Exam 1 Flashcards
1
Q
Study of Movement of drugs in the body across biological membranes from the time of absorption until Elimination
A
Drug Disposition
2
Q
Which one of the Following Procedures is Incorrect in Diagnostic Toxicology:
- Specimens should be taken free of Chemical Contamination or Debris
- Specimens shoud be Washed
- Animal and Tissue Specimens should be Frozen
A
2
*Specimens should NOT be Washed- Washing is a Dilution Step- It will Dilute the amount of Toxin in the Specimen
3
Q
True/False: Most Toxicity Pathologies are Pathoneumonic for Specific Toxins/Poisons
A
False
*Most Clinical Signs/Pathologies are General to all Poisoning and not Specific to any Poison Agent
3
Q
Which Rodenticide are Guinea Pigs Resistant to?
A
Bromethalin
*Guinea Pigs lack the Metabolic Enzymes
4
Q
Six Factors that Affect Distribution of Drugs
A
Physiochemical Properties of the Drug (ex. Lipid Solubility)
Concentration Gradient
Plasma Protein Binding
Blood Flow
Tissue Barriers
Affinity of Drugs to Certain Tissues
5
Q
The Acute LD50 of Cyanide is 2.3 mg/kg Body Weight. What Category of Toxicity does Cyanide Fall into?
A
Highly Toxic
*Toxicity is between 1-50 mg/kg
5
Q
2-PAM is Contraindicated with ____ Toxicity as it can Potentially Increase the Carbamylation Process
A
Carbaryl (Sevin)
6
Q
For a Drug to be Actively Secreted at the Renal Tubules, it has to be Water Soluble (Hydrophilic), Polar and ____
A
Ionized
*This is achieved by Biotransformation for Lipid Soluble, Non polar, Non Ionized Drugs
*Drugs that are Lipid Soluble, Non Polar and Non Ionized in the Renal Tubules, will be Passively Reabsorbed back to the Plasma, and NOT excreted
7
Q
The Highest Dose that Does not cause any death
A
LD0
7
Q
When Diluting a Solution from a Concentrated Stock Solution, the mL needed = _______ X The Volume Required in mL from the Stock
A
(% Required Diluted/ % in the Stock)
*mL Needed = (% Required Dilution/ % in the Stock) X Volume required in mL
7
Q
A
1600g (1.6kg)
7
Q
All of these are Correct about Drug Absorption, Except:
A. The Smaller Molecular Size the Faster the Absorption
B. The Greater the Lipid Solubility, the Greater the Absorption
C. The Lower the Ratio between N/I, The Greater the Absorption
D. Oral Absorption of Liquid Drugs is Faster than Solid Drugs
E. The Higher the Drug Concentration at Absorption Site, the Faster the Absorption
A
C. The lower the Ratio between N/I, The Greater the Absorption
*The HIGHER the Ratio between N/I, The Greater the Absorption
7
Q
All of these are Correct about Drug Absorption, Except:
A. Increased Blood Flow, Increases Drug Absorption
B. Heat or Massage of intramuscular Injection site Increases Blood Flow and Absorption
C. Sympathetic Stimulation Decreases Blood Flow to Skeletal Muscles
D. Sympathetic Stimulation Decreases Blood Flow to the GI Tract and Skin
A
C.
*Sympathetic Stimulation Increases Blood Flow to Skeletal Muscle
7
Q
True/False: Blood Flow, Species, and the Presence of Food and Chemicals in the GI Tract affects Drug Absorption from the GI Tract
A
True
7
Q
Main Organ of Biotransformation (Drug Metabolism)
A
Liver
*Smooth Endoplastic Reticulum
7
Q
High ____ Soluble Drugs are usually Metabolized First in the Liver
A
Lipid
7
Q
Some Drugs are Eliminated Solely through Secretion, However most Drugs are Lipophilic and therefore Must go through the Two Step Process of Secretion and _______ before being Eliminated
A
Biotransformation
7
Q
Drugs used in Vomitting Animals such as Dogs and Cats within 1-2 Hours from Ingestion of the Poison
A
Emetics
*Contraindicated in Unconscousness, Corrosives, Dehydration, Severely ill animals and Unknown Toxicants
7
Q
True/False: There is No Specific Anidote for Pyrethrin/Pyrethroid Toxicity
A
True
*Treatment = Decontamination (Wash Skin) and Avoid Exacerbating the Toxicity
8
Q
Cholecalciferol is a _____ Toxicosis
A
Vitamin D
9
Q
Toxicity that is the Effect of Exposure from 30 days to 90 days
A
Subchronic Toxicity
10
Q
True/False: In Amitraz Toxicity, if Flea and Tick Collar was Ingested the Treatment is to Induce Emesis and/or remove via Endoscopy
A
True
*Need to get the collar out of the patient
10
Q
True/False: Cats are More Sensitive to Naphthalene Toxicity, but Dogs are more likely to Ingest
A
True
*Cats are more Sensitive but Dogs are more Susceptible- Dogs are far more likely to eat Mothballs
11
Q
Water Soluble Alkaloid from Dried Leaves of Nicotiana Tabacum. Feeds can be contaminated with _____ Sulfate, which is used as a plant Insecticide. Animals gain Toxicity through Ingestion of Tobacco Products (Leaves, Cigarettes, Cigars)
A
Nicotine
11
Which Pathway is ACT and PTT Measuring?
**ACT- Intrinsic**
**PTT- Intrinsic**
PT- Extrinsic (Factor VII)
12
Three Factors affecting Simple Diffusion
**Concentration Gradient**
**Lipid Solubility**
**Degree of Ionization**
\*Concentration Gradient- Drugs move across membranes from High Concentration to Low Concentration
\*Ionization- Drugs cross Biological membranes in the NON- Ionized form
12
True/False: Certain Individuals may be Deficient or Lack certain Enzymes due to Genetic Differences
True
13
Organophosphates cause Irreversible Inhibition of Cholinesterases. What Three Pathologies Follow at Receptors?
**First: Muscarinic Receptor Stimulation**
**Second: Nicotinic Receptor Stimulation**
**Last: Nicotinic Blockade**
**\***Normally Patients will be Hyperstimulated, but as things progress you may see Nicotinic Blockade, if you are stimulating the Nerve continuously eventually it is going to Depolarize to the point that it can't repolarize
13
**C. Chlorinated Hydrocarbons**
14
If Toxicity is Greater than \_\_\_\_, it is considered Relatively Harmless
15 g/kg
14
There are several Types of Organophosphates, Some have direct Acetylcholinesterase Activity while others have none and must be _____ before they become Active
**Desulfurated**
\*Need to undergo Liver Metabolism, before they have Acethylchlinesterase Activity
14
**Cholecalciferol** is Mainly excreted in Bile/Feces, however can also be Excreted in ____ at Toxic Levels and can undergo Enterohepatic Recirculation
**Milk**
15
**C. Cholinesterase Activity can be Tested for Either**
**\***Carbamates do not Undergo Storage Activation or Lethal Synthesis
\* Pralidoxime (2-PAM) is not an effective Treatment for Carbamates
16
Six Factors Related to the Drug that Affect Absorption
Molecular Size
Lipid Solubility
Degree of Ionization
Dissolution of Drug in Water
Concentration of Drug at Absorptive Site
Route of Administration
16
Organophosphates are Fairly \_\_\_\_\_, they are readily Absorbed from the GIT, Skin and Mucous Membranes and Well distributed throughout the Body, including the CNS
**Lipophilic**
16
Lab Findings for _Which Rodenticide_ Toxicity:
Hypercalcemia
Hyperphosphatemia
_Decreased_ PTH
Elevated serum Calcidiol (25-dihydroxyvitamin D)
**Cholecalciferol**
17
Any Substance when applied or introduced into the body may interfere with Life Processes or Biological Functions of the cells of the Animal
Poison (Toxicant)
17
True/False: Every Toxin is a Toxicant (Poison), but not every Toxicant (Poison) is a Toxin
True
\*A Toxin is a Toxicant (Poison) from a Biological Source- Ex. Snake Venom. However Lead is a Toxicant, but not a Toxin
17
A Chronicity Factor greater than ____ indicates a Relatively Cumulative Toxicant
2.0
17
True/False: Most Toxicosis DO NOT have Pathognomonic Signs
**True**
\*Most Poisonings have very similar Clinical Signs
18
Accuracy of Chemical Results depends on \_\_\_\_\_. Interpretation of Results should be done Carefully Considering other Evidence
**Sampling**
18
True/False: Cats are more Sensitive to **Pyrethrins** than Dogs
**True**
\*Very Common in Small Animal Practice- _Use of Canine "Spot On" Pyrethrin Products on Felines is a common Presenting Issue_
18
True/False: Decontamination with Soap/Water and Symptomatic Treatment are the Only Treatments for **DEET** Toxicity
**True**
\*DEET Generally has low Toxicity and Mild Signs
18
**Anticoagulant Rodenticides** are Odorless and Tasteless and Formulations are Resistant in the Environment for Weeks to Months. Anticoagulant Rodenticides have a ____ Onset of Action
**Slow**
**\***Will not see Clinical Signs for at least 24 Hours or Longer after Ingestion
_\*Onset of Clinical Signs takes 1-5 Days_
19
Term used to Describe the Deleterious or Undesirable Effects of Poisons
Toxic
20
Four Treatment Principles of Toxicosis
**Symptomatic (Supportive) Treatment**- Respiratory and Cardiovascular
## Footnote
**Removal of Poison**
**Specific (Antidotal) Treatment**
**Observation of the Acutely Poisoned Animal**
20
**Chlorinated Hydrocarbon** Insecticides are HIGHLY \_\_\_\_\_, that leads to Bioaccumulation in the Food Chain
**Lipophilic**
**\***Toxin is Sequestered in Body Fat. If Herbivore has Toxin within its fat and it is Eaten by a Carnivore, the Toxin will now Sequester into the Carnivores Fat- Bioaccumulation
21
**Rotenone** is Considered an _____ and will cause Conjuctivitis, Congestion, Dermatitis, and GI Upset if Ingested
**Irritant**
22
Disease Caused by Exposure to a Poison
Toxicosis
22
Criteria of Diagnosis defined by Clinical Pathology and Chemical Analysis, where Positive Chemical Results Consistent with other Criteria my confirm a Diagnosis
**Laboratory Diagnosis**
**\***_Chemical Analysis- Best way to Confirm a Diagnosis_
\*Should be done by qualified Toxicology Laboratory
\*Negative Lab Results does not Eliminate the Possiblity of Toxicosis
22
Which Color Corresponds to the Intrinsic and Extrinsic Pathways?
