Exam 1 Flashcards
What type of toxic dose: The highest or largest dose which does not result in undesirable or toxic alterations
Highest nontoxic dose (HNTD)
What is the prognosis of Naphthalene?
Reasonable if treated promptly
Do organophosphates get distributed to the CNS?
Yes
What are the natural pyrethrins?
Pyrethrin 1 & 2
Cinerin 1 & 2
Jasmolin 1 & 2
Toxicity level of D-Limonene in cats at 5x recommended dose?
Mild toxicity
What factors can decrease the toxicity of AR?
Pregnancy
Enzyme inducers (phenytoin)
MOA of Bromethalin?
Uncoupling of oxidative phosphorylation
Lack of ATP
Insufficient energy for Na+/K+ pumps
What can be done as symptomatic treatment for chlorinated hydrocarbon toxicity?
Diazepam or barbiturates for seizures
Oxygen, ventilation, fluids
T/F: Younger animals are more sensitive to Cholecalciferol
True
MOa of Ivermectin?
GABA agonist
How does the soil half-life of chlorinated hydrocarbons compare to OPs?
LONGER
2-15 years (few weeks with OPs)
What type of toxicity: The effect produced by daily exposure from one day to 30 days
Subacute toxicity
What precipitate should be used to treat alkaloid poisoning?
Tannic acid
What are the common routes by which organophosphates get into the body?
Oral (contaminated feed)
Dermal
Inhalation
What does a nicotinic blockade from OP poisoning cause?
Paralysis
CNS depression
Coma
Dyspnea
Death (resp. failure)
What are the most characteristic signs of Cholecalciferol?
Hematemesis and melena (GI)
PU/PD (renal)
Depression (neurologic)
What is the antidote for apomorphine?
Naloxone
What lesions are associated with Bromethalin?
Cerebral edema
Diffuse white matter vacuolization through CNS
Which species has less plasma pseudocholinesterase?
Ruminants
Dose for a harmless substance?
>15g/kg
What is the cause of death in high exposure of OPs?
Respiratory failure (paralysis)
In mammals, Rotenone is converted to what kind of metabolite?
Non-toxic metabolites
What clinical signs are associated with Naphthalene?
Mothball breath
Hemolysis, heinz bodies, methemoglobinemia, seizures
Cataracts in neonates
When i say Bromethalin, you say…
Neurotoxicant
What organ metabolizes calcidiol to calcitriol?
Kidney
What species is deficient in acetylating enzymes?
Dogs
Affect of charcoal broiled foods on enzymes?
Induction
What is the adsorbant of choice for toxins?
Activated charcoal
How is Ivermectin excreted?
Feces
What is the significance of the ABCB1 gene in dogs that receive Ivermectin?
Results in ~50x concentration of drug in the CNS
For feed, 100 g/ton = Xppm
110ppm
What type of toxicity: The effect produced by daily exposure for a period of 3 months or more
Chronic
This toxin can cause acute paralysis in dogs from topical exposure
Pyrethrins and Pyrethroids
Low doses of Nicotine can resemble what other toxicity?
OP/CM
Describe the atropine response test
Administer 0.02 mg/kg of atropine
If strong response, then less likely OP toxicity
Atropine treatment for OP toxicity is 0.1-0.5 mg/kg
High doses of Nicotine can resemble what type of drugs?
CNs depressants
What is the prognosis of Cholecalciferol?
Variable - the earlier treatment is started, the better
Severe hypercalcemia = more guarded
Hematemesis or mineralization = poorer prognosis
T/F: When treating for AR, you would test the Vitamin K even after it is discontinued
True
Check PT 24-48 hours after last dose of Vitamin K
The use of ipecac is contraindicated in what species?
Cats
What is the prognosis of Bromethalin?
Mild case - resolve over several weeks
Severe case - grave prognosis
How are dogs commonly poisoned with Ivermectin?
Overdose due to use of large animal products on small animals
Coming in contact with horse feces after treatment
Which biotransformation reaction is deficient in the neonate?
Conjugation
What drugs are examples of extensive first pass effect?
Lidocaine
Propranolol
Morphine
What drug has a strong affinity to kidney tissue?
Aminoglycosides
What nonspecific pathological lesions are associated with OP poisoning?
