Chapter 5 lecture 7-8 Flashcards
What is Toxicodynamic?
- the relationship between the concentration of a toxicant at the site of action &
- the toxic effect at the level of molecule, cell, tissue, organ or organism.
- What the toxicant do to us
What are the factors influencing toxicity?
- Dosage
- Property
- Duration
What are the 7 factors affecting toxicity?
- Species
- Age & sex
- Exposure route
- Dosage, especially dose-time relationship
- ADME
- Form and innate chemical activity
- Presence of other chemicals
How is the toxic response varying between species?
- Differences in metabolism
- anatomical or physiological differences
What is selective toxicity?
- The difference between in toxicity
- Basis for pesticides and drugs
How does Age affect toxicity?
Some are more toxic to infants/elderly
* Parathion & Nitrosamines: More toxic & carcinogenic respectively to young animals.
How does Sex affect toxicity?
- Male rats are 10x sensitive than females for DDT
- Female rats are 2x sensitive for parathions
Why exposure route is influencing toxicity?
Difference in absorption and distribution. Eg. ingested -> GI-> Liver
Blood -> other organs -> Liver
Dosage is important for toxicity, T/F?
Of course true
Also, the the toxic mechanisms and target organs are different for acute and chronic toxicity
Ethanol : CNS depression :: Liver cirrhosis
Arsenic: GI damage :: Skin/Liver Cancer
How does Absorption affect toxicity?
- The ability to absorb
- The rate and extent of absorption
How ADME affect toxicity?
D: lipid solubility
M: Detox and bioactivation
E : Site and rate of excretion
Kidneys are the filter for blood serum, lipid-soluble toxicants are reabsorbed and concentrated in kidney cells.
How does “Form and innate chemical activity” affect toxicity?
Form: Different form different toxicity
Liquid mercury is more toxic than vapour
Innate chem: Some can quickly damage cells -> cell death
-hydrogen cyanide binds to cytochrome oxidase resulting in cellular hypoxia and rapid death
-nicotine binds to cholinergic receptors in the CNS altering nerve conduction and inducing gradual onset of paralysis
Organ specific toxicity vs Systemic toxicity
Specific at target oragn 1 site vs Toxic effects can be multiple sites
The acute, sub, chronic toxicity are under systemic toxicity.
Describe the systemic toxic effect: Carcinogenicity.
- Initiation: normal cell undergoes irreversible change-> mutation change DNA
- Promotion: Promote mutated cells to progress to cancer
Recall what are tumor, benign tumours and malignant tumors
- tumor is simply an uncontrolled growth of cells
- Benign tumors grow at the site of origin; do not invade adjacent tissues or metastasize; and generally, are treatable.
- Malignant tumors (cancer) invade adjacent tissues or migrate to distant sites (metastasis). They are more difficult to treat and often cause death.
Describe systemic toxic effect: Developmental toxicity
- adverse toxic effects to the developing embryo or fetus.
- result fromparent before conception or to the mother and her developing embryo-fetus.
What are the 3 types of developmental toxicity?
- Embryolethality: Failure to conceive, spontaneous abortion or stillbirth
- Embryotoxicity: Growth retardation, or delayed growth of specific organ systems
- Teratogenicity : Irreversible conditions that leave permanent birth defects in living offstring (e.g. missing limbs)
How is developmental toxicity developed?
- Act directly on embryo cells
- Induce mutation in parent’s germ cells
Describe systemic toxic effects:
Genetic Toxicity
results from damage to DNA and altered genetic expression
What are the 3 types of genetic toxicity?
- Gene mutation
- Chromotion aberration: Alter chromosome structure
- Aneuploidy/polyploidy: Decrease/Increase Chromosome no.
What are the 3 types of genetic toxicity?
- Gene mutation
- Chromotion aberration: Alter chromosome structure
- Aneuploidy/polyploidy: Decrease/Increase Chromosome no.
Name some examples of blood and cardiovascular toxicity
-hypoxia due to carbon monoxide binding of hemoglobin preventing transport of oxygen
-decrease in circulating leukocytes due to chloramphenicol damage to bone marrow cells
-leukemia due to benzene damage of bone marrow cells
-arteriosclerosis due to cholesterol accumulation in arteries and veins
Give some examples of dermal toxicity
-dermal irritation due to skin exposure to gasoline
-dermal corrosion due to skin exposure to sodium hydroxide
-dermal hypersensitivity due to skin exposure to poison ivy
-skin cancer due to ingestion of arsenic or skin exposure to UV light
Give some examples of eye toxicity
Cornea and conjunctiva directly exposed to toxicants
* Conjunctivitis and cornea erosion
-acids and strong alkalis may cause severe corneal corrosion
-corticosteroids may cause cataracts
-methanol (wood alcohol) may damage the optic nerve
Give some examples of hepatoxicity
toxicity to the liver, bile duct, and gall
bladder
* Cirrhosis-> chronic fibrosis of liver due to alcohol
Give some examples of immunotoxicity
Toxicity to immune system
-contact dermatitis due to exposure to poison ivy
-systemic lupus erythematosus in workers exposed to hydrazine
-immunosuppression by cocaine
-leukemia induced by benzene
Why are kidneys highly susceptible?
- High volume of blood flow
- Filtrates a large amount of toxins
Give examples of Nephrotoxicity
-decreased ability to excrete body wastes
-inability to maintain body fluid and electrolyte balance
-decreased synthesis of essential hormones (e.g.,
erythropoietin)
Give examples of Neurotoxicity
Damage to CNS and PNS
-neuronopathies (neuron injury)
-axonopathies (axon injury)
-demyelination (loss of axon insulation)
-interference with neurotransmission
Give examples of Reproductive toxicity
Target reproductive systems
-decreased libido and impotence
-infertility
-interrupted pregnancy (abortion, fetal death, or premature
delivery)
-infant death or childhood morbidity
-altered sex ratio and multiple births
-chromosome abnormalities and birth defects
-childhood cancer
Give examples of Respiratory toxicity
UPPER & LOWER respiratory system
-pulmonary irritation
-asthma/bronchitis
-reactive airway disease
-emphysema
-allergic alveolitis
-fibrotic lung disease
-pneumoconiosis
-lung cancer