**Intrinsic- Yellow**
**Extrinsic- Blue**
**\***Common Pathway is Green
23
True/False: If a Drug is Hydrophilic (Water Soluble), Polar, and Ionized it is entirely Excreted by Secretion without undergoing Biotransformation
True
\*Biotransformation only occurs to Lipophilic, Non-Polar or Non-Ionized Drugs in order to Make the Drugs Hydrophilic, Polar and Ionized so that they can be Excreted
\*In order to be excreted from the Body, a Drug must be Hydrophilic, Polar and Ionized- must be achieved by Drug Metabolism (Biotransformation)
24
When Sampling Feeds or Forage for Analysis, Green Forage or Silage should be _____ or Green Forage Dried. The Sample Size should be about a Quart or Kilogram
**Frozen**
**\***Samples should be Taken from different Bales and from different Parts of the Bale
25
The Biological ______ is composed of a Lipid Bilayer, where the Membrane Contains Membrane Proteins and Carbohydrates and the Cells are Seperated by Aqueous Pores and Junctions
Cell Membrane
26
**Tachycardia**
27
Toxicity due to a Single Dose or Multiple Doses during a 24-hour Period
Acute Toxicity
\*One day Exposure
27
Fluid Therapy and Diuretics ____ Renal Excretion of drugs by Reducing the Time needed for Tubular Reabsorption
**Enhance**
**\***Decreasing the Transit Time of the drug through the Tubules, Enhances Drug Excretion
28
True/False: Specimens Submitted for Chemical Analysis in Diagnostic Toxicology should be accompanied with a Complete HIstory, Clinical Signs, Postmortem findings ect.
**True**
28
Of these Four Coagulation Parameters, which will Become Abnormal _First_ with **Anticoagulant Rodenticide** Toxicity:
Activated Clotting Time (ACT)
Prothrombin Time (PT)
Activated Partial Thromboplastin Time (APTT)
Proteins Induced by Vitamin K Antagoists (PIVKA)
**PIVKA**
**\***In Anticoagulant Rodenticide Toxicity, PIVKA will Increase First
**PIVKA, PT, PTT, ACT-** Order in Which they begin to Increase
29
Second Most important Organ for Excretion of Drugs where Drugs may be Transported from the Cells to Bile or Blood by Passive Diffusion or Active Transport
**Liver**
\*Hepatic Excretion
30
1 ppm = \_\_\_\_\_\_%
**\* 1 ppm = 0.0001%**
**\***If you want to convert from ppm to percent, move the decimal 4 places to the Left. If you want to Convert from percent to ppm, move the decimal 4 places to the Right
31
90% of Steady-State Concentration is achieved in ____ Half Lives
**3.3**
\*After 4 Half Lives, the Plasma Concentration is 93.75% of the eventual steady-state plasma concentration
\*Steady State- Is the Plasma Concentration of Drug when the Maintenance Rate of Drug Administration is Equal to the Rate of Elimination
33
**Anticoagulant Rodenticides** are Most Commonly ingested by Pets, mainly Canines, as \_\_\_\_\_\_
**Baits**
**\***Most common Exposure is via Ingestion of Baits
34
Specimens from different Organs should be Packaged _____ in Clean Glass or Plastic Containers that can be tightly Sealed. Waterproof Ink should be used to ____ Specimens and should include the Owners Name, Animals Name and tissue of Specimens
**Separately**
**Label**
**\***Waterproof Labeling is Very Important!
35
The Volume of Fluid which would be Required to Contain the amount of drug in the body if it were uniformly Distributed, and the concentration in that fluid was equal to the concentration in the plasma
Apparent Volume of Distribution (Vd)
\*Extent of Distribution is Measured by the Apparent Volume of Distribution (Vd)
35
Which of the Following is **Correct** about Sampling Forage:
A. Forage should be cut to a Length of 3 Inches
B. Sample Size should be a Quart or Kilogram
C. Forage or Silage should be Frozen or Dried
D. Samples should be Taken from Different Bales
E. Samples should be packaged Tightly and Sealed Airtight
D. All Letters should be Sealed in First Class Mail Envelope
**All of the Above are Correct**
36
The Rate of Tissue Perfusion relative to the Tissue Mass, that affects Distribution of Drugs
Blood Flow
\*Higher Blood Flow = Higher Drug Distribution
\*Lower Blood Flow = Lower Drug Distribution
\*Highly Perfused Tissues- Brain, Liver, Kidneys and Endocrine Glands- will Recieve Higher Distribution of Drugs
37
If the Toxicity is ____ or Less it is considered Extremely Toxic
1 mg/kg
38
Plasma Protein Binding ______ Glomerular Filtration and Renal Drug Excretion
**Decreases**
**\***Only _Unbound Drugs can be Filtered_ and are Eliminated at a Rate Equal to their Creatinine Clearance Rate
\*If the Drug is Bound to Plasm Proteins, it cannot be Filtered
38
Equation to Calculate the Half Life of a Drug
\*You need to Volume of Distribution and the Clearance in order to Calculate the Half Life
\*_Increasing the Volume of Distribution, prolongs the Half Life_
_\*Increasing the Clearance, Decreases the Half Life_
38
All Animals are Susceptible to **Chlorinated Hydrocarbon** Toxicity, but ____ are the Most Sensitive
Cats
38
With **Chlorinated Hydrocarbon** Toxicity, Brain Concentrations are Better Correlated with Toxicosis than _____ Concentrations, which do not Correlate with Severity of Clinical Signs
**Fat**
\*_Brain Concentrations will give a Better Indication of Toxicity than Fat_
38
More than One Correct Answer!
**Fresh, Whole Blood**
**Fresh Frozen Plasma**
**Cryoprecipitate** (Concentrated Coagulation Factors)
\*You need the Clotting Factors- _Frozen Plasma, Stored Whole Blood, and Platelet Rich Plasma Do NOT have Clotting Factors_
39
True/False: **Ivermectin** is Well Distributed in the Body, but Does NOT cross the BBB
**True**
**\***Kept out of CNS by Glycoprotein Efflux Pump
40
Weak Acidic or Weak Basic Drugs cross Biological Membranes in the _____ Form, while Charged Drugs can not Cross Biological Membranes
**Nonionized**
41
Insecticides that Work by _**Reversible** Inhibition of Acetylcholinesterase_
**Carbamates**
42
Type ___ Pyrethroids have a _Greater_ Effect on Sodium Channels leading to More Potent Effects
**2 (Alpha-Cyano Group)**
43
Drug _Molecular Charge_ affects Glomerular Filtration at the Kidney. Largely ____ Charged Molecules are Inhibited by the Proteins in the Capillary Wall leading to less Renal Drug Excretion
**Negatively**
44
Technique for Removal of Poison where the Link Between the Animal and the Sourse of Poisoning is Cut
**Removal of Suspected Source of Poisoning**
**\***Examples of Sources- Feed, Water, Pasture, Pesticides, Chemicals ect.
44
True/False: Alkalinization of Urine will Enhance Excretion of **Nicotine**
**False**
**\***ACIDIFICATION of Urine will Enhance Excretion of Nicotine
45
Overall, **Pyrethrins and Pyrethroids** have Low Toxicity to Mammals, However they are Very Toxic to ____ and some Birds
**Fish**
\* Caution when Using around Fish Tanks/ Koi Ponds. A Dog Treated with _Topical Pyrethrin_ that goes Swimming in your fish pond is a Source of Exposure
46
Drugs with a Molecular Weight less than ____ Dalton charged or uncharged are freely filtered through the glomerular membrane and Excreted Readily by the Kidney
7000 Dalton
48
Three Types of Metabolic Reactions that are Part of _Phase I_ Reactions of Biotransformation
Oxidation
Reduction
Hydrolysis
\*Most Common Type of Biotransformation Reaction- Oxidation- Most Drugs are Metabolized by Oxidation
49
500 ppm = \_\_\_\_%
0.05%
\*Move decimal 4 places to the Left
51
Eliminiation of Most Drugs follows ____ order Kinetics, where the Rate of Removal of Drug from plasma is Proportional to the Concentration present at a given Time
**First**
**\***A Constant _Percent_ of Drug is Eliminated per unit Time
52
Two _Synergistic Compounds_ that are Added to **Pyrethrins** that will slow down the Metabolism and Increase the Toxicity of Pyrethrin in the Insect
**Piperonyl Butoxide**
**MGK-264**
**\***These Synergists Make the Insecticide Last Longer and Increases Toxicity to the Insect
\*There appears to be a Greater Risk of Moderate/ Major Symptoms among those Exposed to Products Containing Pyrethrins and Piperonyl Butoxide than those exposed to Pyrethrins Alone
52
Insecticide that is Readily Absorbed via Inhalation or through Skin that reaches Peak Plasma concentrations within 5 Hours with a Elimination Half-life of Around 24 Hours
**Amitraz**
\*Hangs around in the Body longer
54
Two Assumptions associated with Exposure of 7 mg/kg body weight of Chemically Sprayed Forage:
1. Good Quality Pasture will produce app. __ gram green forage per square foot
2. Grazing animals consume \_\_% of their body weight green Forage
45 grams
3%
54
Specific type of Endocytosis where the cell Engulfs the drug molecules dissolved in Water
Pinocytosis
\*Ex. Sequestration of Aminoglycoside Antibiotics by Renal tubular Cells
55
Active Tubular Secretion occurs in the Proximal Convoluted Tubule of the Kidney. The Convoluted Tubule has an Organic Anion System for Secretion of Organic Acids and an organic Cation System for Secretion of Organic Bases. Both Systems require energy which is provided by the _____ in the Basolateral Membrane
**Sodium Pump**
56
Insecticide that is very commonly used as an Endoparasiticide in Large Animals (Cattle, Swine, Sheep, and Horses) and is Labeled for Prevention of _Heartworm in Dogs and Cats_
**Ivermectin**
58
Insecticides that are Synthetic Analogs of Pyrethrins
**Pyrethroid**
**\***Pyrethroid = Synthetic
Pyrethrin = Natural
\*Not a Big Distinction Clinically between the Two and are Often used Interchangably
59
A Poison (Toxicant) from a Biological Source, such as Plant or Bacterial Toxins
Toxin
\*Poisons are also known as Toxicants. All Toxins are Poisons (Toxicant), but Not all Toxicants are Toxins
60
Insecticide that works by Blocking Oxidative Phosphorylation in the TCA Cycle preventing NADH From being Oxidized to NAD and thus Interfering with Production of ATP
**Rotenone**
**\***Strong Inhibitor of Electron Transport and Cell Respiration will be Inhibited
61
Main Clinical Sign of **Ivermectin** Toxicity
**CNS Depression**
**\***Stupor, Ataxia, Disorientation
62
**B. No**
\*This is Hyperparathyroidism. _PTH should be Decreased_ with _Cholecalciferol_ Toxicity
63
True/False: Drugs can be Poisons and Poisons can be Drugs
True
\*The Dose is the Difference- Treatment versus Toxicity
64
True/False: Charcoal is most effective when Given as soon as Ingestion of a Toxicant is suspected and can be Used as Multiple Doses in Toxicants that undergo Enterohepatic Circulation
**True**
64
**Bromethalin** is Metabolized by N-demethylation in the Liver to the More Toxic Metabolite, \_\_\_\_\_\_
**Desmethylbromethalin**
65
A _____ Test can be Run on Mothballs to See if they Contain **Napththalene**
**Salt Solution**
**\***Put Mothballs in Concentrated Salt Solution and the Naphthalene should Float
66
**A. Weak Base**
**\***Drugs are better absorbed in the NONIONIZED State. They will be _Ionized in the Opposite Environment_ (Ex. Weak Acid in Alkalinized Enviornment) and _NONIONIZED in the Same Enviornment_ (Ex. Weak Base in Alkalinized Enviornment)
\*In an Alkalinized Enviornment, a Weak Base will be nonionized and therefore better absorbed
\*A Weak Acid will be very Ionized in an Alkaline Enviornment
66
If a Canine Ingests a Preventative Flea and Tick Collar, which Toxicity will they most likely Develop?