Pulmonary edema and congestion
Edema of various organs (including brain)
Necrosis in skeletal muscle
What levels of AChE activity are used to determine OP?
<50% activity is suspicious
<25% activity is diagnostic
Is Amitraz distributed to the CNS?
Yes
What is the acute oral LD50 of Amitraz for dogs?
~250mg/kg
Mild signs (sedation) seen in some dogs at 20mg/kg
What type of toxic dose: The lowest dose which produces toxic alterations and administering twice this dose will not cause death
Toxic dose low (TDL)
What is the most toxic of the Carbamates?
Aldicarb
Mimics the structure of ACh
What are xenobiotics?
Foreign chemicals that the body does not produce
Drugs and poisons are xenobiotics
Which reaction phase of biotransformation is the synthetic phase?
Phase 2
What is used to treat cerebral edema due to Bromethalin?
Mannitol +/- dexamethasone
What is the dose with no toxic signs called?
Maximum Tolerated Dose or Minimal Toxic Dose (MTD)
What is the most common biotransformation reaction?
Oxidation
What species is deficient in glucuronyl transferase?
Cats
What specific treatment is used for Naphthalene?
Ascorbic acid - converts MetHgb to Hgb
Methylene blue 1% - faster than ascorbic acid but is an oxidizer
What clinical signs are assocated with CNS stimulation following OP poisoning?
Anxiety
Restlessness
Hyperactivity
Tonic-colonic seizures (CNS depression in ruminants)
What species is most sensitive to OP induced delayed polyneuropathy?
Chickens
T/F: Chlorinated hydrocarbons are highly lipophilic
True
At what dose of nicotine do you see clinical signs in the dog?
1 mg/kg
Convert 1ppm to %
0.0001%
T/F: OPs are extensively metabolized in the liver
True
Clicker question:
If chelation therapy is recommended for a toxicant when levels reach 5mg%, will a blood level of 900mcg/dL require therapy?
No
What is used to treat ARs?
PO Vitamin K1 (phytonadione)
How long should you treat a patient with Warfarin poisoning?
1 week
What pathology is associated with delayed neurotoxicity following OP poisoning?
Degeneration and demyelination of peripheral and spinal motor neurons
Clicker question:
Which of the following factors has the shortest half-life?
A. II
B. VII
C. IX
D. X
B. VII
What is the half-life of Bromethalin in the rat?
5-6 days
What are the poorly perfused tissues?
Bone
Adipose tissue
How do the chemical properties of the metabolite differ from the drug?
Metabolite is more water soluble, polar, and ionized
Which organophosphates have direct acetylcholinesterase activity?
Dichlorvos
Monocrotophos
Trichlorfon
What toxin can cause abortion in cattle?
Anticoagulant Rodenticides from placental hemorrhage
What should you use in cats to induce emesis?
Xylazine
T/F: ARs are largely protein bound
True
What drugs should be avoided when treating Bromethalin?
Magnesium cathartics (CNS depressive)
What is the toxic component of Cholecalficerol?
Vitamin D3
What type of toxicity: The effect of a single dose of multiple doses during a 24 hour period
Acute toxicity
T/F: Pancreatitis has been reportedly found in some dogs with the more lipophilic compounds
True
How long does it take for clinical signs of AR to set in?
1-5 days
T/F: Compared to cholinesterases, chlorinated hydrocarbon toxicity will have less parasympathomimetic signs, and less severe CNS stimulation
False
Less parasympathomimetic signs, MORE severe CNS stimulation
What should you monitor when treating D-Limonene toxicity?
Temperature
Want to avoid hypothermia just as with Pyrethrins
Which species have high levels of oxidative enzymes?
Ruminants
Horses
MOA of DEET?
Unknown
Can cause surface irritation
Clicker question:
Which of the following insecticide toxicants would you expect to have the longest half-life?
A. OPs
B. CMs
C. Chlorinated hydrocarbons
D. Pyrethrins
C. Chlorinated hydrocarbons
Dose for a slightly toxic substance?
0.5g/kg
How do you calculate the standard safety margin?
Ratio between LD1 and ED99
What is the main clinical sign associated with chlorinated hydrocarbons?
CNS stimulation
What is the lowest canine lethal dose of Naphthalene?
~400mg/kg
One mothball can weigh 2.7-4g
How is toxicity expressed in mammals? Birds? Fish?
