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PHARM 100 > Module 6 - Environmental toxicology and Cancer > Flashcards

Module 6 - Environmental toxicology and Cancer Flashcards

1
Q

Environmental toxicants

A

defined as a chemical that is released into the environment and that can produce adverse health effects on living organisms

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2
Q

Acute vs chronic toxicity

A

acute toxicity: associated with a single exposure to a chemical and often a large dose of the chemical
- e.g. chemical spill

chronic toxicity: associated with repeated exposure to small doses of a chemical over a long period of time
- e.g. eating contaminated food

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3
Q

toxic effects of aflatoxin B1

A

aflatoxin B1 is a common food contaminant in Southeast Asia and Central Africa
- acute toxicity of aflatoxin B1 can result in liver necrosis, liver failure, and death, while chronic toxicity of aflatoxin B1 can cause liver cancer

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4
Q

Environmental toxicants

A
  1. air pollution
  2. tobacco smoke
  3. pesticides
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5
Q

Air pollution

A

2 main categories:
- particulate matter and gaseous air pollutants- a mixture of tiny particles composed of non-gaseous pollutants, can be solids or liquid droplets

- they are attributed to both natural and anthropogenic (human influence) sources - carbon monoxide, carbon dioxide, nitrogen oxides, sulfur oxides, hydrogen sulfide, and ozone
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6
Q

Sources of air pollutants

A

Natural air pollutants:
- volcanoes, forest and prairie fires, dust storms

Anthropogenic air pollutants (man-made):
- heating and power, automobiles, industrial processes

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7
Q

Human health and air pollutants

A
  • the predominant health effect associated with air pollution is chemical irritation of the respiratory tract
  • certain subpopulations are particularly susceptible to air pollution, including very young children, older adults, and people with cardiorespiratory disease such as asthma
  • in most cases, the health problem are due to the combined action or particles and sulfur oxides
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8
Q

Tobacco smoke

A

environmental tobacco smoke or second hand smoke is the combination of mainstream smoke and sidestream smoke

health risks of secondhand smoke:
- it has also been suggested that exposure to environmental tobacco smoke carries the same health risks as directly smoking

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9
Q

Pesticides

A
  • unique because, unlike other pollutants, they are used to intentionally kill organisms
  • insecticides and herbicides are the two major classes of pesticides that act as environmental toxicants
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10
Q

Insecticides (2 types)

A

organochilorine insecticides:
- work by increasing the sensitivity of neurons, resulting in increased CNS stimulation that manifests as tremors, convulsions, and eventually, death
- organochlorine insecticide residues in humans, animals, and the environment can present long term problems that are not completely understood → as such they have been largely phased out (DTT)

organophosphorus insecticide:
- first synthesized in world war II to be used as potential warfare agents
- since then selective organophosphorus insecticides have been developed that require metabolic activation to work
- these agents are relatively unstable and break down in the environment, have a small impact on the environment
- they are very toxic to humans

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11
Q

Organophosphorus insecticide in humans

A

they are absorbed through the skin and are the leading cause of poisoning in the agricultural sector

mechanism of action:
- irreversibly inhibit acetylcholinesterase which are responsible for breaking down acetylcholine in the synaptic cleft

effects:
- if AchE inhibited, then acetylcholine is no longer broken down, leading to an increase in acetylcholine in the nervous tissue
- this results in increased acetylcholine-mediated neuronal firing throughout the body, resulting in decreased heart rate, severe difficulty breathing, fecal and urinary incontinence, and blurred vision
- death can occur due to respiratory failure

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12
Q

Herbicides (2 types)

A

agent orange:
- a mixture that was used extensively in the Vietnam war as a defoliant to make it easier to spot targets hidden by tree cover
- it acts by mimicking plant growth leading to plant death
- the major concern with this herbicide is the presence of a chemical called TCDD, which is introduced during the manufacturing process of agent orange

paraquat:
- highly toxic when ingested
- causes cellular damage and when ingested, it causes immediate burns to the mouth and stomach
- regardless of the route of entry, the primary target of paraquat toxicity is the lungs, where cellular damage results in the development of fibrous tissues that inhibit the ability to breathe

