Cholinergic and Anticholinesterase Toxicants Flashcards
(43 cards)
Nervous system overview:
How do the parasympathetic and sympathetic preganglionic and postganglionic fibers?
PS = long preganglionic, short postganglionic
S = short preganglionic, long postganglionic
What neurotransmitter is released by preganglionic fibers of both parasympathetic and sympathetic nerves? What receptor does it bind to?
acetylcholine
nicotinic
What neurotransmitters are used at the postganglionic fibers of parasympathetic and sympathetic nerves? What receptors do they bind to?
PARASYMPATHETIC
- Ach —> M - cardiac and smooth muscles, gland cells, nerve terminals
SYMPATHETIC
- NE —> α, β - cardiac and smooth muscles, gland cells, nerve terminals
- Ach —> M - sweat glands
- D —> D1 - renal vasculature, smooth muscle
- Ach —> N - adrenal medulla, production of Epi
What is unique about the peripheral nervous system of horses?
sweat glands are predominantly under β-adrenergic control
What are the direct and indirect mechanisms of toxicity of autonomic nervous system toxicants?
DIRECT = impairment of neurotransmission, causing structural toxicoses —> neuronopathy, axonopathy, myelinopathy
INDIRECT = alteration of metabolism or blood supply with secondary neuronal dysfunction
What are the 5 steps in neurotransmission?
- synthesis of neurotransmitter
- storage of neurotransmitter in presynaptic cells
- calcium-dependent neurotransmitter release upon stimulation
- interaction with postsynaptic receptors
- termination of neurotransmitter action by reuptake/metabolism
How do cholinergic toxicants generally work?
target any point of neuronal transmission where acetylcholine is used as the neurotransmission
What is the structure of nicotinic and muscarinic receptors?
NICOTINIC = ligand-gated channels that open upon Ach binding (Nn, Nm)
MUSCARINIC = G-protein coupled (M1-M5)
Where are nicotinic receptors found?
Nn - autonomic ganglia firing of post-ganglionic neurons, adrenal medulla secretion of Epi
Nm - NMJ end-plate depolarization and skeletal muscle contraction
Where are muscarinic receptors found?
M1/M3 - glands, stomach, intestine,
M2 - heart
M3 - eye, bronchial muscle
What muscarinic receptors are excitatory? Inhibitory?
EXCITATORY = M1, M3, M5
INHIBITORY = M2, M4
What are the general signs of cholinergic stimulation? What receptors control these reactions?
- Diarrhea, Dyspnea
- Urination
- Miosis
- Bradycardia
- Emesis
- Lacrimation
- Salivation
muscarinic
What is the source of slaframine? What toxicosis does it cause? In plants?
indolizidine alkaloid mycotoxin produced in red clovers (Trifolium spp.) infected with the fungus Rhizoctonia leguminicola
slobber syndrome, clover poisoning, salivary syndrome
Black Patch Disease
In what conditions favor slaframine toxicosis?
periods of wet weather and high humidity
What is the ultimate toxicant of slaframine? How is it produced?
activated by liver microsomal flavoprotein oxidase to a ketoimine metabolite that is chemically similar to acetylcholine
What 2 species are most affected by slaframine toxicosis?
- cattle
- horses
What is the mechanism of toxicity of slaframine?
parasympathomimetic - causes cholinergic stimulation of exocrine and endocrine glands with a high affinity for GI tract muscarinic (M3) receptors
What clinical sign is most associated with slaframine toxicosis? What else is observed?
salivation (slobbers)
DUMBELS - lacrimation, anorexia, diarrhea, urination, bloating, stiffness, respiratory distress, bradycardia, decreased milk production, death is rare
What is a common observation in horses with slaframine toxicosis?
if a horse is kept in the same spot for a decent amount of time, it will salivate so severely that a puddle will form
In what 5 ways can slaframine toxicosis be diagnosed?
- salivation in animals consuming legumes, especially red clovers
- detection of black patch plant lesions
- recovery following removal of offending feedstuff
- detection of toxin in plant material by chemical analysis
- salivary response in guinea pig bioassay
What 7 conditions fit into a differential diagnosis for slaframine toxicosis?`
clinical syndromes that cause salivation:
1. vesicular stomatitis
2. foot and mouth disease
3. ulcerative stomatitis
4. mechanical or chemical irritation of the mouth
5. dental problems
6. glossitis
7. oral foreign body
How is slaframine toxicosis typically treated?
generally not life-threatening and animals recover spontaneously once the offending forage is removed so treatment is not always necessary
What 2 drugs can be used to alleviate clinical signs of slaframine toxicosis?
- Atropine can only reverse muscarinic signs if given early and is not effective once salivation occurs
- antihistamines
