management: give an _______, such as?
    – Control muscle ___________/__________ with what drugs?
    * Administer _________ (Lyovac Antivenin)
    – For high-risk patients (?) or those not responding to symptomatic treatment
    – Be prepared to respond to _________ reaction
A
  1. Supportive and symptomatic
    – Respiratory and cardiovascular support
    – Pain management: give an opioid
    * Morphine, meperidine, butorphanol or fentanyl
    – Control muscle cramping/seizures
    * Benzodiazepines (diazepam) or methocarbamol
    * Administer antivenin (Lyovac Antivenin) for…
    – For high-risk patients (neonatal/geriatric) or those not responding to symptomatic treatment
    – Be prepared to respond to anaphylactic reaction
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10
Q

Botulinum Neurotoxin (BoNT) toxicosis is also called?

A

(Botulism, limberneck, shaker foal syndrome, sausage poisoning)

This is the most potent toxin known to mankind.

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11
Q

BoNT is produced under _______ conditions by?
– There are _____ toxin serotypes, A to G
– Types _____ are the most important in animals. ____: cattle; ____: horses; _____: avian.

A

Produced under anaerobic conditions by
Clostridium botulinum
– There are seven toxin serotypes, A to G
– Types ABCD are the most important in animals.
BCD: cattle; ABC: horses; ABCE: avian.

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12
Q

How does an individual expose themselves/get exposed to the Botulinum toxin?

  1. – Oral: ingestion of _______, ________ preserved food,
    __________ vegetation and _________ (waterfowl)
  2. Via _________ and _____ wounds
A

carrion, poorly, decaying, invertebrates, inhalation, deep

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13
Q

Which species are susceptible to the Botulinum neurotoxin? Which are the most commonly affected?
Which species are relatively resistant to Botulinum neurotoxin?

A

Susceptible species: all but most commonly wild birds, poultry, cattle and horses. Pigs and dogs are relatively resistant

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14
Q

These birds commonly died from what toxin? Explain the pathogensis

A

Active more in summer and fall
Botulinum Neurotoxin (BoNT)
Ontario Oct 2011: Thousands of dead birds litter L.
Huron, Georgian Bay shore
Toxicosis associated with mass fatality of waterfowl.

Carcass-maggot cycle: eat maggots containing BoNT –> dies –> flies deposit eggs in duck –> hatch into maggots –> accumulate with BoNt –> eaten by other ducks which die –> carcass maggot cycle is born and propagates itself.

BoNT may have led to extinction of some avian species.

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15
Q
  1. Zinc metalloprotease is composed of?
  2. BoNT consists of?
  3. What is the mechanism of toxicity of the BoNT?
A
  1. Zinc metalloprotease with a heavy chain (100kD) & light chain (50kD)
  2. BoNT consists of a 150 kDa di-chain
  3. It enters presynaptic nerve endings by endocytosis –> 100kD chain binds to synaptotagmin. Then, blocks ACh release at the NMJ —> flaccid paralysis
    – Inhibits exocytosis of ACh by cleaving proteins essential for fusion of the membrane of synaptic vesicles containing acetylcholine with the neuronal cell membrane
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16
Q

Release of ACh at the nm junction is mediated by?

A

The release of ACh at the NMJ is mediated by a set of SNARE proteins. SNARE proteins are synaptic fusion complexes that allow the membrane of the synaptic vesicle containing ACh to fuse with neuronal cell membrane.
The set of SNARE proteins includes synaptobrevin, SNAP-25, and syntaxin.
After membrane fusion, ACh is released into the synaptic cleft and then binds to receptors on the muscle cell.

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17
Q

How does BoNT inhibit the release of ACh?
Which toxins play what role in this process?
What happens as a result of no ACh release?

A

Once BoNT enters the neuron by endocytosis, the LIGHT chain cleaves sites on the SNARE proteins, preventing the set to form a complex —> blocks ACh release.

