Pharmacokinetics: Absorption & Distribution

Question 1

Define: Pharmacokinetics

Answer 1

The study of factors which determine the amount of chemical agents at their site of action at various times after their application (e.g. absorption, distribution)
i.e. what the body does to a drug

Question 2

List 3 questions that are asked in pharmacokinetics

Answer 2

How much drug reaches the target organ?
Where in the body does the drug go?
How long does the drug stay in the body?

Question 3

Describe the perfect drug

Answer 3

It reaches its biological target
Remains in the body long enough to achieve its therapeutic aim
Does not cause harm while in the body

Question 4

What determines the absorption of a drug?

Answer 4

The chemical properties of a drug determines its absorption

Question 5

Which factor is the most important physical property of a drug in pharmacokinetics?

Answer 5

Lipophilicity/hydrophilicity

Affects absorption, distribution, potency and elimination

Question 6

What is logP a measure of?

Answer 6

How lipophilic/hydrophilic a drug is

- its ability to dissolve in ethanol/water

Question 7

List 3 problems with a drug that is too lipophilic

Answer 7

It would:
Be insoluble in aqueous media (non-polar)
Bind too strongly to plasma proteins
Distribute into lipid bilayers

Question 8

Name a problem with a drug that is too hydrophilic?

Answer 8

It will not be able to cross plasma membranes (too polar)

Question 9

What is pH trapping?

Answer 9

When a molecule passes from one environment/compartment to another via the plasma membrane (e.g. urine to plasma) and can’t pass back through the other way

Question 10

What happens to acidic molecules in pH trapping?

Answer 10

Molecules pass from urine to plasma
Formulated in its unionised form (DH)
Can pass through the membrane and dissociates into its ionised form (D-)
It is therefore trapped due to the H-H equation

Question 11

What happens to basic molecules in pH trapping?

Answer 11

Molecules pass from plasma to urine
Unionised form of the molecule (D) passes through the membrane
Gets protonated once in the other compartment (acidic) = DH+

Question 12

List 4 enteral routes of drug administration

Answer 12

Oral
Sublingual
Rectal
Inhalation

Question 13

List 4 topical routes of drug administration

Answer 13

Skin
Cornea
Vagina
Nasal mucosa

Question 14

List 3 parenteral routes of drug administration

Answer 14

Injection:
Subcutaneous
Intravenous
Intramuscular

Question 15

Which factors decide the method of drug delivery to use?

Answer 15

Speed of delivery - IV fastest
Metabolism of compound - first pass effect for orally administered = decrease in concentration of drug
Targeting - where does the drug need to reach to have desired therapeutic effect?

Question 16

List 4 factors which affect oral absorption (and therefore bioavailability)

Answer 16

GI motility
Splanchnic blood flow (abdominal organs)
Formulation of medicine
Physiochemical properties of drugs

Question 17

Define: Bioavailability (F)

Answer 17

The fraction of administered dose that reaches the systemic circulation

Question 18

List 2 factors which can cause incomplete bioavailability of orally administered drugs

Answer 18

Incomplete absorption (so drug lost in faeces)
First pass metabolism (starts metabolising before it reaches the bloodstream)

Question 19

What is the equation to calculate total body water?

Answer 19

Total body water = 0.6 x body weight

Question 20

What makes up the total body’s water?

Answer 20

Extracellular = interstitial fluid & plasma

Intracellular

Question 21

Define: Volume of distribution

Answer 21

The volume of fluid required to contain the total amount of drug in the body (D) at the same concentration as that present in the plasma (Cp)

Question 22

What is the formula to calculate the volume of distribution (Vd)?

Answer 22

Vd(L) = total amount of drug in the body/blood concentration

–> Vd = D/Cp

Question 23

What does a small Vd mean?

Answer 23

Drug retained in plasma

e. g. affinity to plasma proteins
0. 1 L/kg

Question 24

What does a high Vd mean?

Answer 24

Large distribution of drug around the body

–> 115 L/kg

Question 25

List 4 factors that affect tissue distribution

Answer 25

Physiochemical features of the drug
Pharmacological properties of the drug
Blood flow in the organ/tissue
Barriers of organ/tissue

Question 26

Explain how physiochemical features of the drug affect tissue distribution

Answer 26

Size of the molecule - large = more difficult to cross membrane
pKa of drug - pH difference between plasma and tissue can cause accumulation (pH trapping)

Question 27

Explain how the pharmacological properties of a drug affect tissue distribution

Answer 27

e.g. binding of molecule to plasma or tissue proteins may allow uptake into tissue so it is not available to be active at its therapeutic site

Question 28

Explain how blood flow in the organ/tissue affects the tissue distribution of a drug

Answer 28

Decides the rate at which the drug is distributed to various organs
Therefore drugs are rapidly distributed to highly perfused tissues (e.g. brain, liver, kidney, heart)
Increased blood flow received = increased drug

Question 29

How do barriers of the organ/tissue affect the tissue distribution of a drug?

Answer 29

2 major barriers = blood-brain barrier & placenta
Most drugs that penetrate the placenta and the blood-brain barrier are highly lipophilic
Some drugs bind to glucose transporters to get access to the brain