Introduction Material Flashcards
(172 cards)
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
2
Q
Most common poisoning in dogs?
A
Human food and drugs (legal and illegal).
3
Q
Diagnosis and Treatment
A
Main aspects of clinical Tox
4
Q
Drugs can be poisons and poisons can be drugs…. The difference is
A
The dose (Dose or amount of exposure)
5
Q
Drugs and Poisons are….
A
Xenobiotics (foreign chemicals that the body does not produce)
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
7
Q
Natural Poisons
A
Plant Animals (venom, insect sting, fish toxin) Minerals (lead, zinc) Fungi or bacteria (mycotoxin)
8
Q
Organophosphate and chlorinated hydrocarbon insecticides, organic herbicides are…
A
Synthetic Poisons
9
Q
Toxin
A
BIOTOXIN!! Poison from a biologic process (zootoxins or animal toxins, phytotoxins or plant toxins, bacterial toxins and mycotoxins)
10
Q
Toxicant
A
Can be living or non-living
11
Q
Deleterious or undesirable effects of poisons
A
Toxic
12
Q
Disease caused by exposure to a poison
A
Toxicosis (Poisoning or intoxication)
13
Q
Toxicity
A
Amount of a poison that under certain circumstances will cause toxic effects
14
Q
Toxicity in mammals is
A
LD50 Mg/kg body weight
15
Q
Toxicity in Birds….
A
LC50 (lethal concentration) Mg/kg FEED
16
Q
Toxicity in Fish….
A
LC50 Mg/liter WATER
17
Q
Effect of a single dose or multiple doses during a 24 hour period
A
Acute Toxicity
18
Q
Effect produced by daily exposure from one day to 30 days
A
Subacute Toxicity
19
Q
Effect of exposure from 30 days to 90 days
A
Subchronic Toxicity
20
Q
Effect produced by daily exposure for a period of 3 months or more
A
Chronic Toxicity
21
Q
Chronocity Factor
A
Ratio between acute LD50 and chronic LD50
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
23
Q
Extremely Toxic
A
= 1mg/kg or less
24
Q
Highly Toxic
A
> 1-50 mg/kg
25
Moderately Toxic
\> 50 - 500 mg/kg
26
Slightly Toxic
\> 0.5 - 5 g/kg
27
Practically Nontoxic
\> 5-15 g/kg
28
Relatively Harmless
\>15g/kg
29
Highest NonToxic Dose (HNTD)
The highest or largest dose which does not result in undesirable or toxic alterations (clinical, hematologic, biochemical, or pathologic alterations)
30
This is similar to the highest nontoxic dose
Maximum Tolerated Dose Or Minimal Toxic Dose (MTD)
31
Toxic Dose Low (TDL)
The lowest dose which produces toxic alterations and administering twice the dose will not cause death
32
Toxic Dose High (TDH)
The dose which produces toxic alterations and administering twice the dose WILL result in death
33
No Effect Level (Maximum Nontoxic Level)
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)
34
The dose that causes death in any animal during the period of observation
Lethal Dose
35
LD 0 (zero)
the highest dose that dose not cause any death
36
LD 50
The dose that kills 50% of the animals in the group
37
LD 100
The lowest dose that kills ALL the animals in a group
38
Hazard
Is the danger from the possibility of exposure
39
A poison may be _____ \_\_\_\_\_\_\_\_ but not \_\_\_\_\_\_\_\_\_
Highly Toxic , Hazardous
40
The risk factor can be calculated as the _______ between _______ and _____ \_\_\_\_\_\_
Ratio , toxicity , and use level
41
Toxicology is
The study of poisons (toxicants)
42
Parts per million (ppm) on weight/weight basis
Is the most common method of expressing concentrations in toxicology 1ppm = 1mg / kg
43
Converting from PPM to percent %
Move the decimal point 4 places to the left Ex: 1 ppm - 0.0001%
44
Convert from Percent % to PPM
Move the decimal point 4 places to the right Ex: 0.0001% --\> 1 ppm
45
Diluted Solution from Stock
The mL needed = (% required dilution / % stock ) x required in mL Ex: (2.5% diluted / 50% stock) x 500 mL =
46
Feed to PPM
100g/ton = 110ppm
47
The study of movement of drugs in the body across biological membranes from the time of absorption until elimination
Drug Disposition
48
What are the Stages of Drug Disposition
Absorption Distribution Biotransformation Excretion
49
Biological Cell Membrane
Composed of lipid by layer Contain membrane proteins and carbohydrates There are aqueous pores or junctions between cells
50
Transmembrane movement of water is either by _________________ through aqueous channels or by flow resulting from\_\_\_\_\_\_\_\_\_ or ____________ difference across the membrane
Passive diffusion, osmotic, hydrostatic
51
Paracellular transport of water is through...
Intracellular aqueous pores
52
Tissues that have a barrier mechanism have..
"Tight" intracellular junctions
53
Bulk flow of water can carry...
Small water soluble substances
54
Concentration Gradient
Drugs move across membranes from high concentration to low concentration
55
Lipid Solubility is measured by
Lipid partition coefficient ( the ratio between solubility of drug in lipid to its solubility in water)
56
The higher the lipid solubility the....