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13
Q

Toxicity of agent orange

A
  • TCDD binds to a receptor known as the aryl hydrocarbon receptor, which is involved in the expression of many genes required for normal cellular functioning
  • TCDD manifests as chloracne (a severe form of acne), impairment of liver and CNS function
  • TCDD toxicity is associated with an increased occurrence of certain cancers and may cause birth defects and stillbirths
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14
Q

Toxic effects of specific chemicals

A

lead: a ubiquitous, naturally occurring element found in the environment and in many different chemical compounds
- two main compounds containing lead are lead oxide and tetraethyl lead

found in: old paint, lead-acid car batteries, leaded gasoline

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15
Q

Lead toxicity

A

CNS:
- initial symptoms present as a decrease in appetite, irritability, and fatigue
- if the lead poisoning is not identified, permanent brain damage, known as lead encephalopathy can occur
- results in learning deficits, epilepsy, and blindness

Peripheral and nervous system:
- degeneration of the motor nerves occurs within the peripheral nervous system, which results in the loss of coordination and the appearance of being clumsy

Kidney:
- lead-induced kidney dysfunction is due to the impairment of energy metabolism involving the mitochondria within the kidneys
- the effects on the kidneys are reversible if lead exposure is stopped

blood:
- lead decreases the biosynthesis of heme, the iron-containing component of hemoglobin, leading to the decreased lifespan of red blood cells
- this results in anemia, a condition where inadequate oxygen is being delivered to bodily tissues due to lack of healthy red blood cells
- this effect is reversible once the source of lead is removed

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16
Q

Mercury

A
  • it can be found in the water or the air
  • the main contamination source of mercury is the industry where it is used in the preparation of chlorine and sodium hydroxide as an electrode
  • individuals may be exposed in the air as mercury vapour, or through food
  • the major source of exposure for humans is ingesting fish from mercury-contaminated water
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17
Q

Mercury toxicity (2 types)

A

mercuric toxicity:
- exposure to mercuric mercury occurs through inhalation of vapours containing mercury

menthyl mercury:
- mercury is converted to methylmercury by bacteria and fish in the water
- methyl mercury is the most toxic form of mercury (90% of absorbed through food after eating)

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18
Q

Mechanism of action of methyl mercury

A
  • methyl mercury targets the CNS, where it enters the brain, binds to nerve cell proteins, and leads to nerve cell death
    • acute toxicity results in irritability, numbness tingling, vision and hearing loss, tremor, paralysis
    • chronic toxicity can lead to coma or death
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19
Q

Treatment for mercury toxicity

A
  • Chelating agents (a ligand that binds tightly to metal ions which can be used to remove toxic metals from the body) work for mercuric poisoning
  • methyl poisoning can be treated with charcoal if the mercury was recently ingested, which will prevent the methyl from being absorbed into the body
    • it is important to note: charcoal has no effect on mercury that has already been absorbed into the body
  • damage from long-term mercury exposure can be irreversible
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20
Q

Bisphenol A (BPA)

A
  • an industrial chemical used to make hard, clear plastic known as polycarbonate (reusable water bottles and baby bottles)
  • BPA is also found in epoxy resins, which act as a protective lining on the inside metal based food and beverage cans
  • the main source of exposure to BPA is through the diet where minute quantities of BPA can potentially leach out of containers and into water or food
    • the rate at which this occurs increases with heating, leading to concerns over the effects of microwaving containers composed of partially BPA
21
Q

BPA toxicity

A

has estrogen-like activity, meaning it can bind to estrogen receptors and mimic some effects of estrogen

it has been proposed that synthetically-derived estrogen compounds such as BPA could play a role in reproductive cancers, fertility problems, and altered brain development in infants

General population: exposure to BPA is not expected to pose a health risk to the general population, including newborns and infants

environment: BPA can harm fish and other organisms in the water
- as a precautionary measure, Environment Canada has proposed regulations to limit the max concentration of BPA that can be released into the environment

22
Q

Adverse effects of pharmaceuticals in the environment

A

preclinical and clinical studies have established both the beneficial and toxic effects on humans prior to marketing

Thus, it is possible to predict the adverse effects of pharmaceuticals in drinking water on the human pop
- it is harder to predict the effects on aquatic animal and plant life