BoNT toxins type B, D, F, G cleave synaptobrevin
BoNT toxins type A, C, E cleave SNAP-25
BoNT toxins type C cleave syntaxin

Without ACH release –> msucle uncable to contract –> flaccid paralysis

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18
Q

Of all the SNARE proteins in the SNARE synaptic complex, which are Synaptosome-associated proteins (SNAPs), which are Vesicle-associated proteins (VAMPs), and which are Synaptic-associated proteins?

A

Synaptobrevin - VAMP
SNARE-25 = SNAP
Syntaxin = SNAP

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19
Q
  1. What are the clinical signs of BoNT toxicosis?
  2. Why is BoNT the most potent toxin known to humans?
  3. How would you describe the reflexes of the eyes and throat?
  4. What are the ANS signs?
  5. What results due to respiratory paralysis?
A

Toxic dose: LD50 = 0.1-40ng/kg (IV or IP).
Oral LD50 is 500-700× the IP/IV LD50 dose
1. Sudden death may be the only sign, otherwise it is a
progressive neuromuscular dysfunction. Progressive flaccid paralysis with muscle weakness —> Starts in the rear quarters and ascends to the forequarters then to neck and head. Animals exhibit, ataxia, depression, weakness of
muscles of the tail and tongue [loose (falling)
tongue is common]

  1. Because it requires the smallest amount to cause toxicity.
  2. Poor reflexes of eyes and throat: mydriasis, slow pupillary light response, decreased palpebral and gag reflexes, weak
    vocalization
  3. ANS signs: bradycardia, vomiting, inability to swallow, ileus, constipation or ruminal atony, frequent attempts to urinate (horses)
  4. Recumbency and death from respiratory paralysis
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20
Q

The gag reflex is a reflex contraction of the ______ of the throat and can be evoked by touching the _____ palate. The afferent limb of the reflex is supplied by the ___________ nerve (cranial nerve ____) and the efferent limb is supplied by the ______ nerve (cranial nerve ___). Therefore, depression of the gag reflex may indicate damage to the __________ nerve, or the ________ nerve.

The pupillary light reflex is done by shinning a light on the pupil and a normal reflex is ___________ of the pupil to keep the light _____. The afferent limb is supplied by the ____ nerve (cranial nerve __) and the efferent limb is supplied by the ___________ nerve (cranial nerve ___). Therefore, depression of the pupillary light reflex may indicate damage to the these nerves.
The palpebral (?) reflex is performed by touching/tapping the _________ _______ (skin at the medial corner of the eye) with a finger or a pen and a normal reflex is a _____. The afferent limb is supplied by the __________ nerve (cranial nerve __) and the efferent limb is supplied by the ________ nerve (cranial nerve ____). Therefore, depression of the palpebral reflex may indicate damage to these nerves.

A

back, soft, glossopharyngeal, IX, vagus, X, glossopharyngeal, vagus

constriction, out, optic, II, oculomotor, III

corneal/blink, medial canthus, blink, trigeminal, V, facial, VII

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21
Q
  1. What are the unique signs of BoNt toxicity in foals?
  2. How old are the foals that are typically affected?
  3. Why are foals susceptible to BoNt toxicity?
A

– Foals: tremors (shaker foal syndrome- Toxico-infection, Common in Kentucky and the mid-Atlantic region) in
2-5 weeks old foals

immature GI tract in foals –> more prone to growth of clostridium; different from ingestion of preformed BoNT from feedstuff, contaminated carcasses, rotten veggies.
Foals that succumb to toxicosis suffer from GI ulcers and liver abscesses.

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22
Q

What are the unique signs of BoNt in waterfowl? How do they die?

A

Waterfowl: progressive paralysis of the legs, wings and neck (limber neck) –> death by drowning

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23
Q

How do you dx BoNT? What do you analyze?

A
  • Analysis of serum, GI contents, vomitus, ruminal fluids and feedstuff for toxins
  • Mouse bioassay
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24
Q

How do you treat BoNT?