Faster the drug crosses the membranes
57
Drugs cross membranes in the
Non-ionized form (Lipid soluble and do not carry electric charge)
58
The rate of diffusion depends on the ratio between the ____________ of the drug to the ____________ form.
(N/I) Non-ionized, ionized
59
Ionization of a drug depends on...
PH of the drug Pka of the drug PH of the medium (environment)
60
The pKa of a drug is the pH at which a weak electrolyte is
50% ionized and 50% non-ionized
61
Most drugs are
Weak electrolytes (weak acids or weak bases)
62
Acidic drugs ionized in __________ medium and basic drugs ionized in \_\_\_\_\_\_\_\_\_\_\_medium
Alkaline, acidic
63
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
Higher, higher
64
Quaternary ammonium compounds like d-tubocurarine are
Mostly ionized
65
Phenylbutazone
A weak acid mostly ionized in the stomach
66
Facilitated Diffusion
A carrier mediated transport that DOES NOT NEED ENERGY
67
In facilitated diffusion a drug moves across the membrane from high to low concentration...
At a faster rate (downhill movement)
68
In facilitated diffusion, transporters can move
Drugs from outside the cell to inside or from inside to outside
69
Facilitated diffusion Transporters may act as a _______________ to protect cells from toxic substances by ....
Barrier system Moving them from inside to outside of the cell
70
Movement of glucose across a muscle cell membrane by insulin sensitive glucose transporters is an example of
Facilitated Diffusion
71
In active transport, a drug moves across the membrane from
Low concentration to High concentration (uphill movement)
72
Active transport is a carrier mediated transport
That requires energy
73
Primary active transport uses energy directly from
ATP such as Na/K ATPase
74
Secondary Active Transport
Uses stored energy in the Na electrochemical gradient
75
Active transport is characterized by
Saturability, selectivity, and competitive inhibition by cotransported compounds
76
Specific type of endocytosis where the cell engulfs the drug molecules dissolved in water
Pinocytosis
77
The transport of drugs from the plasma to the tissues
Distribution
78
Factors that affect distribution of drugs
Physiochemical properties Concentration gradient Plasma protein binding Blood Flow Tissue barrier Drug affinity to tissues
79
Acidic drugs bind mainly to
Albumin
80
Basic drugs bind mainly to
Alpha 1 - glycoproteins and lipoproteins
81
What drugs bind to globulin
Steroids
82
Plasma protein binding
Prolongs the half life of the drug
83
Plasma protein binding is generally
Reversible
84
The bound form of the drug is
Inactive, so it cannot be distributed, metabolized or excreted
85
The rate of binding depends
On the amount of the drug
86
Plasma protein binding can be modified by
Disease
87
Highly perfused tissues
brain, liver, kidney, endocrine glands
88
Moderately perfused tissues
Muscle, skin
89
Poorly perfused tissues
Bone, adipose tissue
90
The Blood Brain Barrier (BBB)
- 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
Factors that limit the BBB...
Age Inflammation Trauma Allergic Rxn Severe hypotension Hypoxia High doses of organic solvents (alcohol) Heavy metals
92
Name some Tissue Barriers
Brain Eye Testicles Placenta Mammary glands
93
Tetracycline has an affinity to
Calcium in skeletal tissues
94
Aminoglycosides have an affinity to
Kidney tissue
95
The thyroid gland traps
Iodine
96
The movement of the drug from the tissue to the blood
Redistribution
97
The chemical alteration of the drug molecule by the cells of the animal
Metabolism (biotransformation)
98
Parts per million (ppm) on weight/weight basis
Is the most common method of expressing concentrations in toxicology 1ppm = 1mg / kg
99
Converting from PPM to percent %
Move the decimal point 4 places to the left Ex: 1 ppm - 0.0001%
100
Convert from Percent % to PPM
Move the decimal point 4 places to the right Ex: 0.0001% --\> 1 ppm
101
Diluted Solution from Stock
The mL needed = (% required dilution / % stock ) x required in mL Ex: (2.5% diluted / 50% stock) x 500 mL =
102
Feed to PPM
100g/ton = 110ppm
103
The study of movement of drugs in the body across biological membranes from the time of absorption until elimination
Drug Disposition
104
What are the Stages of Drug Disposition
Absorption Distribution Biotransformation Excretion
105
Biological Cell Membrane
Composed of lipid by layer Contain membrane proteins and carbohydrates There are aqueous pores or junctions between cells
106
Transmembrane movement of water is either by _________________ through aqueous channels or by flow resulting from\_\_\_\_\_\_\_\_\_ or ____________ difference across the membrane
Passive diffusion, osmotic, hydrostatic
107
Paracellular transport of water is through...
Intracellular aqueous pores
108
Tissues that have a barrier mechanism have..
"Tight" intracellular junctions
109
Bulk flow of water can carry...
Small water soluble substances
110
Concentration Gradient
Drugs move across membranes from high concentration to low concentration
111
Lipid Solubility is measured by
Lipid partition coefficient ( the ratio between solubility of drug in lipid to its solubility in water)
112
The higher the lipid solubility the....
