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Toxicology AF > Introduction Material > Flashcards

Introduction Material Flashcards

1
Q

Toxicology is defined as

A

The science of toxicants, their physical properties, sources, toxicity, toxicokinetics, MOA, clinical signs, lesions (post-mortem), lab diagnosis, diagnosis, DDx, and treatment (or prevention) of diseases caused by toxicants

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2
Q

Most common poisoning in dogs?

A

Human food and drugs (legal and illegal).

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3
Q

Diagnosis and Treatment

A

Main aspects of clinical Tox

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4
Q

Drugs can be poisons and poisons can be drugs…. The difference is

A

The dose (Dose or amount of exposure)

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5
Q

Drugs and Poisons are….

A

Xenobiotics (foreign chemicals that the body does not produce)

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6
Q

Any substance (gas, liquid, solid) when applied or introduced into the body that may interfere with life processes or biological functions of the cells of the animals

A

Poison (Toxicant) - can be used interchangeably

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7
Q

Natural Poisons

A

Plant Animals (venom, insect sting, fish toxin) Minerals (lead, zinc) Fungi or bacteria (mycotoxin)

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8
Q

Organophosphate and chlorinated hydrocarbon insecticides, organic herbicides are…

A

Synthetic Poisons

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9
Q

Toxin

A

BIOTOXIN!! Poison from a biologic process (zootoxins or animal toxins, phytotoxins or plant toxins, bacterial toxins and mycotoxins)

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10
Q

Toxicant

A

Can be living or non-living

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11
Q

Deleterious or undesirable effects of poisons

A

Toxic

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12
Q

Disease caused by exposure to a poison

A

Toxicosis (Poisoning or intoxication)

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13
Q

Toxicity

A

Amount of a poison that under certain circumstances will cause toxic effects

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14
Q

Toxicity in mammals is

A

LD50 Mg/kg body weight

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15
Q

Toxicity in Birds….

A

LC50 (lethal concentration) Mg/kg FEED

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16
Q

Toxicity in Fish….

A

LC50 Mg/liter WATER

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17
Q

Effect of a single dose or multiple doses during a 24 hour period

A

Acute Toxicity

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18
Q

Effect produced by daily exposure from one day to 30 days

A

Subacute Toxicity

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19
Q

Effect of exposure from 30 days to 90 days

A

Subchronic Toxicity

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20
Q

Effect produced by daily exposure for a period of 3 months or more

A

Chronic Toxicity

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21
Q

Chronocity Factor

A

Ratio between acute LD50 and chronic LD50

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22
Q

Toxicity values are influenced by several factors…

A

Species, breed, age, individual, sex, dosage of a poison, duration of exposure and other factors

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23
Q

Extremely Toxic

A

= 1mg/kg or less

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24
Q

Highly Toxic

A

> 1-50 mg/kg

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25
Q

Moderately Toxic

A

> 50 - 500 mg/kg

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26
Q

Slightly Toxic

A

> 0.5 - 5 g/kg

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27
Q

Practically Nontoxic

A

> 5-15 g/kg

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28
Q

Relatively Harmless

A

>15g/kg

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29
Q

Highest NonToxic Dose (HNTD)

A

The highest or largest dose which does not result in undesirable or toxic alterations (clinical, hematologic, biochemical, or pathologic alterations)

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30
Q

This is similar to the highest nontoxic dose

A

Maximum Tolerated Dose Or Minimal Toxic Dose (MTD)

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31
Q

Toxic Dose Low (TDL)

A

The lowest dose which produces toxic alterations and administering twice the dose will not cause death

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32
Q

Toxic Dose High (TDH)

A

The dose which produces toxic alterations and administering twice the dose WILL result in death

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33
Q

No Effect Level (Maximum Nontoxic Level)

A

The amount of a chemical that can be ingested without causing any deaths, illness or toxic alterations in any of the animals for the stated period (usually 90 days to 2 years or more depending on the species)

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34
Q

The dose that causes death in any animal during the period of observation

A

Lethal Dose

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35
Q

LD 0 (zero)

A

the highest dose that dose not cause any death

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36
Q

LD 50

A

The dose that kills 50% of the animals in the group

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37
Q

LD 100

A

The lowest dose that kills ALL the animals in a group

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38
Q

Hazard

A

Is the danger from the possibility of exposure

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39
Q

A poison may be _____ ________ but not _________

A

Highly Toxic , Hazardous

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40
Q

The risk factor can be calculated as the _______ between _______ and _____ ______

A

Ratio , toxicity , and use level

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41
Q

Toxicology is

A

The study of poisons (toxicants)

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42
Q

Parts per million (ppm) on weight/weight basis

A

Is the most common method of expressing concentrations in toxicology 1ppm = 1mg / kg

