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CLINICAL TOXICOLOGY > TOXICOKINETICS > Flashcards

TOXICOKINETICS Flashcards

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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
Which toxicant cause adverse effects at the site of exposure
Caustic and Corrosive toxicants
26
Movement of strongly acidic and basic substances and into urine and ph gradient in body systems occur by which method of absorption
Active transport
27
Factors affecting bioavailability
First pass metabolism - reduces P glycoprotein activity - reduces Enterohepatic circulation - enhances
28
Three types of capillaries
Sinusoïdal Fenestrated Continuous
29
Locations of fenestrated epithelium
Hepatic sinusoids Renal peritubular capillaries
30
Examples of organs with specialized barriers
Brain Placenta Testicles
31
Examples of specialized barriers
Oocyte - multiple layers of granulosa cells Spermatogenic cells - supported by tightly joined Sertoli cells
32
Which drugs bind to alpha 1 acid glycoprotein
Neutral and basic drugs
33
Which types of xenobiotics accumulate in the melanin containing cells off the retina and substantia nigra
Organic and inorganic cations Polycyclic aromatic hydrocarbons
34
Which compounds bind to keratin
Thiol reactive metal ions and metalloid compounds
35
Which substances accumulate in adipocytes
Highly lipophilic substances such as chlorinated hydrocarbon insecticides
36
Where does lead accumulate in the body
Deposited in bone by substituting calcium in hydroxyapatite
37
Specialized membrane transport for arsénite, lead or barium ions and thallous ions
Arsénite - Aquaglyceroporin channeled Lead or barium - VG Calcium channels Thallous ion - Na/K/ATPase
38
Specialized membrane transport for alpha amanitin, ochratoxin and mercuric ion and lipoprotein bound toxicants
Alpha amanitin - NTCP Ochratoxin and Mercuric ion - OAT1 and OAT3 Lipoprotein bound toxicants - Lipoprotein receptor
39
Substances that accumulate in cell organelles by ph trapping
Amphipathic compounds with a protonable amine group
40
Substances that accumulate in the cardiac mitochondria by electrophoretic trapping
Local Anaesthetics such as Tetracaine and Bupivacaine
41
Transporters that can export toxicant from cells
ABC transporters P-glycoprotein
42
Which enzyme involved in biotransformation has a slow rate in cats
Glucuronyl transferase
43
Transporters involved in tubule secretion
SLC family- basolateral uptake ABC carrier family - luminal uptake
44
Examples of Solute carrier family receptors
Organic acid transporters Organic base transporters OATP type (Organic anion transporting polypeptides)
45
Which substances are mostly secreted by renal tubules
Hydrophilic organic acids and bases
46
Factor affecting tubular reabsorption
Lipid solubility Molecule size
47
Examples of substances not efficiently removed by liver and kidneys
Nonvolatile highly lipophilic chemicals Polyhalogenated biphenyls and chlorinated hydrocarbon insecticides
48
The three processes for removing highly lipophilic nonvolatile substances
Excretion into mammary gland Excretion into bile Intestinal excretion into intestinal lumen
49
Morphine can be excreted into milk and amphetamine can be excreted into ———
Gastric juice
50
Four categories of enzyme systems
Hydrolysis Reduction Oxidation Conjugation
51
Which enzymes metabolize over half the orally effective drugs
CYP2D6 and CYP3A4
52
In which cases does phase 2 precede phase 1 metabolism
Xenobiotics that undergo direct conjugation such as paracetamol
53
Enzymes responsible for intermediary ( endobiotic) metabolism
Endobiotic metabolising enzymes
54
Enzymes involved in drug metabolism
CYP450 Hepatic microsomal flavin contain monooxygenases (MFMO or FMO) Monoamine oxidase Hydrolases
55
Which form of CYP450 absorbs maximally at 450nm and why
