Chapter 3 (exam 2) Flashcards

1
Q

Toxico/pharmoco-dynamics

A

time course of the effect

-biokinetics/biodynamic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Toxicokinetics

A
  • time course for absorption, distribution, metabolism, and excretion
  • all relates to the concentration at the target site
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Noncompartmental analysis

A
  • kinetic model
  • single dose analysis used in initial phase of pharm testing
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Classical compartmental models

A
  • kinetic model
  • consider multiple does in simplified system of compartments
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Physiologically based pharmokinetics

A
  • kinetic model
  • tissue and organ specific most realistic most complicated
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Compartment

A
  • not a specific organ or tissue
  • empirical model for lab data
  • in-out = storage (mas balance)
  • based on blood plasma conc and conc in tussues are assumed to be proportional
  • tissues that behave differently (depots) are an additional compartment
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Reversible vs irreversible compartment

A

Reversible - X+R equilibrium XR

Not true for a covalent process

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

First Order Kinetics

A
  • rate dependant on the concentration
  • probablility of reaction decreases as [X] decreases
  • most common type in pharmaco/toxicoknietics
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Zero order kinetics

A

constant rate over time

dC/dt = -k

C=Co-kt

Negative linear line

saturated enzyme or transporter

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Second Order Kinetics

A

rate depends on concentration of more than one component

dC/dt = -k[Ca][Cb]

Collapses to pseudo first order when one concentration is high enough to be about constant (ex. GSH normally high enough to not change as compound is metabilized. Follows second order when severely depleted)

dC/dt = -k [A]

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Saturable (capacity limited kinetics)

A
  • also known as Michaelis-Menton
  • at low concentrations, transporters (or metabolic enzymes) are available for additional substrate molecules to interact with

–increase saturation conc increases rate

-high conc all sites are occupied

–increase substrate does not increase rate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Michaelis-Menton Kinetics

A

Probablility of randomly interacting with the enzyme increases with conc but saturated and rate can not increase further

  • below saturation, increase conc increase probability of binding
  • saturated, probability is constant and binding will not increase with increase conc
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Compartment Models

A
  • open model - IV injection no uptake step
  • open model w/first order absorption
  • 2 compartment open model - IV injection, no uptake, 2 different kinetic areas
  • 2 compartment open model with first order absorption
  • Ka=kinetics of absorption (first part of graph)
  • Ke=kinetics of excretion (second part of graph)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Model fitting

A

C = ae-kt+Be-k2t

R2 used to determine best fit

Empirical process

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Physicologically based pharmokinetics model (PBPK)

A
  • measure flow rates, partition coefficient for each compartment
  • expensive
  • lots of data
  • could be very powerful for important toxicants
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Chemical Effects on Enzymes

A
  • enzyme induction
  • enzyme inhibition

–competitive

–uncompetitive

–noncompetitive

Reversible inhibitor-affinity of I may not be equal to the affinity of S

S+E equil E+S Kf

I+E equil E+I KI

17
Q

Competitive inhibition

A

-inhibitor and substrate compete for binding site on the enzyme

Classical-compete for same site

Nonclassical-compete for different sites that cause confirmation change(allosteric effect) and other cannot bind

18
Q

Uncompetitive Inhibition

A

inhibitor binds after the substrate and to a different site, then inhibits the enzyme

-not dependent on substrate conc

19
Q

Noncompetitive Inhibition

A

Binds before or after the substrate and causes confirmation change to inhibit