Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

P1 Spring 2024 > pharmacokinetics exam 1 - > Flashcards

pharmacokinetics exam 1 - Flashcards

1
Q

Overview of course

A

To Introduce and Define Concepts

To Discuss Assays in Pharmacokinetics - is that the immunoassay, radioassay, mass spec. and chromatography?

To Discuss Models in Pharmacokinetics- is that the physiological and compartment based models?

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

Introductory Chart

fill it in
1
2
_____ availiability
3
______ availability
4
5

A
  1. drug dose administered
  2. disintegration/dissolution (PHARMACEUTICAL PHASE)

Pharmaceutical Availability

  1. Absorption Distribution Metabolism Excretion (PHARMACOKINETIC PHASE)
    - Metabolism & Excretion are apart of elimination
    - what body does to drug

Pharmacological Availability

  1. Drug-Target Interaction (PHARMACODYNAMIC PHASE)
  2. Effect
    - what drug does to body
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Parameters of Interest

what change are we interested in with time

fill it in
1
____ _____ ____ absorption
2
_____ _____ _____. elimination
3

A

changes in the amount of drug in the body with time

  1. Amount of Drug Administered

Rate constant for absorption

  1. Amount of Drug In Body

Rate constant for elimination

  1. Amount of Drug Eliminated
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Relationship of drug concentrations to drug response.

what is the goal

what are the 5 categories of the dose that our drug can be in

A

goal: make sure that our drug [ ] is within the therapeutic range or zone

Drug concentration on the Y-axis

toxic

potentially toxic

therapeutic

potentially therapeutic

subtherapeutic

more concentration = more response

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

DRUG CONCENTRATION ASSAYS
how do we find out how much of the drug was absorbed

what are the 7 methods that we can use to determine this

A
  • Biological specimens
  • Blood Concentrations
  • Significance of Plasma Concentrations
  • Plasma Concentration-Time Curve (how [ ] of drug changes with time)
  • Tissue Concentrations
  • Other Body Fluid Concentrations
  • Assays have application in Therapeutics and Forensic Science
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

DRUG CONCENTRATION ASSAYS: Some Assay Types in lab

A
  • Chromatography: (e.g. HPLC separates drug from other substances) - interested in how we got to that drug [ ]
  • Immunoassays e.g. fluorescence immunoassays
  • Radioactive assays (e.g. the TCA-RA assay for serum lidamycin)
  • Mass Spectroscopy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

DRUG CONCENTRATION ASSAYS: Blood Concentrations

what is whole blood

what is serum

what is plasma

A
  • Whole Blood: contains cellular elements and proteins
  • Serum: supernatant obtained after centrifuging coagulated whole blood
  • Plasma: supernatant obtained after centrifuging non-coagulated whole blood
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

PLASMA CONCENTRATION-TIME COURSE AFTER ORAL ADMINISTRATION

what are the features of this graph

A

this is a graph

plasma concentration

onset of action - rise in [drug]

peak concentration

peak time

intensity of response (highest at peak [ ])

Minimum Effective Concentration

Minimum Toxic Concentration

when the slope of the graph comes down - the rate of elimination is more than the rate of absorption

when the slope of the graph rises - [ drug ] rises until it gets to the peak where the drug rate of absorption is the same as eliminated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Model Types

A
  • Physiologically-based models
  • Empirical (Compartment-based) models
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Mammillary Model: Two-Compartment System

what two kinds of compartments are combined

A

Central compartment plus tissue compartment

central compartment to tissue compartment (arrow go back and forth)

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

Catenary Model

describe the arrangement of this

how many compartments are there

A

Multiple tissue compartments are connected and the central compartment like a train

central compartment to tissue compartment I to tissue compartment II to tissue compartment III (arrow goes back and forth)

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

MODEL TYPES CONTRASTED

what are the two types of models

A

PHYSIOLOGICAL MODEL

COMPARTMENTAL MODEL (so is it that we are tracing how the drug flows from one compartment to the other?)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

