Pharmacology 1

Question 1

define the following
Vd
Ka
Ke

Answer 1

Vd = total body volume/volume of distribution
Ka = absorption rate
Ke = elimination rate constant

Question 2

how is concentration of an IV administered drug calculated?

Answer 2

initial concentration = D/Vd

concentration at a concentration at a later later time = depends on Ke (rate of elimination)

Question 3

how can Ke be described?

Answer 3

the fraction of the amount of drug in the body (A) that is eliminated per unit time
e.g if amount of drug in body is 100mg to start with and 10% is eliminated per unit time then Ke = 0.1 (so 10mg has been eliminated leaving 90mg)
then in the next unit time A = 90mg so 9mg is eliminated (10% of 90) leaving 81 etc etc

Question 4

how is rate of elimination calculated in general?

Answer 4

Ke X A

e.g if Ke = 0.2 and A = 100mg then the rate of elimination = 2mg per min

Question 5

most drugs exhibit what type of elimination kinetics?

Answer 5

first order kinetics
where the rate of elimination is directly proportional to drug concentration
drug concentration falls exponentially

Question 6

what is half life?

Answer 6

time taken for Ct to fall by half

inversely related to Ke

Question 7

for drugs that exhibit first order kinetics, how does changing the dose of the drug administered affect plasma concentration, Ke and half life (t1/2)?

Answer 7

changes Cp (plasma concentration) in direct proportion
doesn't affect Ke or half life

Question 8

what is clearance?

Answer 8

the volume of plasma cleared of a drug per unit time

a constant relating the rate of elimination to plasma concentration

Question 9

concept of clearance only applies to what type of drugs?

Answer 9

only drugs which exhibit first order kinetics

Question 10

what does clearance determine?

Answer 10

the maintenance dose rate (dose per unit time required to maintain a given plasma concentration)

Question 11

what does steady state mean in terms of drug dosing?

Answer 11

at steady state the rate of drug administration = rate of drug elimination
both should be equal to clearance (CL) X Cpss (steady state plasma concentration)

Question 12

how is Cpss calculated?

Answer 12

maintenance dose / clearance

Question 13

how is steady state plasma concentration related to infusion rate?

Answer 13

linearly (increasing infusion rate increases plasma concentration directly proportionally)

Question 14

how is time needed to reach steady state plasma concentration related to infusion rate?

Answer 14

it isn’t

time taken is determined by half life of the drug not infusion rate

Question 15

how does steady state differ when achieved via intermittent oral administration rather than continuous infusion?

Answer 15

same principle but when done via intermittent oral administration the plasma concentration fluctuates about a value known as the average steady state value

Question 16

how is average steady state value calculated?

Answer 16

oral bioavailability (F) X dose / CLp X dosage interval

Question 17

what is the volume of distribution?

Answer 17

the volume into which a drug appears to be distributed with a concentration equal to that of plasma
a proportionality constant relating the plasma concentration (Cp) to the amount of drug in the body (A)

Question 18

how is amount of drug in body (A) calculated?

Answer 18

A = Vd X Cp

Question 19

what is the loading dose (LD)?

Answer 19

initial higher dose of a drug given at the beginning of a course of treatment before stepping down to a lower maintenance dose

Question 20

why is a loading dose used?

Answer 20

to decrease the time taken to get to a steady state for drugs with a long half life (digoxin, phenytoin etc)

Question 21

how can loading dose for a drug be estimated?

Answer 21

from the Vd of the drug
for IV drug = Vd X target Cp
for oral drug = Vd X target Cp / F

Question 22

can Vd be altered?

Answer 22

yes
can change in disease (heart failure, liver disease etc)
therefore adjustment of dosage may be needed particularly for drugs with a low therapeutic range

Question 23

what is half life?

Answer 23

time for concentration of the drug in plasma to half

gives an index of the time course of drug accumulation, drug elimination and choice of dose interval

Question 24

what are the independent variables on which half life is dependent?

Answer 24

Vd and clearance (CL)

Question 25

what is zero order kinetics?

Answer 25

drug is initially eliminated at a constant rate rather than at a rate that is proportional to their concentration
can happen when the plasma concentration of a drug is greater Km of an enzyme that metabolises it

Question 26

why should dose increases be made in small increments for drugs with saturateable elimination (zero order kinetics)?

Answer 26

bc the metabolising enzymes can become saturated so small increases in dose cause a large increase in plasma concentration