PUBH 462 Q1

biologically effective dose

the amount of substance needed to reach target cells/organ and produce an effect

toxicokinetics vs toxicodynamics

toxicokinetics is what the body does to the toxin and toxicodynamics is what the drug does to the body

Absorption def

transfer of chemical from site of exposure to internal body surface into the systemic circulation

how do ions that are charged pass through the phospholipid bilayer?

with a transporter protein/ channel / bridge

why is dose important in toxicology?

there needs to be enough of a chemical for it to cause an adverse effect

what is simple diffusion?

this is the primary mechanism and it is when molecules move through the bilayer because the chemical is small or non-polar. Concentration gradient creates a pressure/push for the molecules to move from high concentration to low without energy or special transports/proteins.

what is facilitated diffusion?

this is when molecules use transports/channels and requires the molecules to have structural specificity to move from high to low concentration, but does not require energy.

what are factors that increase skin absorption?

1. breakage/compromise in the skin 2. increased stratum hydration (skin stretches when hydrated, allowing more chemicals in) 3. increased temp (more hot = more concentration gradient because more blood flow) 4. low water solubility of chemical 5. size of the chemical

what are factors that impact the membrane transport of chemicals?

1. charge (charged chemicals do not pass passively) 2. molecular weight/size (small chemicals diffuse passively) 3. lipid solubility (lipid soluble/hydrophic can diffuse passively) 4. membrane thickness/composition (more thick/stratified = less likely)

what factors impact the rate of absorption?

1. concentration of the chemical at the absorbing surface (more concentration = more chemicals moving across) 2. area of the exposed site 3. physiochemical properties (lipid solubility v water solubility) 4. size of toxicant (small = absorbed) 5. epithelial layer

what are the toxicological steps?

1. exposure 2. absorption 3. distribution and metabolism 4. storage OR exertion OR initiation (travels to target site)

where can toxicants get stored?

1. fat (highly lipophilic toxicants) 2. bones 3. liver and kidney 4. plasma proteins

What are factors that increase respiratory absorption?

1. non reactive gases reach alveoli better 2. non-water soluble gets absorbed easier 3. smaller particles/aerosols get absorbed easier

What are some barriers to diffusion found in the body?

1. placenta 2. testes 3. brain these RESTRICT and SLOW DOWN entry and reduce potential of the toxicants

What factors influence distribution in the body?

1. rate of diffusion 2. blood flow to the tissue or organ (higher flow = enhances distribution) 3. ease of crossing cell membranes 4. extend of plasma protein binding (tight bind = harder to remove) 5. volume of distribution

What are the diff types of elimination?

1. renal (kidney) 2. pulmonary elimination (exhaling) 3. fecal (bowels) 4. Biotransformation 3. minor routes (sweat, milk, hair, nails)

What are the 5 things that make a chemical poisonous?

1. route of entry 2. dose 3. toxicity 4. elimination 5. individual susceptibility

what are factors that impact the degree of absorption in the GI tract?

1. the site in the GI tract 2. pH (can change the charge of molecules) 3. time spent in the GI tract 4. physicochemical properties of the chemical

Which atoms tend to be polar?

N, O, P, metals, S, anything with a + or -

What is active transport?

active transport is when particles move against the concentration gradient using energy and a specialized transport to go from low to high concentration. This requires the molecules to have a specific structure to use the channel

What is elimination

all processes that are used by to body to decrease the amount of the toxicant

how does the polarity of a chemical impact how well it can cross a phospholipid bilayer?

chemicals that are polar/hydrophilic/water soluble are less likely to pass the bilayer because they prefer to stay on the outside of the bilayer, which is surrounded by water. Chemicals that are nonpolar, hydrophobic, and not water soluble they easily pass through the bilayer because the inside/tail section has no water

Descriptive Toxicology

concerned directly with toxicity testing, which provides information for safety evaluation and regulatory requirements

regulatory toxicology

deciding whether a drug poses a low risk to be marketed for the stated purpose based on the descriptive and mechanism toxicologies (regulates the toxin)

xenobiotics

foreign chemicals not normally found in the body

What kind of chemcials are typically absorbed by the lungs?

gases, vapors of liquids, aerosols

Mechanistic Toxicology

identifying/understanding mechanisms by which chemicals exert toxic effects on living organisms

what are the three routes of aborption?

inhalation, dermal, and ingestion

What is a phospholipid bilayer and why is it important in toxicology?

it is a cellular membrane that toxins have to pass multiple times to reach the target cell/organ. It has two layers. the head is polar while the tail is non-polar. It is surrounded by water, so the tails connect to one another and create the bilayer because it is hydrophobic.

What part of the lungs do chemicals need to reach to be absorbed through the lungs?

it needs to reach the deepest part of the lungs --> alveoli

What is the purpose of a blood brain barrier?

it prevents toxicants from getting into the brain because it has tightly joined capillaries that are covered in astrocytes

what kind of chemicals can easily penetrate through the skin?

lipophilic chemicals because the skin is impermeable to water

What is distribution?

process of how chemical (after gaining entry into the internal body fluid) agents translocate throughout the fluid compartments of the body

which route of absorption has the highest rates of absorption?

the GI system because it has a large surface area

what is LD 50?

the dose that causes death in 50% of organisms exposed

what are factors that affect toxicity?

the size of the person, age, sex, drugs, route/rate of administration, drug to drug interactions

toxicology

the study of adverse effects of chemicals on living organisms

how does concentration act as a pressure?

there is pressure for the molecules to move across from high to low concentration because it pushes them across. the higher the concentration gradient, the more pressure there is.

what is the difference between the inside and outside of a phospholipid bilayer?

there is water on the outside because the heads are hydrophilic/charged and the inside does not have water because the tails are hydrophobic