Exam I -Organochlorine, OP,Carb, Nicotine, Napthalene, Rotenone Flashcards
(106 cards)
1
Q
What irreversibly inactivates acytylcholinesterase?
A
Organophosphates (OP)
2
Q
What is the major cause of animal poisoning?
A
Organophosphates
3
Q
What is the most common organophosphate?
A
Malathion
4
Q
T/F organophosphates have a various degree of water and lipid solubility
A
True
5
Q
T/F Organophosphates produce a major issue with tissue and environmental residue
A
False - produce little tissue and environmental residue
6
Q
What is responsible for 70% of pesticidal use in the US?
A
Organophosphates
7
Q
Why was Parathion synthesized?
A
To replace DDT as an insecticide
8
Q
Some organophosphates are micro encapsulated, what does this do?
A
Active ingredient is released slowly, increases the duration of activity and reduces toxicity
9
Q
Which one is more lipid soluble, Thiophosphate OP or phosphate OP?
A
Thiophosphate
10
Q
OP degrade relative quickly when exposed to the environment, how long do they generally persist?
A
2-4 weeks
Residues on fruit, vegetables and crops may last longer
11
Q
What will happen if OPs are sealed and stored for 1-2 years?
A
they become more toxic
‘Storage activation’
12
Q
What are examples of OPs that have this ‘storage activation’ ability?
A
Parathion
Malathion
Diazinon
Coumaphos
13
Q
T/F Technical grade chemicals are less pure than reagent grade chemicals
A
True
14
Q
T/F impurities are less toxic
A
False - more toxic
15
Q
How are Organophosphates absorbed?
A
Readily absorbed through: skin mucous membranes, GIT inhalation
16
Q
T/F. OP are extensively metabolized in the liver making them into a “lethal synthesis”
A
True
17
Q
What could continued exposure to OPs lead to?
A
Adaptation to decreased acetylcholinesterase
18
Q
What are they types of OPs?
A
Phosphates and Thiophosphates
19
Q
T/F Thiophsphates are biologically active and phosphates require bioactivation
A
False - phosphates are biologically active and thiophosphates require bioactivation
20
Q
What OPs has direct effect on acetylcholinesterase (AChE) activity?
A
Phosphates
21
Q
Thiophosphates are biologically inactive until transformed by liver to ______
A
-oxon metabolites
22
Q
Thiophosphates are highly ____ soluble and rapidly absorbed in _____ tissue
A
Lipid
Adipose
23
Q
What may slow release of thiophosphates from fat lead to?
A
delayed and/or prolonged cholinesterase inhibition
24
Q
What is the major route by which thiophosphate is eliminated?
A
Paraoxonase - a serum bound enzyme
25
What is the MOA for OPs?
Irreversible inhibition of cholinesterase (ACh accumulates throughout CNS)
1st - muscarinic receptor over stimulation
2nd - nicotinic receptor over stimulation
3rd - nicotinic blockade
26
What could high exposure to OPs lead to?
Respiratory failure, paralysis and death
27
What are the muscarinic effects of OPs overstimulating the PSN?
```
DUMBELLS
Diarrhea
Urination
Miosis
Bronchospasm
Emesis
Lachrymation
Salivation
```
28
What are the nicotinic effects of OPs overstimulation?
Acetylcholine accumulation at the neuromuscular junction causes initial stimulation or fasciculations in muscle groups
29
What would stimulation of the SNS lead to?
sweating, hypertension and tachycardia
30
what does the recovery of OPs ultimately depend on?
On the generation of new enzyme or Ach-esterase in critical tissue
31
What will be the delayed effect of OPs after 10-14 day exposure?
Organophosphate-induced delayed polyneuropathy
32
What occurs in organophosphate induced delayed polyneuropathy?
Distal degeneration of long/large diameter motor and sensory axons of peripheral nerves and spinal cord
33
What clinical signs will you see with organophosphate induced delayed polyneuropathy?
Muscle weakness, ataxia, rear limb paralysis
34
When does organophosphate induced intermediate syndrome occur?
2-4 days after acute cholinergic effect and signs of the acute effects are no longer obvious
35
what sings will you see with organophosphate induced intermediate syndrome?
weakness of respiratory muscles (diaphragm, intercostal) and accessory muscles, including neck muscles and of proximal limb muscles
36
MOA for OPs?
Irreversible inhibition of cholinesterase
| Non competitive inhibition
37
How fast is the onset of OP toxicity?
15min - 1 hr
38
How would you be able to detect OP toxicosis?