**Amitraz Toxicity**
68
**Emetic of Choice in Dogs** that works by Activating Central Dopamine Receptors that can be Given IV, IM, SC, or instilled into the Conjunctival Sac
**Apomorphine**
\*Commonly Administered into the Conjunctival Sac
\*Antidote to Apomorphine = Naloxone
68
Most Common cause of Death in High Exposure cases of Organophosphate Toxicity
**Respiratory Failure (Paralysis)**
70
Which is **Correct** about Telephone Instructions to Clients for Treatment of Toxicosis:
A. Animal should be Isolated in a quiet Place to avoid Further Stress
B. In case of Topical Exposure, the skin and eyes should be Cleansed with Copious Amounts of Water or Shampoo
C. If Oral Toxicosis, Induce Emesis with 3% or Less Hydrogen Peroxide
**All of the Above are Correct**
**\***Hydrogen Peroxide must be 3% or Less Concentration
71
In Active Tubular Secretion, Drugs move ____ their Electrochemical Gradient
**Against**
72
Drug Eliminiation is Measured by _____ or Total Body Clearance
**Half Life (T1/2)**
**\***Half Life- Time Required for the Body to Eliminate one-Half of the Drug it contains
73
Specimens Submitted for Diagnostic Toxicology will be evaluated for Toxicants Qualitatively and \_\_\_\_\_\_. Specimens should be Representing, Avoiding Dilution, Contamination and Putrefaction
**Quantitatevely**
\*If the Specimen undergoes Contamination or Putrefaction, that will affect the level of Toxin
74
True/False: The Source of **Cholecalciferol** Toxicosis is commonly by Ingestion of Pesticides for Control of Rats/Mice
**True**
75
True/False: **Pyrethrins** are Most Commonly used as Insecticidal "Spot On" Treatments for Cats
**False**
\*Most Commonly Used as Insecticidal "Spot On" Treatments for _Dogs_
76
Pigs are Deficient in _____ Conjugating Enzymes
**Sulfate**
77
Main Clinical Sign of **Chlorinated Hydrocarbon** Toxicity is \_\_\_\_\_
**CNS Stimulation**
**\***Ex. Salivation, Vomiting, Tremors, Spastic Gait, Tonic-Clonic Seizures, Ect
79
1 ppm = \_\_\_\_mg/kg
\* **1 ppm (Part per Million) = 1 mg/kg**
**1 kg = 1000 g**
**1 g = 1000 mg**
**1 ppb ( part per billion) = 1 ug/ kg**
**1 ppt ( part per trillion) = 1 ng/ kg**
**1 ppm = 1 ug/ g**
\*ug = Microgram
80
The Dose that causes death in any animal during the period of Observation
Lethal Dose
81
Anything that **_Increases_** Glomerular Filtration or Active Tubular Secretion will _____ Excretion of the Drug, while Anything that **_Increases_** Passive Tubular Reabsorption will _____ Excretion of the Drug
**Increases**
**Decrease**
\*_Excretion = (Glomerular Filtration + Active Tubular Secretion) - Tubular Reabsorption_
_\*_Reabsorption- the Drug is going back into the Body
82
Newborn and Geriatric Patients may have ____ Biotransformation than Adults
Less
\*Not Producing as many Metabolic Enzymes
82
Four Factors affecting Glomerular Filtration of a Drug
Glomerular Filtration Rate (Blood Flow)
Molecular Size
Molecular Charge
Plasma Protein Binding
83
**D. 4 Weeks (28 Days)**
\* If unknown Rodenticide, always treat at least 3-4 Weeks
84
True/False: **D-Limonene** is Treated by Decontamination (Shampoo with Mild Dish Soap) and Monitoring for Iatrogenic _Hyperthermia_
**False**
\*Monitor for Iatrogenic **Hypothermia**
**\***I_n **D-Limonene and Pyrethrins**- Watch for Hypothermia- These Patients will be Hypotensive and Hypothermia will Prolong Metabolism of the Toxin_
85
Which Species is more Susceptible to Poisoning? (Dogs or Cats)
Dogs
\*Cats are Sensitive about what they eat. Because of their Sensitivity, they are not very Susceptible to Toxicants
\*Dogs are More Susceptible because they Have Low Sensitivity and will eat Anything
85
True/False: In Diagnostic Toxicology, Positive Results DO NOT always mean Intoxication
**True!!!**
**\***Positive Lab Results do NOT Gaurantee Toxicosis
_**\***Negative Results do not always mean that Poisoning did not occur_
86
Carrier-mediated Transport that Does **Not** Need Energy, where a drug moves across the membrane from High Concentration to Low Concentration at a Faster Rate
Facilitated Diffusion
\*Transporters can Move Drugs from Outside the cell into the Cell or from Inside the Cell outside the Cell
87
Which Rodenticides _Inhibit Vitamin K Epoxide Reductase ,_ which Reduces Carboxylation and Activation of Precursors of Clotting Factors II, VII, IX, and X
**Anticoagulant Rodenticides**
88
Most common Type of Biotransformation Reaction in Phase II Drug Metabolism
Glucuronidation
\*Conjugation to Glucuronic Acid
90
Technique for Removal of Poison using Precipitation, Adsorption, and Ion Trapping
**Decreasing the Rate of Absorption**
**\***_Adsorption by use of Activated Charcoal is Very Commonly done_
92
The Rate of Drug Elimination from the Body, by all Routes, Relative to the Concentration of Drug in Plasma
**Total Body Clearance (ClB)**
93
Examples of ______ Include:
1. Active Drug (Aspirin) to Active Metabolite (Salicylic Acid)
2. Inactive Drug to Active Metabolite
3. Nontoxic Drug to Toxic Metabolite
**Biotransformation**
94
For Estimating Dosages when Exposure is based on Consumption of Green Forage that has been sprayed, Every Animal Ingests green Forage that has been sprayed by a chemical at a rate of 1 lb/ acre, will be approximately exposed to \_\_\_mg per Body Weight
7
\* 1 lb of Chemical / acre = 7 mg/kg body weight Exposed
96
Criteria of Diagnosis that Includes both Gross and Microscopic Examinations, where Negative Results are as Good as Positive Results
**Postmortem Findings**
\*The Presence or Absense of Postmortem Lesions are Important
98
True/False: **Cholecalciferol** can be excreted through Milk from the Mother to the Neonate
**True**
99
Which Drug is Given as a Treatment for **Organophosphate** Poisoning
**Atropine**
**\***Atropine will Antagonize the _Muscarinic Signs_
100
**C. Hypothermia may Further Alter Sodium Channel Kinetics**
**\***Hypothermia will Alter Sodium Channel Kinetics and can Prolong Clinical Signs. Hypothermia may also _decrease Hepatic Bioactivation_ of the Drug.
