week 3

Question 1

define drug elimination

Answer 1

when a drug is irreversibly removed from the body, can happen via metabolism or excretion

Question 2

define drug metabolism/biotransformation

Answer 2

= the process of chemical modification of drugs usually by enzymatic reaction within the body

Question 3

define catabolic reaction

Answer 3

breakdown

Question 4

define anabolic reaction

Answer 4

synthesis

Question 5

two main organs involved in elimination

Answer 5

liver & kidney

Question 6

define prodrug

Answer 6

drug is inactive before metabolism e.g., codeine (latex of poppy flower)

Question 7

define active drug

Answer 7

drug takes effect directly (three types when metabolised)

Question 8

list the three types of metabolites of an active drug

Answer 8

Less active metabolite
More active metabolite
Inactivate metabolite

Question 9

what is the common property of a compound after it has been metabolised

Answer 9

results mostly in the formation of more water-soluble compounds (hydrophilic) so it can be excreted through urine

Question 10

what are the two phases of metabolism

Answer 10

phase 1: forms a derivative (functionalisation)

phase 2: conjugation = forms a further molecule making it more water soluble

Question 11

do all drugs go through all phases

Answer 11

no and some don’t get metabolised at all

Question 12

define phase 1 & example of reactions

Answer 12

= introducing a reactive (polar functional) group

• catabolic

1. oxidation
2. reduction
3. hydrolisis = more water soluble

Question 13

what is the main enzyme that is responsible for the reactions in phase 1 of metabolism

Answer 13

CYP3A4/5

Question 14

where are enzymes located

Answer 14

• liver, ER

Question 15

how do the drugs reach the enzymes

Answer 15

they must cross the plasma membrane

Question 16

what is different about the large family of enzymes called cytochrome P459 enzymes

Answer 16

• amino acid sequence
• sensitivity to inhibitors & inducers
• specificity of catalysed reaction

Question 17

define phase 2

Answer 17

= conjugation (attach) drug with endogenous substance = transferase enzymes

• anabolic

Question 18

what does phase 2 usually result in

Answer 18

the production of inactive products

Question 19

where does phase 2 commonly occur

Answer 19

the liver

Question 20

define stereoisomers

Answer 20

two or more compounds differing only in spatial arrangement of their atoms

Question 21

define stereoselectivity

Answer 21

• even though the drug is the same their stereoisomer may diff in pharmacological effect & metabolism
• one might be linked to toxicity

Question 22

factors that affect metabolism

Answer 22

• genetic factors
• induction & inhibition cytochrome P450 enzymes
• concentration-dependent biotransformation
• disease-induced factors

Question 23

define an inducer

Answer 23

makes the enzyme work faster = more substrate becomes the product so less warfin for example (table)  could be bad more clotting (therapeutic failure)

Question 24

define an inhibitor

Answer 24

inhibit enzymes = inhibit enzyme = inhibit metabolise = increase substrate = toxicity: internal bleeding e.g., increase grapefruit juice consumption

Question 25

define excretion

Answer 25

= removal of a drug or metabolite from the body

Question 26

in what form are most drugs excreted

Answer 26

unchanged (20%) or as polar metabolites

Question 27

routes of drug excretion

Answer 27

1. kidneys 2. hepatobiliary system 3. pulmonary 4. sweat, saliva, tears 5. breast milk

Question 28

what are the three important processes that can affect drug renal excretion

Answer 28

1. Glomerular filtration = drugs cross glomerular filter freely, unless highly bound to plasma protein (then would go to efferent) 2. Active tubular secretion = basic drugs in their pronated form are transported by organic cation transporters (OCTs) while acidic drugs are transported by organic anion transporters (OATs) (needs energy) 3. Passive tubular reabsorption = lipid-soluble drugs are not efficiently excreted in the urine because they are passively reabsorbed along with water by diffusion across the tubular barrier

Question 29

example of alcohol metabolised

Answer 29

aka ethanol is metabolised into acetaldehyde & if lacking the enzyme to further metabolise build up of acetaldehyde = causes flushing of face

Question 30

what proteins are important to carry drugs in hepatobiliary x3

Answer 30

Organic cation transporters (OCTs) organic anion transporters (OATs) P-glycoproteins (P-gps)

Question 31

what happens in the hepatobiliary circulation (excretion) x3

Answer 31

- drugs are transported from plasma to bile - After reaching the small intestine, drugs can be reabsorbed to be excreted by the kidneys or recirculate (hepatobiliary system) until completely excreted in the urine or faeces - Glucuronide conjugated drugs can be metabolised in the intestine & the free drug reabsorbed can be reactivated

Question 32

factors that can affect excretion - drug interactions

Answer 32

- altering protein binding & hence filtration - inhibiting tubular secretion - altering urine flow

Question 33

define elimination half life

Answer 33

time taken for plasma concentration (Cp) to decrease by half

Question 34

how does the half-life assist in prescribing drugs x3

Answer 34

``` o Duration of action after single dose. The longer the half-life, the longer the plasma concentration in the therapeutic range oDosing frequency (how often have to take it) oTime required to reach steady state (need of a loading dose) ```

Question 35

the usual time for drug elimination

Answer 35

6 half lifes

Question 36

half life in comparison to Vd & clearance

Answer 36

o T ½ is directly proportional to volume of distribution & inversely proportional to total clearance (CLtot)

Question 37

define clearance

Answer 37

o Clearance is the volume of plasma that is “cleared” completely of the drug per unit time (L/H

Question 38

what is the equation for clearance

Answer 38

rate of elimination divided by the plasma concentration

Question 39

how does the total clearance assist in prescribing drugs

Answer 39

- determines maintenance does & rate of administration

Question 40

define steady state

Answer 40

rate of input to the body is equal to the rate of elimination

Question 41

at what time does steady state usually occur

Answer 41

after 3-5 half lives with repeated dosing or sustained release of drug

Question 42

equation for steady state x 2

Answer 42

1. rate of drug administration divided by clearance | 2. if the drug is taken orally then Fx dose divided by the total clearance x dosing interval

Question 43

equation for initial concentration

Answer 43

q (administered dose) divided by volume of distribution

Question 44

what does CL stand for

Answer 44

clearance

Question 45

define elimination rate constant

Answer 45

(kel) represents the fraction of drug in the body eliminated per unit time (1/time)

Question 46

equation for kel x2

Answer 46

0.693 divided t1/2 total clearance divided by volume distribution

Question 47

what does a kel of 0.4 s^-1 mean

Answer 47

that 40% of the drug is eliminated each second

Question 48

what are the two types of elimination kinetics

Answer 48

1. first-order elimination kinetics | 2. zero-order kinetics

Question 49

define first order kinetics of elimination

Answer 49

constant proportion of drug is eliminated per unit of time = concentration changes amount = curve on the graph

Question 50

define zero-order kinetics (saturation)

Answer 50

= constant amount of drug is eliminated per unit of time = independent of concentration = negative linear line

Question 51

for a drug to be metabolised and excreted needs to be absorbed into which compartment

Answer 51

central compartment

Question 52

importance of pharmacokinetics x4

Answer 52

Drug development Individualised dose regimens Rational dose adjustment Determining loading dose

Question 53

most drugs are secreted into the renal tubule via

Answer 53

active transport