Distribution

Question 1

What is distribution?

Answer 1

The reversible movement of drugs from the systematic circulation to the cells and interstitial tissues

Question 2

What do highly porous capillaries allow?

Answer 2

Paracellular diffusion

Question 3

What does the penetration of drugs into cells depend on?

Answer 3

Molecular size, lipid solubility and degree of ionisation

Question 4

Why may lipid solubility be important to a drug?

Answer 4

Some drug receptors are situation within cells

Question 5

What is HMG CoA reductase

Answer 5

The enzyme inhibited by the statin group of drugs used to lower bloop lipids in the treatment of hyperlipidaemia

Question 6

Why can insulin not cross the plasma membrane?

Answer 6

Too large (large molecular mass)

Question 7

Why can atracurium not cross the plasma membrane?

Answer 7

Highly ionised

Question 8

What is perfusion?

Answer 8

Blood flow

Question 9

Where is onset of action slower?

Answer 9

Skin, fat and bone

Question 10

What is the distribution of hydrophilic and large molecular weight drugs rate-limited by?

Answer 10

The permeability of the blood-tissue boundary

Question 11

Why does anaesthetic thiopental have a very short duration of action?

Answer 11

Time-dependent redistribution into fat, depletion in the brain.

Question 12

What is redistribution

Answer 12

The transfer of a drug from the brain, back into the blood and then into peripheral organs

Question 13

How do polar drugs exit the blood brain barrier?

Answer 13

Carrier-mediated transport

Question 14

How do large hydrophilic drugs exit the blood brain barrier?

Answer 14

Fenestrations

Question 15

How can some drugs be pumped back into the lumen?

Answer 15

P-glycoprotein, situated on the luminal surface of the endothelial cell plasma membrane

Question 16

Why is the CNS surrounded by a barrier?

Answer 16

Make it difficult for hydrophilic substances to penetrate, tight junctions do not allow paracellular diffusion

Question 17

Give three examples of drugs which can penetrate the blood-brain barrier by carrier mediated transport

Answer 17

1. Salicyclic acid
2. Valproic acid
3. L-DOPA

Question 18

How is L-DOPA transported into the brain?

Answer 18

By the L-system, transports large neutral amino acids

Question 19

What is required in the brain to treat Parkinson’s disease and why is this a problem?

Answer 19

Dopamine, cannot cross the blood brain barrier

Question 20

What converts L-DOPA to dopamine and why is this a problem?

Answer 20

DOPA decaroboxylase, converts L-DOPA in the periphery, reducing the amount able to cross the BBB

Question 21

What does carbidopa do?

Answer 21

Blocks DOPA decarboxylase, cannot cross the BBB, serves to increase peripheral L-DOPA levels and does not inhibit dopamine conversion in the brain.

Question 22

What is the placenta?

Answer 22

A structure that separates foetal and maternal blood

Question 23

How does the placenta behave?

Answer 23

Like a lipid membrane, acts as a metabolic barrier contains a variety of enzymes cyt p450s, dependent mono-oxygenases and monoamine oxidases to metabolise substrates.

Question 24

What can bound drugs not do?

Answer 24

Exit the blood system due to the high molecular mass of the protein-drug complex.

Question 25

What is the effect of aspirin on warfarin?

Answer 25

Increases the unbound concentration and enhances its pharmalogical effects

Question 26

What is a sequestered drug?

Answer 26

one which has accumulated to a concentration higher than in blood or plasma.

Question 27

What happens to highly lipid soluble drugs in adipose tissue?

Answer 27

Accumulates such that their concentration in this tissue is many times that in blood.