  1. Decontaminate: __________, _______ lavage, activated ________
  2. Supportive and symptomatic treatment
    – __________, ________ for muscle function, _______ for muscarinic signs, and IV _______
    * Remove the ________ causing the toxicosis
    * Provide __________ support
    – ________ feeding and watering
    * Administer antitoxin if Dx is made _______; Polyvalent (anti- ____ and anti- _____) and monovalent (anti-___) antitoxins are
    available for adult horses and foals & should be given ASAP
  • Administer an antibiotic
    – Such as?
  • ________ wound for animals suffering from wound botulism
A
  • Decontaminate: emesis, gastric lavage, activated charcoal
  • Supportive and symptomatic treatment
    – Ventilation, physostigmine for muscle function, atropine for muscarinic signs, and IV fluids
  • Remove the feedstuff causing the toxicosis
  • Provide nutritional support
    – Hand feeding and watering
  • Administer antitoxin if Dx is made early; Polyvalent (anti-B and anti-C) and monovalent (anti-B) antitoxins are
    available for adult horses and foals & should be given ASAP
  • Administer an antibiotic
    – Penicillin, metronidazole or amoxicillin
  • Debride wound for animals suffering from
    wound botulism
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25
Name the sources of tick paralysis in the U.S.? Austrailia? Does toxicity occur year-round?
* Sources – Female ticks especially Dermacentor andersoni and D. variabilis {USA} – Ixodes and Amblyomma sp. (Australia) – Toxicity is seasonal = seasonal activity of ticks
26
Which species are most susceptible to suffering from tick paralysis?
Susceptible species: cattle, sheep, horses, dogs and rarely cats
27
How do ticks induce paralysis on their victims? The toxins (_____________ secreted from tick _________ glands) block _____ release at the NMJ and inhibit __________ of ______ motor neurons → paralysis
Mechanisms of Toxicity: The toxins (holocyclotoxins secreted from tick salivary glands) block ACh release at the NMJ and inhibit depolarization of lower motor neurons → paralysis
28
Clinical signs of tick paralysis. 1. How long does it take for clinical signs to appear? 2. What form of paralysis ensues? Where does it begin? Where does it end? 3. What other clinical signs do victims exhibit? 4. What occurs due to laryngeal paresis?
1. One tick is all it takes. Signs appear 5-9 days after attachment of toxigenic tick 2. Ascending flaccid paralysis begins in the pelvic limbs and ascends to whole body 3. Animals show apprehension, ataxia, wide-based stance, cranial nerve dysfunction, e.g., depression of gag reflexes - glossopharyngeal and vagus, mydriasis, anisocoria - oculomotor) and respiratory paralysis →death 4. Anorexia and change of phonation in dogs due to laryngeal paresis
29
How do you diagnose tick paralysis?
Presence of ticks associated with sudden appearance of limb weakness and/or respiratory impairment. The tick may no longer be attached but may see bite mark.
30
Tx of tick paralysis?
* Removal of tick(s) --> recovery in 72h * Application of an acaricide * Support respiration in severe cases
31
1. What toxin can be seen in this image? 2. What is the source of this toxin? 3. The ADME of this toxin is the same as? 4. What is the MOT of this toxin? 5. What are the clinical signs of Anatoxin-a toxicity?
1. Anatoxin-a 2. Sources: blue-green algae (Anabaena sp.) 3. ADME: same as anatoxin-a(s) 4. MOT: nicotinic agonist 5. Clinical signs: nicotinic (similar to succinylcholine overdose). Rapid onset of muscle rigidity and tremors, cyanosis, convulsions, then paralysis and respiratory distress leading to death
32
How would you Dx Antitoxin-a paralysis? * History of recent ________ with or ______ of _____-_____ ________ and compatible clinical signs * Compatible ______/________ biochemical changes – Reduced ____________ activity * Examine water for appropriate ______ type * ________ bioassay with __________ water * Identify toxin in water by?