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43
Q

Converting from PPM to percent %

A

Move the decimal point 4 places to the left Ex: 1 ppm - 0.0001%

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44
Q

Convert from Percent % to PPM

A

Move the decimal point 4 places to the right Ex: 0.0001% –> 1 ppm

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45
Q

Diluted Solution from Stock

A

The mL needed = (% required dilution / % stock ) x required in mL Ex: (2.5% diluted / 50% stock) x 500 mL =

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46
Q

Feed to PPM

A

100g/ton = 110ppm

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47
Q

The study of movement of drugs in the body across biological membranes from the time of absorption until elimination

A

Drug Disposition

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48
Q

What are the Stages of Drug Disposition

A

Absorption Distribution Biotransformation Excretion

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49
Q

Biological Cell Membrane

A

Composed of lipid by layer Contain membrane proteins and carbohydrates There are aqueous pores or junctions between cells

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50
Q

Transmembrane movement of water is either by _________________ through aqueous channels or by flow resulting from_________ or ____________ difference across the membrane

A

Passive diffusion, osmotic, hydrostatic

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51
Q

Paracellular transport of water is through…

A

Intracellular aqueous pores

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52
Q

Tissues that have a barrier mechanism have..

A

“Tight” intracellular junctions

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53
Q

Bulk flow of water can carry…

A

Small water soluble substances

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54
Q

Concentration Gradient

A

Drugs move across membranes from high concentration to low concentration

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55
Q

Lipid Solubility is measured by

A

Lipid partition coefficient ( the ratio between solubility of drug in lipid to its solubility in water)

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56
Q

The higher the lipid solubility the….

A

Faster the drug crosses the membranes

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57
Q

Drugs cross membranes in the

A

Non-ionized form (Lipid soluble and do not carry electric charge)

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58
Q

The rate of diffusion depends on the ratio between the ____________ of the drug to the ____________ form.

A

(N/I) Non-ionized, ionized

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59
Q

Ionization of a drug depends on…

A

PH of the drug Pka of the drug PH of the medium (environment)

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60
Q

The pKa of a drug is the pH at which a weak electrolyte is

A

50% ionized and 50% non-ionized

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61
Q

Most drugs are

A

Weak electrolytes (weak acids or weak bases)

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62
Q

Acidic drugs ionized in __________ medium and basic drugs ionized in ___________medium

A

Alkaline, acidic

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63
Q

The higher the pKa of a weak acid the _______ is N/I and the lower the pKa of a weak base the ________ is N/I

A

Higher, higher

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64
Q

Quaternary ammonium compounds like d-tubocurarine are

A

Mostly ionized

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65
Q

Phenylbutazone

A

A weak acid mostly ionized in the stomach

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66
Q

Facilitated Diffusion

A

A carrier mediated transport that DOES NOT NEED ENERGY

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67
Q

In facilitated diffusion a drug moves across the membrane from high to low concentration…

A

At a faster rate (downhill movement)

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68
Q

In facilitated diffusion, transporters can move

A

Drugs from outside the cell to inside or from inside to outside

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69
Q

Facilitated diffusion Transporters may act as a _______________ to protect cells from toxic substances by ….

A

Barrier system Moving them from inside to outside of the cell

70
Q

Movement of glucose across a muscle cell membrane by insulin sensitive glucose transporters is an example of

A

Facilitated Diffusion

71
Q

In active transport, a drug moves across the membrane from

A

Low concentration to High concentration (uphill movement)

72
Q

Active transport is a carrier mediated transport

A

That requires energy

73
Q

Primary active transport uses energy directly from

A

ATP such as Na/K ATPase

74
Q

Secondary Active Transport

A

Uses stored energy in the Na electrochemical gradient

75
Q

Active transport is characterized by

A

Saturability, selectivity, and competitive inhibition by cotransported compounds

76
Q

Specific type of endocytosis where the cell engulfs the drug molecules dissolved in water

A

Pinocytosis

77
Q

The transport of drugs from the plasma to the tissues

A

Distribution

78
Q

Factors that affect distribution of drugs

A

Physiochemical properties Concentration gradient Plasma protein binding Blood Flow Tissue barrier Drug affinity to tissues

79
Q

Acidic drugs bind mainly to

A

Albumin

80
Q

Basic drugs bind mainly to

A

Alpha 1 - glycoproteins and lipoproteins

81
Q

What drugs bind to globulin

A

Steroids

82
Q

Plasma protein binding

A

Prolongs the half life of the drug

83
Q

Plasma protein binding is generally

A

Reversible

84
Q

The bound form of the drug is

A

Inactive, so it cannot be distributed, metabolized or excreted

85
Q

The rate of binding depends

A

On the amount of the drug

86
Q

Plasma protein binding can be modified by

A

Disease

87
Q

Highly perfused tissues

A

brain, liver, kidney, endocrine glands

88
Q

Moderately perfused tissues

A

Muscle, skin

89
Q

Poorly perfused tissues

A

Bone, adipose tissue

90
Q

The Blood Brain Barrier (BBB)