Analysis of stomach/rumen contents
Analysis of hair/skin
may find residues in fat/liver with OPs that are more lipophilic
39
Why would you normally not use the liver/kidney to assess a patient for OP toxicity?
rapid metabolism
40
How could you do a laboratory diagnosis of OP toxicity?
By Plasma acetylcholinesterase activity level
41
What activity level of acetylcholinesterase is diagnostic of OP toxicity?
less than 50% activity is suspicious and less than 25% activity is diagnostic
42
How could you clinically diagnose OP toxicity?
Do a Atropine response test - administer atropine and wait 15 mins.
If positive - dry skin/mucous membranes, increased HR, dilated pupils, decreased bowel sounds
If negative - few or no signs seen
43
How could you treat an animal with OPs toxicosis?
Emesis if ingested and no respiratory depression or seizures seen.
activated charcoal
Wash gently is on skin
Atropine
44
What should you avoid giving a patient with OPs toxicosis?
Phenothiazines, Aminoglycosides, muscle relaxants, drugs that depress respiration (opioids)
45
What drug could you give as a specific physiologic antagonist to OPs?
Atropine
46
What drug could you give that will reverse the OP binding on the acetylcholinesterase?
Pralidoxime or 2PAM
47
How could you treat OP induced delayed polyneuropahty?
symptomatic therapy only
48
How could you treat OP induced intermediate syndrome?
```
Supportive care (rest, nutrition, ventilation)
2-PAM in severe cases
May last for weeks
```
49
What is the prognosis of OP toxicosis?
Overall "Guarded"
| Depends on each situation
50
What Carbomate is the most toxic?
Aldibarb
51
Do carbamates undergo storage activation?
no
52
T/F Carbamates penetrate the CNS, require hepatic bioactivation, have a slower onset and longer duration than OPs
FALSE
Do NOT penetrate the CNS
Do NOT require hepatic bioactivation
Faster onset and shorter duration than OPs
53
What are carbamates MOA?
REVERSIBLE inhibition of acetylcholinesterase
| Competitive inhibition
54
What signs will you see with carbamate poisoning?
```
SLUD
Salivation
Lacrimation
Urination
Diarrhea
```
55
How do animals usually die from carbamate toxicity?
Respiratory failure and hypoxia due to bronchoconstriction leading to tracheobronchial secretrion and pulmonary edema.
56
Would you be able to detect carbamate drug residues in tissue, blood or secretions?
no, because of rapid metabolism
57
How could you treat carbamate toxicity?
Atropine - same as for OPs
58
Could you also use oxides or 2-PAM in carbamate toxicity like in OP toxicity?
its not reliably effective against carbamates
59
What was naphthalene first registered as in the US?
Pesticide - then as an insecticide and pest repellent
60
What are mothballs?
Pesticides - slowly release of gas vapor kills and repel moths and their larva and other insects
61
The old version of mothballs contained naphthalene, which were highly toxic and flammable, what do the new version of them contain?
Paradichlorobenzene - less toxic
62
How could you tell which type of mothball you have?
Do a float test - add the ball in saturated salt water, if it floats, its naphthalene based, if it doesnt float, its paradichlorobenzene
63
Where is naphthalene derived from?
Crude oil or coal tar
64
Which animal is more susceptible to naphthalene, cats or dogs?
Cats more sensitive, but dogs more likely to ingest.
65
What is the lowest canine lethal dose of naphthalene?
~400 mg/kg
| One naphthalene mothball can be toxic
66
How could naphthalene be absorbed?
Orally or dermally
67
What increased the absorption of naphthalene?
oils - its lipid soluble. acid in the stomach delays absorption
68
What could repeated exposure to naphthalene cause in the eyes and skin?
Cataracts and skin irritation/rash
69
Naphthalene enters the bloodstream and is rapidly distributed, crosses the placenta and is excreted in milk. Where would you find high concentrations of it?
In adipose tissue, kidneys, liver, and lungs
70
Naphthalene is metabolized in the liver by hepatic enzymes (CYP450), the metabolites can then form epoxides or quinone, which may cause
cellular damage (hemolysis of RBCs)
71
how are naphthalene metabolites excreted?
in urine and bile
72
What is Naphthalene MOA?
Oxidation products (oxides) in the circulation can cause methemoglobinemia and hemolysis
- decreased ability to bind oxygen
- leads to cellular/tissue hypoxia
73
What major signs of toxicity would you see with naphthalene?
```
Vomiting
Mothball scented breath
Pale or brown gums
Weakness or lethargy
Labored breathing
Tremors
Seizures
```
74
T/F Mothballs dissolve quickly when ingested and toxicity is very short lived
False - mothballs dissolve slowly when ingested (acid stomach) and toxicity can be delayed by several days
75
How could you diagnose naphthalene toxicity?