PHYSIOLOGICAL MODEL

what is drug concentration predicted from

what do pathophysiological conditions influence

what can animal data be used to predict and by what

what kind of data is practically hard to obtain

what is the goal of this

A

Drug concentrations predicted from tissue size, blood flow, blood drug concentrations and tissue drug concentrations

Pathophysiological conditions influence data and therefore the model

Animal data (from several species) may be used to predict human data by extrapolation

Experimental data required for this is practically difficult to obtain

goal is to Predict realistic tissue drug concentrations

predictions are more realistic but we do not have the luxury of weighing the liver

on exam

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

COMPARTMENTAL MODEL

what about the data is required

what does pathophysiological conditions influence

is extrapolation possible, why or why not

is difficult to obtain data required

is it limited or unlimited

A

Data fitting required

Pathophysiological conditions influence data and therefore the model

Extrapolation (applying to) is not possible because Vd is only a mathematical construct and has a less exact relationship to blood flow and volume

Difficult to obtain data not required

Limited in this regard

in the clinical, we use this model more

on exam

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

Biopharmaceutics

it is the study of the relationship between what

what do some authorities include pharmacokinetics as a branch of

what is the definition in simple terms

A

The study of the relationship between the
nature and intensity of the biological effects AND the physicochemical properties of the drug

  • Some authorities include Pharmacokinetics as a branch of Biopharmaceutics

so the influence of the physicochemical properties of the drug and the nature and intensity of the biological effect

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Biopharmaceutics (Continued)

what are the 4 factors of interest

A

Factors of interest influence:
1. Drug stability
2. Drug release rate-product
3. Dissolution/release rate- absorption site
4. Systemic absorption

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Biopharmaceutics (Continued)

what are the formulation properties of interest

A

Some formulation properties of interest:
- type of dosage form
- pharmaceutical process used in preparing it
- presence (or absence) of adjuncts
- physical state
- particle size and surface area
- chemical nature (salt, complex, ester, etc…)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Pharmacokinetics

what does the word mean

what is it a math analysis of _____ time courses

what is it the science of ____, ____ & _____

relationship between ____ administration, the______ of its distribution and the concentrations attained in different ______

A

pharmakon (drug) and kinetikos (motion)
* Math analyses of ADME time courses

  • The science of the kinetics of absorption, distribution and elimination of drugs
  • relationship between drug administration, the time-course of its distribution and the concentrations attained in different regions
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Pharmacokinetics: Experimental Aspects

what sampling techniques are developed

assay methods are developed for what

what kind of collection and techniques are developed

A

Development of biologic sampling techniques

  • Development of assay methods for drugs and metabolites
  • Development of data collection and manipulation techniques
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Pharmacokinetics: Theoretical Aspects

these are models that predict what following drug adminstration

what is classical pharmacokinetics

A

Models that predict drug disposition following drug administration

  • Classical pharmacokinetics: model development and parameter estimation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Pharmacokinetics: Clinical Aspects

what are the considerations

what strategies are optimized

TDM for drugs that have what

what factors are considered in population pharmacokinetics

A

Patient-specific considerations

  • Optimized dosing strategies
  • Therapeutic drug monitoring (“TDM”) for drugs with a narrow therapeutic index
  • Population Pharmacokinetics: age, gender, ethnic, genetic considerations
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Toxicokinetics

what is pharmacokinetics applied to

what is it applied to

what are saturated

A

application of pharmacokinetic principles to toxicology

  • Applied to the interpretation of pre-clinical toxicity data and their extrapolation to humans
  • Non-linear pharmacokinetics at toxic doses
    – saturation of enzymes and other molecules involved in processes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Pharmacodynamics

what is it the relationship between

in other words what the ____ does to the _____

while pharmacokinetics is….

A

relationship between drug concentration at the site of action and the pharmacologic response

  • “What the drug does to the body”

while pharmacokinetics is what the body does to the drug (ADME)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

DRUG CONCENTRATION ASSAYS: Obtaining Biological Specimens

what kind of method involves parenteral or surgical intervention

what kind of samples are obtained by invasive methods

what kind of samples are obtained by non-invasive methods

A

Invasive methods involve parenteral or surgical intervention.