Reduced form due to the presence of bound CO
56
Location of CYP450
Smooth endoplasmic reticulum
57
How does CYP450 act as electron donor and acceptor
Changing the oxidation stage of bound iron between +2 and +3
58
Most abundant CYP450 enzymes in the liver
CYP3A4 CYP2Cx
59
Conjugation reactions
Glucuronidation Sulfonation Acetylation Methylation Conjugation with glutathione Conjugation with amino acids
60
Which conjugation reactions produce lipophilic products
Methylation Acetylation
61
Which conjugation reaction involve reactions with higher energy cofactors
Glucuronidation Acetylation Methylation Sulfonation
62
Which conjugation pathways involve reactions with activated xenobiotics
Conjugation with glutathione and amino acids
63
Most conjugation enzymes are located in the cytosol except——-
UDP GT which are microsomal
64
Enzyme, cofactor and transferred group in glucuronidation
Enzyme —- UDP GT Cofactor - UDP-GA Transferred group - Glucuronic acid
65
Enzyme, cofactor and transferred group in Sulfonation
Enzyme - Sulfonyltranaferses Cofactor - PAPS Transferred group - Sulfone
66
Enzyme, cofactor and transferred group in acetylation
Enzyme - N acetyl transferase Cofactor- Acetyl CoA Transferred group - acetyl
67
Enzyme, cofactor and transferred group in methylation
Enzyme - methyl transferase Cofactor - S-adenosylmethionine Transferred group- methyl
68
Which amino acids make up glutathione
Glutamate Cysteine Glycine
69
Which conjugation has high capacity but low affinity
Glucuronidation
70
Which conjugation has low capacity but high affinity
Sulfonation
71
Which amino acid conjugate with their carbonyl group and produce toxic metabolites
Proline Serine
72
Amino acids that conjugate with their amino ends producing benign metabolites
Taurine Glutamine Glycine
73
Which form of NAT is responsible for slow acetylators
Mutations in NAT2 gene
74
Slow acetylators exhibit higher incidence of adverse effects form which drugs
Clonazepam Procainamide Hydralazine Sulfonamides Isoniazid
75
Types of NAT
NAT1-Monomorphic NAT2-Polymorphic
76
Compound ma which are substrates for acetylation
Aromatic amines Hydrazines Hydrazines
77
Types of acetylators
Slow and fast acetylators
78
Which type of acetylators are predisposed to bladder cancers
Slow acetylators
79
Which type of acetylators are more predisposed to colon cancers form earring red meat
Fast acetylators
80
Causes of bladder and colon cancer
Bladder- Bicyclic aromatic amines from cigarette Colon- Heterocyclic aromatic amines from red meat
81
Substrates for the various methyltransferases
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
Examples of thiopurine drugs
Azathioprine 6-Mercapptopurine Thioguanine
83
Examples of reactive nucleophiles
HCN CO H2S N2
84
Examples of substances that can produce superoxide radical
Paraquat Nitrofurantoin Doxorubicin
85
Why avoid iron supplement during infection
Iron is involve in the Fenton reaction which generates the hydroxyl radical
86
Methods for détoxication of électrophiles
Conjugation with glutathione spontaneously or facilitated by glutathione s transferases
87
Detoxification of free radicals
Superoxide dismutase Catalase Glutathione peroxidase
88
Forms of Superoxide dismutase and the location
Cu and Zn SOD- Cytosolic Mn SOD- Mitochondrial
89
Examples of antioxidants which detoxify peroxyl radicals
Glutathione Vitamin E Vitamin C Uric acid
90
Examples of proteins that contain transition metal centers
Myoglobin Hemoglobin Cytochrome C
91
In which part of the body is uric acid an antioxidant and where is it a prooxidant
Antioxidant in plasma Prooxidant in cells
92
Why is cysteine not given in the pure form but given as N acetyl cysteine
Cysteine causes toxicity
93
Which enzyme is incapacitated by ONOO-
Mn-SOD

CLINICAL TOXICOLOGY (14 decks)

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