\*Patients are normally Hyperthermic due to Muscle Tremors
102
Three Categories of **Chlorinated Hydrocarbons**
**Diphenyl Aliphatics**- DDT
**Aryl Hydrocarbons**- Lindane
**Cyclodienes**- Aldrine/Toxaphene
102
A Large amount of Which Insecticide is Excreted in Feces of Horses and is a potential Source of Toxicity for Canines
**Ivermectin**
103
Carrier-Mediated Transport that Requires Energy, where a Drug moves across the Membrane from Low Concentration to High Concentration
Active Transport
\*Low concentration to High concentration (Uphill)
103
**Chlorinated Hydrocarbons** are HIGHLY Lipophilic and are able to Persist in the Enviornment within Soil with a Half-Life between ______ Years
**2-15 Years**
**\***Chlorinated Hydrocarbons- Can Stay in Soil for VERY Long time and can Bioaccumulate in the Food Chain
103
True/False: There is No Specific Antidote for _Chlorinated Hydrocarbons._ Treatment is a Combination of Decontamination and Symptomatic Treatment
**True**
**\***Decontamination- Induce Emesis, Wash with Soap and Water
Symptomatic Treatment- Diazepam to Control Seizures/ Oxygenation
105
In Diagnostic Toxicology, Blood Samples should be _____ while other Body Fluids should be Frozen
**Refrigerated**
**\***We never Freeze Whole Blood- Whole Blood needs to be Refridgerated. All other Body Fluids can be Frozen
\*Whole Blood needs to Be Refrigerated, while Serum, Plasma and Tissue have to be Frozen _Immediately_
105
True/False: Cats are more Sensitive to **DEET** Toxicity than Dogs
**True**
**\***Young Animals may be more Sensitive as well
106
Which of the Following is **Incorrect** about Transporting Specimen:
A. Liquids (Blood ect.) should be Shipped in Glass or Heavy Plastic Containers that can be Tightly Sealed
B. Tissue Specimen can be Transported in Ziplock Plastic Bags, Glass or Plastic Containers
C. Samples should be Wrapped Together for Mailing
**C.**
\*Samples should be Wrapped _Individually_ for Mailing
107
Insecticide that has Low and Incomplete Absorption from the GI Tract, and is _Far More Toxic when Inhaled_ than when Ingested
**Rotenone**
**\***_Well Absorbed via Gills in Fish- Inhalation- More toxic to Fish_
108
An Acutely Poisoned Animal must be considered as an \_\_\_\_\_, where Control of Life Threatening Conditions should be the First Approach in this case
**Emergency**
**\***Most poisoning Cases are Acute
108
Match these Rodenticides to their Side Effects:
1. Anticoagulant Rodenticides A. Hypercalcemia
2. Cholecalciferol B. Bleeding
3. Bromethalin C. Neurotoxicant
**Anticoagulant Rodenticides- Bleeding**
**Cholecalciferol- Hypercalcemia**
**Bromethalin- Neurotoxicant**
109
Insecticides that are Extracts of Pyrethrum Flowers and sometimes advertised as "Natural"
**Pyrethrins**
109
Insecticide that is Commonly Found in Flea and Tick Collars and as a Topical Therapy for Generalized Demodicosis. It is Particularly useful for Certain _Mites and Ticks because it Paralyzes the Mouth Parts_
**Amitraz**
**\***Not labelled for Cats or Horses
110
Factors Altering ______ include:
Species
Individual
Route of Administration
Enzyme Inducers/Inhibitors
Liver Disease
Hepatic Blood Flow
**Biotransformation**
112
Four Stages of Drug Disposition
**Absorption**
**Distribution**
**Biotransformation**
**Excretion**
114
Need a Diluted Solution of 500 ppm from a Stock Solution that is 1000 ppm and we need to make 500mL. How many mL of Stock Solution is needed?
**250mL**
\*mL of Stock = (500ppm/1000ppm) x 500 mL
\*Diluted Solution = 250 mL of Stock Solution and 250 mL of Water
114
Which Insecticide is commonly Combined with Other Insecticides in Pet Products and can Increase the Dermal Absorption of other Products, such as Pyrethrins, leading to a Higher Chance of Toxicity
**DEET**
**\***DEET is commonly Combined with other Insecticides, such as Pyrethroid, in Pet Products and will Increase the Absorption of the Other Product leading to a higher risk of Pyrethrin Toxicity
115
Calculation for Apparent Volume of Distribution (Vd)
\*The Amount of Drug in the Body = the Dose IV
\*For IV the Vd = Dose (mg/kg) / Plasma Drug Concentration (mg/L)
115
**DEET** Toxicity can lead to CNS \_\_\_\_\_, and Clinical Signs such as Hypersalivation, Vomiting, Tremors and Seizures
**Excitation**
116
Factors that _____ Anticoagulant Rodenticide Toxicity:
Vitamin K Deficiency
Liver Disease
Enzyme Inhibitors
Trauma/Surgery
Renal Insufficiency
**Enhance**
**\***Enzyme Inhibitors will Prevent Metabolism
117
Standard Measurement of Toxicity in Mammals
LD50
\*Lethal Dose in 50% of the Population. AKA Median Lethal Dose (MLD)
\*LD50 is a measure of Toxicity and therefore measured in mg/kg Body Weight
118
Which Two Diuretics are most commonly used to Enhance Drug Excretion in Poisoning
**Mannitol**
**Furosemide**
**\***Only use Diuretics if the Patient is Well Hydrated
119
True/False: Liver Disease, Kidney Disease, Age, Urine pH Modifiers, Fluid Therapy, Diuretics, and Plasma Protein Binding all Affect Renal Excretion
**True**
\*Neonates don't have a fully functional mechanisms of Excretion- Secretion is less in Neonates
\*Diuretics can be used only if the animal is well Hydrated
120
Fat acts as a "Sink" for **Chlorinated Hydrocarbons**, where Redistribution occurs when Equilibrium is Reached. _____ can Disrupt Equilibrium and lead to Re-emerging Clinical Signs of Toxicity
**Weight Loss**
\*If the Animal starts Loosing Weight/Fat, then suddenly there will be a Lot of Chemical in the Blood stream, leading to Re-emergence of Clinical Signs
121
Lesion Associated with **Bromethalin** Toxicity
**Cerebral Edema**
123
True/False: Hepatic Blood Flow, Plasma Protein Binding, Age, Sex, Diet and Nutrition all affect Biotransformation
True
125
**273 g/ton**
\*100 g / ton = 110 ppm
126
Transport of Drugs from the Plasma to the Tissues (Site of Action, Site of Storage or Site of Biotransformation)
Distribution
127
Test where we Administer Atropine at 0.02mg/kg, where a _Strong Response to a Low Dose of Atropine_ ( Mydriasis, Significant Increase in HR, and Dry Mouth within 15 MInutes) means is it **LESS** Likely to be Organophosphate Poisoning
**Atropine Response Test**
\*Strong Response = Not Organophosphate Poisoning
128
True/False: The Higher the Lipid Solubility of the Drugs, the Faster the Drug crosses cell Membranes
True
\*Simple Diffusion- Lipid Solubility is a Factor
129
\_\_\_\_\_\_ of Toxicosis depends Mainly on History of Exposure, Clinical Signs and the Presence or Absence of Lesions
**Diagnosis**
130
Between Dogs and Cats, who is most _Sensitive_ to Poisoning?
Cats
\*Cats are More Sensitive to Poisoning because they are Deficient in many Oxidative Enzymes and Conjugation enzymes to Glucoronic Acid
\*Large Animals are more Tolerant than Small Animals to Poisoning, and Dogs are More Tolerant than Cats to Poisoning
132
Insecticide that is **_Highly Toxic to Canines_** with Oral LD50 of 9.2 mg/kg and Clinical Signs Reported at 1mg/kg
**Nicotine**
**\***_Very Toxic to Dogs_- Ingestion of Cigarette, Cigar, Nicotine Patches ect.
133
The Chemical Alteration of the Drug Molecule by the Cells of the Animal
Drug Metabolism (Biotransformation)
134
Warfarin has an Acute LD50 of 1.6 and a 90-day LD50 of 0.077. Warfarin's Chronicity Factor is 21.0. Is Warfarin a Cumulative Toxicant?
Yes
\*Chronicity Factor is Greater than 2. Warfarin is Cumulative and therefore is Not Rapidly Excreted
\*Warfarin is more likely to become Toxic if given More than Once. If only given once, it is not likely to be Toxic
135
Insecticide that at Low Doses _Simulates Post Synaptic Nicotinic Receptors_. At High Doses, Stimulation will be Followed by Nicotinic Blockage
**Nicotine**
136
True/False: Toxicity Values are influenced by Several Factors including Species, Breed, Age, Sex, Dosage and Duration of Exposure
True
137
**B. It Delays Metabolism of the Drug in Insects**
**\***Prolongs the presence of the Insecticide in the Insect
138
**Naphthalene** is Derived from Petrolium Hydrocarbons and will ____ at Room Temperature
**Sublimate**
\*Sublimate- Go Directly from Solid to Gas Form- At Room temperature Naphthalene will turn into a Gas
140
True/False: Nutrition plays an important role in the Regulation of Drug Conjugations and Malnutrition and Undernutrition may Decrease Biotransformation
True
141
4.2 grams
\*4200mg = 4.2 grams
142
True/False: Activated Charcoal is Considered a Universal Antedote for Toxocosis because it Adsorbs almost 99% of Chemicals
**True**
143
Renal Excretion of Nicotine is Decreased in ____ pH, and will Increase Re-absorption of the **Nicotine** back into the Body. Therefore, ____ Urine pH Enhances Excretion
**Alkaline**
**Acidic**
\*Acidify the Urine to Enhance Urinary Excretion
144
Transfer of the Drug from the Site of Administration to the Circulation
Absorption
146
The LD50 of Urea is 0.45 g/kg Body Weight. What is the Toxicity of Urea?
Moderately Toxic
\*0.45 g/kg Falls between 50-500 mg/kg
\*(can also be written as 450 mg/kg)
1g = 1000 mg
\*Side Note- In class Shokry said the Answer was Slightly Toxic, but In reality it is Borderline Slightly Toxic and Moderately Toxic
146
True/False: The Metabolites of Phase II Biotransformation (Conjugation) are usually Inactive, Water Soluble (Hydrophilic),
Polar and Ionized
True
\*After Conjugation (Phase II), drugs will be Inactive, Hydrophilic, Polar and Ionized and therefore ready for Excretion
148
\_\_\_\_\_ Diagnosis may be Reached by using all Criteria of Diagnosis including Laboratory Work
**Confirmed**
149
**D. Cats**
150
Insecticides that Work by _Delaying the Closure of Sodium Ion Channels in the Axonal Membrane_ of the Insect leading to a "Knockdown Effect" of Rapid Paralysis where the Insect is Immobile but not Dead
**Pyrethrins/Pyrethroids**
151
If we have a 5% Concentrated Stock Solution and we need to make
1 L 1%. How much mL is needed from the 5%?
200 mL
\* (1%/5%) X 1000 mL
\*1 L = 1000 mL
(Take 200 mL from the 5% Stock Solution and add 800 mL (to Equal 1000mL) and now we have 1000 mL of 1% Solution
153
True/False: **D-Limonene** is Lipid Soluble, Readily absorbed through GI and Skin Contanct and is Widely Distributed throughout the Body
**True**
153
\_\_\_\_ Generation **Anticoagulant Rodenticides** are Less Potent and become Most Toxic when Ingested Daily for about a Week
**First**
**\***Ex. Warfarin
154
The needed Solution Dilution is 1:1000 and the Stock Solution is 1% and we Want to make 1 Quart, how many mL of Solution do we Need?