Hematologic changes - hemolysis, hemoglobinuria, Heinz bodies
Methemoglobinemia - blood s a chocolate brown color
76
What are your Ddx for naphthalene toxicity?
Heinz bodies due to acetaminophen, onions, nitrates
77
How could you treat naphthalene toxicity?
```
Emesis then activated charcoal +/- cathartics
Sodium bicarbonate (can reduce precipitation of hemoglobin in the kidneys)
```
78
How could you specifically treat methemoglobinemia?
Ascorbic acid
| Methylene blue 1%
79
How does ascorbic acid work?
Reduces methemoglobin to hemoglobin by a non enzymatic reserve mechanism
80
How does methylene blue 1% work?
Acts rapidly and works through its conversion to leucomethylene blue, which acts as a reducing agent converting methemoglobin to hemoglobin
81
Why should you not use methylene blue in cats?
because feline RBCs are susceptible to oxidative injury
82
T/F Nicotine is a lipid soluble alkaloid readily absorbed through the skin, mucous membranes and respiratory tract
False - its a water soluble alkaloid. rest is true
83
The liver readily extracts nicotine from circulation and makes two principal oxidative metabolites cottoning and nicotine-1-N-oxide, how are they excreted?
By the kidneys - renal excretion is increased in acidic or low urine pH. If urine pH is increased, re-absorpiton will occur
84
Nicotine is a potent stimulant of ____ nervous system
Parasympathetic
85
What does nicotine mimic at low doses?
acetylcholine and stimulates post-synaptic nicotinic receptors (CNS, ganglia, neuromuscular junctions)
86
what would high dosed of nicotine cause?
stimulation will be followed by blockage (persistent depolarization)
87
What does nicotine stimulate to cause auto decontamination?
Stimulates the Chemo-receptor trigger zone (CRTZ) to initiate vomiting
88
What are the clinical signs of early nicotine toxicity?
Ataxia, lethargy, hypersalivation, vomiting (CRTZ reaction), bradycardia (vagal stimulation), tremors, convulsions
89
What are the clinical signs of late or high dose toxicity with nicotine?
CNS depression, tachycardia, vasodilation, paralysis or respiratory muscles and death
90
What will your Ddx be for nicotine toxicity?
```
Strychnine
Methylxanthines
Tremorgenic mycotoxins
Organophosphates
Carbamates
Depressants
```
91
How could you treat nicotine toxicity?
```
Emesis, gastric lavage
Activated charcoal
Enhance excretion - IV fluids
Atropine (for PSN effects)
Diazepam (seizures)
```
92
What should you avoid giving animals with nicotine toxicity?
Antacids - they raise pH and increase GI absorption and decrease excretion
93
What is a direct nicotinic antagonist drug used in humans (has no known use in animals)?
Mecamylamine
94
What is the prognosis of an animal with nicotine toxicity?
if the animal survives first hrs, its good
| If animal ingested large amounts - survival is grave to poor
95
Where does rotenone come from?
Plant extract - jicama vine plant and roots of several members of fabaceae
96
What is rotenone used for?
Pets/horses - lice/tick
Chickens - mites
crops for aphids (plant lice)
Rivers/lakes to kill unwanted fish
97
T/F Rotenone has minor and transient environmental side effects, its readily degraded upon exposure to warm air and light, and more hydrophilic than lipophilic
False - its more lipophilic than hydrophilic. all else is true
98
What route of absorption is rotenone more toxic?
Inhalation - direct pathway to circulatory system
99
GI tract and dermal absorption is low and incomplete with rotenone, unless if mixed with what?
fats/oils
100
Rotenone is metabolized in the liver and excreted in urine/feces within ___ hrs
24
101
Rotenone is highly neurotoxic to ___ and cold blooded animals
Fish
102
T/F In fish, route of exposure to rotenone is through the gills or trachea, it passes directly into the bloodstream through the gills and converted to highly toxic metabolites in the liver
True
103
T/F Rotenone is highly toxic to humans, mammals, and birds. Route of exposure is typically through the gut
False - its not highly toxic to these species
104
What is the MOA of rotenone?
- Blocks oxidative phosphorylation in the citric acid cycle (TCA cycle)
- interferes with the mitochondria electron transport chain and NADH during ATP production
105
What clinical signs will you see with rotenone?
Irritant - conjunctivitis, congestion, dermatitis
Depression, convulsions
PO - GI tract irritant, convulsions, muscle tremors, lethargy, incontinente,
Pulmonary irritation, asphyxia
106
How could you treat rotenone toxicity?
No specific treatment
Detoxification if appropriate
Supportive treatment (treat seizures, hypoglycemia)
