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Fundamentals of Toxicology > Unit 2 Mechanisms > Flashcards

Unit 2 Mechanisms Flashcards

1
Q

Renal Tox: Cadmium

A

Cd binds to MT in the liver -> Cd blocks receptors in the kidney -> Cd increases -> **inhibits ETC ** -> mitochondrial dysfunction -> ROS -> apoptosis

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2
Q

Renal Tox: Silica

A

Silica inhalation -> Silica accumulates in the Proximal Convulated Tubule -> Mitochondrial dysfunction
-> ROS -> inflammation -> fibrosis -> chronic kidney damage -> decreased eGFR

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3
Q

Renal Tox: NSAIDS

A
  • Glomerular toxicant
  • **Cox-2 **inhibits PGE2 -> vasoconstriction -> decreased eGFR
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4
Q

Liver Tox: Acetaminophen (APAP)

A
  • APAP metabolized into NAPQI -> decreased GSH -> protein adducts -> ROS -> necrosis -> DAMPS -> innate immune response -> inflammation -> tissue repair
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5
Q

Liver Tox: TCE

A

TCE is metabolized into TCE epoxide -> acyl chloride -> reactive aldehyde -> irreversibly binds to DNA and proteins -> genotoxicity

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6
Q

Liver Tox: CCL4

A

Necrosis -> Fibrous -> Cirrohosis

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7
Q

Liver Tox: Ethanol

A

Ethanol -> ADH -> Aldehyde -> Acetic Acid -> Excreted

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8
Q

Liver Tox: Ethanol Overdose

A

Ethanol metabolized by CYP450 -> ROS -> mitochondrial dysfunction -> apoptosis

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9
Q

Liver Tox: APAP and Ethanol

A
  • Ethanol is metabolized by CYP450
  • APAP metabolized into NAPQI -> protein adducts -> ROS -> mitochondrial dysfunction -> necrosis

NAC -> Increases depleted GSH

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10
Q

Respiratory Tox: Silica

A

Silica inhalation -> immune response -> proteolytic enzyme release -> cytokine release -> chronic inflammation -> fibroblast proliferation -> fibrosis

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11
Q

Respiratory Tox: Coal Dust

A

Coal dust inhaltion -> immune response -> chronic exposure -> alveolar wall injury -> emphysema (alveoli lung damage, shortness of breath)

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12
Q

Respiratory Tox: Asbestos

A

Asbestos inhalation -> immune response -> chronic inflammation -> mitochondrial dysfunction -> ROS -> dna damage -> high cell turn over rate -> mutations -> cancer

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13
Q

Respiratory Tox: PM 2.5

A
  • Small, toxic particulate matter that damages the alveolar region of the lungs
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14
Q

Respiratory Tox: ARDS - DAD

A
  • Exudative (alveolar-capillary barrier damage -> edema)
  • Proliferative (edema reabsorbed -> recovery of alveolar-capillary barrier)
  • Fibrotic (recovery not possible, decreased lung compliance)
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15
Q

Respiratory Tox: ARDS - DAD Mechanism

A

Hyperoxia damages ATI pneumocytes and alveolar macrophages -> ROS -> macrophages release neutrophil chemotactic compounds -> neutrophil recruitment -> lung tissue damage

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16
Q

Respiratory Tox: High Pb

A

High Pb -> more blood soluble -> slower onset and offset time

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17
Q

Respiratory Tox: Lower Pb

A

Lower Pb -> less blood soluble -> faster onset and offset

18
Q

Cardio Tox: Blood Flow

A

RA -> Tricuspid Valve -> RV -> Pulmonary Valve -> Lungs -> LA -> Mitral Valve -> LV -> Aorta -> Body