**100mL**
\*To Change 1:1000 to a Percent:
(1/1000) x (X/100) = 0.1%
mL From Stock = (0.1% / 1%) x 1000mL
mL from Stock = 100 mL
Diluted Solution will be 100mL Stock and 900mL Water
\*Side Note: 1 Quart = 1 L = 1000 mL
156
If Toxicity is Greater Than \_\_\_\_\_, it is considered Moderately Toxic
50-500 mg/kg
157
List the Four Vitamin K Dependant Factors
**II (Prothrombin), VII, IX, X**
158
True/False: Conjugation (Glucuronidation) is Deficient in Neonates
**True**
158
Five Criteria of Diagnosis
Case History
Clinical Signs
Postmortem Findings
Laboratory Diagnosis
Laboratory Animal Tests
158
Which Insecticides work by _Slowing Sodium Influx and Inhibiting Potassium Efflux_ in Peripheral Nerves and Brain Leading to Partial Depolarization causing Repetitive Firing of Neurons (Stimulation)
**Chlorinated Hydrocarbons**
**\***Leads to _Nervous System (CNS) Excitation_
160
The Ratio Between Acute LD50 and Chronic LD50
Chronocity Factor
\*When the Chronic Toxicity (90-day LD50) value is close to the Acute Toxicity (Acute LD50) Value, the Chemical is not Cumulative
\*If the Acute Toxicity (Acute LD50) is much greater than the Chronic Toxicity (90-day LD50), then the chemical is Cumulative
161
**B. Pituitary Dependent Hyperadrenocorticism**
**\***o,p-DDD is the same as Mitotaine
162
Physiological Antidote for Treatment of **Amitraz Toxicity**
**Yohimibine or Atipamezole**
**(Alpha 2 Antagonists)**
163
Insecticide that Works as a _GABA Agonist_ leading to CNS Depression
**Ivermectin**
**\***GABA- Inhibitory Neurotransmitter in CNS
165
Of the Vitamin K Factors (II, VII, IX, and X), which has the SHORTEST Half-Life?
**VII**
\*PT measures Factor VII- _PT will be Prolonged First (after PIVKA)_!
PIVKA , PT, PTT, ACT
\*You can Check PT in Clinic, but PIVKA must be sent out. Therefore PT is usually chosen for Testing first
166
**C. Neurogenic Vasodilation**
**\*KNOW FOR TEST**
167
Which Two Organophosphates are More Lipophilic leading to More Sequestration in Fat and can stay in the Body Longer?
**Dichlorvos**
**Chlorpyrifos**
**\***Only two Organophosphates where you get Tissue Accumulation
169
Name the Two Types of Passive Diffusion. Which one is Hydrophilic and Which is Lipophilic?
**Simple Diffusion** (Lipophilic)
**Transmembrane and Paracellular Movement** (Aqueous Pores)
\*If a Drug with Water Soluble (Hydrophilic) it will pass through the Aqueous Pores
\*If a Drug is Lipophilic it will travel via Simple Diffusion
170
True/False: Sublingual and Inhalation have Very Rapid Drug Absorption Rates
**True**
170
Less Common **Bromethalin** Toxicity that is seen with a Supralethal Dose that leads to Muscle Tremors, Hyperexcitability, and Seizures
**Acute**
**\*Less Common-** Poor Prognosis- Most likely Patient will Die
171
**No**
**\* 5% = 5g/100mL = 50mg/mL**
5% (_add a Zero to make it Mg/mL_)
5mg% = 5mg/100mL = 5mg/dL = 5000 mcg/ dL
\*We recommend it at a level of 5000 mcg/dL and we have a level of 900 mcg/dL, which is not High enough
173
Need a Diluted Solution of 500 ppm from a Stock Solution that is 1% and we need to make 1 Pint. How many mL of Stock Solution is needed?
**25mL**
\*500 ppm = 0.05%
mL from Stock = (0.05% / 1%) x 500 mL
\*Side Note: 1 Pint = 500 mL
175
In Diagnostic Toxicology, Positive Results may be helpful in Aiding Diagnosis, but ____ Results do not Eliminate the Possibility of Intoxication
Negative
176
With **Carbamates**, Laboratory Diagnosis of Cholinesterase Levels can produce _____ Results because Binding is Reversible and "Reactivation" of ACh can Occur during Transit
**False Negative**
**\***Need to Analyze the Sample VERY Fast before the Sample begins to Re-activate
178
Which of the Following is Correct for Obtaining a **Serum** Sample:
A. Use Clean, Dry Syringes, Needles or Tubes
B. Avoid Hemolysis of Sample by Avoiding Pressure/Shaking
C. Allow enough Time for Blood to Clot (1-2 hours)
D. Put Tubes with Blood in Oblique Position to Obtain more Serum
E. Obtain Serum by Centrifugation
F. All of the Above are Correct
F. All of the Above
179
Continued Exposure of Organosphosphates can lead to _____ due to Enzyme Induction, Functional Adaptation to Decrease Esterases and Adaptation of ACh Receptors to Excessive Amounts of ACh (Receptor Down Regulation)
**Tolerance**
181
Toxicity that is the effect produced by daily exposure for a period of 3 months or more
Chronic Toxicity
\*Greater than 90 days
182
True/False: Physiological Factors (Ex. Exercise), Drugs and Disease can Alter Blood Flow and Drug Distribution
True
183
Results of ____ include Changes in Physiochemical Properties of the Drug where the Metabolite is more Water Soluble, Polar and Ionized
Biotransformation
184
100 g / ton = ____ ppm
110
184
**C. Enterohepatic Recirculation**
**\***Lipophilic Drugs in the Bile are Reabsorbed back into Circulation
184
Main Clinical Signs of **Anticoagulant Rodenticides** is \_\_\_\_\_
**Hemorrhage**
**\***If Rodenticide was the Cause of Death, then Hemorrhage should be found Somewhere
186
**Organophosphates** cause _Muscarinic, Nicotinic, and CNS_ stimulation. What are some Clinical Signs you would Expect the Patient to Present with?
Muscarinic- **DUMBELS**
Nicotinic- **Tremors, Twitching, Spasms**
CNS- **Anxiety, Hyperactivity, Tonic-clonic Seizures**
**\***These are the Most common Clinical Signs to see in Patients with Organophosphate Toxicity- Mainly Tremors!!!
188
Tetracyclines to the Calcium in Skeletal Tissues, Aminoglycosides to Kidney Tissue and Trapping of Iodine by the Thyroid Gland are examples of ____ of Drugs to Certain Tissues
Affinity
189
The Movement of the Drug from the Tissues to the Blood
Redistribution
191
Common Clinical Signs of _Which Rodenticide_:
PU/PD
GI Bleeding (Hematomesis/Melena)
Depression/ Muscle Twitching
**Cholecalciferol**
**\***PU/PD- VERY Common due to Hypercalcemia and Renal Damage (Soft Tissue Mineralization)
192
Which Toxicity is characterized by these Clinical Signs:
Ataxia/Weakness
Paralysis
CNS Depression
_Hypotension_
_Patient Smells like Lemons_
**D-Limonene**
\*Hypotension caused by Vasodilation
193
True/False: **Bromethalin** creates Bait Shyness
**False**
**\***No Bait Shyness with Bromethalin. Ingestion of the Bait is the main source of Bromethalin Toxicosis
194
True/False: Metabolites of _Phase I_ Biotransformation are More or Less Water Soluble, Inactive, less Active, or More Active
True
196
**Nicotine** is Absorbed Well by Inhalation and from Intact Skin, but poorly via Ingestion. However, _____ of the Stomach will Increase Absorption
**Alkalinization**
**\***_Nicotine is a Weak Base_ and will be Nonionized in Alkaline enviornments
197
Irritating Insecticide whose Oxidation Products causes **Methemoglobinemia** and Hemolysis leading to Tissue Hypoxia
**Naphthalene**
**\***Blood will be a _Brown Color_
199
Hepatic Enzymes responsible for Drug Metabolism Lack \_\_\_\_\_. These Microsomal Enzymes cause Oxidation, Reduction, Hydrolysis, and Conjugation to Glucoronic Acid
Specificity
200
**4 mg/kg**
202
Main Treatment for **Cholecalciferol** Toxicity
**Decontamination**
\*Emesis, Activated Charcoal- Repeated Doses
203
Technique for Removal of Poison that uses Fluid Therapy, Diuretics, Urine pH Modifiers, Peritoneal Dialysis, and Hemodialysis
**Enhancing Elimination**
204
Drugs may be Transported from the Hepatic Cells to ____ or Blood by Passive diffusion or Active Transport
**Bile**
**\***Lipophilic Drugs in Bile will Undergo Enterohepatic Recycling and Pro-long the Half Life of the Drug
\*Drugs are excreted in Bile either Unchanged or as Glucuronides. Acidic, Basic and Neutral Drugs can be excreted in bile by Active Transport
205
Two Specific Treatments for **Naphthalene** Toxicity used to Treat Methemoglobinuria
**Ascorbic Acid**
**Methylene Blue 1%**
**\***Neither of these Work very Well
206
Henderson and Hasselbalch Equations for an Acid and Base
\*Drugs cross Biological Membranes in the Non-Ionized Form. The Rate of Diffusion depends on the Ratio between the Non-Ionized form of the Drug to the Ionized Form (N/I)
\*The Higher the pka of a weak Acid, the Higher the N/I
\*The Lower the pka of a weak Base, the Higher the N/I
\*The Higher the N/I = more Drug crossing Membrane
208
_Second_ Generation **Anticoagulant Rodenticides** have ____ Half-Lives, compared to First Generation.