Mammals - LD50 in mg/kg body weight
Birds - LC50 in mg/kg feed
Fish - LC50 in mg/liter water
What type of toxic dose: Smaller to the highest nontoxic dose
Maximum tolerated dose or minimal toxic dose (MTD)
What is the prognosis of D-Limonene toxicity?
Exelent in sublethal toxicosis
Usually resolves within 6-12 hours
Are dogs or cats more sensitive to DEET?
Cats
What is the prognosis of Rotenone?
Generally good for mammals
Poor for fish and reptiles
What are our Chlorinated Hydrocarbons (Organochlorines)?
Diphenyl aliphatics (DDT, methoxychlor)
Aryl hydrocarbons (Lindane)
Cyclodienes (Aldrin, Toxaphene)
What are some lab findings of AR?
+/- anemia
Mild thrombocytopenia
Hypoproteinemia
Does Ivermectin cross the BBB?
Not typically
Dose for a moderately toxic substance?
> 50-500mg/kg
What is the ratio between acute LD50 and chronic LD50?
Chronicity factor
T/F: Cats are more sensitive to D-Limonene than dogs
True
How long does it take for acute clinical signs or Bromethalin to set in (less common)?
2-24 hours
CNS excitatory signs
Usually with a supralethal dose
Clicker Question:
Which of the following aspects of toxicity are the same between OP and CM insecticides?
A. both toxicants undergo storage activation
B. both toxicants undergo lethal synthesis
C. cholinesterase activity can be tested for either
D. Pralidoxime is an effective treatment for either
C. cholinesterase activity can be tested for either
What drugs can cause the ABCB1 mutation?
Cyclosporine
Ketoconazole
Verapamil
Which species lacks oxidative enzymes?
Birds
MOA of OPs?
Irreversible inhibition of cholinesterases
Increase ACh at all cholinergic sites
What are our enzyme inducers?
Phenobarbital
Phenylbutazone
Griseofulvin
Rifampin
Chlorinated hydrocarbon insecticides
MOA of Naphthalene?
Oxidation products cause methemoglobinemia and hemolysis
Leads to tissue hypoxia
Clicker Question:
All of the following are general contraindications to inducing emesis after toxin ingestion EXCEPT:
A. patient is depressed/unconscious
B. patient is seizuring/high risk of seizures
C. known enterohepatic recirculation
D. known corrosive toxin
C. known enterohepatic recirculation
Clicker question:
Which of the following toxicants is primarily a CNS depressant?
A. Chlorinated hydrocarbon
B. CM
C. Amitraz
D. Pyrethrin
C. Amitraz
What drug can be effective in treating OP?
2-PAM
May not be efective against some OPs
May not be effective if “aging” has occurred (12-24 hours)
What is the point of adding Piperonyl butoxide of MGK-264 to PP?
Inhibits pyrethrin metabolism by insects
How long will it take to see clinical signs after OP poisoning?
15 minutes - 1 hour
What mammalian species is most effected by Rotenone?
Pigs
Highest toxicity in fish and cold-blooded animals
MOA of DDT-type chlorinated hydrocarbons
Slow Na+ influx and inhibit K+ efflux leading to partial depolarization
Causes repetitive firing of neuron - axonal hyperactivity
T/F: After treatment of AR, the patient is more sensitive to another exposure shortly after treatment
True
Lower toxic dose if repeated exposure within few weeks of treatment
What should be tested for direct detection of OP?
Stomach or rumen contents
Hair/skin with dermal exposure
What species is most sensitive to chlorinated hydrocarbons?
Cats
Is there a specific antidote for chlorinated hydrocarbon toxicity?
No
Are 1st or 2nd generation ARs more toxic?
Second
ARs: What treatment should be done when there are clinical signs, bleeding, PCV <15%
Give clotting factors and RBCs
Vitamin K
Supportive care
When Cortisone undergoes biotransformation, what happens?
Inactive drug -> active metabolite (Hydrocortisone/Cortisol)
What drugs can be used to treat seizures caused by PP toxicity?
Diazepam
Barbiturates
Propofol CRI
Nicotine is better absorbed in what pH environment?
Alkaline
T/F: Plant charcoal is more effective than animal charcoal?
True
How do you calculate the therapeutic index?
