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CLINICAL TOXICOLOGY > TOXICOKINETICS > Flashcards

TOXICOKINETICS Flashcards

1
Q

What is toxicology

A

Study of poisons and their effects on humans or
Adverse effects of chemical or physical avens on living organisms

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2
Q

What was the state poison of the Greeks

A

Hemlock

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3
Q

A Chinese arrow poison

A

Aconite

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4
Q

Toxin Used both as a poison and an antidote

A

Opium

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5
Q

Who made the first attempt to classify poisons

A

Dioscorides

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6
Q

Who had an expeditious suicide poison hidden in his pen

A

Demosthenes

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7
Q

How did Cleopatra die

A

Falling on her asp

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8
Q

Who regularly ingested mixture of poisons to protect himself against assassination

A

Mithridates

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9
Q

Contribution of Hippocrates to toxicology

A

Talked about poisons Clinical toxicology principles pertaining to bioavailability in therapy and overdosage

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10
Q

Famous quote of Paracelsus pertaining to poisons

A

All things are poison and nothing is without poison only the dose makes a thing not a poison

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11
Q

Who is the modern father of toxicology

A

Mathieu Orfila

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12
Q

Why is Mathieu Orfila considered the father of modern toxicology

A

First toxicologist to use autopsy material SHS chemical analysis systematically as legal proof of poisoning

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13
Q

Branches of toxicology

A

Molecular
Environmental
Reproductive and Developmental
Regulatory
Clinical

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14
Q

How does toxicology contribute to physiology and pharmacology

A

Using toxic chemicals up understand physiological phenomena

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15
Q

What is a poison or toxicant

A

Interferes with homeostasis of organism or life processes of its cells but it’s one inherent qualities without acting mechanistically and irrespective of temperature

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16
Q

Hazardous vs Toxic

A

Hazardous - can cause harm
Toxic - produces adverse effects in living organisms

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17
Q

Poison vs Toxin vs Toxicant

A

Toxicant includes both toxins and poisons

Poisons - both natural and synthetic harmful substances

Toxin- natural only

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18
Q

Types of toxins

A

Zootoxin
Bacterial toxins - endotoxins and exotoxin
Phytotoxins
Mycotoxins

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19
Q

Toxicosis or poisoning

A

State of being poisoned

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20
Q

What is an ultimate toxicant

A

Chemical species that reacts with the endogenous target molecule

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21
Q

What species can act as the ultimate toxicant

A

Original chemical
Metabolite
Reactive oxygen or nitrogen species generated during biotransformation

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22
Q

Factors that promote delivery to target site

A

Absorption
Distribution toward target
Reabsorption
Toxication

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23
Q

Factors that reduce delivery to the target site

A

Presystemic elimination
Distribution away from the target
Excretion
Toxication

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24
Q

Intensity of a toxic effect depend primarily on ….. and …….

A

Concentration and persistence of the ultimate toxicant at the site of action

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25
Q

Which toxicant cause adverse effects at the site of exposure

A

Caustic and Corrosive toxicants

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26
Q

Movement of strongly acidic and basic substances and into urine and ph gradient in body systems occur by which method of absorption

A

Active transport

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27
Q

Factors affecting bioavailability

A

First pass metabolism - reduces
P glycoprotein activity - reduces
Enterohepatic circulation - enhances

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28
Q

Three types of capillaries

A

Sinusoïdal
Fenestrated
Continuous

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29
Q

Locations of fenestrated epithelium

A

Hepatic sinusoids
Renal peritubular capillaries

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30
Q

Examples of organs with specialized barriers

A

Brain
Placenta
Testicles

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31
Q

Examples of specialized barriers

A

Oocyte - multiple layers of granulosa cells
Spermatogenic cells - supported by tightly joined Sertoli cells

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32
Q

Which drugs bind to alpha 1 acid glycoprotein

A

Neutral and basic drugs

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33
Q

Which types of xenobiotics accumulate in the melanin containing cells off the retina and substantia nigra