A
  • Tight capillary endothelial junctions
  • Presence of glial cells
  • Flow of the CSF into venous drainage
  • Active transport mechanisms for extrusion of organic acids or bases
91
Q

Factors that limit the BBB…

A

Age Inflammation Trauma Allergic Rxn Severe hypotension Hypoxia High doses of organic solvents (alcohol) Heavy metals

92
Q

Name some Tissue Barriers

A

Brain Eye Testicles Placenta Mammary glands

93
Q

Tetracycline has an affinity to

A

Calcium in skeletal tissues

94
Q

Aminoglycosides have an affinity to

A

Kidney tissue

95
Q

The thyroid gland traps

A

Iodine

96
Q

The movement of the drug from the tissue to the blood

A

Redistribution

97
Q

The chemical alteration of the drug molecule by the cells of the animal

A

Metabolism (biotransformation)

98
Q

Parts per million (ppm) on weight/weight basis

A

Is the most common method of expressing concentrations in toxicology 1ppm = 1mg / kg

99
Q

Converting from PPM to percent %

A

Move the decimal point 4 places to the left Ex: 1 ppm - 0.0001%

100
Q

Convert from Percent % to PPM

A

Move the decimal point 4 places to the right Ex: 0.0001% –> 1 ppm

101
Q

Diluted Solution from Stock

A

The mL needed = (% required dilution / % stock ) x required in mL Ex: (2.5% diluted / 50% stock) x 500 mL =

102
Q

Feed to PPM

A

100g/ton = 110ppm

103
Q

The study of movement of drugs in the body across biological membranes from the time of absorption until elimination

A

Drug Disposition

104
Q

What are the Stages of Drug Disposition

A

Absorption Distribution Biotransformation Excretion

105
Q

Biological Cell Membrane

A

Composed of lipid by layer Contain membrane proteins and carbohydrates There are aqueous pores or junctions between cells

106
Q

Transmembrane movement of water is either by _________________ through aqueous channels or by flow resulting from_________ or ____________ difference across the membrane

A

Passive diffusion, osmotic, hydrostatic

107
Q

Paracellular transport of water is through…

A

Intracellular aqueous pores

108
Q

Tissues that have a barrier mechanism have..

A

“Tight” intracellular junctions

109
Q

Bulk flow of water can carry…

A

Small water soluble substances

110
Q

Concentration Gradient

A

Drugs move across membranes from high concentration to low concentration

111
Q

Lipid Solubility is measured by

A

Lipid partition coefficient ( the ratio between solubility of drug in lipid to its solubility in water)

112
Q

The higher the lipid solubility the….

A

Faster the drug crosses the membranes

113
Q

Drugs cross membranes in the

A

Non-ionized form (Lipid soluble and do not carry electric charge)

114
Q

The rate of diffusion depends on the ratio between the ____________ of the drug to the ____________ form.

A

(N/I) Non-ionized, ionized

115
Q

Ionization of a drug depends on…

A

PH of the drug Pka of the drug PH of the medium (environment)

116
Q

The pKa of a drug is the pH at which a weak electrolyte is

A

50% ionized and 50% non-ionized

117
Q

Most drugs are

A

Weak electrolytes (weak acids or weak bases)

118
Q

Acidic drugs ionized in __________ medium and basic drugs ionized in ___________medium

A

Alkaline, acidic

119
Q

The higher the pKa of a weak acid the _______ is N/I and the lower the pKa of a weak base the ________ is N/I

A

Higher, higher

120
Q

Quaternary ammonium compounds like d-tubocurarine are

A

Mostly ionized

121
Q

Phenylbutazone

A

A weak acid mostly ionized in the stomach

122
Q

Facilitated Diffusion

A

A carrier mediated transport that DOES NOT NEED ENERGY

123
Q

In facilitated diffusion a drug moves across the membrane from high to low concentration…

A

At a faster rate (downhill movement)

124
Q

In facilitated diffusion, transporters can move

A

Drugs from outside the cell to inside or from inside to outside

125
Q

Facilitated diffusion Transporters may act as a _______________ to protect cells from toxic substances by ….

