Quantitative Aspects of Drug Action

Question 1

Drug definition

Answer 1

A chemical compound that when applied to a biological system alters its function in a specific manner

Question 2

affinity definition

Answer 2

chemical forces involved in the association of a drug with the receptor. Determine occupation

Question 3

efficacy definition

Answer 3

ability of a drug to activate the receptor and produce a response. Determines activation

Question 4

agonist definition

Answer 4

molecule that binds to receptor and produces a response

Question 5

antagonist definition

Answer 5

molecule that binds with high affinity but zero efficacy

Question 6

therapeutic window definition

Answer 6

a range of doses that produce a therapeutic response without causing significant adverse effect in patients

Question 7

what is above the therapeutic window + below?

Answer 7

above- side effects

below- sub-therapeutic

Question 8

therapeutic index definition

Answer 8

Ratio between the minimum effective concentration and the minimum toxic concentration

Question 9

EC50 definition

Answer 9

the minimum effective dose for 50% of the population

Question 10

LD50 definition

Answer 10

the lethal dose of a drug for 50% of the population

Question 11

four main processes of pharmokinetics when a drug is taken +

Answer 11

ADME

Absorption- process of drug entering the systemic circulation

Distribution- movement from body fluids to organs/compartments

Metabolism- breakdown of drugs

Excretion- removal of drugs

Question 12

different factors that affect absorption

Answer 12

charge, lipophilicity, size

Question 13

why is lipid solubility important?

Answer 13

need to diffuse through lipid bilayer of epithelia to enter circulation

Question 14

are drugs generally acidic or basic + why is this important?

Answer 14

generally weak acids and bases so equilibrium is weighted towards non-ionised forms at 7.4 pH

Question 15

pKa definition

Answer 15

the pH were the drug exists as 50% ionised and 50% unionised

Question 16

where are acidic drugs absorbed? why?

Answer 16

stomach, were the pH is 3 so less likely to become ionised

Question 17

where are basic drugs absorbed + why?

Answer 17

small intestine, where the pH is 9 so less likely to become ionised

Question 18

partition coefficient definition

Answer 18

measure of the relative solubility of a compound in aqueous and lipid environments, critical determinant of drug absorption

ratio of lipid solubility to aqueous solubilty

Question 19

what does a high partition coefficient mean? + what can it lead to?

Answer 19

more membrane soluble

some drugs remain trapped in body fat

Question 20

distribution definition

Answer 20

how drugs equilibrate after entering the body

Question 21

at equilibrium what can be said about the distribution of the drug?

Answer 21

concentration of the nonionised molecules is the same in each compartment

there is more drug in larger body compartments

Question 22

volume of distribution definition

Answer 22

the volume of fluid required to contain the total amount of drug in the body at the same concentration as that is present in the plasma

Question 23

volume of distribution formula

Answer 23

dose/plasma concentration

Question 24

what does the volume of distribution represent?

Answer 24

the degree to which a drug is distributed in body tissue rather than plasma

Question 25

what does a higher Vd mean?

Answer 25

greater amount of tissue distribution

Question 26

plasma protein effect

Answer 26

bind to free drugs

reduce their ability to diffuse into tissue fluid, reducing renal clearance of drugs

Question 27

where does drug metabolism mainly take place?

Answer 27

liver

Question 28

two phases of metabolism + briefly processes that occur

Answer 28

phase 1- oxidation and reduction, hydrolysis

phase 2- conjugation using glycine, glutathione, methylation, acetylation, sulfation

Question 29

clearance definition

Answer 29

volume of plasma that is cleared of drug per unit of time

does not say how much drug is cleared, as this depends on volume of distribution

Question 30

clearance equation

Answer 30

rate of elimination/plasma concentration

Question 31

what does chemical modification do to the drug?

Answer 31

inactivates it

Question 32

half life definition

Answer 32

the period of time required for the concentration or amount of a drug in the body to be reduced by half

Question 33

what does a drug’s plasma half life depend on?

Answer 33

how quickly it is excreted or translocated to another compartment of destroyed

governed by clearance and distribution

Question 34

elimination is first order, what does this mean?

Answer 34

the time taken for half the drug to be eliminated is constant

Question 35

what is done to maintain prolonged therapeutic activity?

Answer 35

repeated oral dose regimens

Question 36

what does the time profile for repeated oral dose regimens look like?

Answer 36

concentration of drug drops after each dose but no longer drops as far as it did before

eventually begins to plateau

Question 37

time profile for continuous intravenous infusion described

Answer 37

drug is infuesed for a long period of time at a constant rate

concentrations increase until they approach a constant concentration

this is where the rate of elimination is equal to the infusion rate

Question 38

why must drugs be metabolised?

Answer 38

need to be made polar so they can be excreted from the body (prevents reabsorption)

Question 39

where may drugs be uptaken? + found in main two excrements

Answer 39

gut

bile and urine

Question 40

renal effect

Answer 40

lipid solubility and pKa can effect excretion at the kidneys

if the urine is acidic/alkaline the drugs may become non ionised or ionised and thus reabsorbed or excreted