Kinetics of elimination and Volume of distribution

Question 1

Volume of distribution (Vd) definition

Answer 1

Apparent volume that would accommodate all the drug in the body in a concentration the same as present in plasma.

Question 2

Volume of distribution (Vd) equation

Answer 2

Vd = M (dose of the drug adminstered) / C (plasma concentration)

Question 3

Significance of volume of distribution

Answer 3

1) Drugs highly bound to plasma proteins have small Vd = plasma volume
2) Drugs highly bound to tissue proteins have large Vd = total body water
3) Abnormal accumulation of body fluids as edema may increase Vd of water soluble drugs
4) Useful to calculate loading dose which is the initial large dose to reach a target therapeutic concentration (C).

Question 4

When to use haemodyalysis when there is toxicity?

Answer 4

For drugs with small volume of distribution because high volume of distribution of a drug means it is bound to tissue proteins and not present in the blood

Question 5

Loading dose definition

Answer 5

Dose needed to reach certain concentration of the drug in plasma

Question 6

High volume of distribution means that the drug distributes …

Answer 6

Intracellular

Question 7

Low volume of distribution means that the drug distributes

Answer 7

intravascular

Question 8

Loading dose equation

Answer 8

Loading dose = Vd x C (target theraputic concentration) / F (Bioavailability in case of oral drug)

Question 9

Drug elimination is the ……… and ………..

Answer 9

metabolic inactivation …… excretion

Question 10

Clearance definition

Answer 10

The clearance (CL) of a drug is the theoretical volume of plasma from which the drug is completely removed in a unit time

Question 11

Clearance calculation

Answer 11

CL= Rate of Elimination / Plasma Concentration

Question 12

The rate of elimination can be ……. or ……

Answer 12

First order kinetics

Zero order kinetics

Question 13

First order kinetics definition

Answer 13

A constant fraction or percentage of the drug present in the body is eliminated in unit time.

Question 14

Zero order kinetics

Answer 14

Constant amount of the drug is eliminated in unit time

Question 15

In first order kinetics, The rate of elimination is ……….. to the drug concentration

Answer 15

directly proportional

Question 16

In zero order kinetics, The rate of elimination ……….. irrespective of drug concentration

Answer 16

remains constant

Question 17

In first order kinetics, the T half-life is ….

Answer 17

CONSTANT

Question 18

In zero order kinetics, the T Half-life ….

Answer 18

INCREASES WITH THE DRUG CONCENTRATION

Question 19

In first order kinetics, the clearance of the drug

Answer 19

remains constant

Question 20

In zero order kinetics, the clearance of the drug

Answer 20

decreases as the concentration of the drug increases

might lead to toxicity

Question 21

First order kinetics drug examples

Answer 21

• Most of drugs which do not saturate the elimination processes (transporters, enzymes, blood flow, etc.) over the therapeutic concentration range
• Phenytoin, asprin and ethanol in small doses

Question 22

Zeroorder kinetics drug examples

Answer 22

Phenytoin, asprin and ethanol in large doses

Due to saturation of enzymes and transporters.

Question 23

Plasma half life (t1/2) definition

Answer 23

The Plasma half-life (t1/2) of a drug is the time taken for its plasma concentration to be reduced to half of its original value.

Question 24

After 4 T-half-lives, ……% of the drug is eliminated

Answer 24

94

Question 25

Plasma half-life calculation

Answer 25

T(1/2) = (0.693 x Vd) / CL

Question 26

Drugs with low T-half life could be administered by 2 ways:

Answer 26

1) To take the dose after the time finishes

2) Administer the dose through an IV drip /infusion

Question 27

Significance of T(1/2) life:

Answer 27

1) Determination of the dosing interval (t)
2) Calculation of the maintenance dose
3) Determination of the time needed to reach a steady state concentration “Css”

Question 28

Maintenance dose definition

Answer 28

Required dose to maintain steady concentration of drug

Question 29

Most drugs are taken after the T1/2 life why?

Answer 29

To ensure continuous concentration with minimal fluctuations

Question 30

Steady state concentration definition

Answer 30

The plasma concentration of the drug at which the rate of adminstration equals the rate of elimination