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1. Toxicology > Clinical toxicology lecture 1 > Flashcards

Clinical toxicology lecture 1 Flashcards

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1
Q

Hemlock

A

Drink it as a Greek capital punishment

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2
Q

Aconite

A

Soldiers dipping arrows

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3
Q

What did King Mithridates do?

A

Sampled poisons to build resistance

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4
Q

Paracelsus

A

Father of modern toxicology
Said that all substances are poisons, the dose determines if a remedy or poison

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5
Q

Threshold dose

A

Highest dose that doesn’t cause obvious adverse effects

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6
Q

ED1

A

Effective Dose, dosage affective in 1% of the population

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7
Q

NOEL

A

Highest dose where no significant effect occurs

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8
Q

LOEL

A

Lowest dose where a significan effect occurs

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9
Q

NOAEL

A

No observable adverse effect level

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10
Q

Dosage

A

Amount of toxin/ drug per body wt (mg/kg/day)

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11
Q

Dose

A

Total amount the animal receives

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12
Q

Acute responses/ effects

A

Redness, swelling, pain

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13
Q

Chronic responses/ effects

A

Contraction, organization, loss of pain

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14
Q

Timely effect of toxins

A

(Fastest) peracute –> acute –> subacute –> subchronic –> chronic –> accumulation –> delayed

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15
Q

Which gov organization approved drugs?

A

FDA

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16
Q

Acute toxicity

A

Single and short term exposure
Effects observed <24 hours

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17
Q

Subacute toxicity

A

Repeat exposure to small doses
30 days or less, two week studies
Effects cellular functions and tissues

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18
Q

Subchronic toxicity

A

Repeated exposure
Study of toxic effects for 1-3 months

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19
Q

Chronic toxicity

A

Long term exposure
Used to demonstrate general toxicity and carcinogensis
Period usually > one year

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20
Q

Chronicity factor (CR)

A

Ratio of acute chronic LD50
CR= acute LD50/ chronic LD50
Chemical accumulates if CR >2

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21
Q

Inhereited sensitivities of MDR1 gene mutation

A

Ivermectin
Butorphenol
Anticancer drugs (doxrubricin, vincristine)
Acepromazine
Immodium
Mibemycin
Erythomycin
Rifampin

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22
Q

Routes of administration

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A

Oral*
IV, IM, SC
Dermal*
Inhalation*
Intrathecal
Sublingual
Intraocular
Transdermal

23
Q

Factors influencing toxic responses

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A
  1. Composition of sample (purity & solubility)
  2. Physiological features (species, age, gender)
  3. Route of administration
  4. Pathological conditions (liver & kidney)
  5. Diet (ingredients, quality & quantity)
24
Q

Exposure

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A

Poison/ drugs gain entry —> drugs transported to site of action —> drugs bind to receptors (DR complex) —> initiates rx (effect/ response) —> drug removed from receptor —> drug excreted from body

25
Dose response relationship
Biological response is related to the dose Different in different species as well as the same species
26
How is dose response used?
To determine margin of safety Optimize dosage schedule (efficacy) Predict toxicity poisoning
27
Biological variation
Dose can produce a variety of responses in a population Determines repulse of a large # of individuals Predicts the response of an individual within a certain range of probability
28
How is Dose-response plotted?
Log dose v. Percent response
29
Methods to predict dose response relationships
1. Graded DR (overall effect) 2. Frequency/ Quantal DR (% responding/ population)
30
Therapeutic index
TI= LD50/ ED50 Ratio between lethal dose (50%) and effective dose (50%)- no units
31
Margin of safety (MS/MoS/ SSM)
MS= LD1/ ED99 Ratio between lethal dose (1%) and effective dose (99%)- no units BETTER SAFETY ASSESSMENT THAN TI
32
Toxicokinetics abbreviated
Concentration: Cp Volume of distribution (Vdss) Clearance (Cl) Bioavailability (F)
33
Half life
t1/2 Time required to decrease concentration to one half
34
Parts per _____ conversions
1 ppm = mg/kg= ug/g 1 ppb = ug/kg= ng/g 1 ppt = ng/kg= pg/g
35
Expression of chemical concentrations
Kg= 1000 g 1g =1000 mg 1 mg= 1000 ug 1 ug = 1000 ng 1 ng= 1000 pg
36
To convert PPM to %…
Move decimal 4 points to the left 1 ppm: 0.0001% 10 ppm: 0.001% *to convert % to PPM move to right*
37
Additive effects
When 2 or more chemicals combine and produce a chemical with a total effect equal to the sum of the effects of each inidival chemical in the rx Ex: 1+1=2
38
Synergistic effects
The combined effect of 2 compounds are drastically greater than the sum of 2 effects Ex: 1+1=10
39
Antagonism
Toxic effect of chemical A (agonist) can be reduced when give with chemical B (antagonist) Ex; 1+1=0
40
Antagonist are used as_________
Antidotes (because they reduce toxicity)
41
Potentiation
A chemical doesn’t have a specific toxic effect, makes another chemical more toxic Ex: 1+0= 2
42
Routes of exposure/ administration
1. Oral/ GI (water or fat soluble) 2. Dermal- percutaneous (environmental contaminants) 3. Inhalation, respiratory, pulmonary (gas, liquid, solid, size of particles)
43
Oral/ GI
Generally toxicants in food or water Some unstable in acidic stomach Some taken up by liver and partially destroyed Some removed in stomach, duodenum, large bowel and feces
44
Dermal/ Percutaneous
Toxicants must be in a soluble vehicle, capable to penetrating keratin, and enter a BV
45
What other factors contribute to dermal administration?
Duration fo exposure PPE/ skin protectants Integrity of the skin
46
What does distribution depend on?
Blood flow Ability to cross the cell wall Lipid solubility/ physiochemical properties
47
Central compartment
High perfused (blood flow to tissues) Blood, kidney, liver
48
Peripheral compartment
Less blood flow tissues Fat, bone, muscle
49
Biotransformation/ Metabolism organ capabilities
Greatest: liver Major potential: kidney, GIT, skin Great fetus potential: brain, heart, placenta
50
Objective of biotransformation
Make chemical more soluble Enhance urinary and binary excretion Decrease toxicity fo chemicals
51
Storage of xenobiotics
Storage can be a protective mechanism and potentiate toxicosis
52
Storage sites in the body
Depending on the drug: Fat, plasma proteins, bone, liver, kidneys, BBB
53
FARAD: Residue Avoidance Database
Computer based program designed to provide practical info on how to avoid drug , pesticide, and environmental contaminant residue problems Target: livestock producers, extension specialists and vets

1. Toxicology (14 decks)

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