Toxicology and Pharmacokinetics: Key Concepts and Definitions

LOAEL

the lowest dose possible where adverse effects are noticed

NOAEL

the highest dose where no adverse effect is seen

Threshold

the minimum amount of a dose in order to cause a measurable effect

toxicological endpoint

a measurable point where a scientist can say toxicity has occurred following exposure

LD50

the lethal dosage amount that would kill 50% of a given population

additive effect

1+1=2

a toxic substance + another toxic substance causes a combined effect not greater than those 2 effects combined

synergistic effect

1+1>2

a toxic substance + another toxic substance causes a greater combined effect than just those 2 effects combined

potentation

0+1>1

a nontoxic substance + a toxic substance causes a greater combined effect than what the original toxic substance caused

antagonism

1+1<2

a toxic substance + another toxic substance causes an effect less than the combined effect of both substances

competitive antagonism

the agonist & antagonist compete to bind to the same active site on a receptor

non-competitive antagonism

the antagonist binds to an allosteric site rather than the active site to inhibit the agonist

functional antagonism

the agonist or antagonist cancel each other by binding to different receptors which effects cancel out

chemical antagonism

the antagonist interacts specifically with the agonist in order to neutralize it

first pass effect

The initial metabolism in the liver of a drug absorbed from the gastrointestinal tract before the drug reaches systemic circulation through the bloodstream.

filtration

a transport process using blood pressure to force fluid and small molecules thru semipermeable membranes

passive (simple) diffusion

a transport process that goes with the concentration gradient, from high to low. No energy required

active transport

a transport process that goes against the concentration gradient, from low to high. ATP required

facilitated diffusion

a transport process that helps larger polar molecules cross the bilayer with the help of channel proteins with the concentration gradient

Fick's Law

a physics law stating particles will move from high concentration to low concentration

Implications of binding toxicants to plasma proteins

- Lowers immediate toxicity

- Slows removal from body

- Can only be diffused actively or faciliated

Implications of low, high, or very high Vd

- Low Vd: Stays in blood, easy to remove

- High Vd: Enters tissues, longer lasting

- Very high Vd: Stored in fat, hard to remove

Function 1 of the Blood-Brain Barrier

Tight junctions seal brain capillaries

Function 2 of the Blood-Brain Barrier

Selective transport for key molecules

Function 3 of the Blood-Brain Barrier

Pump toxins out

Function 4 of the Blood-Brain Barrier

Astrocyte end-feet support barrier

What is an example of competitive antagonism?

naloxone binds to the same receptor as opioids

What is an example of non-competitive antagonism?

ketamine binds to another site on the NMDA receptor, preventing glutamate from binding

What is an example of functional antagonism?

EpiPen when someone goes into anaphylactic shock, counters histamine

What is an example of chemical antagonism?

antacids help to decrease gastric acidity

Example 1 of the Liver Toxicity

High blood flow: Liver gets more toxicants from portal vein.

Example 2 of the Liver Toxicity

First-pass effect: Toxicants absorbed first go to liver.

Example 3 of the Liver Toxicity

Metabolism: Liver enzymes turn toxicants into reactive forms

Example 4 of the Liver Toxicity

Storage: Liver holds fat-soluble or bound toxicants.

Route 1 of how compounds enter the renal tubule

Glomerular filtration

Route 2 of how compounds enter the renal tubule

Tubular secretion

Route 3 of how compounds enter the renal tubule

Diffusion from peritubular capillaries

MW Urine Excretion Range

300 daltons & below

MW Bile Excretion Range

500 daltons & above