PNS III - Neuromuscular Flashcards
1
Q
Briefly discuss the physiology of the neuromuscular junction.
A
- the neuromuscular junction is a cholinergic synapse between a motor neuron and skeletal muscle
- action potential arrives at terminal button of motor neuron causing the opening of Ca channels
- this causes the release of ACh which binds to nicotinic receptors on the muscle fiber
- binding to these causes the opening of Na channels and sodium rushes back into the fiber and stimulates the action potential
2
Q
What is the origin of the phrase ‘black widow spider’?
A
- the female eats the male after mating
3
Q
Name the black widow spider toxin. What is the mechanism of action of this toxin?
A
- a-latrotoxin
- binds to 2 neuronal receptors (neurexins, calcium independent receptor for latrotoxin [CIRL]) causing release of neurotransmitters via 2 mechanisms
- Ca-independent and Ca- dependent
- this inhibits presynaptic neurotransmitter reuptake
4
Q
Differentiate the Ca-dependent and Ca-independent mechanisms of action of a-latrotoxin.
A
- Ca dependent
- affects ACh, GABA, glutamate
- direct action via CIRL
- Ca independent
- catecholamines (dopamine, EPI, NE)
- neurexin receptor, pore formation - Ca entry
5
Q
Name the drugs recommended for control of muscle cramping in black widow toxicosis.
A
- benzodiazepines (diazepam)
- methocarbamol
6
Q
Is there an antivenin for black widow venom?
A
- yes, Lyovac Antivenin
- used for high risk patients (neonates, geriatric) or those not responding to symptomatic treatment
- be prepared to respond to anaphylactic reaction
7
Q
Name the sources of botulinum neurotoxin toxin.
A
- Clostridium botulinum
8
Q
Which botulinum toxin subtype(s) most commonly affect animals and birds?
A
- A, B, C, D - most important in animals
- cattle - B, C, D
- horse - A, B, C
- avian - A, B, C, E
9
Q
Provide the mechanism of toxicity of botulinum toxin and the resulting clinical signs.
A
- toxins enter presynaptic nerve endings by endocytosis, light chain bonds to synaptotagmin
- blocks release of ACh at neuromuscular junction - flaccid paralysis
- inhibits exocytosis of ACh by cleaving proteins essential for fusion of the vesicle membrane with the neuronal cell membrane
- clinical signs
- sudden death progressive neuromuscular dysfunction, progressive flaccid paralysis
- ataxia, depression, weakness of tongue and tail
- poor reflexes of eyes and throat - mydriasis, slow pupillary light response, decreased palpebral reflex, decreased gag reflex, weak vocalization
- ANS signs - bradycardia, vomiting, inability to swallow, ileus, constipation, ruminal atony, frequent attempts to urinate (horses)
10
Q
Name the proteins involved in the docking of ACh vesicles at the presynaptic cell membrane. Identify the botulinum toxin subtypes that affect these proteins.
A
- SNARE and NSF proteins
- SNARE includes synaptobrevin (VAMP), SNAP-25, syntaxin
- A, B, C, D, E, F, G
- B, D, F, G - cleave synaptobrevin (VAMP)
- A, C, E - cleave SNAP
- C - cleaves syntaxin
11
Q
What are the characteristic signs of botulism in foals and waterfowl?
A
- foals - tremors, shaker foal syndrome
- waterfowl - progressive paralysis of neck (limberneck), wings, legs
- death by drowning
12
Q
What is the diagnosis of botulinum toxicosis based on?
A
- analysis of serum, GI contents, vomit, ruminal fluids, and feed for the toxin
- mouse bioassay
13
Q
Describe the treatment procedures for botulinum toxicosis.
A
- decontaminate
- emesis, gastric lavage, charcoal
- supportive and symptomatic care
- ventilation, physostigmine for muscle function with atropine for muscarinic signs, IV fluids, remove bad feed
- nutritional support - hand feeding and watering
- antitoxin if diagnosis made early
- polyvalent (anti-B and anti-C) and monovalent (anti-B) antitoxins available for adult horses and foals and should be given ASAP
- antibiotic - penicillin, metronidazole, amoxicillin
- debride wounds for animals suffering from wound botulism
14
Q
Name two tick species associated with tick paralysis in North America.
A
- Dermacentor andersoni
- Dermacentor variables
15
Q
Provide the mechanism of action of tick toxins. What is the general name of these toxins?
A
- holocyclotoxins block ACh release at neuromuscular junction and inhibit depolarization of lower motor neurons - leading to paralysis
16
Q
How is tick paralysis treated?
A
- remove tick, tick dip solution, support respiration in severe cases
17
Q
What is anatoxin-a? Provide the mechanism of action of anatoxin-a including clinical signs associated with its action.
A
- nicotinic agonist produced by blue-green algae
- rapid onset of muscle rigidity and tremors, cyanosis, convulsion
- paralysis and respiratory distress leading to death
18
Q
Differentiate between anatoxin-a and anatoxin-a(s) toxicoses.
A
- anatoxin-a
- agonist of nicotinic ACh receptors at both neuromuscular junction and neurons
- stimulation at neuromuscular junction in weakness, respiratory paralysis, death
- anatoxin-a(s)
- irreversible acetylcholinesterase inhibitor in PNS
- build up of ACh results in ataxia, seizures, respiratory arrest, death
- ”s” - salivation
19
Q
Describe the diagnostic procedures for anatoxin-a toxicosis.
A
- evidence of ingestion of blue-green algae and compatible clinical signs
- decreased cholinesterase activity in blood and plasma
- examine water for appropriate algae type
- mouse bioassay with suspect water
- identify toxin in water by HPLC or GC-MS
20
Q
Why is it difficult to treat anatoxin-a toxicosis?