**Exception: Deoxygenated blood from the heart to the veins via the Pulmonary Artery **

19
Q

Cardio Tox: Doxorubicin

A
  • Inflammatory response -> macrophages
20
Q

Cardio Tox: TCA

A

TCA -> HERG channel inhibitor -> QT prolongation -> heart arrythmia

21
Q

Cardio Tox: Glycosides

A

Glycosides -> Na/K ATPase inhibitor -> increase in Ca 2+
-> mitochondrial dysfunction -> ROS -> protein adducts

22
Q

Cardio Tox: Action Potentials

A

Na⁺ influx (Phase 0) → K⁺ efflux + Cl⁻ (Phase 1) → Ca²⁺ influx / K⁺ efflux (Phase 2) → K⁺ efflux (Phase 3) → Stable K⁺ balance (Phase 4).

23
Q

Dermal Tox: Irritant Dermatitis

A
  • Low doses, multiple encounters
  • RXNS at skin point of contact
  • No immune response
  • Chemical burn (Ammonia)
24
Q

Dermal Tox: Allergic Irritant

A
  • Previous encounter needed
  • Type IV Hypersensitivy (Langerhan Cells -> T cells -> Th1)
  • Delayed RXN (48 hrs - 72 hrs)
  • Poison Ivy
25
Q

Dermal Tox: Major Skin Components

A
  • Epidermis (kertainocytes, langerhand cells, merkel cells, melanocytes)
  • Dermis (blood vessels, collagen, glands)
  • Hypodermis (adipose tissue)
26
Q

Dermal Tox: Absorption

A
  • Straneum Corenum -> Epidermis -> Dermis
  • Hydrophobic, Lipophilic
  • Molecular weight, concentration, duration
27
Q

Dermal Tox: UV Radiation DNA Damage

A
  • UV Radiation -> Thymine dimers -> DNA damage -> mutations -> Cox 1/2 activated -> PGE2 -> PGE2 binds EPI and EP4 receptors -> inflammation -> cell proliferation -> cancer
28
Q

Dermal Tox: Protoporphyria

A

Genetic defect inhibits heme production -> protoporphyria build up -> UV radiation interacts w/ protoporphyria and oxygen -> ROS -> protein adducts -> lipid peroxidase -> tissue damage

29
Q

Neuro Tox: Methyl Mercury

A

Sulfhydrl bindings -> ROS -> mitochondrial dysfunction -> inhibits glycolysis, protein and nucleic acid synthesis

30
Q

Neuro Tox: Domoic Acid

A

Increase in glutamate -> increase in Ca2+ -> mitochondrial dysfunction -> loss of ATP -> neuronal death

31
Q

Neuro Tox: Carbon disulfide/n-hexane

A
  • crosslinking neurofilament proteins -> adducts -> protein modification -> distal axonopathy
32
Q

Neuro Tox: Triethylin

A

Metabolic inhibitor -> mitochondrial dysfunction -> loss of ATP in the oligodendrocytes

33
Q

Neuro Tox: Colchicine/Taxol

A

destabilizies microtubles/stabilizes microtubules

34
Q

Neuro Tox: Organophosphates

A

Organophosphates bind to Serine residue -> inhibits AchE from converting into Ach -> overstimulated nervous system

35
Q

Neuro Tox: Botox

A

Botox inhibits the release of Ach at the synapse by targeting and cleaving SNARE proteins -> muscle paralysis

36
Q

Neuro Tox: Cocaine and Amphetamine

A

blocks dopamine reuptake -> dopamine accumulates in the synpases -> ROS -> mitochondrial dysfunction -> neurodegeneration

37
Q

Immuno Tox: Innate

A
  • Fast, non specific
  • No memory
  • Macrophages, Neutrophils
  • Phagocytosis
38
Q

Immuno Tox: Adapative

A
  • Slow, specific
  • Memory
  • T cells -> B cells
39
Q

Immuno Tox: Hypersensitivity IV

A
  • Fast
  • Langerhan cells -> T cells -> Th1
40
Q

Immuno Tox: Hypersensitivy I

A

Fundamentals of Toxicology (2 decks)

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