A

Barrier system Moving them from inside to outside of the cell

126
Q

Movement of glucose across a muscle cell membrane by insulin sensitive glucose transporters is an example of

A

Facilitated Diffusion

127
Q

In active transport, a drug moves across the membrane from

A

Low concentration to High concentration (uphill movement)

128
Q

Active transport is a carrier mediated transport

A

That requires energy

129
Q

Primary active transport uses energy directly from

A

ATP such as Na/K ATPase

130
Q

Secondary Active Transport

A

Uses stored energy in the Na electrochemical gradient

131
Q

Active transport is characterized by

A

Saturability, selectivity, and competitive inhibition by cotransported compounds

132
Q

Specific type of endocytosis where the cell engulfs the drug molecules dissolved in water

A

Pinocytosis

133
Q

The transport of drugs from the plasma to the tissues

A

Distribution

134
Q

Factors that affect distribution of drugs

A

Physiochemical properties Concentration gradient Plasma protein binding Blood Flow Tissue barrier Drug affinity to tissues

135
Q

Acidic drugs bind mainly to

A

Albumin

136
Q

Basic drugs bind mainly to

A

Alpha 1 - glycoproteins and lipoproteins

137
Q

What drugs bind to globulin

A

Steroids

138
Q

Plasma protein binding

A

Prolongs the half life of the drug

139
Q

Plasma protein binding is generally

A

Reversible

140
Q

The bound form of the drug is

A

Inactive, so it cannot be distributed, metabolized or excreted

141
Q

The rate of binding depends

A

On the amount of the drug

142
Q

Plasma protein binding can be modified by

A

Disease

143
Q

Highly perfused tissues

A

brain, liver, kidney, endocrine glands

144
Q

Moderately perfused tissues

A

Muscle, skin

145
Q

Poorly perfused tissues

A

Bone, adipose tissue

146
Q

The Blood Brain Barrier (BBB)

A

Tight capillary endothelial junctions Presence of glial cells Flow of the CSF into venous drainage Active transport mechanisms for extrusion of organic acids or bases

147
Q

Factors that limit the BBB…

A

Age Inflammation Trauma Allergic Rxn Severe hypotension Hypoxia High doses of organic solvents (alcohol) Heavy metals

148
Q

Name some Tissue Barriers

A

Brain Eye Testicles Placenta Mammary glands

149
Q

Tetracycline has an affinity to

A

Calcium in skeletal tissues

150
Q

Aminoglycosides have an affinity to

A

Kidney tissue

151
Q

The thyroid gland traps

A

Iodine

152
Q

The movement of the drug from the tissue to the blood

A

Redistribution

153
Q

The chemical alteration of the drug molecule by the cells of the animal

A

Metabolism (biotransformation)

154
Q

What are the changes in physiological properties of a drug as a result of biotransformation

A

The metabolite is more water soluble, polar and ionized

155
Q

Changes in pharmacological activity as a result of biotransformation

A

Bioinactivation or detoxification (most drugs)

Bioactivation or lethal synthesis (few drugs)

156
Q

Sites of Biotransformation

A

*LIVER

Smooth endoplasmic reticulum (microsomes)

Hepatocyte cytoplasm, mitochondria, lysosomes, nuclear envelope, plasma membrane

*OTHER TISSUES

nervous tissue, kidney, GI tract, lungs and skin

*PLASMA

157
Q

Phase I reactions

A

Oxidation

Reduction

Hydrolysis

158
Q

Phase II Reactions

A

Conjugation

159
Q

Factors Altering Biotransformation

A

Species

Individual

Route of Administration

Enzyme Inducers

Distribution and Storage

Age

Sex

Diet and Nutrition

Liver Disease

Hepatic Blood Flow

Plasma Protein Binding

Body Temperature

Environmental Factors

160
Q

Cats are deficient in…

A

glucuronyl transferases

hydroxylation

dealkylation

161
Q

Dogs lack….

A

acetylating enzymes

162
Q

Ruminants have _________________ than horses, dogs, and cats

A

less plasma pseudochoinesterases

163
Q

What species have high levels of oxidative enzymes

A

Ruminants and horses

164
Q

Species deficient in sulfate conjugating enzymes

A

pigs

165
Q

Lacks oxidative enzymes

A

Birds

166
Q

low levels of metabolizing enzymes

A

Fish

167
Q

Enzyme inducers

A

Drugs that stimulate the liver to produce more metabolic enzymes

Ex: phenobarb, phenylbutazone, griseofulvin, rifampin

168
Q

Enzyme inhibitors

A

Drugs that inhibit the liver to produce metabolic enzymes

Ex: chloramphenicol, cimetidine, ketoconazole

-may lead to drug drug interactions

169
Q

Have less biotransformation then adults

A

newborns and geriatrics

170
Q

T/F:

Charcoal broiled foods are enzyme inducers

A

TRUE

CYP1A

171
Q

Grapefruit juice

A

Enzyme inhibitor (CYP3A)

172
Q

Malnutrition and undernutrition

A

may decrease biotransformation

Toxicology AF (1 decks)

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