  • Samples obtained by invasive methods include blood, spinal fluid, tissue biopsy, and synovial fluid
  • Samples obtained by non-invasive methods include saliva, milk, urine, feces, and expired air
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

DRUG CONCENTRATION ASSAYS: Data Obtained from Biological Specimens

what is it the outcome of

what is it the formation of

amount of drug transported where

A

The pharmacologic or toxicologic outcome of drug dosing

  • Metabolite formation
  • Amount of drug transported into tissue or region
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

DRUG CONCENTRATION ASSAYS: Blood Concentrations

what does whole blood contain

what is serum

what is plasma

A

Whole Blood: contains cellular elements and proteins

  • Serum: supernatant obtained after centrifuging coagulated whole blood
  • Plasma: supernatant obtained after centrifuging non-coagulated whole blood
27
Q

PLASMA CONCENTRATION-TIME COURSE AFTER ORAL ADMINISTRATION labels

what is:

peak concentration: or Cmax

onset of action:

duration of action:

curve trends upward:

curve trends downward:

between MEC & MTC:

the graph rises because the more and more of it is absorbed

peak time:

NTI:

intensity

AUC

A

peak concentration: or Cmax, when the rate of elimination is the same as the rate of absorption

onset of action: time to get to MEC

duration of action: how long you are at MEC

curve trends upward: rate of elimination of less than rate of absorption - absorption is faster than elimination

curve trends downward: rate of elimination of faster than rate of absorption - absorption is slower than elimination

between MEC & MTC: therapeutic index/window

the graph rises because the more and more of it is absorbed

peak time: time to get to MEC

NTI: dose to treat you is not that different that different than dose to kill you

intensity: as you increase the [ ], the response becomes more and more intense

AUC: area under curve - how much drug the patient has been exposed to

28
Q

PLASMA CONCENTRATION-TIME COURSE

what is AUC the measure of

what two kind of studies is it useful in

A

The AUC is a measure of the amount of drug the patient has been exposed to

  • AUC useful in toxicity profile studies
  • AUC useful in bioequivalence studies
29
Q

DRUG CONCENTRATION ASSAYS: Tissue Concentrations

what are biopsies

what is the disadvantage of this

A

Biopsies: small tissue samples removed on rare occasions for diagnostic purposes

  • Disadvantage: blood flow and drug concentrations not uniform within tissues
30
Q

DRUG CONCENTRATION ASSAYS: Plasma Concentrations

what is it useful for

pharmacodynamic response is sometimes more important than what

A

Useful for optimization of individual dosage

  • Other relevant pharmacokinetic information is needed in order to use plasma concentrations beneficially
  • Pharmacodynamic response sometimes more important than plasma drug levels e.g. INR for anti-coagulants and ECG for cardiotonic drugs
31
Q

DRUG CONCENTRATION ASSAYS: Urine and Fecal Concentrations

what urine concentration of the drug an indirect indication of

what does fecal drug concentration indicate

A

Urine concentration of drug is an indirect indication of the systemic concentration of the drug

  • Fecal drug concentration indicates lack of absorption after oral dose administration, or biliary secretion after systemic absorption
32
Q

DRUG CONCENTRATION ASSAYS: Saliva Concentrations

what does it approximate to and why

when taken after equilibrium, what does it provide a good indication of

A

Approximates to free drug in plasma because free drug freely diffuses into saliva

  • When taken after equilibrium with plasma drug concentrations, provides a good indication of free drug levels in body (weak acids and weak bases have good correlations to plasma drug levels)
33
Q

Some Pharmacokinetic Concepts

A

Model
* Pharmacokinetic parameter
* Pharmacokinetic Functions and prediction

34
Q

Some Pharmacokinetic Concepts:
Model

it is a model that uses mathematical terms to describe what kind of relationships

what can a model be used to do

A

A construct that uses mathematical terms to describe quantitative relationships.

