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mechanism of disease > Principles Of Toxicology > Flashcards

Principles Of Toxicology Flashcards

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1
Q

Toxicology

A

Study of adverse effects of xenobiotics on living organisms

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2
Q

Hippocrate participation in toxicology

A

Added number of poisons and clinical toxicology principles pertaining to bioavailability in therapy and overdosage

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3
Q

Paracelsus participation in toxicology

A

Found toxicon As a chemical entity

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4
Q

Divisions of Toxicology

A 
Descriptive
 risk assessment 
mechanistic 
informational
 regulatory
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5
Q

Descriptive toxicology

A

Involves experiments to provide standards toxicological data

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6
Q

Mechanistic toxicology

A

Identification and understanding of cellular biochemical and molecular mechanism by which chemicals exert toxic affects on organisms

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7
Q

Risk assessments toxicology

A

Demonstration of an adverse outcome observed in laboratory animals and to see if it’s directly relevant to humans

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8
Q

Informational toxicology

A

Collection collation dissemination of toxicological information

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9
Q

Regulatory toxicology

A

Evaluation of is enable data to make decision about application

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10
Q

Toxin

A

Toxic substances produced by biological system such as plants animals fungi or bacteria

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11
Q

Toxicant

A

Toxic substances produced by all my projects of anthropogenic activities

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12
Q

Is zeralanone a toxin or a toxicant

A

Toxin because produced by mold

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13
Q

Is dioxin a toxin or toxicant

A

Toxicant because produced by combustion if chlorinated organic chemicals

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14
Q

Toxic agents classification

A

Physical states
chemical stability or reactivity
general chemical structure
poisoning potential

Biochemical mechanism of action

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15
Q

Toxicity

A

Property of an agent to adversely affect an organism

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16
Q

Hazard

A

Potential for toxicity of an agent to be realized in a particular situation

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17
Q

Risk

A

Probability that a hazard will be realized

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18
Q

Safety

A

Probability that hazard will not be realized

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19
Q

Undesired effect

A

In therapeutics drugs address a primary objective so all the other effects Are referred as undesirable