Ration between LD50 and ED50
The larger the value, the wider the safety margin
Charcoal is considered a universal antidote except for what two toxins?
Ammonia
Cyanide
Clicker Question:
Chlorinated hydrocarbons like DDt are highly lipophilic and excreted in the bile. This suggests that they likely undergo which of the following?
A. first-pass metabolism
B. lethal synthesis
C. enterohepatic recirculation
D. poor distribution into fat
C. enterohepatic recirculation
What are the moderately perfused tissues?
Muscle
Skin
How long should you treat a patient with AR poisoning but you dont know which one was ingested?
3-4 weeks
If a patient comes to your clinic and smells like lemons, what do you think could cause this?
D-Limonene
What clinical signs are associated with early stimulation of Nicotine?
Ataxia
Vomiting
Bradycardia
Tremors
Convulsions
What factors can predispose an animal to Cholecalciferol toxicity?
Renal disease
Hyperparathyroidism
High calcium/phos in diet
T/F: Dogs are more sensitive to PP than cats
False
Cats are more sensitive than dogs
What can be tested for Nicotine?
Urine
Stomach contents
Kidney
Liver
Blood
MOA of Amitraz?
Alpha-2 adrenergic agonist in the CNS
What is the most serious clinical sign associated with Amitraz?
Cardiovascular colapse and respiratory failure
What proetin do acidic drugs tend to bind to?
Albumin
Define a poison (toxicant)
Any substance when applied or introduced into the body may interfere with life processes or biological functions of the cells of the animal
What makes up phase 2 metabolic reactions?
Conjugation
What is the only microsomal conjugation reaction?
Glucuronidation
Describe the severity of PP
Generally acute, mild toxicity
What would you do to treat intermediate OP syndrome?
Supportive care
2-PAM may have benefit (nicotinic sites)
What will increase the toxicity of Amitraz?
Meperidine and sympathomimetic amines
Stress, debilitation, age, toy breeds
What precipitate should be used to treat lead poisoning?
Sulfate
T/F: There are no specific pathological lesions associated with chlorinated hydrocarbons
True
Clicker question:
If a patient presents with hypercalcemia and significantly elevated PTH, would Cholecalciferol be the top differential on your list?
No
MOA of Rotenone?
Blocks oxidative phosphorylation in the TCA cycle which prevents NADH from being oxadized to NAD and therefore interfering with production of ATP
What is the amount of chemical that can be ingested w/o causing deaths, illness or tixic alterations called?
No-effect level (Maximum nontoxic level)
What is the main clinical sign associated with ARs?
Hemorrhage
Signs depend on site of bleeding
What would you do to treat OP induced delayed polyneuropathy?
Symptomatic therapy only
T/F: Carbamates require bioactivation
Therefore more toxic than some OPs in very young patients
False
When I say Cholecalciferol, you say…
Hypercalcemia
What is the most common source of Naphthalene poisoning?
Mothballs
What are our enzyme inhibitors?
Chloramphenicol
Cimetidine
Ketoconazole
What condition may reduce the effect of Vitamin K1 in treating AR?
Liver failure
What clinical signs in dogs/cats are associated with DEET?
Basically CNS excitement signs:
Hypersalivation
Vomiting
hyperexcitability
Tremors
Ataxia
Seizures
MOA of D-Limonene?
Unknown (possible vasodilation)
The presence of alpha-cyano moiety has what effect on the metabolism?
Decreases the rate of hydrolysis
What are the primary targets of Bromethalin?
Brain and spinal cord
How is Bromethalin metabolized in the liver and what is the metabolite?
N-demethylation to desmethylbromethalin (more toxic)
Describe OP induced intermediate syndrome
Seen with massive doses, lipophilic agents, or more chronic exposure
No muscarinic signs or muscle fasciculations
What type of toxic dose: The amount of a chemical that can be ingested without causing any deaths, illness or toxic alterations in any of the anumals for the stated period (usually 90 days to two years or more depending on the species)
No-effect level (maximum nontoxic level)
What are the signs of OP induced delayed polyneuropathy?
Muscle weakness
Ataxia
Rear limb paralysis
Renal excretion of Nicotine is favored in what pH environment?
Acidic
MOA of Aryl hydrocarbons and Cyclodienes?
