pharmacokinetic and ADME

Question 1

define pharmacokinetics

Answer 1

A branch of pharmacology that studies the kinetic change or movement of a drug in the body over time.

Question 2

what does ADME stand for in pharmacokinetics?

Answer 2

A = Absorption

D = Distribution

M = Metabolism

E = Elimination

ADME refers to the process of a drug in the body

Question 3

What is the therapeutic window?

Answer 3

the time range between injury and treatment during which the drug treatment is still effective

Question 4

what do MTC and MEC refer to in regards to the plasma concentration of a drug

Answer 4

MTC = maximal tolerated concentration

MEC = minimum efficacious concentration

Question 5

this image shows the ideal but impossible plasma concentration-time relationship for drug administration

why is this impossible?

Answer 5

unless injected intravenously, there will always be a delay between the time of administration and the drug reaching the blood plasma

Question 6

how was this drug administered based on the graph?

Answer 6

intravenous injection

Question 7

what causes the decline after the drug concentration peaks in the blood plasma

Answer 7

the drug is metabolised and excreted

Question 8

name some absorption routes of drug administration through…

• lungs?
• gut?
• muscle?
• skin?

Answer 8

• lungs

inhalation of gases

• gut

Oral, Rectal, sublingual

• muscle

intramuscular injection

• skins

subcutaneous injection/cream

Question 9

which of these lines shows the time course of plasma levels for:

• Oral
• i.m
• i.v.

Answer 9

Question 10

what are the two main absorption mechanisms?

and how do they work?

Answer 10

passive diffusion - drugs cross the cell membrane according to their physio-chemical properties, no energy is required

active diffusion - drugs cross the cell membrane by carrier or transporter proteins

Question 11

The two forms of passive diffusion are transcellular diffusion and paracellular diffusion

Whats the difference between them?

Answer 11

transcellular diffusion - involves permeating through the cell

paracellular diffusion - involves the drug moving in between the cells

Question 12

there are 3 forms of active transport

1. active efflux
2. carrier-mediated transport
3. endocytosis

briefly describe them

Answer 12

• Active efflux, certain types of transporters on the apical (external) (e.g. gut) and basal (internal) (blood) surfaces efflux the drug back to the apical side of the cell membrane.
• Carrier-mediated transport involves the uptake of the drug from the apical side of the membrane into the basal side.
• Endocytosis does not require transporter proteins but still requires energy. It involves the transport of the drug through cells via vesicles

Question 13

Drug distribution is the reversible transfer of drugs between the site of measurements and other sites within the body

what are some factors which greatly determine a drug’s distribution from the blood plasma?

Answer 13

• lipid solubility
• membrane permeability
• Plasma Protein binding
• size
• blood perfusion (ability to travel in the blood)
• ionisation state of the drug

Question 14

What tissue depots?

Answer 14

different tissues in the body in which drugs can accumulate, the distribution of these drugs depends on blood flow to that tissue

Question 15

in the blood-brain barrier (BBB) diffusion is only possible for _____ soluble drugs, _____ soluble drugs tend to diffuse more slowly

Answer 15

in the blood-brain barrier (BBB) diffusion is only possible for lipid-soluble drugs, water soluble drugs tend to diffuse more slowly

Question 16

the placenta controls blood flow to the foetus, what is the distribution of drugs to the foetus limited by

Answer 16

• lipid solubility
• size

Question 17

define volume distribution (Vd)

what does a Vd > 40 litres suggest about the drug distribution?

what does Vd < 10 litres suggests about the drug distribution?

Answer 17

• The theoretical volume that would be necessary to contain the total amount of an administered drug at the same concentration that it is observed in the blood plasma
• Vd > 40 litres indicates storage of drug in tissues
• Vd < 10 litres suggests drug is largely restricted to plasma and interstitial fluid

Question 18

what are two other inter-individual variability factors in drug response

Answer 18

• plasma protein binding
• body weight

Question 19

metabolism is the irreversible loss of drug from the body by biochemical conversion

what two roles does it have in the pharmacokinetics of drugs?

Answer 19

• limits the life of a substance in the body
• promotes excretion and reduces the binding affinity

Question 20

what 3 properties do metabolic reactions increase when metabolising a drug

Answer 20

1. water solubility
2. reactivity
3. size

Question 21

• Most metabolism occurs in the liver
• this is known as first-pass metabolisms and functions to reduce the bioavailability of a compound

first-pass metabolism is a two step process

Phase I and Phase II, what do these phases involve

Answer 21

• Phase I = oxidation, reduction, hydrolysis - creates a functional group
• Phase II = conjugation - polar group added to functional group

Question 22

metabolism can often lead to the production of reactive metabolites, what is the impact of these?

Answer 22

• Inactive pro-drug converted to an active agent by metabolism
• Metabolite responsible for side effect profile

Question 23

• Pharmacokinetic models allow the calculation of the appropriate dose and dosing interval

basic PK calculations are based on concentration-time curves using what measurement of area

Answer 23

AUC - area under curve

Question 24

on a concentration-time curve,

what is the Cmax?

what is Tmax?

Answer 24

Cmax = the peak concentration of drug in plasma

Tmax = time at which the peak concentration occurred

Question 25

what’s the difference between AUC and AUMC on a concentration-time curve

Answer 25