pharmacokinetics and clearance

Question 1

what is pharmacodynamics

Answer 1

what a drug does to our body

Question 2

what is pharmacokinetics

Answer 2

what our body does to drugs

Question 3

what is the changing concentration of drug in the body a result of

Answer 3

absorption, distribution, metabolism and excretion

Question 4

what is an important consideration regarding drug concentrations

Answer 4

for a drug to have the clinically desired effect it usually needs to be maintained at a certain concentration, at its site of action for the required amount of time

Question 5

what is the therapeutic window

Answer 5

at a dose between what is toxic and the minimal dose at which it has a therapeutic effect

Question 6

what journey does the term absorption refer to

Answer 6

from where drug was administered to the blood plasma

Question 7

where can drugs be adminstered

Answer 7

gut, skin, muscle, CSF or lungs

Question 8

what drugs are not absorbed

Answer 8

intravenous drugs are introduced directly to the plasma

Question 9

where do most drugs have to reach to have their physiological effect

Answer 9

blood plasma

Question 10

what 2 forms do drugs usually exist

Answer 10

bound to proteins and unbound

Question 11

what form of drug is clinically useful

Answer 11

unbound

Question 12

what is bound drug referred to

Answer 12

drug reservoir as binding is reversible

Question 13

describe drug distribution in well perfused tissues vs poorly perfused

Answer 13

drug circulation is achieved by circulation so..
well perfused eg heart liver kidneys - rapid
poorly perfused eg fat and skeletal muscle - slow

Question 14

4 body fluid compartments

Answer 14

plasma water 5%
interstitial water 16%
intracellular water 35%
transcellular water 2%

Question 15

where do water-soluble drugs stay largely

Answer 15

eg atenolol
largely in blood and interstitial fluid

Question 16

where do lipid-soluble drugs largely stay

Answer 16

eg opioid fentanyl
concentrates in fat

Question 17

where does the majority of drug metabolism occur

Answer 17

liver

Question 18

what other organs and tissues contribute to drug metabolism

Answer 18

GI tract mucosa, kidneys and lungs

Question 19

what does a drug have to do to be metabolised by the liver and why?

Answer 19

must enter a hepatocyte - crossing the plasma membrane - means hydrophobic drugs are more easily metabolised by the liver

Question 20

how can hydrophilic drugs enter a hepatocyte

Answer 20

membrane transport proteins

Question 21

what do liver enzymes do to drugs

Answer 21

generally modify them to make them inactive or more easily excreted

Question 22

what are prodrugs

Answer 22

modified by the liver to form the pharmacologically active molecule
eg perindopril, ace inhibitor, metabolised to form perindoprilat, which has a therapeutic effects

Question 23

what are the 2 types of metabolic reactions drugs can be modified by

Answer 23

phase 1 - catabolic
phase 2 - anabolic

Question 24

describe phase 2 metabolic reactions

Answer 24

result in the attachment of a chemical group ie conjugation of the drug. most common groups incl sulfate, glucuronyl, added molecules which then form the point of attachment for the conjugation reaction

Question 25

describe where metabolising liver enzymes are embedded

Answer 25

in the SER

Question 26

what is the most important system of enzymes for drug metabolism in the liver

Answer 26

cytochrome P450 CYP system these are haem proteins and add one atom of oxygen to the drug molecule to form a hydroxyl group

Question 27

what are other potential routes for drug excretion

Answer 27

biliary excretion, faeces, respiration

Question 28

what is the predominant route of drug excretion

Answer 28

renal

Question 29

why is it important to know a drugs clearance rate

Answer 29

determining dosage, higher clearance = higher dose clearance low = low levels needed to maintain a therapeutic concnetration

Question 30

what does the rate of drug excretion depend on

Answer 30

on a balance between drug filtration, secretion and reaborption

Question 31

how does the drug get to the glomerulus

Answer 31

afferent arteriole

Question 32

what drug is filtered at the glomerulus

Answer 32

only the unbound

Question 33

what influences drug filtration

Answer 33

as well as protein binding, the size of the drug also small drugs not protein-bound can be filtered but larger drugs eg Heparin, even when protein-bound cant be filtered and are poorly excreted by the kidneys

Question 34

3 factors affecting the amount of drug filtered into the Bownman's capsule

Answer 34

renal blood flow glomerular filtration rate plasma protein binding

Question 35

what can drug molecules do for more rapid excretion

Answer 35

can be actively secreted into the renal tubule

Question 36

are secretory mechanisms specific?