Na+ channel effects and also may inhibit GABA
Because Chlorinated hydrocarbons are highly lipophilic, what can this lead to?
Bioaccumulation in the food chain
Where in the body would you look for Rotenone for a diagnosis?
Stomach contents
Urine
Feces
Liver (postmortem)
The metabolite of what drug causes adrenal necrosis?
Midotane
Metabolite = O,P-DDD
What is the species order of sensitivity for ARs?
Pigs -> dogs/cats -> ruminants -> horses -> chickens
What toxin is toxic to fleas at all life stages?
D-Limonene
What are the plant sources for Rotenone?
Derris elliptica
Jicama seeds
What lesions are associated with Cholecalciferol?
Hemorrhagic gastroenteritis
Mineralization
What are the main tissue barriers?
Brain
Eye
Testicles
Placenta
Mammary gland
Where in the body can you find chlorinated hydrocarbons?
If insecticide is in blood, liver, or brain at significant concentrations
T/F: Second-generation ARs have short half-lives
False
Long half-lives
What plant is teratogenic to sows and cattle?
Nicotiana tabacum (Nicotine)
Clicker question:
What condition in canine patients is commonly treated with
O,P-DDD?
A. Hypoadrenocorticism (Addison’s)
B. Pituitary dependent hyperadrenocorticism(Cushing’s)
C. Overdose of exogenous corticosteroids
D. Primary pituitary hyperplasia
B. Cushing’s
Clicker question:
If AR intoxication is suspected but you do not know what specific rodenticide was ingested. How long should you treat with vitamin K1?
A. 96 hours
B. 1 week
C. 10 days
D. 4 weeks
D. 4 weeks
What is the highest dose that does not result in undesirable/toxic effects called
Highest Nontoxic Dose (HNTD)
What is the elimination half-life of Amitraz and how long does it take to reach peak plasma concentrations?
~24 hours
Peak concentration after 5 hours
What clinical signs in rabbits/rats are associated with DEET?
Depression
Excitation
Ataxia
Tremors
Seizures
Coma
What is the main clinical sign associated with Ivermectin?
CNS depression
What is the most common conjugation reaction?
Glucuronic acid
What protein do basic drugs tend to bing to?
Acid alpha1-glycoproteins
Lipoproteins
MOA of PP?
Delay closure of sodium ion channels in the axonal membrane of the insect
May inhibit ATPase
Type 2 pyrethroids have a greater effect on sodium channels and interfere with GABA at high concentrations
What is the best way to enhance excretion of Nicotine?
IV fluids
Acidification of the urine
What are the highly perfused tissues?
Brain
Liver
Kidney
Endocrine glands
What is the prognosis of chlorinated hydrocarbon toxicity?
Guarded to good depending on dose and early detoxification
When diagnosing DEET, what level is considered diagnostic?
20ppm
How do you treat CM toxicity?
Atropine just like for OPs
What lab changes will you see with Cholecalciferol?
Hypercalcemia, hyperphosphatemia
Elevated calcidiol and calcitriol
Decreased PTH
What is the prognosis of DEET?
If sublethal exposure, usually respond in 24-72 hours
Which organophosphate has more significant tissue accumulation?
Dichlorvos because it is more lipophilic
What are the synthetic pyrethrins?
First generation (type 1) do not contain an alpha-cyano moiety
Second generation (type 2) do contain the alpha-cyano moeity which increases their insecticidal potency
What type of exposure is most common with PP?
Dermal
Ingestion and inhalation are possible too
What clinical signs will you see later on after Nicotine exposure?
CNS depression
Tachycardia
Paralysis of respiratory muscles causing death
ARs: What treatment should be done for very recent exposure and normal coag panel?
Decontamination (emesis, activated charcoal)
Start Vitamin K to be safe
What drug is used to treat muscle tremors caused by PP toxicity?
Methocarbamol
What drug is contraindicated with Carbaryl poisoning (CM)?
2-PAM
Can potentially increase the carbamylation process
Which species is deficient in sulfate conjugating enzymes?
Pigs
What effect does grapefruit have on enzymes?
Inhibitor
What is the lowest dose which produces toic alterations and administering 2x this dose will NOT cause death called?
Toxic Dose LOW (TDL)
Clicker question:
Which of the following is not one of the vitamin K dependent factors?
