11/9 Pharmacology

Question 1

The fractional extent to which a dose of drug reaches the systemic circulation.

Answer 1

Bioavailability (F)

Question 2

what is the equation for bioavailability (F)?

Answer 2

F= [AUC/Dose]/[AUC IV/ Dose IV] where AUC is are under the curve of concentration vs. Time

Question 3

the reduction in bioavailability of a drug that results from its metabolism or excretion prior to reaching the systemic circulation

Answer 3

First-pass elimination

Question 4

what is the equation for first pass elimination?

Answer 4

F=(1-ER) * f where f is the fractional absorption and ER is the extraction ration

Question 5

what is the F for IV drugs?

Answer 5

1 of course since it all reaches the circutlation

Question 6

which of the following most correctly discribes the first pass effect of pharmacology?

Answer 6

elimination of enterally administered drugs by metabolism or excretion before it gets to the circulation.

Question 7

how does absorption compare to bioavailability

Answer 7

this is a common mistake…they are not the same!!! absorption is the rate that drug initally enters the body system. Bioavailability is the amount of drug that is in the circulatin after first pass effects.

Question 8

what are the factors that affect the bioavailability of a drug?

Answer 8

depends on the route of administration and is a function of absorption and first pass elimination.

Question 9

what is the conceptially way of explaining the math of bioavailabilty

Answer 9

the ratio of the conc. of the drug per time per the dose given compared to the what it would be for an IV administered drug.

Question 10

what are the two organs of first pass elimination?

Answer 10

the liver and the lungs

Question 11

the 2/3 rule!!! (you missed it on the last test after all!)

Answer 11

Kg * 2/3 =water; water2/3 is Intracellular; water1/3 is extracellular. 2/3 of extracellular is interestitial and 1/3 of extracellular is intravascular. then fat is

Question 12

a measure of the apparent space in the body available to contain the drug

Answer 12

Volume of distribution (Vd)

Question 13

Equation for the Volume of distribution

Answer 13

Vdist=F*Dose/Cpo; where F is bioavailability and Cpo is plasma concentration time zero.

Question 14

What is the thereputic concentration line on the conc. vs. time graph?

Answer 14

it indicates the conc. of drug that is needed to be active as intended as a drug in the body.

Question 15

conceptually how do we find the volume of distribution?

Answer 15

look at the conc. at the begining of the elimination phase extrapulate back to imagine a theoretical plasma concentration time zero and then determine the amount of drug that made it to systemic circulation (bioavailability) and then figure out the total volume that would be needed to contain that amount of drug at that conc.

Question 16

what is Extraction ratio?

Answer 16

it is first pass metabolism or excretion – first pass effects.

Question 17

how do we find Cpo or the plasma concentration time zero in order to find the volume of disttribution?

Answer 17

we look at the elimination phase and then linearly extrapolate that back to the time zero and the concentration that would result is the Cp0

Question 18

what does Vd actually tell us!!

Answer 18

how widely is the drug distributed out of the plasma – big volume of distribution would say that the drug is widely distributed throughout the body (esp. to the fat) and a low Vd would say that the drug is mostly in the circulation.

Question 19

what is the compartment models of a drug

Answer 19

a way to model the loss of a drug that may be to a one compartment or “volume of distribution” or to multiple compartments to model the loss of the drug accuretly in the body. Math: the sum of first order solutions for each compartment (in terms of the nateral number) is the conc. as a function of time.

Question 20

a measure of the body efficiency in eliminating the drug

Answer 20

Clearance

Question 21

how do we express clearence (units)

Answer 21

Expressed as volume of plasma completely cleared of drug per time. (theoretical elimination of the drug piece-wise from the circulation) units of Volume (of plasma cleared)

Question 22

how would changes in renal function change the clearance

Answer 22

kidney function down–clearence down; kidney function up – clearence up

Question 23

what is first order elimination?

Answer 23

it is based on a first order differential equation model: the rate of drug eliniated is proportional to plasma concentration.

Question 24

what is zero-order elimination of a drug?

Answer 24

the rate of drug elimination is constant and independent of plams concentraton, and there-fore clearence and half life are not meaningful.

Question 25

what is the clinical significance of saturatinon of first order elimination?

Answer 25

you shift to zero order elimination and the concentratioin of the drug will not fall as quickly so it would be easy to over-dose if you continue to dose!

Question 26

what happens has you drink alcohol a lot and the later drinks seem to have more effect

Answer 26

moving from first order to zero order elimination!

Question 27

what is the equation for the conc. of the drug vs. time?

Answer 27

it is the plasma concentration time zero times natural number raised to neg. elimination rate constant times time.

Question 28

what is the relation between time half life and elimination rate constant?

Answer 28

t1/2=ln(2)/k

Question 29

what is the relation between elimination rate constant and the clearence and volume of distribution?

Answer 29

k=CL/Vd

Question 30

what is the relation between t1/2 and Vd/CL

Answer 30

t1/2 = ln(2) * Vd/ (CL)

Question 31

how do I find a total clearence if there are multiple routes to clearence?

Answer 31

just add clearence together.

Question 32

Is drug elimination half-life = effect half-life?

Answer 32

not at all!!!!

Question 33

what may affect drug clearance?

Answer 33

organ perfusion and function

Question 34

what is the goal with a dosing regimen?

Answer 34

to have rate of drug in equal to the rate of drug out so that you will come to equilibrium.

Question 35

equation for rate of drug in = to rate of drug out i.e. what is the equation for rate of drug in and the equation for rate of drug out (equal to each other)

Answer 35

F*Dose/t = CL * Css where the F is bioavailability and t is dosing interval, and Css is steady state conc. and CL is clearance, TC therapeutic conc. TD is toxic dose.

Question 36

how many half lives does it take to reach a drug concentration steady state

Answer 36

4-5

Question 37

what is the main affecter of the magnitude of concentration fluctuations?

Answer 37

The dosing interval!! the more often you dose, the smaller the peak conc. will be!

Question 38

what is a loading dose

Answer 38

a dose that can be used to rapidly achieve therapeutic concentrations….LD = [Css * Vd]/F; this is just the Vd equation rearranged.