Lecture 9 - Pharmacokinetics

Question 1

define pharmacokinetics

Answer 1

what the body does to a drug

Question 2

how can the ways of getting a drug to a patient be changed?

Answer 2

formulation

site of administration

Question 3

how does formulation change how the drug gets to the patient?

Answer 3

solid (rate of action depends on dissolution)
liquid
patient compliance is important (less frequent is easier)

Question 4

how does site of administration change how the drug gets to the patient?

Answer 4

local

systemic - enteral or parenteral

Question 5

define oral bioavailability

Answer 5

proportion of the dose given orally that reaches the systemic circulation in an unchanged form

Question 6

how can bioavailability be expressed?

Answer 6

amount or rate

Question 7

how is bioavailability expressed as amount?

Answer 7

measured by area under curve of blood drug level vs time

Question 8

how is bioavailability expressed as rate?

Answer 8

measured by peak height and rate of rise of drug level in blood

Question 9

what is the therapeutic ratio?

Answer 9

maximum tolerated dose/minimum effective dose OR ld50 (lethal dose to 50% of people)/ed50 (effective dose in 50% of people)

Question 10

what is the first pass effect?

Answer 10

substances absorbed from the lumen of the ileum enter venous blood, the hepatic portal vein and pass through the liver where it may be extensively metabolised

Question 11

how much of an oral dose of paracetamol is usually metabolised by the first pass effect?

Answer 11

90%

Question 12

define drug distribution

Answer 12

the theoretical volume into which a drug has distributed assuming that this is occurring instantaenously

Question 13

how is drug distribution calculated?

Answer 13

amount given/plasma concentration at time 0

Question 14

what level of the drug exerts an effect?

Answer 14

free level NOT the total

Question 15

when is the free level of the drug important?

Answer 15

if the drug is highly bound to albumin

if the drug has a small volume of distributionif the drug has a low therapeutic index

Question 16

what is an object drug?

Answer 16

class 1 drug
used at a dose much lower than the number of albumin binding sites

Question 17

what is a precipitant drug?

Answer 17

class 2 drug
used at a dose greater than the available albumin binding sites

Question 18

what happens when class 1 and class 2 drugs are administered simultaneously?

Answer 18

class 1 are displaced by class 2, raising free levels of the object drug
higher risk of toxicity

Question 19

what are the precipitant drugs for the object drug warfarin?

Answer 19

sulphonamides
aspirin
phenytoin

Question 20

what are the precipitant drugs for the object drug tolbutamide?

Answer 20

sulphonamides

aspirin

Question 21

what is the precipitant drug for the object drug phenytoin?

Answer 21

valproate

Question 22

how is rate of drug metabolism calculated?

Answer 22

vmax[C]/km+[C]

Question 23

when is a drug metabolised by first order kinetics?

Answer 23

when a drug is used at a concentration lower than km

Question 24

what is the rate of metabolism with first order kinetics?

Answer 24

vmax[C]/km

Question 25

what does first order kinetics mean?

Answer 25

metabolism is proportional to drug concentration

Question 26

what is the graph of first order kinetics?

Answer 26

straight line when a log scale on the y axis vs time

Question 27

when is a drug metabolised by zero order kinetics?

Answer 27

when a drug is used at a concentration much higher than km

Question 28

what is the rate of metabolism with zero order kinetics?

Answer 28

vmax[C]/[C]

Question 29

what does zero order kinetics mean?

Answer 29

the enzyme is saturated so the rate of decline of plasma drug level is constant, regardless of concentration

Question 30

what is the graph of zero order kinetics?

Answer 30

straight line when normal (not log) plasma concentration is plotted against time

Question 31

when will a steady state be reached with zero order kinetics?

Answer 31

within 5 half lives of the drug

Question 32

if an immediate effect is needed with zero order kinetics, what is done?

Answer 32

loading dose

Question 33

what does first order kinetics give?

Answer 33

predictable therapeutic response from dose increases

Question 34

what does zero order kinetics give?

Answer 34

therapeutic response that can suddenly escalate as elimination mechanisms saturate

Question 35

what is phase 1 of drug metabolism?

Answer 35

a reactive group is exposed on the parent molecule or added to the molecule generates a reactive intermediate that can be conjugated with a water soluble molecule to form a water soluble complex

Question 36

what are the most common chemical reactions in phase 1?

Answer 36

oxidation reduction hydrolysis

Question 37

what does phase 1 require?

Answer 37

cytochrome p450 and nadphenzymes are inducible and inhibitable

Question 38

what drugs does phenobarbitone induce?

Answer 38

warfarin | phenytoin

Question 39

what drug does rifampicin induce?

Answer 39

oral contraceptive

Question 40

what drug do cigarettes induce?

Answer 40

theophylline

Question 41

what drugs does cimetidine inhibit?

Answer 41

warfarin | diazepam

Question 42

how can drugs bypass phase 1?

Answer 42

already have a reactive group on their molecule

Question 43

what is phase 2 of drug metabolism?

Answer 43

reactive intermediate from phase 1 is conjugated with a polar molecule to form a water soluble complex

Question 44

what is the most common conjugate?

Answer 44

glucoronic acid

Question 45

what is glucoronic acid?

Answer 45

available by product of cell metabolism

Question 46

what can drugs be conjugated with?

Answer 46

glucoronic acid sulphate ions glutathione

Question 47

what does phase 2 require?

Answer 47

specific enzymes | uridine diphosphate glucoronic acid (udpga) - high energy cofactor

Question 48

how does the kidney control drug excretion?

Answer 48

only free unbound drug is filtered through glomerulus drugs can be actively secreted by the tubule urine pH can determine how much of the drug is excreted

Question 49

how will urine pH affect drug excretion?

Answer 49

for weak acids - alkaline urine will make the drug ionised so there will be less tubular absorption - increase excretion for weak bases - acidic urine will increase excretion as the base will be ionised so the drug stays in the lumen