midterm Flashcards
toxicology
-“The study of poisons and their actions in the
animal body
* Things that poison animals may also poison
people
describe the difference between toxin and toxicant
- Toxin: poisons that originate from a biological source
-Toxicant: poison of man-made or synthetic origin
dose
- “The dose defines the poison”
- A substance can be safe at one dose, but higher at another
- Units: amount of poison per unit body weight
- Dose dose not =concentration
- Most important factor in considering exposure to poisons
-median lethal dose
Median lethal dose = LD5
- Estimation of lethality
- Dose that kills 50% of the test species
- Specific for route and species
dose response
-A toxic effect is proportional to the dose of a substance
* Higher dose = more severe toxic effect
* Response can be lethality, reproductive effects,
effects on the immune system
* Exception: idiosyncratic reactions
* Adverse drug reactions
duration of exposure
- Acute: effects occur within 24 hours of exposure
- Sub-acute: >24 hours to <30 days
- Sub-chronic: 1-3 months of repeated exposures
- Chronic: effects produced by prolonged exposure (>3 months)
- Poisons with a low LD50 tend to be acutely toxic
- Chronic toxicity results from prolonged, repeated exposure
- LD50 is not a good estimate of chronic toxicity
T O X I C O K I N E T I C S
- Toxicity is guided by pharmacokinetics (“toxicokinetics”)
- For an agent to cause toxicity, it needs to interact with its target site at a sufficient dose
-absorption
-distribution
-metabolism
-elimination
distribution
- Factor of organ perfusion, diffusion of the toxic substance, the affinity of the toxic substance for
a certain organ/tissue, binding to plasma proteins - Highly perfused organs: liver, kidney, heart, lung, intestines, brain
- Tend to get the highest exposure to poisons
- Poorly perfused: skin, connective tissue, fat
D E T O X I F I C A T I O N / B I O T R A N S F O R M A T I O N phases
phase 1: Oxidation, hydrolysis, reduction: lipophilic →
more water soluble
phase 2: conjugation
phase 3: elimination via urine, bile, exhalation
-mostly happens in liver
Bioactivation
-metabolism of a parent compound to a more toxic metabolite
* Important examples in veterinary medicine
* Acetaminophen (Tylenol cats)
* Ethylene glycol (antifreeze)
* Bromethalin (rodenticide)
intraspecies differences
- Most individuals fall within the bell curve for a dose-
response relationship - Individuals can respond differently to a given dose of a poison
- Inherent differences in ADME, other factors
- Examples
- Ivermectin and ABC delta-1
- Bedlington terriers and Cu accumulation
- “Treat the patient, not the poison
age and toxicosis
-very young and very old are more susceptible to toxins.
-reduced ability to detoxify, eliminate, and reduced barrier functions.
physiochemical properties of the toxin
-state: gas, aqueous, solid
-size: smaller particles faster
-lipophilicity: passes membranes easily
-acid/base: * Henderson-Hasselbach
* Affects the ionization of a compound in solution → absorption
* Presence/absence of food in stomach
health and physiological status and toxicosis
- Liver and/or kidney disease
- Impaired ability to clear toxic substances from the body
- General debilitation
- Pregnancy, lactation
- Gastrointestinal inflammation
two goals of diagnostics in toxicology
-Confirming exposure to a toxic dose
* Monitoring clinical signs resulting from poisoning
pre analytical errors in sampling
-sample collection:
wrong sample
liver (not enough)
blood/ serum plasma (not enough, hemolysis)
-sample transportation: weather, packaging
-lead to inaccurate results and misdiagnosis
hemolysis in blood sample
- Compromises interpretation of iron, zinc, magnesium,
and chemistry panel - Causes of hemolysis:
- Delayed separation of serum from clot
- Freezing whole blood
- Inadequate centrifugation
- Wrong needle/syringe
- Inadequate volume collected
- Vigorous mixing
- Exception: hemolysis from poisoning
emergency blood panel tests
– four tests:
* Blood glucose
* Total protein
* BUN
* PCV
- Very helpful starting point
- Some toxins cause hypoglycemia
- BUN: kidney problems
- PCV: plasma colour, anemia
blood gas analysis
- Venous versus arterial
- Ionized and total calcium: hyper- and hypocalcemia
- Acid-base status
- pH, pCO2, HCO3, base excess (BE)
- Electrolytes (Na, K, Mg)
- Glucose
- Lactate
in clinic imaging
- T-FAST: air, fluid:
- B-lines: “wet” lung problems
- Pulmonary edema, bleeding
- A-FAST: free abdominal fluid or hemorrhage:
- Radiographs
- Abdominal ultrasound
coagulation panel
- Not all clinics, but many emergency clinics
- Prothrombin time (PT): extrinsic and common pathway
- Partial thromboplastin time (PTT): intrinsic and common pathway
- Considerations:
- Fill up to the line
- Clean venipunctur
VDL: metals and minerals test
- Inductively coupled plasma mass spectrometry (ICP-MS)
- In general: plasma/serum , liver
- Plasma/serum: 2 mL (red or green top tube)
- Liver: 2-5 g fresh or frozen – ship on ice packs
- Liver biopsies: at least 0.2 g
- Lead: 90% of lead is bound to red blood cells
- Heparinized whole blood (green top tube) – ship on ice packs
- Tissue (liver, kidney, etc)
VDL: pesticides
- High performance liquid chromatography (HPLC), liquid chromatography mass spectrometry
(LC/MS), gas chromatography mass spectrometry (GC/MS) - Samples to submit:
- Any suspect bait materials
- Stomach contents: strychnine, OP/carbamates
- Whole blood: acetylcholinesterase activity (OP/carbamates)
- Brain: acetylcholinesterase activity (OP/carbamates)
VDL: water analysis
-Algal toxins: 20 mL of water stored at -4°C: Ship on ice packs
* Metals and trace minerals
* Nitrate
* Drug/pesticide residues
* Some provincial labs offer farm water testing for free