PNS I - ANS I Flashcards
What are the components of the PNS?
- afferent division
- sensory stimuli, visceral stimuli
- efferent division
- somatic nervous system - motor neurons
- autonomic nervous system - sympathetic nervous system, parasympathetic nervous system
Identify the key steps in neurotransmission.
- synthesis of neurotransmitters
- storage of neurotransmitters in presynaptic cell
- calcium dependent neurotransmitter release upon stimulation
- interaction with postsynaptic receptors
- termination of neurotransmitter action by reuptake and metabolism
Identify the biochemical mechanism most commonly impaired by nervous system toxicants. Why is this mechanism highly vulnerable to toxicants?
- impairs neurotransmission
- alters metabolism, impairs oxygen and blood supply, ion balance disrupted
Name the various types of cholinergic receptors including one location for each receptor named.
- nicotinic N
- ligand gated
- autonomic ganglia, adrenal medulla
- nicotinic M
- ligand gated
- neuromuscular junction
- muscarinic M1/M3
- protein coupled
- stomach, intestine
- sweat, lacrimal, and salivary glands
- muscarinic M2
- protein coupled
- heart
- muscarinic M3
- protein coupled
- bronchial muscle, bronchial glands, eye
Which subtype of muscarinic receptors is found in the heart? How do these receptors influence cardiac function?
- muscarinic M2
- decrease rate of SA node and decrease conduction velocity at AV node
What does DUMBELS stand for? Name two toxicoses characterized by DUMBELS.
- DUMBELS
- diarrhea, dyspnea
- urination
- miosis (constricted pupil)
- bradycardia
- emesis
- lacrimation
- salivation
- slaframine, organophosphates, carbamates
Name the source of slaframine. What environmental conditions favor this toxicosis?
- red clovers infected with fungus Rhizoctonia leguminicola that produces indolizidine alkaloid mycotoxin
- black patch disease of plants
- also associated with white clover, soybean, kudzu, cowpea, blue lupine, alfalfa
- wet weather and high humidity favor this toxicosis
What is the ultimate toxicant of slaframine and how/where is it formed?
- ketoimine metabolite
- formed in liver when slaframine is activated by the enzyme flavoprotein oxidase
Provide the mechanism of action of slaframine?
- cholinergic stimulation of exocrine and endocrine glands
- slaframine has a high affinity GIT M3 receptors
Name one prominent clinical sign of slaframine toxicosis.
- excessive salivation (slobbers)
Provide two DDx for slaframine toxicosis.
- vesicular stomatitis
- foot and mouth disease
- ulcerative stomatitis
- mechanical or chemical irritation of the mouth
- dental problems
- glossitis
- oral foreign body
Identify a drug that can be used to treat slaframine toxicosis. What is the purpose of its use?
- atropine - will reverse muscarinic signs if given early (before excessive salivation)
- antihistamines - may alleviate some clinical signs
- important to note that animals usually recover spontaneously once bad forage removed
- slaframine toxicosis is generally not life threatening
Name a synthetic anticholinesterase.
- organophosphates
- carbamates
- pharmaceuticals
- physostigmine
- neostigmine
- edrophonium
- pyridostigmine
Explain how anticholinesterase toxicants cause a cholinergic crisis.
- they inhibit the action of acetylcholinesterase, which breaks down acetylcholine
- this causes a buildup of acetylcholine in nerve synapses and neuromuscular junctions
- causing continuous stimulation of nervous, glandular, GIT, and muscular cholinergic receptors
- AKA stimulation of muscarinic and nicotinic receptors
Name a domestic animal species that is highly susceptible to organophosphate toxicity. Provide a reason for this high sensitivity.
- cats - majority f cholinesterase activity in cats is in the blood
- bulls are very susceptible to chlorpyrifos - correlates with high testosterone levels
What are the differences and similarities in the mechanisms of action of organophosphates and carbamates?
- both cause tier effects by inhibiting acetylcholinesterase
- OPs do this by phosphorylating the enzyme, which is irreversible
- binding of CMs cause the enzyme to undergo carbomylation, which is reversible due to CMs low affinity for the enzyme binding sites
- they will spontaneously dislodge from the enzyme
What are the three categories of signs seen in animals following organophosphate poisoning?
- muscarinic
- first to appear
- preceded by apprehension or uneasiness
- DUMBELS
- nicotinic
- neuromuscular
- twitching, tremors, convulsions, seizures
- tachycardia, mydriasis (dilated pupil)
- weakness, paresis, paralysis
- death due to paralysis of respiratory muscles
- CNS
- stimulation followed by severe depression leading to coma and death
- anxiety, restlessness, stiffness, ataxia
- food animals - hyperactivity and seizures
- dogs - hyperactivity and clonic-tonic seizures
- respiratory paralysis
Name two tests that can be used for Dx of organophosphate toxicosis.
- atropine test
- cholinesterase activity in heparinized whole blood
Identify two DDx for organophosphate toxicosis
- tremorgenic mycotoxicosis
- amitraz toxicosis
- pyrethrin, pyrethroid toxicosis
- pancreatitis
- garbage intoxication
- blue green algae toxicosis
- muscarinic mushrooms
- cationic surfactants
Name two drugs used to treat organophosphate poisoning and their mechanisms of action.
- atropine
- blocks muscarinic ACh receptors and relieves muscarinic but not nicotinic signs
- pralidoxime (2-PAM)
- reactivates AChE (before aging)
- ineffective for CMs
What is the purpose of using diazepam for treating organophosphate poisoning?
- treats convulsions
Other than acute toxicity, name two syndromes associated with organophosphates.
- intermediate syndrome (IMS)
- inhibits acetylcholinesterase, but there is no muscarinic receptors associated hypersecretory activity
- OP induced delayed polyneuropathy (OPIDP)
- degeneration of long and large diameter motor and sensory axons of both peripheral and spinal cord neurons
- “ginger jake”
Provide a characteristic of organophosphate that causes the intermediate syndrome.
- they are preferentially distributed to muscles and have higher affinity for nicotinic ACh receptors
What enzyme is inhibited by organophosphates to cause delayed neuropathy syndrome? What is the function of this enzyme?
- neuropathy target esterase (NTE)
- essential for call signaling and nerve development
Name the plasma enzymes involved in organophosphate metabolism. What kind of reactions do these enzymes catalyze?
- esterase - catalyze hydrolysis
- splits esters into an acid and an alcohol
Explain “lethal synthesis” and “aging” as applied to organophosphate toxicity?
- lethal synthesis
- when something non toxic is converted to a poison in the body
- OPs swap its sulfur for an oxygen (desulfuation) in liver
- aging
- when OP-cholinesterase bond is strengthened by the loss of an alkyl group
- this converts the inhibited enzyme into a non reactivable form
Name a natural anticholinesterase and the organisms that produce it.
- anatoxin-a
- produced by blue green algae
- cyanobacteria
- Anabaene
- Aphanizomenon
- Oscillaatoria
Identify weather conditions that favor blue-green algal blooms.
- stagnant eutrophic (high nutrient) bodies of water during warm calm weather
- wind concentrates algal growth along shorelines
Describe the treatment/management of anatoxin-a(s) toxicosis.
- atropine
- decontaminate - emesis, charcoal, cathartic
- bathe if dermal exposure
- remove animal from contaminated water and treat water with copper sulfate
Provide the mechanism of action of tropane alkaloids.
- anticholinergic
- competes with ACh at postsynaptic muscarinic receptors and autonomic ganglia
Name two plants that contain tropane alkaloids.
- belladonna (Atropa belladonna) - deadly nightshade, sleeping nightshade
- black henbane (Hyoscyamus niger) - poison tobacco, stinking nightshade, insane root
- Datura stramonium - Jamestown weed, devil’s trumpet, mad apple, stinkweed
Identify a drug that can be used in the treatment of tropane alkaloids toxicosis and its purpose
- sedatives and anticonvulsants - diazepam or barbiturate
- treat seizures