A

Organic and inorganic cations
Polycyclic aromatic hydrocarbons

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34
Q

Which compounds bind to keratin

A

Thiol reactive metal ions and metalloid compounds

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35
Q

Which substances accumulate in adipocytes

A

Highly lipophilic substances such as chlorinated hydrocarbon insecticides

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36
Q

Where does lead accumulate in the body

A

Deposited in bone by substituting calcium in hydroxyapatite

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37
Q

Specialized membrane transport for arsénite, lead or barium ions and thallous ions

A

Arsénite - Aquaglyceroporin channeled

Lead or barium - VG Calcium channels

Thallous ion - Na/K/ATPase

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38
Q

Specialized membrane transport for alpha amanitin, ochratoxin and mercuric ion and lipoprotein bound toxicants

A

Alpha amanitin - NTCP
Ochratoxin and Mercuric ion - OAT1 and OAT3
Lipoprotein bound toxicants - Lipoprotein receptor

39
Q

Substances that accumulate in cell organelles by ph trapping

A

Amphipathic compounds with a protonable amine group

40
Q

Substances that accumulate in the cardiac mitochondria by electrophoretic trapping

A

Local Anaesthetics such as Tetracaine and Bupivacaine

41
Q

Transporters that can export toxicant from cells

A

ABC transporters
P-glycoprotein

42
Q

Which enzyme involved in biotransformation has a slow rate in cats

A

Glucuronyl transferase

43
Q

Transporters involved in tubule secretion

A

SLC family- basolateral uptake
ABC carrier family - luminal uptake

44
Q

Examples of Solute carrier family receptors

A

Organic acid transporters
Organic base transporters
OATP type (Organic anion transporting polypeptides)

45
Q

Which substances are mostly secreted by renal tubules

A

Hydrophilic organic acids and bases

46
Q

Factor affecting tubular reabsorption

A

Lipid solubility
Molecule size

47
Q

Examples of substances not efficiently removed by liver and kidneys

A

Nonvolatile highly lipophilic chemicals
Polyhalogenated biphenyls and chlorinated hydrocarbon insecticides

48
Q

The three processes for removing highly lipophilic nonvolatile substances

A

Excretion into mammary gland
Excretion into bile
Intestinal excretion into intestinal lumen

49
Q

Morphine can be excreted into milk and amphetamine can be excreted into ———

A

Gastric juice

50
Q

Four categories of enzyme systems

A

Hydrolysis
Reduction
Oxidation
Conjugation

51
Q

Which enzymes metabolize over half the orally effective drugs

A

CYP2D6 and CYP3A4

52
Q

In which cases does phase 2 precede phase 1 metabolism

A

Xenobiotics that undergo direct conjugation such as paracetamol

53
Q

Enzymes responsible for intermediary ( endobiotic) metabolism

A

Endobiotic metabolising enzymes

54
Q

Enzymes involved in drug metabolism

A

CYP450

Hepatic microsomal flavin contain
monooxygenases (MFMO or FMO)

Monoamine oxidase

Hydrolases

55
Q

Which form of CYP450 absorbs maximally at 450nm and why

A

Reduced form due to the presence of bound CO

56
Q

Location of CYP450

A

Smooth endoplasmic reticulum

57
Q

How does CYP450 act as electron donor and acceptor

A

Changing the oxidation stage of bound iron between +2 and +3

58
Q

Most abundant CYP450 enzymes in the liver

A

CYP3A4
CYP2Cx

59
Q

Conjugation reactions

A

Glucuronidation
Sulfonation
Acetylation
Methylation
Conjugation with glutathione
Conjugation with amino acids

