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Foundation of animal health and disease 1 > Module 8 > Flashcards

Module 8 Flashcards

Introduction to Toxins

1
Q

What is a toxin

A

A material which causes adverse health effects when it contacts or enters the body.

• Toxic is the term used to describe the effects of a poison on biological systems

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2
Q

Types of toxins

A 
Metals
Mycotoxin & bacterial toxins eg. perennial ryegrass staggers eg. blue green algae 
PHARMACEUTICAL  DRUGS 
PESTICIDES 
POISONOUS PLANTS & ANIMALS
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3
Q

What does dose-reponse relationship mean

A

Describes the relationship between the amount (dose) of the toxin and the effect of the toxin on the body

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4
Q

What are the three dose-response curve

A

Therapeutic effect(ED), toxic effect(TD), lethal effect(LD)

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5
Q

What is the margin of safety

A

Calculated as the dose that is lethal in 1% of animals divided by the dose that is ‘effective’ in 99% of animals

Margin of safety =LD1/ED99

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6
Q

What are the 4 processes or toxicokinetics

A

Absorption Distribution Metabolism Excretion

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7
Q

Where does the absorption take place

A

Gastrointestinal

Respiratory

Dermal

(Injection)

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8
Q

Four main mechanisms by which small molecules cross cell membranes

A
  1. Diffusion directly through lipid membrane
  2. Diffusion through aqueous pores formed by aquaporins
  3. Interaction with solute carrier or other membrane transporter
  4. Pinocytosis (mainly for macromolecules)
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9
Q

Where is one of the most important site for toxin absorption

A

gastrointestinal tract

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10
Q

What factors affect rate of absorption

A

pH, GI motility, GI surface area, lipid solubility (lipid soluble substances absorbed more readily than water-soluble substances)

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11
Q

What act as a barrier to toxin absorption from gastrointestinal tract

A
  • Digestive enzymes in saliva, stomach and intestines
  • Alteration in pH; in particular acidity of stomach contents
  • Motility of the gastrointestinal tract
  • Interactions with food and other drugs in the gastrointestinal lumen
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12
Q

How does the absorption of respiratory tract work

A

generally gasses, vapours, aerosols or volatile liquids.

Most absorption occur via lungs

  • Epithelial cells lining the alveoli are thin so distance for chemical diffusion is very short
  • Epithelial cells also in very close contact with capillaries, so chemicals are rapidly removed by the blood
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13
Q

Absorption through the skin

A

Skin relatively impermeable
toxins must pass through several cell layers before entering the small blood capillaries in the dermis

Toxins pass through the skin via passive diffusion and enter the systemic circulation through venous and lymphatic capillaries in the dermis

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14
Q

What is the rate limiting step for Absorption through the skin

A

Outermost layer is the stratum corneum (keratinised cells)

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15
Q

What affects the distribution of toxin

A

primarily by blood flow and the rate of diffusion out of the capillary bed and into the tissues

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16
Q

Where does toxin first distributed to

A

water compartments (plasma, interstitial, intra-cellular)

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17
Q

Where does the secondary area that toxin will be distributed to?

A

determined largely by tissue affinity – some toxins accumulate in specific organs

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18
Q

What are the body fluid “compartments”

A

Plasma water
interstitial water (center of the all the compartment)
Intracellular water
Fat

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19
Q

What is the apparent volume of distribution(Vd)

A

Amount of drug in the body(Q) present at the same concentration as that present in the plasma (Cp)

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20
Q

What is the equation of Volume of distribution (Vd)

A

Vd = Q/Cp

Vd = Total dose (amount of drug in the body)/plasma concentration of drug

21
Q

What is plasma concentration of drug

A

plasma concentration of drug (Cp) is the amount of toxin left in the PLASMA COMPARTMENT

22
Q

What is Q

A

It is the amount of drug in all the compartment(INTERSTITIAL FLUID COMPARTMENT, the whole body)

23
Q

What does Vd tell us

A

high tissue affinity will be dissolved in a large volume and therefore have a large Vd

24
Q

Three key factors determining toxin distribution

A

Size and ability to pass through the vascular endothelium (cells lining blood vessels)
Ability to bind to plasma proteins
Lipid solubility

25
Q

What does the binding/storage of toxin in tissue impact

A

determining distribution (e.g fat, liver bone)

26
Q

Does the tissue site of toxic accumulation be its site of toxic action

A

Often it is not

27
Q

Will Any toxin stored in tissues will be in equilibrium with the ‘free’ portion of the toxin in plasma?