**Long**
**\***Warfarin is a First Generation with a Half Life of only 19 Hours. Diphenadione and Brodifacoum are _Second Generation_ with Half Lives of 4.5 and 6 Days
209
Syndrome that is Associated with Cats and the _More Lipophilic_ Agents due to Chronic Exposure to **Organophosphates.** This Syndrome is Characterized by _No Muscarinic Signs_ but a Wide Range of Muscle Fasciculations and CNS Signs
**Intermediate Syndrome**
210
One of the Oldest Botanical Insecticides that is used in Home/Garden, Lice/Tick Treament for Pets and Horses as well as Mites on Chickens
**Rotenone**
**\***Used in Fish Research- _Restricted Substance_
211
The _____ the pka of a Weak Acid, the Greater the N/I, and the _____ the pka of a Weak Base, the Greater the N/I
**Higher**
**Lower**
211
Name the Treatments for Each **Anticoagulant Rodenticide** Toxicity:
A. Exposure/Normal Coagulation Panel
B. Exposure/ Prolonged Coagulation Factors
C. Bleeding/ PCV \> 15-20%
D. Bleeding/PCV
A. _Exposure/Normal Coagulation Panel_ - **Decontamination/ Start Vitamin K**
B. _Exposure/ Prolonged Coagulation_- **Vitamin K/ Consider Giving Clotting Factors**
C. _Bleeding/ PCV \> 15-20%_ - **Vitamin K/ Give Clotting Factors/ Consider giving RBCs (Fresh Whole Blood)**
D. _Bleeding/PCV - **Vitamin K/ Give Clotting Factors and Fresh Whole Blood**_
212
Level in Feed (ppm) = (\_\_\_\_\_) / (% of Feed consumed Daily)
Toxicity (mg/kg)
214
True/False: Microsomal Enzyme Inducers Increase Toxicity of Drugs that are Bioactivated into Toxic Metabolites
False
\*Microsomal Enzyme Inducers **Decrease** Toxicity of Drugs whose Metabolites are Toxic
215
Organophospohates that Require Desulfuration in the Liver will be Activated by Liver Metabolism, known as \_\_\_\_\_
**Lethal Synthesis**
**\***Less Toxic Substance being Metabolized into a More Toxic Substance
216
Phase II Biotransformation Reaction where a Combination of a Drug or its Metabolite is Mixed with an Endogenous Substance most commonly Resulting in Glucuronic Acid
Conjugation
\*Conjugation to Glucuronic Acid is the most Common Conjugation Reaction
217
Which of the Following about **Anticoagulant Rodenticides** is Incorrect:
A. Largely Bound to Plasma Proteins
B. Slow Onset of Action ( \>24 Hours before Clinical Signs)
C. Achieves High Concentrations in the Liver
D. Crosses the Placenta and Excreted in Milk
E. All the Above are Correct
**E. All the Above are Correct**
218
**0.03mL**
\*1% = 10mg/mL
300mcg = 0.03mg
219
Most common Type of Biotransformation Reaction in Phase I Drug Metabolism
Oxidation
220
The Movement of Glucose across a muscle cell membrane by Insulin-Sensitive Glucose Transporter is an Example of ____ Diffusion
Facilitated
221
The Extent of Absorption is Measured by Systemic Bioavailability (F%). What is the Equation to Calculate Systemic Bioavailability?
\*Systemic Bioavailability- the Fraction of the Dose which reaches the Systemic Circulation Intact
\*AUC- Area under the plasma concentration-time curve
223
If Toxicity is is Greater than \_\_\_\_, it is considered Practically Nontoxic
5-15 g/kg
224
Insecticide that is _Very Toxic to Fish and Cold Blooded Animals_, with a Generally Low Toxicity for Mammals
**Rotenone**
**\***_In Fish/Insects it is converted to Highly Toxic Metabolites, while in Mammals it is generally Converted to Non-Toxic Metabolites_
225
The amount of a Poison in mg/kg Body Weight that under certain circumstances will cause Toxic Effects
Toxicity (Expressed in mg/kg Body Weight)
\*Toxicity = Amount. Must be a Numerical Number
225
The Danger from the Possibility of Exposure
Hazard (Risk)
\*A Poison may be Highly Toxic but not Hazardous. Hazard has to do with the Exposure Rate. Ex. A Fish Toxin is Highly Toxic but has a Low Hazard. Ex. Aspirin has a Lower Toxicity but is Very Hazardous
\*Risk (aka Hazard) is defined by a Comparison of Toxicity and use Level
226
The Lowest Dose which Produces Toxic Alterations and Administering Twice this Dose will not Cause Death
Toxic Dose Low (TDL)
227
Orally Administered Non Absorbed Drugs and Drugs excreted in Bile that are Not Reabsorbed are excreted in \_\_\_\_\_
Feces
227
**A. Alteration of Neuronal Sodium Channels**
229
Drug _____ depends on the Ratio between the Uncharged (Nonionized) and Charged (Ionized) Drug
**Diffusion**
230
Rodenticide that Produces _Changes Mainly in the Spinal Cord and Brain_, leading to Alterations in Fluid Movement and Cerebral Edema
**Bromethalin**
232
Passive tubular Reabsorption occurs in the Proximal and Distal Convoluted Tubules for _____ Forms of Weak Acids and Weak Bases
**Nonionized**
234
**D. _Irreversible_ Inhibition of Acetylcholinesterase**
**\***Acetylcholine gets released and is normally Broken Down by Acetylcholinesterase. Acetylcholine Increases because it is not being Broken Down
235
**A. GI Bleeding**
236
If **Organophosphate** Toxicity eventually leads to Nicotinic Blockade, what are some Clinical Signs you will see?
Nicotinic Blockade- **Paralysis, CNS Depression, Coma, Dsypnea**
**\***Usually leads to Death causd by Respiratory Failure
238
Volatile Compounds, such as Inhalation Anesthetics are mainly Excreted via \_\_\_\_\_
**Expired Air**
240
Symptomatic (Supportive) Treatment of Toxicosis can be Cardiovascular, where Adequate Circulatory Volume is Provided by Blood Transfusion or ____ Therapy depending on Hypovolemia
**Fluid Therapy**
**\***Fluid Therapy is very commonly Given in Patients with Toxicosis
242
\_\_\_\_\_\_\_ is Microsomal, but all other Conjugations are Nonmicrosomal
**Glucuronidation**
243
**Chlorinated Hydrocarbon** Metabolites are Lipophilic in Bile, and can be Reabsorbed via \_\_\_\_\_\_
**Enterohepatic Recycling**
245
The Blood-Brain Barrier Functions by Tight ____ endothelial Junctions, Glial Cells, and Active Transport Mechanisms for Extrustion of Organic Acids and Bases
Capillary
246
Water Soluble, Ionized and ____ Drugs are Excreted in Urine
**Polar**
247
True/False: **Anticoagulant Rodenticides** can lead to Relay (Secondary) Toxicosis in Swine, Dogs and Cats who eat Rats/Mice that have Ingested the Toxin
**True**
248
**Bromethalin** is Highly Lipophilic and Widely Distributed in the Body, with Highest Concentrations in the Fat and \_\_\_\_
**Brain**
\*Bromethalin will get into the Brain
250
Insecticide that works as an _Alpha-2 Adrenergic Agonist in the CNS_
**Amitraz**
251
Muscle Relaxant Drug that is used to _Treat the Fine Muscle Tremors_ assocaited with **Pyrethrins** Toxicity
**Methocarbamol**
252
90 ppm is High Enough to Cause Toxicity
253
Hepatic Blood Flow may be Decreased due to Liver Disease or Drugs resulting in ___ Biotransformation
Decreased
254
With **Amitraz** Toxicity, the most common Clinical Sign is _____ and may Last for 24-72 Hours
**Transient Sedation**
**\***Massive Exposure to Amitraz can Cause Cardiovascular Collapse and Respiratory Failure. However, Most Patients Only experience Transient Sedation for a Short period of Time and then are Fine
255
**Emetic Drug of Choice in Cats** that is an Alpha 2 Agonist which is Administered IV but causes CNS Depression for Several Hours
**Xylazine**
257
**Cholecalciferol** Causes ____ and Hyperphosphatemia due to:
Increased Calcium GI Absorption
Decreased Calcium Renal Excretion
**Hypercalcemia**
\*_Massive Overdose of Vitamin D_
_\*When Calcium Levels Rise enough it will cause Mineralization of Soft Tissues leading to Tissue Damage and Renal Ischemia_
258
True/False: Ruminants and Horses have High Levels of Oxidative enzymes and are Less Likely to get Drug Toxicity
True
\*The More Oxidative Enzymes the Animal Has, the Less Likely to become Poisoned/Toxic
\*Side Note- Birds, Fish, and Reptiles are very Deficient in Oxidative Enzymes and therefore are more likely to get Drug Toxicity. Birds Lack Oxidative Enzymes
259
Technique for Reducing the Amount of Toxicant Absorbed where Activated Charcoal physically Binds to the Toxicant