A. II
B. VI
C. IX
D. X
B. VI
How long will ARs persist in the environment?
Weeks to months
Which species has low levels of drug metabolizing enzymes?
Fish
What is used to treat seizures/tremors due to Bromethalin?
Diazepam, phenobarbital
What electrolytes are lost because of Cholecalciferol?
Sodium and potassium
What happens when Rotenone comes into contact with nerve axons?
Anesthetic effect
What is the most common clinical sign associated with Amitraz?
Sedation lasting 24-72 hours
With ARs, what species can be poisoned by relay toxicosis?
Swine, dogs, and cats
Which has a faster onset and shorter duration of action? OPs or Carmabates
Carbamates
What % hydrogen peroxide should be used to induce emesis?
3%
T/F: Pyrethrins bind more strongly at lower temperatures
True
Dose for an extremely toxic substance?
≤ 1mg/kg
Chemical composition of metabolite conjugates?
Inactive
Water soluble
What is the prognosis of Ivermectin?
Depends on exposure and ability to pay for care
Generally no long-term sequelae if they survive
What are the most commonly used diuretics?
mannitol
Furosemide
What type of toxic dose: The dose which produces toxic alterations and administering twice this dose will result in death
Toxic high dose (THD)
Clicker question:
What is the MOA of the organochlorine toxicants?
A. Alteration of neuronal sodium channels
B. Increased release of GABA
C. Reversible inhibition of AChE
D. Acute cerebral edema
A. Alteration of neuronal sodium channels
What is it called when OPs that require desulfuration are activated by liver metabolism?
Lethal synthesis
Less toxic to youn patients
More toxic if enzyme inducers are present
What organ metabolizes Cholecalciferol to calcidiol?
Liver
How is Bromethalin excreted?
Mainly in bile
Small amount in urine
What is the prognosis of AR?
Generally treatable depending on where hemorrhage has occurred
What is the prognosis of Amitraz?
Pretty good
The RBCs of what species are more susceptible to oxidative injury?
Cats
T/F: Bromethalin is effective against warfarin-resistant rodents
True
What trype of enzymes can enzyme inducers induce?
Microsomal
What is the dose which produces toxic alterations and administering 2x this dose WILL cause death called?
Toxic Dose HIGH (TDH)
What drugs should be avoided in the treatment of OP?
Phenothiazines
Aminoglycosides
muscle relaxants
Drugs that depress respiration (opioids)
What are the predominant clinical signs of Rotenone?
Depression and convulsions
What type of toxicity: The effect of exposure drom 30 days to 90 days
Subchronic toxicity
What precipitate should be used to treat oxalate poisoning?
Calcium
Which of the following blood products would you use for a hemorrhaging AR patient?
A. Fresh frozen plasma
B. Frozen plasma
C. Fresh whole blood
D. Stored whole blood
E. Cryoprecipitate
F. Platelet-rich plasma
A,C,E
What is “storage activation” and which organophosphates are subject to it?
If sealed and stored 1-2 years, it is more toxic
Parathion
Malathion
Diazinon
Coumaphos
MOA of Caholecalciferol?
Causes hypercalcemia and hyperphosphatemia
Increased GI absorption and decreased renal excretion of Ca2+
How long after exposure to OP does OP induced delayed polyneuropathy occur?
10-14 days
What should be avoided when treating DEET?
Magnesium cathartics (may cause CNS depression)
MOA of CMs?
Reversible inhibition of AChE
AChE can hydrolyze CMs but at a slower rate than ACh (~15-30 minutes compared to ~150 microseconds
When Parathion undergoes biotransformation, what happens?
Nontoxic drug -> toxic metabolite (Paroxon)
Toxicity level of D-Limonene in cats at 15x recommended dose?
Severe toxicity lasting for 5 hours
Clicker question:
If you wanted to use Ivomec® extra-label and you know that toxicity can be seen at doses as low as 300mcg for a 1kg kitten, how many milliliters of undiluted (1%) Ivomec® would that be?
A. 0.003mL
B. 0.03mL
C. 0.3mL
D. 3mL
B. 0.03mL
In fish and insects, Rotenone is converted to what type of metabolite?
Highly toxic metabolites
Which organophosphates have no acetylcholinesterase activity and must be desulfurated before they become active?