Faster the drug crosses the membranes
113
Drugs cross membranes in the
Non-ionized form (Lipid soluble and do not carry electric charge)
114
The rate of diffusion depends on the ratio between the ____________ of the drug to the ____________ form.
(N/I) Non-ionized, ionized
115
Ionization of a drug depends on...
PH of the drug Pka of the drug PH of the medium (environment)
116
The pKa of a drug is the pH at which a weak electrolyte is
50% ionized and 50% non-ionized
117
Most drugs are
Weak electrolytes (weak acids or weak bases)
118
Acidic drugs ionized in __________ medium and basic drugs ionized in \_\_\_\_\_\_\_\_\_\_\_medium
Alkaline, acidic
119
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
Higher, higher
120
Quaternary ammonium compounds like d-tubocurarine are
Mostly ionized
121
Phenylbutazone
A weak acid mostly ionized in the stomach
122
Facilitated Diffusion
A carrier mediated transport that DOES NOT NEED ENERGY
123
In facilitated diffusion a drug moves across the membrane from high to low concentration...
At a faster rate (downhill movement)
124
In facilitated diffusion, transporters can move
Drugs from outside the cell to inside or from inside to outside
125
Facilitated diffusion Transporters may act as a _______________ to protect cells from toxic substances by ....
Barrier system Moving them from inside to outside of the cell
126
Movement of glucose across a muscle cell membrane by insulin sensitive glucose transporters is an example of
Facilitated Diffusion
127
In active transport, a drug moves across the membrane from
Low concentration to High concentration (uphill movement)
128
Active transport is a carrier mediated transport
That requires energy
129
Primary active transport uses energy directly from
ATP such as Na/K ATPase
130
Secondary Active Transport
Uses stored energy in the Na electrochemical gradient
131
Active transport is characterized by
Saturability, selectivity, and competitive inhibition by cotransported compounds
132
Specific type of endocytosis where the cell engulfs the drug molecules dissolved in water
Pinocytosis
133
The transport of drugs from the plasma to the tissues
Distribution
134
Factors that affect distribution of drugs
Physiochemical properties Concentration gradient Plasma protein binding Blood Flow Tissue barrier Drug affinity to tissues
135
Acidic drugs bind mainly to
Albumin
136
Basic drugs bind mainly to
Alpha 1 - glycoproteins and lipoproteins
137
What drugs bind to globulin
Steroids
138
Plasma protein binding
Prolongs the half life of the drug
139
Plasma protein binding is generally
Reversible
140
The bound form of the drug is
Inactive, so it cannot be distributed, metabolized or excreted
141
The rate of binding depends
On the amount of the drug
142
Plasma protein binding can be modified by
Disease
143
Highly perfused tissues
brain, liver, kidney, endocrine glands
144
Moderately perfused tissues
Muscle, skin
145
Poorly perfused tissues
Bone, adipose tissue
146
The Blood Brain Barrier (BBB)
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
Factors that limit the BBB...
Age Inflammation Trauma Allergic Rxn Severe hypotension Hypoxia High doses of organic solvents (alcohol) Heavy metals
148
Name some Tissue Barriers
Brain Eye Testicles Placenta Mammary glands
149
Tetracycline has an affinity to
Calcium in skeletal tissues
150
Aminoglycosides have an affinity to
Kidney tissue
151
The thyroid gland traps
Iodine
152
The movement of the drug from the tissue to the blood
Redistribution
153
The chemical alteration of the drug molecule by the cells of the animal
Metabolism (biotransformation)
154
What are the changes in physiological properties of a drug as a result of biotransformation
The metabolite is more water soluble, polar and ionized
155
Changes in pharmacological activity as a result of biotransformation
Bioinactivation or detoxification (most drugs)
Bioactivation or lethal synthesis (few drugs)
156
Sites of Biotransformation
\***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
Phase I reactions
Oxidation
Reduction
Hydrolysis
158
Phase II Reactions
Conjugation
159
Factors Altering Biotransformation
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
Cats are deficient in...
glucuronyl transferases
hydroxylation
dealkylation
161
Dogs lack....
acetylating enzymes
162
Ruminants have _________________ than horses, dogs, and cats
less plasma pseudochoinesterases
163
What species have high levels of oxidative enzymes
Ruminants and horses
164
Species deficient in sulfate conjugating enzymes
pigs
165
Lacks oxidative enzymes
Birds
166
low levels of metabolizing enzymes
Fish
167
Enzyme inducers
Drugs that stimulate the liver to produce more metabolic enzymes
Ex: phenobarb, phenylbutazone, griseofulvin, rifampin
168
Enzyme inhibitors
Drugs that inhibit the liver to produce metabolic enzymes
Ex: chloramphenicol, cimetidine, ketoconazole
-may lead to drug drug interactions
169
Have less biotransformation then adults
newborns and geriatrics
170
T/F:
Charcoal broiled foods are enzyme inducers
TRUE
CYP1A
171
Grapefruit juice
Enzyme inhibitor (CYP3A)
172
Malnutrition and undernutrition
may decrease biotransformation