* History of recent contact with or ingestion of blue- green algae and compatible clinical signs * Compatible blood/plasma biochemical changes – Reduced cholinesterase activity * Examine water for appropriate algae type * Mouse bioassay with suspect water * Identify toxin in water by HPLC or GC-MS
33
Tx tick paralysis 1. Is there an antidote? 2. Is treatment even possible? 3. What treatment can you provide? What would you do in the environment?
1. No antidote 2. Rapidity of onset may make Tx impossible 3. Supportive and symptomatic treatment – Aggressive respiratory support and seizure control * Decontaminate – Induce emesis then administer activated charcoal and a cathartic. Bathe animal * Fence off contaminated ponds and lakes to prevent exposure
34
What fish are pictured below? What toxin do they possess?
Tetrodotoxin source Sources: Puffer fish, frogs, newts
35
What is the MOT of Tetrodotoxin? What are the clinical signs?
* MOT: Inhibits fast Na+ channels in nerves and muscles - Fast Na+ channels means that the channel is activated very quickly (within milliseconds) after opening, allowing Na+ to enter —> depolarization for seconds (longer) as opposed to milliseconds). * Signs: paralysis
36
Where are the toxins Saxitoxin and Neosaxitoxin sourced from?
Sources: cockles, mussels, clams, oysters
37
What is the MOT of Saxitoxin and Neosaxitoxin?
The toxins are secreted by dinoflagellates and blue-green algae. Once secreted, they block Na+channels —> paralysis Cause Paralytic shellfish poisoning (PSP) Contaminate shellfish & water
38
Where are Ionophores sourced from? How do Ionophores benefit the US economy?
Sources: coccidiostats and growth promotants such as: 1. monensin (Rumensin®, Coban®) (Used in the beef and dairy industries to prevent coccidiosis and improve feed efficacy. Also increases the production of propionic acid which prevent bloat. Also alters rumen bacteria and increases C and nitrogen retention). 2. lasalocid (Bovatec®, Avatec®) 3. narasin (Maxiban®,Monteban®) 4. salinomycin (Biocox®, Saccox®) 5. maduramicin (Cygro®) 6. laidlomycin propionate (Cattlyst®). Ionophores save $1 billion/year for the US cattle industry
39
What is the MOT of Ionophores?
* Bind and preferentially transport cations across cell membranes either by acting as an ion channel or ion carrier. - Transport cations DOWN concentration gradient. – Net effect is ion (Na+, K+, Ca++, H+) imbalance and deficits in the function of excitable tissues * Neurons, muscles – Mitochondrial ion imbalance --> decreased ATP
40
What are the clinical signs of Ionophores? 1. Which animals are most sensitive to Ionophore toxicity? 2. What body system clinical signs do you see? 3. What are the earliest signs to develop?
Clinical Signs 1. Horses are 10× more sensitive than cattle 2. Neurologic, muscular, GI and cardiac signs 3. Food refusal and watery diarrhea are the earliest signs to develop – Weakness, ataxia, paresis/paralysis, tremors, stumbling, exaggerated stepping, dyspnea, sweating, tachycardia, jugular pulse, hesitation to move or turn, recumbency, rumen atony, dehydration and death
41
How would you diagnose Ionophore toxicity? * Clinical signs and ___________ * Identification of ionophores in _____ and animal _________ * ________ and _______________
* Clinical signs and pathology * Identification of ionophores in diet and animal tissues * ECG and echocardiography
42
1. Is there a specific antidote for Ionophore toxicity? 2. How would you treat Ionophore toxicity otherwise?
1. There is no specific antidote * Decontamination: emesis in dogs/cats, administer activated charcoal and cathartic * Supportive therapy: IV fluids, minimize stress (keep quiet) * Antioxidants: vitamin E or selenium (given prior to appearance of clinical signs)
43
1. What plant is pictured below? 2. What is an alternative name for this plant? 3. Where can it be found?
Larkspur – Delphinium (Poison Weed, Stagger Weed) * it is a Perennial, erect herbs (3-6 ft) * Mostly found in western USA
