pharmacokinetics exam 1 - Flashcards

Question

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

Answer 1

The pharmacologic or toxicologic outcome of drug dosing * Metabolite formation * Amount of drug transported into tissue or region

Answer 2

Whole Blood: contains cellular elements and proteins * Serum: supernatant obtained after centrifuging coagulated whole blood * Plasma: supernatant obtained after centrifuging non-coagulated whole blood

Answer 3

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

Answer 4

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

Answer 5

Biopsies: small tissue samples removed on rare occasions for diagnostic purposes * Disadvantage: blood flow and drug concentrations not uniform within tissues

Answer 6

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

Answer 7

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

Answer 8

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)

Answer 9

Model * Pharmacokinetic parameter * Pharmacokinetic Functions and prediction

Answer 10

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

Answer 11

A constant for a given drug determined from experimental data * Value depends on – model used – method and timing of sampling – method of analysis

Answer 12

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....

Answer 13

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

Answer 14

Physiologically-based models Empirical (Compartment-based) models

Answer 15

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

Answer 16

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

Answer 17

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

Answer 18

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

Answer 19

there is no therapeutic effect dose makes the posion

Answer 20

Central compartment plus tissue compartment central compartment <--> tissue compartment ke coming down from a central compartment

Answer 21

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.

Answer 22

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

Answer 23

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

Answer 24

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

Answer 25

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):

Answer 26

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)

Answer 27

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

Answer 28

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

Answer 29

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

Answer 30

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

Answer 31

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)

Answer 32

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.

Answer 33

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:

Answer 34

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

Answer 35

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.

Answer 36

* 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

Answer 37

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 :

Answer 38

* 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

Answer 39

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