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20
Q

Diphenhydramine side effects

A

Used to reduce histamine response in allergies but can cause CNS depression

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21
Q

Deleterious side effect

A

Never desirable side effect

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22
Q

Type of toxic reactions

A

Pharmacological
pathological
genotoxic

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23
Q

Allergic reactions

A

Adverse reaction from sensitization to particular chemical or to a similar one

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24
Q

Do you have dose response relationship in allergic reaction

A

No

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25
Four types of hyper sensitivity
Type one anaphylactic mediated by IGE antibodies Type two cytolytic reaction mediated by IgG and IGM antibodies By activating complement system Type three or arthus reaction mediated by IgG with generation of antigen antibody complexes which will fix complements Type 4 or delayed hypersensitivity due to T lymphocytes and macrophages
26
Main target of type one hypersensitivity
G.I. tract - food allergies skin - urticaria , atopic dermatitis respiratory system - rhinitis is asthma Vasculature - anaphylactic shock
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Examples of type two allergic response is
Penicillin hemolytic anemia Methyldopa autoimmune hemolytic anemia Quinidine thrombocytopenic purpura Sulfonamide granulocytopenia
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Serum sickness caused by
Type iii hypersensitivity
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Idiosyncratic forms
Extreme sensitivity to low Dose Extreme insensitivity to high doses
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Descriptives of response
Local vs systemic Reversible vs irreversible Immediate vs delayed Graded vs quantal
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System most affected in order of frequency
``` CNS Heart Circulatory system Blood Hematopoietic system ```
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Chemical carcinogens types
Genotoxic Non genotoxic
33
Test used to screen for carcinogenicity
Mutagenicity test ( Ames test with salmonella typhimuriumwith enzyme phosphoribosyl ATP Synthétase required for histidine synthesis Test on lab rodents with chemical at high dosage and autopsy at death
34
Drugs interactions
Competition at receptor ( atropine and organophosphate) Non receptor interaction (heparin and aspirin causing bleeding )
35
Additive effect of two drugs
Equals the sum of the effects of each agent given alone | 2+3=5
36
Synergistic effect of drugs
Combines effects of two chemicals exceeds the sum of the effects of each agents given alone (3+2=20)
37
Potentiation of drugs
Increased effects of ataxic agents acting simultaneously with a non toxic one
38
Antagonism
Interference of one chemical with action of another
39
Functional or physiological antagonism
To chemicals produce opposite effect on the same physiological function
40
Chemical antagonism or inactivation
Reaction between two chemicals to neutralize their effects
41
Dispositional antagonism
Alteration of the disposition of a substance so that less of the agents reaches the target organ or it’s persistence there is reduced
42
Receptor antagonism
Blockades of the effects of an | Agonist with an appropriate antagonist that competes for the same site
43
Tolerance
Decreased responsiveness to a toxic effects of a chemical resulting from prior exposure to that chemical or to a structurally related chemical
44
To mechanisms of Tolerance
Decreased amount of toxicant reaching sites where toxic effect is produced Reduced responsiveness of tissue to the chemical
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2 chemicals that produce dispositional tolerance
``` Carbon tetrachloride (tolerance to itself by reducing formation of reactive metabolite ) cadmium (bind to metallithionein rather than macromolecules ) ```
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Major factors of exposure that influence toxicity
Route of exposure duration of exposure frequency of exposure
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Type of routes and sites of exposure
Ingestion Inhalation Dermal topical Injection
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Units of amount of chemical entering the body dose
Milligram per kilogram
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Doseis dependent upon
``` Environmental concentration properties of the toxicant frequency of exposure length of exposure exposure pathway ```
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As those of a toxicants increases , the response …
Also increases
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ED50
Effective dose At which 50% of the population showed a response
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LD50
Lethal dose to 50% of population
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Therapeutic index
Ratio of dose required to produce a toxic effects and the dose needed to elicit the desired therapeutic response
54
Margin of safety
Toxic dose 1% over effective dose 99%
55
Paradigms of adverse effects
``` On target Off target Drug producing toxic metabolites Drug stimulating certain immune response Idiosyncratic responses ```
56
On target toxic effect
Exaggeration of the desired pharmacologic effect
57
On target toxic effect causes
Overdosing alterations in PK Changes in drug receptor interaction
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Off target Toxic effects
Drug interacts with unintended target
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Example of a drug with an off target toxic affects
Terfenadine antihistamine inhibits also cardiac K+ channel leading to fatal cardiac arrythmias Rafemic thalidomide , R enantiomer was effective sedative and S Enantiomer a teratogen B adrénergiques antagonists used for B1 on heart cause bronchonstriction at B2
60
Drugs with production of toxic metabolites example
Acetaminophen metabolized by glucuronidation and sulfation CYP450 forms n acetyl benzoquinoneimime Which is directly conjugated to glutathione depleting glutathione when acetaminophen above therapeutics range Accumulation of n acetyl benzoquinoneimine forms toxic proteins to liver
61
Drugs with harmful immune responses
Some drugs can act as haptens When bind to protein in the body, trigger immune response Some drugs already large enough to trigger directly immune response
62
Two principal immune mechanism of drug that produce adverse effects
Hypersensitivity responses | Autoimmune reaction
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Drugs involved in type one hypersensitivity reaction
Penicillin acting like hapten
64
Drugs involved in type 2 hypersensitivity reactions
Penicillin | Quinidine
65
Drugs involved in type three hypersensitivity reactions
Buproprion | Cefaclor
66
Direct involved in type 4hypersensitivity reaction
Ciprofloxacin
67
Drugs that can initiate auto immunity responses
Methyldopa- can cause hemolytic anemia by attacking rhesus Hydralazine Isoniazid Procainamide
68
Idiosyncratic toxicity
Drugs with toxicity that the mechanism is difficult to explain

mechanism of disease (22 decks)

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