44
What species are susceptible to Larkspur – Delphinium? What species can tolerate a large amount of Larkspur?
Mainly cattle, horses as well * Sheep tolerate 4-5x the amount of larkspur lethal to cattle Sheep used for biological control of larkspur
45
Larkspur toxicosis is the main cause of?
Main cause of cattle losses in western ranges ($10K p.a. for average cattle herd)
46
What are the toxic principles of Larkspur?
* Diterpene alkaloids: methyllycaconitine (MLA) and 14-deacetylnudicauline (DAN) – DAN is more toxic, but MLA occurs in greater quantity – High concentrations in early growth
47
What is the MOT of Larkspur? Where does it act on in order to induce toxicosis? Where in the cattle’s body is most sensitive?
* Act at postsynaptic nicotinic cholinergic receptors – Block the action of ACh at the NMJ – MLA also blocks ACh receptors in the CNS * Cholinergic receptors of cattle are the most sensitive
48
What are the clinical signs of Larkspur toxicosis? 1. What is the most common clinical sign in cattle? 2. What physiologic systems are mainly affected? 3. List the other common clinical signs
1. Most common sign in cattle is sudden death * When evident, signs are nervous, muscular and gastrointestinal – Hyperirritability, confusion, muscle tremors, convulsions, stiffness and weakness – Constipation, bloat, oral irritation, salivation, nausea, vomiting – Collapse with head downhill, prostration and inhalation pneumonia
49
How do you diagnose Larkspur toxicosis?
Evidence of larkspur having been grazed by animals and plant presence in ruminal contents. Also presence of bloat and ruminal contents in bronchi
50
How do you treat Larkspur toxicosis? * Move animals to ____ pasture * Decontaminate: activated ________ and _______ * Inhibitors of __________, e.g., ___________ * Avoid ______ and ________ of the animal * Relieve bloat by stomach _____ or _________ * Give antibiotics for inhalation _________
* Move animals to new pasture * Decontaminate: activated charcoal and cathartic * Inhibitors of cholinesterase, e.g., physostigmine * Avoid stress and excitement of the animal * Relieve bloat by stomach tube or trocarization * Give antibiotics for inhalation pneumonia
51
What plant is pictured below? What is the significance of this plant? Where is this plant found?
Locoweeds – Astragalus & Oxytropis (vetches, milk-vetches) Probably “the most economically significant” toxic plant in the US * Habitat: all of North America * Most poisonings occur in Pacific Northwest Family: Leguminosae (Pea family)
52
What is are the toxic principles of milk-vetches?
* Nitropropanol glycosides (e.g., miserotoxins): hydrolyzed to nitrotoxins by rumen microbes * Nitrotoxins: 3-nitro-1-propanol (3-NPOH) & 3 nitropropionic acid (3-NPA) – 3-NPOH is absorbed and metabolized in the liver to 3-NPA which is responsible for toxicity – If ingested as 3-NPA, most of it is biodegraded in the GI tract = lower toxicity * Other toxins: indolizidine alkaloid (swainsonine) & selenium (discussed in CNS & skin toxicants)
53
1. How many kg/day of Locoweed would you have to consume to cause toxicosis? 2. Which species are most susceptible? 3. Toxicosis is most acute in which species? 4. During what season does Locoweed toxicosis occur?
1. 6kg/day for 5 days causes toxicosis 2. Susceptible species: cattle, horses, sheep, and wild herbivores 3. Lactating cattle are the most likely to be poisoned 4. Toxicosis is more acute in sheep and horses 5. Toxicosis is seen mainly in midsummer
54
What is the MOT of Locoweed/Milk-vetches?
* 3-NPA inhibits the Krebs cycle leading to decreased energy (ATP) production and loss of cellular homeostasis – Krebs cycle enzymes succinate dehydrogenase, fumerase and aspartase are inhibited * Causes axonal degeneration in spinal cord * 3-NPA produces hypotension via vasodilatory and cardiodepressor activities * Induction of methemoglobinemia: Nitrotoxins are metabolized to nitrites which oxidize Hb
55