**Adsorption**
**\***Charcoal is not very effective against Ammonia, Cyanide, Heavy Metal Salts ect.
260
Insecticides that are Subject to "Storage Activation" where if they are Sealed and Stored for 1-2 Years they can become _More Toxic_
**Organophosphates**
262
Later Synthesized Carbamate that Mimics the structure of Acetylcholine and is the **most Toxic** of the Carbamates
**Aldicarb**
264
**B. PT**
\*PIVKA will not be available in the clinic, therefore, PT is the Best
266
Insecticide that is a Common Insect Repellant used for Control of Mosquitoes, Flies and Ticks that is found in Products such as "Off"
**DEET**
**\***Concentration of DEET can range from 5% to 100%, but generally less than 10% in those marketed for pets
267
\_\_\_\_ Generation Synthetic Pyrethrins do Not Contain an Alpha-Cyano Moiety, while _____ Generation Synthetic Pyrethrins Do contain the Alpha-Cyano Moeity which Increases their Insecticidal Potency
**First Generation** (Type I)- Do NOT
**Second Generation** (Type 2)- Does
268
Most Common Source of **Naphthalene** Toxicity is Ingestion of \_\_\_\_\_
**Mothballs**
**\***Old Fashon Mothballs contain Naphthalene
269
Increasing Renal \_\_\_\_\_, Increases GFR and Leads to More Renal Drug Excretion
**Blood Flow**
Increasing Renal Blood Flow = Increasing Drug Excretion
Decreasing Renal Blood Flow = Decreasing Drug Excretion
\*In Renal Failure and Heart Failure Patients, you get Decreased Renal Blood Flow, and Decreased Renal Drug Excretion
270
The ____ of a drug is the pH at which a weak electrolyte is 50% Ionized and 50% Non Ionized
pKa
\*_Acidic Drugs Ionize in Alkaline Mediums and Basic Drugs Ionize in Acidic Mediums_
271
Treatment for **Nicotine** Toxicosis Includes Inducing Emesis and Activated Charcoal. However ____ should be Avoided because it would Increase Absorption and Reduce Excretion of Nicotine
**Antacids**
_**\***Avoid Antacids in Nicotine Treatment_
272
Clinical Signs associated with the Initial Signs of Muscarinic Stimulation from **Organophosphate** Poisoning
(DUMBELS)
D- Diarrhea
U- Urination
M- Myosis
B- Bronchoconstriction and Bradycardia
E- Emesis
L- Lacrimation
S- Salivation
273
Alkanization of the Urine pH by _IV Sodium Bicarbonate_ Enhances Renal Excretion of Weak ____ drugs such as Aspirin or Phenobarbital
**Acidic**
**\***Use IV Sodium Bicarbonate
275
Syndrome that occurs after Surviving Acute **Organophosphate** Poisoning characterized by signs of Muscle Weakness, Ataxia and Rear Limb Paralysis
**Delayed Polyneuropathy**
**\***Occurs 10-14 Days after Exposure. _Chickens_ are the Most sensitive to this effect!!!
276
Mainstay of Treatment for **Anticoagulant Rodenticide** Toxicity
**Vitamin K1**
**\***Oral Route Recommended- Do not give IV
\*Vitamin K1 Does NOT stop Bleeding, it just Enhances Coagulation Factors
277
**C. Known Enterohepatic Recirculation**
278
True/False: While Drugs and Poisons have the same Principles for Pharmacokinetics, they are different because Poisons are always reversible, while Drugs can be Reversible or Irreversible
False
\*Drugs should always be Reversible, while Poisons can be Reversible or Irreversible
279
True/False: If Mammals are Exposed to a High enough Dose of **Pyrethrins** to Show Clinical Sings, the Signs Include _Generalized Muscle Tremors, Depression, Blindess, and Progressive Seizures_
**True**
\*Predominant Sign- _Fine Muscle Tremors_
280
Organophosphates that Undergo Lethal Synthesis in the Liver will be _____ Toxic to Young Patients and ____ Toxic if Enzyme Inducers are Present
**Less**
**More**
**\***Young Animals- Liver Metabolism isn't completely Developed
281
Standard Measurement of Drug Efficiency/ Therapeutic Dose in Mammals
ED50
\*Effective Dose in 50% of the Population. AKA Median Effective Dose (MED)
282
Which of the Following Are used as Treatments for Cardiovascular Issues with Toxicosis:
A. Cardiac Stimulants - Atropine/ 10% Calcium Gluconate
B. Hypotension- Fluid Therapy
C. Acidosis- IV Sodium Bicarbonate/ Lactated Ringers
D. Alkalosis- IV Normal Saline/ Ammonium Chloride
E. Pain- Opioids
**All of the Above are Correct**
**\***All of these are used as Cardiovascular Treatments for Patients with Toxicosis
283
**B. Alkalinize the Urine (Bicarbonate)**
284
True/False: Most Toxic Diagnosis are Generally made based on History of Exposure, Appropriate Clinical Signs and Ruling out other Causes
**True**
**\***Most Poisons don't have Pathonumonic Lesions or Clinical Signs
285
Significant _____ Recycling prolongs the Half-Life of the Drug
**Enterohepatic**
_\*Conjugates of Lipophilic Compounds excreted in Bile can be Hydrolized in the Intestine to Lipid Soluble Free Drugs that can be Reabsorbed via Enterohepatic Circulation_
286
Once **Nicotine** is Absorbed, it is well Distributed, Metabolized in the Liver and Excreted in ____ and Urine
**Bile**
**\***Half Life of 2 Hours
287
Which Breed of Dog classically gets **Ivermectin** Toxicity?
**Collies**
\*MDR1 Gene Mutation
288
\_\_\_\_\_ Gene Mutation encodes the P-Glycoprotein which is a Component of the Blood Brain Barrier. Deletion Mutation of this Gene Results in 50x's the concentration of Certain Drugs (Ivermectin) in the CNS
**MDR1**
**(aka ABCB1)**
**\***Collies lack the MDR1 Gene- Never use Ivermectin
289
_Criteria of Diagnosis_ characterized by:
Looking for Evidence
Relying on Information Provided by the Owner
Making Sure the Animal has Ingested/Been Exposed to the Poison
**Case History**
**\***Most Important Criteria in Diagnosing Toxicosis
291
If Toxicity is Greater Than \_\_\_\_\_, it is considered Highly Toxic
1-50 mg/kg
292
Removal or Clearance of the Drug from the Body
Excretion
293
\_\_\_\_\_ Diagnosis can be Reached when the History and Clinical Signs are Supported by Circumstantial Evidence and Identification of the Source of Poisoning
**Presumptive**
294
The Highest or Largest Dose which does not Result in Undesirable or Toxic Alterations
Maximum Tolerated Dose (MTD)
\*AKA Minimal Toxic Dose
\*This Dose is between the Effective Dose Range and the Toxic Dose Range
295
\_\_\_\_\_\_ Generation **Anticoagulant Rodenticides** are More Potent and are Toxic after One Dose
**Second**
**\***Ex. Brodifacoum and Diphacinone
297
**727 g**
298
\_\_\_\_\_ Diagnosis of Toxicosis can be Obtained by detailed Case History and through Clinical and Postmortem Examinations
Tentative
299
Symptomatic (Supportive) Treatment of Toxicosis where Patients recieve a Tracheostomay under Anesthesia or Cuffed Endotracheal Tube in Unconscious Animals where Artificial Respiration is Provided using Respirators or even an Anesthetic Machine
**Respiration Treatment**
**\***AKA Life Support
300
The Vd of Penicillin is 0.2-0.3 L/kg. How is Penicillin Distributed in the Body?
Limited Distribution
\*Tends to Stay in the Plasma
301
Insecticide that is used in OTC Products, usually Shampoos, for Control of Lice, Fleas, Ticks and more Recently is becoming available as _Essential Oils_
**D-Limonene**
**\***Toxic to the _Flea_ at all life stages- Dries them out and Kills them
302
True/False: Plasma Protein Binding Increases Drug Biotransformation
False
\*Decreases- not as much Drug getting to the Liver
304
Which of the Following is NOT a Treatment for Organophosphate Toxicity:
A. Induce Emesis if Recent, NOT if Depressed or Seizuring
B. Wash Gently with Soapy Water if Dermal Exposure
C. Activated Charcoal
D. Oxygen and Fluids
E. All the Above are Acceptable Treatments
**E. All the Above**
305
When Testing for **Anticoagulant Rodenticides** we are going to be Testing for _____ of Coagulation Parameters, Including:
Activated Clotting Time (ACT)
Prothrombin Time (PT)
Activated Partial Thromboplastin Time (APTT)
Proteins Induced by Vitamin K Antagoists (PIVKA)
**Prolongation**
306
Drugs, such as Chloramphenicol, that Inhibit the Liver to Produce Metabolic Enzymes that may lead to Drug-Drug Interactions
Microsomal Enzyme Inhibitors
307
Accurate and Confirmed _____ is the most important Aspect in dealing with Toxicosis
**Diagnosis**
**\***Specific Treatment and Prevention is based on Accurate Diagnosis
309
Specific Antedote for **Organophosphates** that is a Cholinesterase Reactivating Oxime
**2-PAM (Pralidoxime, Protopam)**
**\***2-PAM binds to the Organophosphate and causes a molecular Change which releases it from the Acetylcholinesterase, so that it can go back to breaking down Acetylcholine
\*_Aging- if the Organophosphate has been bound to Acetylcholinesterase for a long time (\>24 Hours), it will undergo aging and now the Bond is so Strong that even the 2-PAM cannot pull it off_
310
What is the Difference between Plasma and Serum
**Plasma Contains Proteins**
**Serum DOES NOT contain Proteins**
**\***Don't use Anti-coagulant to get Serum. You use Anti-coagulant (Heparin) to Collect Plasma
311
Metabolic Reaction that is considered a _Phase II_ Reaction of Biotransformation
Conjugation
312
Criteria of Diagnosis characterized as Administration of Susptected Material (Food or Water) to a Susceptible Animal and Observing its effects that is usually done by the Toxicology Laboratory
**Laboratory Animal Tests**
\*Normally Food or Water Testing
314
True/False: **Carbamates** Undergo "Storage Activation" and Require Hepatic Bioactivation
**False**
\* C_arbamates DO NOT undergo Storage Activation and DO NOT Require Hepatic Bioactivation_
_\*_No Hepatic Bioactivation- Thus Carbamates are more Toxic than some Organophosphates in very young patients
314
Which Rodencitide works by _Uncoupling of Oxidative Phosphorylation_ that Reduces ATP Production leading to Insufficient Energy for Na+/K+ Ion Pumps
**Bromethalin**
315
Weak Acids are more Ionized in an ____ Medium, and Weak Bases are more Ionized in an\_\_\_\_\_ Medium
**Weak Acids- Alkaline Medium**
**Weak Bases- Acidic Medium**
317
Predominant way that Drugs cross Cell Membranes
Simple Diffusion
\*Most Drugs are Lipophilic
318
Two Main Clinical Signs associated with **Nicotine** Toxicity
**Tremors and Convulsions**
\*Within 1 Hour of Exposure
\*May also see Ataxia, Hypersalivation, and Vomiting
\*Later (At Higher Doses) you may see CNS Depression, Paralysis
320
True/False: Activated Charcoal is a Common Treatment for **Pyrethrin/Pyrethroid** Toxicity
**False**
**\***_Activated Charcoal is Generally Not used_- Pyrethroid/Pyrethins are so Rapidly absorbed and Metabolized, the Activated Charcoal does not make a Difference
321
If Toxicity is Greater Than \_\_\_\_\_, it is considered Slightly Toxic
0.5-5 g/kg
322
Clinical Signs associated with What Insecticide Poisoning:
Mothball Breath
Salivation/Vomiting
Hemolysis
Heinz Bodies
Methemoglobinemia
**Naphthalene**
323
Caffine has an Acute LD50 of 192.0 and a 90-day LD50 of 150. The Chronicity Factor is 1.3. Is Caffine a Cumulative Toxicant?