23
Q

History of air pollution problems: use in agriculture

A

the use of antibiotics in agriculture is primarily responsible for the increased levels of antibiotics in groundwater and soils

pharmaceuticals are used to treat farm animals, the agent is excreted, and the resulting manure is spread on the fields as fertilizer
- this leads to the contamination of soil, groundwater, and eventually waterways

24
Q

History of air pollution problems: treatment of pets

A

treatment of animals with pharmaceuticals will be metabolized and excreted as they are in humans, and will find their way into surface and groundwater systems

25
Q

History of air pollution problems: disposal of medication

A

about 25% of all unused drugs are washed down the sink or flushed down the toilet, which find their way into sewage discharge

about 30% of all unused drugs are thrown into the garbage and disposed of in a landfill, which can contaminate groundwater

26
Q

History of air pollution problems: aquaculture

A

the use of antibiotics are used to prevent disease and to promote rapid growth and maturity

as aquaculture is concentrated at certain locales, high local concentrations of antibiotics may exist

27
Q

History of air pollution problems: human prescriptions

A

the administration and excretion of prescription drugs is one of the major sources of pharmaceuticals in the environment

a percentage of all drugs consumed by humans are excreted unchanged or as active metabolites
- these excreted drugs are passed into the municipal waste water systems
- treatment of sewage may or may no remove the pharmaceuticals prior to entry of the treated sewage into the environment

28
Q

History of air pollution problems: manufacturing process

A

Pharmaceutical discharge from manufacturing plants has a major effect on local surface and groundwater

the impact of this source of pharmaceutical release on the environment will increase over time, as the chemical facilities are moving to developing countries that have less environmental standards than North America

29
Q

6 common ways pharmaceuticals enter the environment

A
  1. livestock
  2. companion animals
  3. inappropriate disposal of used containers and unused medicine
  4. aquaculture
  5. wastewater treatments (prescription drugs)
  6. manufacturing process
30
Q

Major classes of pharmaceuticals in the environment

A
  1. neuroactive drugs (antidepressants, antiepileptics)
  2. steroid hormones (estrogen)
  3. antibiotics (enhance animal growth)
  4. antihypertensive drugs (treat hypertension)
  5. analgesics (ibuprofen, naproxen, and acetylsalicylic acid)
31
Q

Human risk assessment of pharmaceuticals in the environment

A

2 sources:
- drinking water
- bioaccumulation in food sources

32
Q

Concentration of pharmaceuticals in the environment

A

determined by:
1. the extent of use
2. dose administered
3. persistence in the environment
4. ability of sewage treatment to remove agent

33
Q

Daily intake calculation

A

estimate concentration x average concentration

34
Q

Fold difference

A

therapeutic dose / daily intake

*convert therapeutic dose if in mg
- 5mg = 5000 ug

35
Q

Interpreting daily intake calculation

A

exposure to calculated daily intake will or will not have an adverse effect on human health

36
Q

Interpreting fold difference calculation

A

the daily exposure to total pharmaceutical is calculated fold difference times less or more than the minimum therapeutic dose

37
Q

The minimum therapeutic dose for risk assessment

A
  • application of the minimum therapeutic dose for risk assessment is valid for most pharmaceuticals
  • one group of drugs where this method fails is the anticancer drugs, as significant toxicities occur at the minimum therapeutic dose
  • a different uncertainty factor needs to be employed for risk assessment of cancer chemo
  • overall, most authorities have concluded that exposure of the human population to pharmaceuticals in the environment, at least based on current research, do not pose a health risk
38
Q

Most common types of cancer:

A
  • lung
  • breast
  • colorectal
  • prostate
  • lung cancer is the leading cause of death
39
Q

Key features of a cancer cell

A
  • cancer is a generic term for a large number of diseases that involve abnormal groups of cells

all cancers share 3 features:
- cell growth and division:
- the ability to proliferate indefinitely
- invasion:
- the ability to invade surrounding normal tissue
- metastisis:
- the ability to spread throughout the body

40
Q

Causes of cancer

A

2 types:
1. genetics - can contribute to a variation in response to carcinogens
2. environmental factors - environmental chemicals, diet, and infections

41
Q

Steps in carcinogenesis (development of cancer)

