Lect 2 - Pharmacokinetics

Question 1

what is does ADME stand for

Answer 1

Absorption
Distribution
Metabolism
Excretion

Question 2

what are the different ways drugs can be administered and eliminated

Answer 2

administered

1. oral or rectal
2. percutaneous (skin)
3. intravenous
4. intramuscular
5. intrathecal
6. inhalation

excretion

1. liver - kidney - urine
2. faeces
3. milk, sweat
4. expiration

Question 3

what is “free drug”, what do non-free drugs bind to

Answer 3

free drug - drugs that are not bound to carrier protein, e.g. albumin

only the free drug causes effects (active)

non-free drugs (acidic) mostly bind to albumin

the less bound the drug, the higher it’s efficiency

Question 4

what is the most common protein drugs bind to

Answer 4

albumin

Question 5

is binding saturable

Answer 5

binding is saturable, so at certain concentration which binding is saturated, additional drugs added are all free

if binding is reversible, there will be an equilibrium

Question 6

define clearance

Answer 6

the irreversible elimination of drug either in form of unchanged in the urine or metabolised into other chemicals

Question 7

how do we quantify clearance, what are the two ways we talk about clearance, and what determines maximum clearance

Answer 7

volume of blood cleared unit per time such as through kidney or liver

or you can talk about it as whole body i.e. sum of all organs

minimum = 0
max = the blood flow rate through organ

Question 8

why is clearance important

Answer 8

it determines maintenance dose, i.e. steady state, which refers to the situation where the overall intake of a drug is fairly in dynamic equilibrium with its elimination

drug in = drug out

Question 9

what is maintenance dose

Answer 9

dose required to maintain target plasma concentration at steady state, i.e. drug in = drug out

MD = [steady-state] X clearance

Question 10

what is the volume of distribution

Answer 10

theoretical plasma volume that the total amount of administered drug would have to occupy, if it were uniformly distributed in the plasma, to provide the same concentration as it currently is in blood plasma

Question 11

how do we calculate volume of distribution, and what do the numbers indicate

Answer 11

V = drug total/drug in plasma (L)

higher numbers indicated that the drug is mostly distributed in rest of the body

Question 12

what is it important to know volume of distribution, what is the loading dose,

Answer 12

this help us find the loading dose

LD = VoD X total drug plasma concentration

the loading dose ensure we reach the therapeutic drug level quickly

Question 13

define half life

Answer 13

time taken for drug to be reduced by half

Question 14

what is important about first-order kinetic and half-life

Answer 14

the half life will not change with dose variations according to first order kinetics

Question 15

what are the two things half life can tell us

Answer 15

1. duration of a drug after single dose
2. how long it takes to reach steady state with constant dosing
3. we can also infer dosing frequency from the above information

Question 16

what is the definitive difference between 1-compartment and 2-compartment pharmacokinetics model

Answer 16

1-compartment doesn’t require a distribution stage. i.e. dose -> central ->peripheral

Question 17

what is the first-pass effect, what organ is responsible, are there individual differences

Answer 17

this refers to the extraction and metabolism (drug concentration is greatly reduced) of orally ingested drugs before it reaches systemic circulation

this reduces the bioavailability of the drug

this is achieved by the liver

this is differs for each individual

Question 18

what are some ways first-pass effect can be negated

Answer 18

Alternative routes of administration like suppository, intravenous, intramuscular, inhalational aerosol, transdermal and sublingual avoid the first-pass effect because they allow drugs to be absorbed directly into the systemic circulation

Question 19

define bioavailability

Answer 19

refers to the amount of drug that reaches systemic circulation

this is expressed as a fraction of the total dose