Drug Distribution

Question 1

How do drugs move across the epithelium/endothelium?

Answer 1

Paracellular

Transcellular = pinocytosis, active transport and diffusion

Question 2

Which barrier is more permeable for metabolism of substances?

Answer 2

Liver endothelium

Question 3

Which barrier is more permeable for substances to be eliminated?

Answer 3

Renal endothelium in the glomerulus

Question 4

Which barrier is less permeable to protect sensitive organs?

Answer 4

Blood-Brain barrier, to protect sensitive organs from circulating chemicals or pathogens.

Question 5

What is pKa?

Answer 5

The hydrogen ion concentration (pH) at which:
50% of the drug is ionised
50% is un-ionised

Question 7

What is the solubility of Unionised drugs?

Answer 7

They are lipid soluble, so diffuse across the membrane.

Question 8

What are plasma proteins?

Answer 8

Plasma proteins are major transporters of endogenous lipids and steroid hormones.

Question 9

What is protein binding?

Answer 9

In the blood, drugs can bind to plasma proteins. Drugs can exist in bound and unbound forms, this is a reversible reaction.

Question 10

What is the importance of protein binding?

Answer 10

Some proteins are too large to pass through epithelia/endothelial
Only free drugs can bind their site of action (receptors/enzymes)

Question 11

What are the implications on bound proteins?

Answer 11

They remain in the blood
Unable to exert their pharmacological effect
Cannot be metabolised or excreted
Becomes ‘stored in reservoirs’ and can impact volume of distribution

Question 12

Which drug type can reach equilibrium across different compartments?

Answer 12

Unbound drugs can reach an equilibrium across different compartments.
Bound drugs can’t.

Question 13

Which proteins can act as a reservoir?

Answer 13

Bound proteins.

Question 14

What effect does protein binding have on a drug’s half life?

Answer 14

Heavily protein Bound drugs have a longer half life.

Question 15

What factors affect protein binding?

drug factors

Answer 15

Affinity of drug to protein binding sites
Drug concentration
Plasma protein concentration

Question 16

Which protein plasma is the most important for drug binding?

Answer 16

Albumin

Question 17

What is the solubility of ionised drugs?

Answer 17

They are Insoluble so don’t diffuse across the membrane.

Question 18

Why is there a change in the curve when a drug is given at a higher dose?

Answer 18

Plasma proteins become saturated.

Most drugs are given at doses that wouldn’t cause plasma proteins saturation

Question 19

Where is tissue binding?

Answer 19

Fat
Bone
Muscle

Question 20

Which drug can travel more easily across a cell membrane?

Answer 20

Highly lipophilic drugs

Question 21

How do bisphosphonates work?

Answer 21

By binding to calcium in bones and inhibits resorption.

Question 22

How is osteoporosis caused?

Answer 22

By increased resorption which causes thinning of the bones, increasing the risk of fractures.

Question 23

What are two examples of bisphosphonates?

Answer 23

Alendronic acid - via tablet once a week

Zoledronic acid - via injection once a year

Question 24

Where do highly lipophilic drugs bind?

Answer 24

To fat stores

Question 25

Why would a drug wear off more quickly in an overweight patient?

Answer 25

Overweight patients have a greater ratio of lipid to other body tissue.
Calculating a dose according to weight doesn’t take this into account in the ratio.
Drugs that are highly lipid bound will distribute more freely in overweight patients than underweight patients .

Question 26

What is the Volume of distribution?

definition

Answer 26

The apparent volume into which a drug disperses in order to produce the observed plasma concentration.

Question 27

What is the equation for volume of distribution?

Answer 27

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

Question 28

What is the extent of distribution of a drug throughout the body?

Answer 28

Plasma
Interstitial fluid
Intracellular fluid
Fat

Question 29

What happens if a drug remains in the plasma?

Answer 29

Volume of drug distribution will be low

Drug dose can be low

Question 30

What happens if a drug disperses to other fluids/tissues?

Answer 30

Volume of distribution will be high

Drug dose need needs to be high

Question 31

What drug factors affect volume of distribution?

Answer 31

Plasma protein binding
Tissue binding
Physiochemical properties of drug: size, charge, pKa, lipid solubility, water solubility

Question 32

What are patient factors that affect volume of distribution?

Answer 32

Age, sex, level of hydration, body muscle/ fat proportion

Water distribution

Question 33

Why is volume of distribution useful?

Answer 33

It’s a guide for loading (initial) doses of drugs.

Question 34

Volume of distribution of drugs, give examples of high and low values:

Answer 34

Heparin = 5L
Gentamicin = 18L
Chloroquine = 13,000L