A
- there is no antidote
- onset is so rapid that treatment may not be possible
21
Q
Give 3 examples of ionophores. Provide the mechanism of action of ionophores.
A
- sources - coccidiostats (parasite treatment), growth promotants
- monesin - rumesin, coban
- lasalocid - bovatec, avatec
- narasin - maxiban, monteban
- salinomycin - biocox, saccox
- laidlomycin propionate - cattlyst
- binds and preferentially transports cations across cell membranes
- net effect is ion imbalance (Na, K, Ca, H) and deficits in the function of excitable tissues (neurons and muscles)
- mitochondrial ion imbalance leads to decreased ATP
22
Q
Name the body systems most affected during ionophore toxicosis.
A
- neurologic
- muscular
- GI
- cardiovascular
23
Q
Describe the treatment of ionophore toxicosis.
A
- no specific antidote
- decontamination
- emesis in dogs and cats, charcoal, cathartic
- supportive therapy
- IV fluids, minimize stress
- antioxidants
- vitamin E, selenium
24
Q
In which geographic region of the US does larkspur poisoning commonly occur?
A
- western US
25
What are the toxic agents in larkspur?
- diterpene alkaloids
- methyllcaconitine (MLA)
- 14-deacetylnudicauline (DAN)
- DAN is more toxic, but MLA occurs in greater quantities
26
Which domestic animal species is most susceptible to larkspur toxins? Why are sheep used for biological control of larkspur?
- cattle are most susceptible
- sheep used for biological control becase they can tolerate 4-5x the amount lethal to cattle
- can eat it without getting sick and trample stalks
27
Provide the mechanisms of toxicity of larkspur toxins?
- block nicotinic receptors of ACh at neuromuscular junctions and in CNS (MLA)
28
Describe the diagnostic procedures for larkspur toxicosis.
- evidence that animals have grazed it
- plant presence in ruminal contents
- presence of bloat and ruminal contents in bronchi
29
Describe the treatment of larkspur toxicosis.
- decontaminate - charcoal, cathartic
- move animals to new pasture
- give cholinesterase inhibitors (physostigmine)
- avoid stress and excitement
- relieve bloat by stomach tube or trocarisation
- antibiotics for inhalation pneumonia
30
In which geographic region of the US are locoweeds most commonly found?
- pacific northwest
31
Name the toxins present in locoweeds. Which of these toxins cause neuromuscular toxicity?
- nitroptopanol glycosides (miserotoxins)
- hydrolyzed to nitrotoxins by rumen microbes
- nitrotoxins - 3-NPOH, 3-NPA
- 3-NPOH is absorbed and metabolized in the liver to 3-NPA
- 3-NPA is responsible for toxicity
- if ingested as 3-NPA, most of it is biodegraded in the GI tract, so there is a lower toxicity
- 3-NPA causes axonal degeneration in the spinal cord
- indolizidine alkaloid (swainsonine) and selenium
- CNS and skin toxicity
32
What is nitrotoxicosis? Provide the clinical signs of this condition.
- nitrotoxicosis - the clinical signs associated with nitrotoxin ingestion and toxicosis
- acute
- constipation, ataxia, staggering gait, recumbency, death from cardiac-respiratory failure
- in most cases, signs are gradual
- dyspnea, salivation, weakness, muscular spasms, docile appearance, goose-stepping, cracker heels, fetlock knuckling, posterior paresis/paralysis
- loss of body condition as toxicosis progresses
33
Identify a locoweed toxin and provide its mechanism of action.
- 3-NPA inhibits the krebs cycle leading to decreased energy (ATP) production and loss of cellular homeostasis
- axonal degradation in spinal cord, hypotension via vasodilation and cardiodepression
34
Describe the diagnostic procedures for nitrotoxicosis.
- clinical signs, evidence of plant consumption
- gross and histo respiratory and neuro lesions
- identification of NPA and NPH in plasma and serum by HPLC
35
Describe the treatment of nitrotoxicosis.
- withdraw animals from source of plant
- cattle will avoid locoweed when other forage available
- toxin concentration decreases rapidly as plants mature and undergo senescence
36
Name two sources of tremorgenic mycotoxins.
- tremorgenic forages - bermuda grass, ryegrass, dallis grass
- moldy cheese, bread, walnuts, and pasta
- garbage
37
Identify the mycotoxins referred to as tremorgens and the fungi that produce them. Which of these mycotoxins affect dogs?
- dogs
- Penicillium crustosum produces penitrem A
- Penicillium roquefort produces roquefortine C
- livestock
- Acemonium lolii produces lilitrem B
- Claviceps paspali produces paspalitrem
38
Provide the mechanisms of action of tremorgens and the main clinical signs of toxicosis.
- tremorgens cause presynaptic release of ACh and prolong depolarization at the neuromuscular junction
- facilitate transmission at motor end plate
- reduce levels of GABA and glycine
- CNS stimulation
- cerebral vasoconstriction
- leads to anoxia and CNS signs
- opisthotonus
- spasm of muscles causing backward arching of head, neck, and spine
39
Describe the decontamination procedures for tremorgenic mycotoxicosis in dogs.
- asymptomatic animals
- emesis, activated charcoal, cathartic
- symptomatic animals
- sedate/anesthesia and perform gastric lavage, then give activated charcoal and cathartic
40
Describe the treatment of tremorgenic mycotoxicosis in dogs.
- decontaminate then symptomatic and supportive therapy
- diazepam to control agitation, seizures, muscle tremors
- in patients that do not repsond to diazepam use methocarbamol or barbiturate
- IV fluids
41
Describe the treatment of tremorgenic mycotoxicosis in livestock.
- replace contaminated forage and keep animals in a quiet place until recovery