What are the Clinical Signs of Nitrotoxicosis? (Acute vs gradual signs)
* Acute: constipation, ataxia, staggering gait, recumbency and death from cardio- respiratory failure * In most cases signs are gradual: dyspnea, salivation, weakness, muscular spasms, docile appearance, goose-stepping, ‘cracker heels - Clicking of dew claws of rear limbs ’, knuckling of fetlocks, and posterior paresis/paralysis. There is loss of body condition as the toxicosis progresses
56
How do you diagnose Locoweed/milk-vetches toxicosis? * Clinical signs, evidence of plant __________ * Gross and histopathological ____________ and __________ lesions * Identification of ______ and ______ in plasma/serum by HPLC
* Clinical signs, evidence of plant consumption * Gross and histopathological respiratory and neurological lesions * Identification of NPA and NPOH in plasma/serum by HPLC
57
Tx milk vetches
* Withdraw animals from source of plant – Cattle avoid locoweeds when other forage is available, and toxin concentration decreases rapidly as plants mature and undergo senescence
58
List the sources of Tremorgenic Mycotoxins.
Sources: tremorgenic forages (e.g., ryegrass, Dallis grass, Bermuda grass), moldy cheese, bread, walnuts and pasta, garbage
59
Which species are most susceptible to Tremorgenic mycotoxin toxicity? What are the toxic principles of Tremorgenic mycotoxin toxicity?
Species: dogs, sheep, horses (sheep and horses are the most commonly poisoned livestock) * Toxic principles – Penitrem A and roquefortine C (Penicillium crustosum and P. roqueforti ) – dogs – Lolitrem B (Acremonium lolil) --> Livestock – Paspalitrems (Claviceps paspali) --> Livestock
60
Small breeds of dogs showed _______ after ingesting one slice of moldy (Tremorgenic mycotoxin) bread. Why? Because Tremorgenic mycotoxins are rapidly absorbed in the _____ tract and excreted via _____. Signs of Tremorgenic toxicosis in cattle occur after ___ days of grazing on contaminated forage. Signs in dogs can occur ____ min after ingestion
Toxicity and ADME * Toxicity: 0.5mg/kg purified penitrem A given IP causes acute tremors in dogs. Small breeds of dogs showed tremors after ingesting one slice of moldy bread * ADME: Tremorgenic mycotoxins are rapidly absorbed from the GI tract and excreted via bile * Signs in cattle occur after 7 days of grazing on contaminated forage. Signs in dogs can occur 15 min after ingestion
61
Mechanisms of Toxicity * Tremorgens cause presynaptic release of _____ and ________ depolarization at the NMJ. Facilitate transmission at motor endplate * Reduce levels of ____ & _____, both of which are? —> _____ stimulation * Cerebral vasoconstriction —> _______ —> CNS signs
ACh, prolong, GABA, glycine, inhibitory AA NT, CNS, anoxia
62
Why is the main clinical sign of Tremorgenic toxicity?
Opisthotonus * Restlessness, irritability, panting, tremors leading to spastic ataxia, hypermetria, opisthotonus, seizures, tetany, muscle fasciculation, tachycardia, hyperexcitation, vocalization, hyperthermia, exhaustion and recumbency in severe cases * Livestock appear normal at rest. When incited to move they exhibit stiff spastic gait, muscle spasms and tetanic seizures
63
How do you diagnose Tremorgenic Mycotoxin toxicity?
* Analysis of suspect feed, vomitus, stomach contents, and lavage washings may help to confirm diagnosis
64
How would you treat Tremorgenic toxicosis? 1. In asymptomatic animals? 2. In Symptomatic animals?
* Decontaminate – Asymptomatic animals: emesis, activated charcoal and a cathartic – Symptomatic animals: sedate/anesthetize and perform gastric lavage then give activated charcoal and a cathartic * Symptomatic and supportive therapy – Diazepam to control agitation, seizures and/or muscle tremors * Use methocarbamol or a barbiturate for patients who do not respond to diazepam – Give IV fluids * For livestock: replace contaminated forage and keep animal in quite place till recovery
Toxicology
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