Bromophos
Diazinon
Fenthion
Parathion
What is the only fluid that you do not freeze for sample collection?
Whole blood - refrigerate it!!!
When Aspirin undergoes biotransformation, what happens?
Active drug -> active metabolite (Salicylic acid)
What drugs should be avoided when treating Nicotine toxicity?
Antacids (which would increase absorption and reduce excretion)
T/F: As a result of bioinactivation, most drugs are bioinactivated or detoxified
True
What species is deficient in hydroxylation and dealkylation?
Cats
What tissue acts as a “sink” for chlorinated hydrocarbons?
Fat
Half-life can be weeks to months
Weight loss can disrupt equilibrium
1ppm = what mg/kg?
1mg/kg
T/F: Inhalation of Rotenone is more toxic than ingestion
True
How long does it take for ARs to reach peak blood level?
6-12 hours
What do you do to treat Cholecalciferol?
Treat the hypercalcemia
Is there a specific antidote for Amitraz?
Yes
Atipamezole (better) or Yohimbine
How is Cholecalciferol excreted from the body?
Mainly in bile/feces
MOA of ARs?
Inhibit vitamin K epoxide reductase
Reduces vitamin K precursors
Second-generation are more potent than first-generation
Clicker question:
Which of the following tests is most appropriate for follow-up monitoring of a patient who has been treated for AR toxicosis?
A. PIVKA
B. PT
C. PTT
D. ACT
B. PT
What factors can enhance AR toxicity?
Vitamin K deficiency
Liver disease
Enzyme inhibitors (cimetidine)
Trauma, surgery
T/F: Nicotine stimulates the CRTZ
True
How long does it take for clinical signs of Cholecalciferol to appear?
24-36 hours
ARs: What treatment should be done when there are clinical signs, bleeding, but PCV > 15-20% and stable?
Vitamin K
Clotting factors (FFP, cryoprecipitate)
Consider giving RBCs (fresh whole blood)
How long should you treat a patient with Brodifacoum poisoning?
4 weeks
Which of the coagulation parameters is the first to be affected by ARs?
- PIVKA
- PT
- PTT (when 70% gone)
- ACT (when 95% gone)
How much more sensitive are insect sodium channels than mammalian ones?
1000x
Dose for a highly toxic substance?
1-50mg/kg
Administration of sodium bicarbonate will enhance the excretion of what drugs?
Weak acids
Ex: NSAIDs, phenobarbital
How long does it take for subacute clinical signs to set in (more common)?
2-3 days, progress over 1-2 weeks
CNS depression
What is it important to monitor when treating PP toxicity?
Temperature
Hypothermia can prolong clinical signs
What drug is commonly trapped by the thyroid gland?
Iodine
What makes up phase 1 of metabolic reactions?
Oxidation
Reduction
Hydrolysis
T/F: Ipecac increases the effectiveness of activated charcoal?
False
Decreases the effectiveness
What is the prognosis of PP toxicity?
Generally very good
Clicker question:
Which of the following findings would make you the least worried about the risk of renal failure?
A. Hematuria
B. Hemoglobinuria
C. Myoglobinuria
A. Hematuria
What are other possible DDx of Amitraz?
CNS depressants
Ethanol
Ivermectin
Ethylene glycol
Marijuana
What is the elimination half-life of Ivermectin?
~2 days
When I say Anticoagulant Rodenticides, you say…
Bleeding
Dose for a practically nontoxic substance?
> 5-15g/kg
What species is resistant to Bromethalin and why?
Guinea pigs because they lack the correct metabolic enzymes
How long after dermal exposure to D-Limonene does it take to reach maximal blood concentration?
10 minutes
What drug has a strong affinity to calcium in skeletal tissues?
Tetracycline
Administration of ammonium chloride or methionine enhance the excretion of what drugs?
Weak bases
Ex: alkaloids, amphetamines
T/F: CNS stimulants may increase the toxicity of DEET
False
CNS depressants
What clinical signs are associated with nicotinic stimulation from OP poisoning?
Muscle fasciculation
Tremors
Twitching
Spasm
Hypertonicity
Stiff gait
ARs: What treatment should be done when there are no clinical signs but prolonged coags?
Vitamin K
Consider giving clotting factors (FFP, cryoprecipitate)
What does Nicotine mimic at low doses?
ACh