No
\*Chronicity Factor is Less than 2. Caffine is Non-Cumulative and therefore is Rapidly Excreted
324
The Dose which Produces Toxic Alterations and Administering Twice this Dose will result in Death
Toxic Dose High (TDH)
325
True/False: Chlorinated Hydrocarbons are Highly Lipophilic therefore Readily Absorbed and Distributed to all Body Tissues, including Brain, Liver, Kidney and ADIPOSE Tissue
**True**
326
Drugs that Stimulate the Liver to Produce more Metabolic Enzymes that may lead to Tolerance or Drug-Drug Interactions
Microsomal Enzyme Inducers
\*May Decrease Risk of Toxicity with some Drugs
\*Ex. Phenobarbital
327
Two Predominant Clinical Signs associated with **Rotenone** Toxicity
**General Depression**
**Convulsions**
328
Technique for Removal of Poison from the Skin, Mucous Membranes, and GI Tract via Emetics, Gastric Lavage, Rumenotomy and Purgatives
**Removal of Poison from the Site of Absorption**
**\*AKA Decontamination**
329
_1 ppm = 1 mg/kg_
_1 ppm = 1 mg/L_
0. 8 mg/ L = 0.8 mg/ 1000mL
(0. 8 mg / 1000 mL ) / 10 = **0.08 mg/100mL = 0.08mg%**
_\*1 mg/100mL = mg% = mg/dL- KNOW_
(0.08 mg/ 100 mL) / 100 = 0.0008 mg/ mL
_1 mg = 1000 micrograms_
(0.0008 mg/mL ) x 1000 = **0.8 mcg / mL**
**\*KNOW HOW TO DO THIS FOR THE EXAM**
331
Toxicology is the Science of \_\_\_\_\_
Poisons (Toxicants)
332
\_\_\_\_\_\_ (mg/kg) = ppm in Feed X % of Feed consumed Daily
Toxicity
333
Five Factors of Drug Absorption related to the Animal
Blood Flow
Absorbing Surface Area
Connective Tissue
Species
Individual
335
\_\_\_\_\_\_ (Activated Vitamin D) is Metabolized in the Liver to \_\_\_\_\_(25-hydroxycholecalciferol), which is transportred to the Kidney and Metabolized to ____ (1,25-dihydroxycholecalciferol), which is _VERY Potent_
**Cholecalciferol-** Activated Vitamin D
**Calcidiol**- Liver (Form in Circulation)
**Calcitriol**- Kidney (Very Potent)
\*Calcitriol Massively Increases _Calcium_ by working on Bone, Kidney, and GI Tract
336
True/False: Diagnostic Testing for **Nicotine Toxicity** includes Testing Urine, Stomach Contents, Kidney, Liver and Blood for Nicotine
True
337
_Atropine_ can be used as a Treatment for Both Organophosphate and Carbamate Toxicity, however ______ is not Reliably Effective against Carbamates
**2-PAM**
**\***Reversible Binding of Carbamates reduces the Benefit of 2-PAM
338
Common Lesion of **Cholecalciferol** Toxicity
**Hemorrhagic Gastroenteritis**
**\***Also Mineralization of Affected Tissues
339
The Mechanism of Action for **D-Limonene** is Unknown, however it may work through Central and peripheral _____ due to an Undetermined Neuronal Mechanism
**Vasodilation**
340
Laboratory Test that Correlates well to Brain Cholinesterase activity that can be used to Detect **Organophosphate** Toxicity
**Acetylcholinesterase Activity Level**
**\***Refrigerate and Asses ASAP to Preserve Activity
\*_If Acetylcholinesterase Activity Level is **Normal, that is Diagnostic for Organophosphate Poisoning**_
341
The Upper Part of the Small Intestine, \_\_\_\_\_, is the main site of Absorption for all drugs given orally because of the Extensive Surface Area and Rich Blood Supply. The Rate of Absorption depends on the Rate of \_\_\_\_\_
Duodenum
Gastric Emptying
342
Biotransformation most Commonly Results in _______ and Detoxification of Drugs
**Bioinactivation**
**\***Rarely Biotransformation Results in Bioactivation or Lethal Synthesis
343
True/False: **Pyrethrins/ Pyrethroids** are Lipid Soluble, Very Well Absorbed, and Rapidly Metabolized in GIT, Plasma and Liver
**True**
**\***Rapidly Metabolized- Pyrethrins don't last Long in the Environment or Animal- Usually Metabolized and Excreted within 24 Hours
344
Urea has a Toxicity of 300 mg/kg and a Use Level of 100mg/kg. Urea's Risk Ratio is 3:1. Monensin has a Toxicity of 20 mg/kg and a Use Level of 1mg/kg. Monensin has a Risk Ratio of 20:1. Which Toxicosis has a Much Higher Risk (Hazard)?
Urea
\*The Risk of Urea Toxicosis would be higher than the Risk of Monensin Toxicosis, even though Monensin is much more Toxic than Urea.
345
**Weak Basic Drugs** are Excreted in _____ because of Ion Trapping that can lead to Drug Residues, Treatment of Mastitis Systemically, and Possible Adverse Effect on the Newborn
**Milk**
\*_Weak Basic Drugs_ are Excreted in Milk
_\*High pKa_ Drugs will have High Levels in Milk
346
If the Milk : Plasma Ratio is \< 1, then Drug is mainly found in \_\_\_\_\_\_
**Plasma**
\*If the Milk:Plasma Ratio = 1, then the amount of Drug in Milk is equal to the amount of Drug in Plasma
347
Plasma Protein Binding Acidic Drugs mainly bind to \_\_\_\_, while Basic drugs bind mainly to acid alpha1-glycoprotein. Plasma Protein binding is Reversible and Prolongs the half life of the Drug. The Bound Form is inactive and cannot be Distributed, Metabolized or Excreted by glomerular Filtration
Albumin
\*Ex. Warfarin binds 90% to Plasma Proteins
\*The Rate of Binding depends mainly on the amount of Drug
348
What does it mean if the Vd for a Drug is 2 Liters / Kg Body Weight?
The Cutoff Point is 1. If the **Vd is \> than 1 L/kg** Body Weight, then the Drug is **Widely Distributed**
\*If a Dog is 10kg, then the Vd is 20L
349
5 Main Routes of Drug Excretion
**Renal** (Main Route of Excretion)
**Hepatic** - Main Organ of Biotransformation
**Feces**
**Milk**
**Semen**
\*Saliva, Eggs, Hair, Feathers, Sweat Glands and Expired Air are Minor Routes of Drug Excretion
350
Toxicity that is the Effect Produced by daily exposure from One day to 30 Days
Subacute Toxicity
351
Three Physiological Processes of Renal Excretion
**Glomerular Filtration**
**Active Tubular Secretion**
**Passive Tubular Reabsorption**
352
Factors that _____ Biotransformation
Hypothermia
Shock
Anesthesia
Animals in the Tropics
**Decrease**
**\***Animals in the Tropics may have Less Biotransformation
353
True/False: Dogs are deficient in most Oxidative Enzymes and Glucuronidation leading to Higher Chances of Drug Toxicity
False
\*CATS
\*Cats are Deficient in Glucuronyl Transferases
\*Aspirin is only given to cats every 48 hours because it is not Metabolized as fast as in Dogs
354
**C. Amitraz**
**\***The Other three are primarily CNS Stimulants
355
**Pyrethrins** bind more Strongly at ____ Temperatures. Insect Sodium Channels are \_\_\_\_x's More Sensitive to Pyrethrins than Mammalian Sodium Channels
**Lower**
**1000Xs**
**\***Insect Body Temperature = 25 Degrees Celsius
Mammalian Body Temperature = 38 Degrees Celsius
\*Pyrethrins have Low Toxicity in Mammals, because their Temperature is Higher and Pyrethrins cannot Bind as Well
\*_Insect Metabolism of Pyrethrins is much Slower than Mammals_
**All of these Factors make Pyrethrins Effective Against Insects with Low Toxicity to Mammalian Species**
357
Which Insecticide works by _Irreversible_ Inhibition of Cholinesterases, that Increases ACh at all Cholinergic Sites
**Organophosphates**
\*Acytelcholine Cannot be Broken Down
358
Organophosphates Degrade quickly in the Environment, most Persist ____ Weeks and can Penetrate Intact Skin and Waxy coatings of Leaves and Fruits
**2-4 Weeks**
359
\_\_\_\_\_\_, aka _Activated Vitamin D3_, is Absorbed from the GI Tract and Binds to the Vitamin D binding Protein in Plamsa for Transportation to the Liver
**Cholecalciferol**
**\***Cholecalciferol is _Metabolized in the Liver to Calcidiol_ (25-Hydroxycholecalciferol)
\*Calcidiol (25-Hydrocholecalciferol) is Trasported to the Kidney and Metabolized to Calcitriol (1,25-Dihydroxycholecalciferol)
360
True/False: Biotransformation is the first phase of Drug Elimination
True
361
True/False: Laboratory Animal Testing is Important for Bacterial, Fungal and Plant Toxins and Feed Additives in Animal Feeds
True
362
True/False: Age, Inflammation, Trauma, Allergic Reactions, Severe Hypotension, and Hypoxia Do Not Influence the Blood Brain Barrier
False
\*All these factors influence the Blood Brain Barrier
\*Animal must be older to have an Effective Blood Brain Barrier
363
Acidification of the Urine pH by Oral _Ammonium chloride or Methionine_ Enhances renal Excretion of Weak ____ Drugs such as Amphetamine
**Basic**
**\***Use ORAL Ammonium Chloride or Methionine
364
More Common **Bromethalin** Toxicity that develop within _2-3 Days_ Post Exposure that progresses into Hind-Limb Ataxia, Paresis, Paralysis, CNS Depression ect.
**Subacute**
**\*** 2-3 days to Onset
\*Higher chance for Survival