A

3 main steps:

  1. inhalation of procarcinogens and ends with a normal or cancer cell
  2. promotion - once a cell has been mutated by an initiator, it is susceptible to the effects of promoters, these compounds promote the division and proliferation of the cell, giving rise to many cells with the same genetic defect as the original initiated cell (cell multiplication)
  3. progression - the rapid growth of tumours once they are established, increasing the malignancy of the tumour, in general, cancer is characterized by a long latent period between the time of exposure and the development to the disease
42
Q

Steps in carcinogenesis (development of cancer)

A

3 main steps:

  1. inhalation of procarcinogens and ends with a normal or cancer cell
  2. promotion - once a cell has been mutated by an initiator, it is susceptible to the effects of promoters, these compounds promote the division and proliferation of the cell, giving rise to many cells with the same genetic defect as the original initiated cell (cell multiplication)
  3. progression - the rapid growth of tumours once they are established, increasing the malignancy of the tumour, in general, cancer is characterized by a long latent period between the time of exposure and the development to the disease
43
Q

Environmental factors and cancer risk

A
  1. tobacco smoke - lung, esophageal, bladder, and pancreatic cancers
  2. adult diet - saturated animal fat and red meat are strongly linked to cancer of the colon, rectum, and prostate, high intake of salt has been linked to stomach cancer
  3. occupational factors - carcinogens in the workplace (asbestos, benzene, formaldehyde, ionizing radiation, soot)
  4. viruses and bacterial infections
    - bacterial = helicobacter pylori (stomach ulcers) and stomach cancer
    - viruses = Hep B and C cause liver cancer, HPV can cause cervical cancer
44
Q

Cancer prevention

A
  1. avoid sun exposure (skin cancer)
  2. monitor alcohol intake (mouth and liver cancer)
  3. eliminate tobacco use (lung cancer)
  4. eat healthily (fruits and veg, reduce red meat and saturated fat)
  5. be active (combat carcinogens)
  6. get vaccinated (reduce viruses that cause cancer)
45
Q

Goals of cancer treatment

A
  1. prevent cancer
  2. cure cancer
  3. control cancer
  4. relieve symptoms
46
Q

Drugs used for the treatment of cancer

A

surgery, chemotherapy, radiation, and bone marrow transplant

chemotherapy:
- act by slowing the growth of rapidly dividing cells
- in general, it inhibits DNA synthesis, protein synthesis, or cell division, in a variety of ways
- newer agents act directly against the abnormal protein in cancer cells and are more targetted therapy than the traditional chemo drugs

47
Q

Chemo drugs

A

alkylating agents:
- bind to and interfere with DNA replication

mitotic inhibitors:
- affect microtubule function and the formation of the mitotic spindle, thereby preventing cell division

hormones and hormone antagonists:
- are used to treat hormone-sensitive tumours by suppressing cell division

biologicals:
- a number of drugs derived through molecular biological techniques inhibit cell replication by blocking cytokines which normally control cell growth
- some drugs are also antibodies to these cytokines

48
Q

how do chemotherapeutics utilize the concept of selective toxicity to target cancer cells?

A

cancer cells divide continuously whereas most normal cells are in a non-dividing state
- one way to target them is to target continuously dividing cells

49
Q

Principles of cancer

A

when designing a cancer chemotherapy regimen some factors are considered:

  1. benefit risk assessment
    - weight the benefits of chemotherapy versus the adverse effects of treatment in each clinical situation
    - each type of cancer chemo is associated with its own toxicities
    • the decision whether not to continue will need to be reevaluated prior to each treatment
  2. combination chemotherapy:
    chemo drugs are used in combination because:
    • development of resistance:
    • cancer cells can develop resistance to chemotherapeutic drugs
    • cancer cells are less likely to develop resistance when attacked by a variety of drugs that act in different ways

occurrence of toxicities:
- chemo drugs have low therapeutic indexes
- if a single drug was used, it would not be possible to increase dose beyond a certain level
- using a combination of drugs allows for the selection of chemotherapies with different toxicities
- the dose of each chemo drug and the schedule for taking the drugs are carefully evaluated and designed to maximize the anticancer effect while minimizing toxicity

PHARM 100 (6 decks)

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