drug distribution

Question 1

what must a drug do after it has been absorbed?

Answer 1

it must be available for biological action and distribution to tissues

Question 2

what conditions must be met for a drug to become active?

Answer 2

drug must leave the bloodstream and enter the inter or intracellular spaces

Question 3

what factors affect the way that a drug is distributed throughout tissues?

Answer 3

plasma protein binding
tissue perfusion
membrane characteristics
transport mechanisms
diseases
other drugs
elimination

Question 4

what membrane characteristics can affect tissue distribution?

Answer 4

the blood-brain barrier
blood-testes/ovary barrier
whether the drug is lipid soluble
whether the drug is actively transported or not

Question 5

what are some examples of plasma proteins that drugs bind to?

Answer 5

albumin

alpha 1 glycoprotein

Question 6

what form of the drug is biologically active?

Answer 6

the unbound form

Question 7

is binding reversible or irreversible?

Answer 7

reversible

Question 8

what can change the amount of bound drug?

Answer 8

renal failure
hypoalbuminaemia
pregnancy
other drugs
saturability of binding

Question 9

what percentage of the drug has to be bound for protein binding to be an important factor?

Answer 9

more than 90%

Question 10

does tissue distribution have to be large or small in order for protein binding to be an important factor?

Answer 10

small

Question 11

what is the apparent volume of distribution? (Vd)

Answer 11

the volume in which a drug seems to distribute within the body

Question 12

what does a higher volume of distribution indicate?

Answer 12

a greater ability of the drug to diffuse into and through membranes

Question 13

what should the the theoretical volume of distribution be?

Answer 13

40L

Question 14

what would the Vd be if the drug stays in the extracellular fluid but cannot penetrate cells?

Answer 14

12L

Question 15

what would the Vd be in a drug that is highly protein bound?

Answer 15

3L

Question 16

what would the Vd be if the drug was sequestered in the extravascular lipid compartment?

Answer 16

> 40L

Question 17

what is clearance defined as?

Answer 17

the theoretical volume of fluid from which a drug is completely removed over a period of time?

Question 18

what is clearance a measure of?

Answer 18

elimination

Question 19

what is renal clearance dependent on?

Answer 19

concentration of drug and urine flow rate

Question 20

what is hepatic clearance dependent on?

Answer 20

metabolism and biliary excretion

Question 21

what is the half life of a drug?

Answer 21

the time taken for the drug concentration in the blood to decline to half of the current value

Question 22

how is the half life calculated?

Answer 22

o.693Vd/Cl

Question 23

what does the half life of a drug depend on?

Answer 23

volume of distribution and rate of clearance

Question 24

what effect does prolongation of the half life of a drug have?

Answer 24

increases the toxicity of the drug due to a reduction in clearance or due to a large volume of distribution

Question 25

what clinical application does knowledge of a drugs half life have?

Answer 25

allows us to figure out how often a drug needs to be administered

Question 26

how many doses of a drug does it usually take for plasma levels of said drug to stabilise? (steady state)

Answer 26

4-5

Question 27

what is drug elimination?

Answer 27

removal of active drug from the body

Question 28

what does drug elimination determine?

Answer 28

length of action of the drug

Question 29

what 2 parts is drug elimination made up of?

Answer 29

metabolism (usually in the liver) | excretion (usually in the kidney but also the biliary system/gut and lung)

Question 30

what are the 3 principal mechanisms employed by the kidney with regards to drug excretion?

Answer 30

glomerular filtration passive tubular reabsorption active tubular secretion

Question 31

when would an unbound drug NOT be filtered at the glomerulus?

Answer 31

if the molecular size, charge or shape is excessively large

Question 32

what happens if the glomerular filtration rate is decreased?

Answer 32

clearance is reduced

Question 33

what happens to the concentration of a drug as the filtrate moves down the renal tubule?

Answer 33

it increases

Question 34

where does passive diffusion occur in the kidney?

Answer 34

the distal tubule and collecting duct

Question 35

what are the only drugs that are reabsorbed in passive tubular reabsorption?

Answer 35

un ionised drugs

Question 36

what kinds of drugs are actively secreted into the proximal tubule?

Answer 36

acidic and basic compounds

Question 37

what kinds of drugs is active tubular secretion most important in eliminating?

Answer 37

protein bound cationic and anionic drugs

Question 38

what is the term given for when drugs are reabsorbed from the bile into the circulation?

Answer 38

entero-hepatic circulation

Question 39

when does entero-hepatic circulation continue until?

Answer 39

until the drug is metabolised in the liver or excreted by the kidneys