A model may be used to:
1. predict drug concentrations over time
2. optimize dosage regimen for the individual patient
3. correlate drug concentration with effects
4. estimate possible accumulation of drugs/ metabolites
5. evaluate bioequivalences
6. explain drug interactions
7. describe how physiology or disease affects drug ADME

35
Q

Some Pharmacokinetic Concepts: Pharmacokinetic Parameter

what does the value depend on

A

A constant for a given drug determined from experimental data

  • Value depends on
    – model used
    – method and timing of sampling
    – method of analysis
36
Q

Pharmacokinetic Parameter (continued)

what is VD

what is ke

what is t1/2

A

E.g.
– VD (the volume within which the drug is distributed),

– ke (governs the rate at which the drug concentration decreases over time)

– t1/2 (the time needed for the quantity of a drug to be reduced by one-half), etc….

37
Q

Some Pharmacokinetic Concepts: Pharmacokinetic Functions

what is it a relationship between

what can it be used to describe and predict over time

A

Relationship between an independent variable and a dependent variable i.e. using pharmacokinetic parameters

  • Can be used to describe and predict drug concentrations in the body over time
38
Q

what are the two Model Types

A

Physiologically-based models

Empirical (Compartment-based) models

39
Q

Physiologic Models

what is it also called

what is blood flow

what is it based on

A

Also called Blood Flow Models OR Perfusion Models i.e. blood flow is the means by which a drug is distributed to various tissues

  • Based on actual anatomical and physiological data e.g. known tissue volume is used rather than an estimated Volume of Distribution
  • volume that is actually measured, actual rates are determined
40
Q

Compartment Models
- these are empirical compartments

what is a compartment
- what is similar between them
- because of that, is it similar or different to physiological or anatomical regions

A

A compartment is a tissue or tissue group that has similar blood flow and drug affinity, rather than a physiological or anatomical region.

** Mammillary Model - breast, usually there are 2 of them. Uses 2 compartments that are connected. Central and peripheral that are connected
**Catenary Model - cars of a train, they are not all connected to the central compartment

41
Q

Compartment Models II

what are the features

A

Features:
-Linear assumptions
-Use of rate constants for both drug entry and exit
-Open system
-following the introduction of the drug into a compartment, drug concentrations in other compartments of the system may be estimated
- may have the same richness of blood supply, same affinity, etc

are not actual anatomical entities like the anatomical compartment

42
Q

Mammillary Model: One Compartment System

where is the drug added and eliminated

A

The drug is added to and eliminated from a central compartment (plasma and highly perfused tissues such as liver and kidney)

intravenous drug injection
central compartment –> ke
- instantly there is distribution to the whole compartment

Following first-order Drug absorption
ka —> central compartment —->ke

can determine:
clearance
half-life
volume of distribution
rate of elimination

as long as the drug becomes bioavailable, elimination and distribution take place

43
Q

until you get to the MEC,

A

there is no therapeutic effect

dose makes the posion

44
Q

Mammillary Model: Two-Compartment System

A

Central compartment plus tissue compartment

central compartment <–> tissue compartment

ke coming down from a central compartment

45
Q

Differential Calculus

A

determining a variable’s rate of change

  • the amount of a drug in the body changes over time (the independent variable).
  • For the variables x and y, dx/dy represents a change in x with respect to y; the expression d denotes a small change.
46
Q

if C = 12 -2t what is dC/dt

A

dC/dt = -2 because
if y = c
dy/dx = 0

12 is a constant so it goes away

if y = x^n
dy/dx = nx^n-1

47
Q

Integral Calculus

A

Integration is the converse of differentiation and is the summation of
f(x). dx

  • If f(x) = y = ax, then the integral is:
    integral ax . dx
48
Q

Integral Calculus II

A

When x and the boundaries a and b are specified, the expression is a definite integral of the function y = ax i.e. the sum of individual areas under the graph of that function.

if we divide the trapezoid under the curve we can add up the trapezoid to get the AUC

49
Q

Integral Calculus: Trapezoidal Rule

A

The Trapezoidal Rule is used to calculate the area under the curve (AUC) between times tn and tn -1 (corresponding to concentrations Cn and Cn – 1):