60
Q

Which conjugation reactions produce lipophilic products

A

Methylation
Acetylation

61
Q

Which conjugation reaction involve reactions with higher energy cofactors

A

Glucuronidation
Acetylation
Methylation
Sulfonation

62
Q

Which conjugation pathways involve reactions with activated xenobiotics

A

Conjugation with glutathione and amino acids

63
Q

Most conjugation enzymes are located in the cytosol except——-

A

UDP GT which are microsomal

64
Q

Enzyme, cofactor and transferred group in glucuronidation

A

Enzyme —- UDP GT
Cofactor - UDP-GA
Transferred group - Glucuronic acid

65
Q

Enzyme, cofactor and transferred group in Sulfonation

A

Enzyme - Sulfonyltranaferses
Cofactor - PAPS
Transferred group - Sulfone

66
Q

Enzyme, cofactor and transferred group in acetylation

A

Enzyme - N acetyl transferase
Cofactor- Acetyl CoA
Transferred group - acetyl

67
Q

Enzyme, cofactor and transferred group in methylation

A

Enzyme - methyl transferase
Cofactor - S-adenosylmethionine
Transferred group- methyl

68
Q

Which amino acids make up glutathione

A

Glutamate
Cysteine
Glycine

69
Q

Which conjugation has high capacity but low affinity

A

Glucuronidation

70
Q

Which conjugation has low capacity but high affinity

A

Sulfonation

71
Q

Which amino acid conjugate with their carbonyl group and produce toxic metabolites

A

Proline
Serine

72
Q

Amino acids that conjugate with their amino ends producing benign metabolites

A

Taurine
Glutamine
Glycine

73
Q

Which form of NAT is responsible for slow acetylators

A

Mutations in NAT2 gene

74
Q

Slow acetylators exhibit higher incidence of adverse effects form which drugs

A

Clonazepam
Procainamide
Hydralazine
Sulfonamides
Isoniazid

75
Q

Types of NAT

A

NAT1-Monomorphic
NAT2-Polymorphic

76
Q

Compound ma which are substrates for acetylation

A

Aromatic amines
Hydrazines
Hydrazines

77
Q

Types of acetylators

A

Slow and fast acetylators

78
Q

Which type of acetylators are predisposed to bladder cancers

A

Slow acetylators

79
Q

Which type of acetylators are more predisposed to colon cancers form earring red meat

A

Fast acetylators

80
Q

Causes of bladder and colon cancer

A

Bladder- Bicyclic aromatic amines from cigarette
Colon- Heterocyclic aromatic amines from red meat

81
Q

Substrates for the various methyltransferases

A

COMT- dopamine, norepinephrine, METHYLDOPA
PNMT- norepinephrine to epinephrine
HNMT- Drugs that contain an imidazole ring
NNMT- Serotonin and Tryptophan
TPMT- Aromatic and Heterocyclic sulfhydryl compounds

82
Q

Examples of thiopurine drugs

A

Azathioprine
6-Mercapptopurine
Thioguanine

83
Q

Examples of reactive nucleophiles

A

HCN
CO
H2S
N2

84
Q

Examples of substances that can produce superoxide radical

A

Paraquat
Nitrofurantoin
Doxorubicin

85
Q

Why avoid iron supplement during infection

A

Iron is involve in the Fenton reaction which generates the hydroxyl radical

86
Q

Methods for détoxication of électrophiles

A

Conjugation with glutathione spontaneously or facilitated by glutathione s transferases

87
Q

Detoxification of free radicals

A

Superoxide dismutase
Catalase
Glutathione peroxidase

88
Q

Forms of Superoxide dismutase and the location

A

Cu and Zn SOD- Cytosolic

Mn SOD- Mitochondrial

89
Q

Examples of antioxidants which detoxify peroxyl radicals

A

Glutathione
Vitamin E
Vitamin C
Uric acid

90
Q

Examples of proteins that contain transition metal centers

A

Myoglobin
Hemoglobin
Cytochrome C

91
Q

In which part of the body is uric acid an antioxidant and where is it a prooxidant

A

Antioxidant in plasma
Prooxidant in cells

92
Q

Why is cysteine not given in the pure form but given as N acetyl cysteine

A

Cysteine causes toxicity

93
Q

Which enzyme is incapacitated by ONOO-

A

Mn-SOD

CLINICAL TOXICOLOGY (14 decks)

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