A

Yes, and it will be continually release into the circulation to be metabolised

28
Q

What is the definition of metabolism of toxin

A

involves altering the physical properties of the toxin, from those favouring absorption (lipophilic) to those favouring excretion in urine and faeces (hydrophilic)

29
Q

Where does most metabolism occur?

A

liver

30
Q

What effect does metabolism have on the effect of toxin

A

It can significantly alter the biological effects of the toxin.
In most cases, metabolism terminates the effects of the toxin, however, in some cases the transformation initiates the effects of the toxin

31
Q

What is phase 1 of metabolic reaction

A
  • Catabolic (ie. Oxidation, reduction or hydrolysis)
  • Usually form more chemically reactive products
  • Often involve cytochrome P450 enzymes in liver
32
Q

What is phase 2 of metabolic reaction

A

• Anabolic (involve conjugation)
• Usually lead to inactive products
• Mostly occurs in liver, but also kidney and lung
-

33
Q

Where does venous blood from the gastrointestinal tract go?

A

Liver > right side of heart > lungs > left side of heart > arterial circulation to body

34
Q

Does the Metabolic reaction phase go sequentially

A

yes, Both phases decrease lipid solubility, facilitating elimination in urine

35
Q

Where are metabolism occur before circulation, Hepatic ‘first pass’ effect

A

Liver

36
Q

Why does the hepatic ‘first pass effect’ matter?

A

Because toxic have different effect depending on route of exposure.
The presence of liver disease may alter the toxicokinetics of toxins absorbed from the gastrointestinal tract

37
Q

Does metabolise BEFORE they reach the systemic circulation

A

toxins absorbed from the gastrointestinal tract may be metabolised BEFORE they reach the systemic circulation

38
Q

What are two main route of excretion

A

hepatobiliary excretion
-Leading to elimination in faeces

urinary excretion
-Leading to elimination in urine

39
Q

What are the 3 fundamental processes in renal excretion of toxins

A
  1. Glomerular filtration -low molecular weight toxins
    - if toxin bound to plasma proteins, only free (unbound) drug is filtered
  2. Active tubular secretion
    - Toxins transferred into the renal tubules through nonselective carrier systems
    - Can achieve excretion when toxin is bound to plasma proteins
  3. Passive diffusion across tubular epithelium
    - Filtered drug can be passively reabsorbed back into the peritubular capillary (down the concentration gradient)
    - Lipid soluble toxins are readily reabsorbed by diffusion and therefore are not efficiently excreted in the urine
    1
40
Q

How is Excretion of toxins from the kidneys is quantified by

A

renal clearance (CLr)

41
Q

What is the definition of clearance in the toxin processes

A

the volume of plasma containing the amount of substance that is removed from the body by the kidneys per unit time

CLr=𝐶𝑢 x 𝑉𝑢/Cp

Where C u = urinary concentration, Vu = rate of flow of urine, Cp =plasma concentration

42
Q

What does Renal clearance

A

indicates the efficiency of removal of the toxin from the circulation , high clearance indicates rapid removal of the toxin

43
Q

What is the One compartment model

A

In the one compartment model, toxin rapidly equilibrates (mixes uniformly) between blood and tissues

44
Q

How is the movement of toxin on the one compartment model

A

Absorption into the One compartment Volume = Vd then proceeds to metabolism & excretion

45
Q

What is the first order elimination

A

Constant proportion of the toxin is eliminated per unit time (drug concentration declines exponentially for unit of drug vs time graph, Linear for log units of drug vs time graph)

46
Q

What is Zero order elimination

A

Constant mass of the toxin is eliminated per unit time

Declines linearly for plasma concentration vs time graph

Declines exponentially for Log units of drug vs time graph

47
Q

Does rate of toxin elimination dependent of plasma concentration

A

No

48
Q

What do we use toxicokinetic modelling for?

A

To predict the behaviour and effects of toxins in animals

Foundation of animal health and disease 1 (16 decks)

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