50
Q

Integral Calculus: Trapezoidal Rule II

A

The total AUC is obtained by the summation of the AUC between each consecutive time interval using the trapezoidal rule

  • More accurate as the number of data points increases (rule assumes linear function between points on the curve; this is lost if there is too much spacing between points)
51
Q

Integral Calculus: Trapezoidal Rule III

A

If Cpn last observed concentration at time tn and k  slope of the curve at its terminal point, the full area
under the curve is given by :
the eqn

52
Q

Graphs

A

Time is plotted on the abscissa; drug
concentration on the ordinate

  • Straight lines (equation y = mx + b) are
    very useful for extrapolation and prediction
  • Where physiological variables are linearly related, rectangular coordinate graph paper is sufficient

m = slope
b = y-intercept

we are going to linearize relationships

53
Q

Graphs: SemiLog Transformations

A

Ten-fold increase in numbers along the ordinate, but not the abscissa

54
Q

Graphs: Slopes

A

Slopes are very important for the purpose of extrapolation

  • The value of the slope of a graph may be determined from any two points on it:
  • For rectangular coordinate graphs :
    Slope = (y2 -y1)/x2 –x1
  • For semilog graphs, the y values must be converted to logarithms: the slope of semilog plot
    Slope = (log y2 -log y1)/ x2 –x1
55
Q

Graphs: Difficulties

A

It is possible to fit a given set of points with more than one curve. Solution? (choose the simpler hypothesis)

  • Extrapolation assumes that the same trend as exists in the given data points applies beyond them; this may not be so (this assumption may only be safely held for interpolation)
56
Q

Graphs: Regression III

A

The least squares method is one way of obtaining a theoretical line; one that minimizes the deviation of the observed data points from the theoretical line.

57
Q

Dimensional Analysis

A

The numbers and the units on both sides of an equation must be balanced

  • If in doubt, check an equation by using the correct units on either side of the equation.
  • For ascertaining the units of the diffusion constant D in Fick’s Law, the rate of drug diffusion:
58
Q

Rates and Orders of Reactions:
Rate

A

This is the velocity with which the reaction occurs
* For
drug A → drug B the rate may be expressed as –dA/ dt
(if the quantity of A decreases with time) OR as +dB/ dt (B increases with time)

  • Since B may not be known or may be difficult to collect and assay, by measuring the amount of A at given time points, the rate of the reaction may be determined.
    33
59
Q

Rates and Orders of Reactions:
Order

A

The order of a drug reaction is a reference to how the rate of the reaction is influenced by the drug concentration

  • If the amount of a drug decreases by a constant amount in a constant time interval, the reaction is zero-order
  • If the drug amount decreases in proportion to the amount of drug remaining, the reaction is first order. For most drugs, the overall rate of elimination follows first-order kinetics
  • Where there are two reactants and the reaction proceeds at a rate proportional to the product of their concentrations, the kinetics is second order.
60
Q

Rates and Orders of Reactions: Zero Order Reactions

A
  • dA/dt = -ko
    -ko = the zero order rate constant for drug A
    decreasing at a constant interval t
    A = -ko t + Ao
    Ao = the amount of the drug at time t = 0
  • Units are mass/ time
  • The concentration C may be substituted for the amount A
61
Q

Rates and Orders of Reactions: Zero Order Reactions II

A

Half-life (t1/2)  the period required for the amount of a drug to decrease by one-half * The half-life of a zero order reaction is not constant. It is given by :

62
Q

Rates and Orders of Reactions: First Order Reactions

A
  • dA/ dt  - kA
    k = first order rate constant,
    A = the amount of drug remaining
    A  Aoe-kt
    ln A-ktln Ao
    log A = -kt + ln Ao

log A = -(kt)/2.3 + log Ao
* Units: time -1

eqn is not linear

63
Q

if I plot a set of data on a semi-log and on standard rectangular paper, how do I know if the rxn is zero or first order?

A

zero order:
a straight line on standard rectangular paper
not a straight line on semi-log paper

first order:
no straight line on standard rectangular paper
straight line on semi-log paper

P1 Spring 2024 (57 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions