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Tox Exam 1 > PNS I - ANS I > Flashcards

PNS I - ANS I Flashcards

1
Q

What are the components of the PNS?

A
  • afferent division
    • sensory stimuli, visceral stimuli
  • efferent division
    • somatic nervous system - motor neurons
    • autonomic nervous system - sympathetic nervous system, parasympathetic nervous system
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2
Q

Identify the key steps in neurotransmission.

A
  • 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
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3
Q

Identify the biochemical mechanism most commonly impaired by nervous system toxicants. Why is this mechanism highly vulnerable to toxicants?

A
  • impairs neurotransmission
  • alters metabolism, impairs oxygen and blood supply, ion balance disrupted
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4
Q

Name the various types of cholinergic receptors including one location for each receptor named.

A
  • 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
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5
Q

Which subtype of muscarinic receptors is found in the heart? How do these receptors influence cardiac function?

A
  • muscarinic M2
  • decrease rate of SA node and decrease conduction velocity at AV node
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6
Q

What does DUMBELS stand for? Name two toxicoses characterized by DUMBELS.

A
  • DUMBELS
    • diarrhea, dyspnea
    • urination
    • miosis (constricted pupil)
    • bradycardia
    • emesis
    • lacrimation
    • salivation
  • slaframine, organophosphates, carbamates
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7
Q

Name the source of slaframine. What environmental conditions favor this toxicosis?

A
  • 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
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8
Q

What is the ultimate toxicant of slaframine and how/where is it formed?

A
  • ketoimine metabolite
  • formed in liver when slaframine is activated by the enzyme flavoprotein oxidase
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9
Q

Provide the mechanism of action of slaframine?

A
  • cholinergic stimulation of exocrine and endocrine glands
  • slaframine has a high affinity GIT M3 receptors
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10
Q

Name one prominent clinical sign of slaframine toxicosis.

A
  • excessive salivation (slobbers)
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11
Q

Provide two DDx for slaframine toxicosis.

A
  • vesicular stomatitis
  • foot and mouth disease
  • ulcerative stomatitis
  • mechanical or chemical irritation of the mouth
  • dental problems
  • glossitis
  • oral foreign body
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12
Q

Identify a drug that can be used to treat slaframine toxicosis. What is the purpose of its use?

A
  • 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
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13
Q

Name a synthetic anticholinesterase.

A
  • organophosphates
  • carbamates
  • pharmaceuticals
    • physostigmine
    • neostigmine
    • edrophonium
    • pyridostigmine
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14
Q

Explain how anticholinesterase toxicants cause a cholinergic crisis.

A
  • 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
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15
Q

Name a domestic animal species that is highly susceptible to organophosphate toxicity. Provide a reason for this high sensitivity.

A
  • cats - majority f cholinesterase activity in cats is in the blood
  • bulls are very susceptible to chlorpyrifos - correlates with high testosterone levels
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16
Q

What are the differences and similarities in the mechanisms of action of organophosphates and carbamates?

A
  • 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
17
Q

What are the three categories of signs seen in animals following organophosphate poisoning?

A
  • 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
18
Q

Name two tests that can be used for Dx of organophosphate toxicosis.

A
  • atropine test
  • cholinesterase activity in heparinized whole blood
19
Q

Identify two DDx for organophosphate toxicosis

A
  • tremorgenic mycotoxicosis
  • amitraz toxicosis
  • pyrethrin, pyrethroid toxicosis
  • pancreatitis
  • garbage intoxication
  • blue green algae toxicosis
  • muscarinic mushrooms
  • cationic surfactants
20
Q

Name two drugs used to treat organophosphate poisoning and their mechanisms of action.

A
  • atropine
    • blocks muscarinic ACh receptors and relieves muscarinic but not nicotinic signs
  • pralidoxime (2-PAM)
    • reactivates AChE (before aging)
    • ineffective for CMs
21
Q

What is the purpose of using diazepam for treating organophosphate poisoning?

A
  • treats convulsions
22
Q

Other than acute toxicity, name two syndromes associated with organophosphates.

A
  • 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”
23
Q

Provide a characteristic of organophosphate that causes the intermediate syndrome.

A
  • they are preferentially distributed to muscles and have higher affinity for nicotinic ACh receptors
24
Q

What enzyme is inhibited by organophosphates to cause delayed neuropathy syndrome? What is the function of this enzyme?

A
  • neuropathy target esterase (NTE)
  • essential for call signaling and nerve development
25
Q

Name the plasma enzymes involved in organophosphate metabolism. What kind of reactions do these enzymes catalyze?

A
  • esterase - catalyze hydrolysis
  • splits esters into an acid and an alcohol
26
Q

Explain “lethal synthesis” and “aging” as applied to organophosphate toxicity?

A
  • 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
27
Q

Name a natural anticholinesterase and the organisms that produce it.

A
  • anatoxin-a
    • produced by blue green algae
    • cyanobacteria
      • Anabaene
      • Aphanizomenon
      • Oscillaatoria
28
Q

Identify weather conditions that favor blue-green algal blooms.

A
  • stagnant eutrophic (high nutrient) bodies of water during warm calm weather
  • wind concentrates algal growth along shorelines
29
Q

Describe the treatment/management of anatoxin-a(s) toxicosis.

A
  • atropine
  • decontaminate - emesis, charcoal, cathartic
  • bathe if dermal exposure
  • remove animal from contaminated water and treat water with copper sulfate
30
Q

Provide the mechanism of action of tropane alkaloids.

A
  • anticholinergic
  • competes with ACh at postsynaptic muscarinic receptors and autonomic ganglia
31
Q

Name two plants that contain tropane alkaloids.

A
  • 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
32
Q

Identify a drug that can be used in the treatment of tropane alkaloids toxicosis and its purpose

A
  • sedatives and anticonvulsants - diazepam or barbiturate
  • treat seizures

Tox Exam 1 (6 decks)

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