Answer 36

not specific for the drug but take advantage of molecular similarities between the drug and naturally occuring substances

Question 37

how are organic bases transported

Answer 37

eg PAH transported in cationic form, against their electrochemical gradient by OAT (organic anionic transporter) family proteins

Question 38

how are organic bases transported

Answer 38

eg morphine in their cationic forms by OCT (organic cationic transporter) familt protein

Question 39

describe the effect of plasma binding on drug excretion

Answer 39

relatively small effect at the PCT since there are highly efficient transporters that mediate active secretion which removes unbound drug and decreases plasma protein binding

Question 40

what increases the conc of drug in tubular lumen

Answer 40

glomerular filtration and tubular secretion

Question 41

what decreases conc of drug in tubular lumen

Answer 41

reabsorption

Question 42

what factors influence amount of drug reabsorbed

Answer 42

urine flow rate, lipid solubility of the drug and whether or not it is ionised

Question 43

what happens if the tubule is freely permeable to a drug

Answer 43

as water is reabsorbed along the length of the tubule, the drug can be reabsorbed passively with its conc gradient this means that the lipid-soluble drugs which can cross the tubular cell membrane are excreted poorly by the kidneys, whereas polar drugs which don't cross the tubular membrane easily are excreted well

Question 44

what is degree of ionisation dependent on

Answer 44

on the pH of the fluid it is dissolved in

Question 45

does ionisation increase or decrease reabsorption

Answer 45

decreased reabsorption of drug

Question 46

describe drugs as acids or bases

Answer 46

can be weak acids or bases weak acids = become anionic in an alkaline urine (give up H+) -> excretion increases weak bases = become cationic in an acidic urine (bind to H+ ions) and excretion is increased

Question 47

what is ion trapping

Answer 47

when the charged form of the drug remains in the tubules and more of it is excreted

Question 48

how can we increase a drugs excretion

Answer 48

pH of urine can be changed to favour the charged form which cant be easily reabsorbed

Question 49

how can the effect of pH on drug excretion be predicted

Answer 49

Henderson-Hasselbalch relationship

Question 50

how would increasing urine flow rate affect drug reabsorption

Answer 50

decrease

Question 51

explain why polar drugs eliminated primarily by the kidneys which isn't activated by metabolism must be used with special care in patients with renal disease

Answer 51

if not activated by metabolism, then renal excretion primarily determines duration of action, dose may need modified if GFR is reduced

Question 52

what pH would the renal tubular fluid normally be at the PCT and beyond, and as a result would the excretion of acids or bases usually be favoured

Answer 52

normally acidic pH favouring base excretion

Question 53

define reabsorption

Answer 53

the process by which water and solutes are removed by the nephron from the tubular fluid

Question 54

define secretion

Answer 54

the process by which substances are created and discharged by the gland and

Question 55

what is clearance

Answer 55

removal of substances from the plasma and their excretion in the urine

Question 56

what is the clearance of a solute

Answer 56

removal of substances from the plasma and their excretion in urine as a substance

Question 57

example of a substance which is completely cleared

Answer 57

PAH

Question 58

what is the GFR

Answer 58

vol of fluid filtered from the renal glomerular capillaries into the Bowman's capsule per unit time

Question 59

criteria for a substance to be used to measure GFR

Answer 59

freely filterable by the glomerulus neither reabsorbed nor secreted from the tubules must be inert