Absorption and Distribution

Question 1

What are the 4 stages of pharmacokinetics?

Answer 1

1. Absorption
2. Distribution
3. Metabolism
4. Excretion

Question 2

What is absorption?

Answer 2

Transfer of the drug from site of administration into the general or systemic circulation

Question 3

If drugs given orally are wanting to reach small intestine, how are they protected?

Answer 3

Bulking agents added

Question 4

How does particle size affect absorption?

Answer 4

Has to breakdown into small enough particles to be absorbed via GI tract

If disintegrates slowly, the rate at which the drug is absorbed is limited by the rate of release and dissolution of drug from formulation

Question 5

How much of drug needs to disintegrate in GI tract to form solution before becoming absorbed?

Answer 5

75%

Question 6

How does formulation of particle affect absorption?

Answer 6

Has to be lipid soluble to be absorbed by gut (phospholipid bilayer)

Highly polar agents are absorbed slowly and incompletely

Question 7

What do GI tract enzymes/acid aid in?

Answer 7

Breaking down drugs

Question 8

How does slow motility of GI tract affect absorption?

Answer 8

Reduced absorption as takes long to reach SI

Question 9

How does hypermotility / slow motility of GI tract affect absorption?

Answer 9

Hypermotility –> Bowels are moving excessively, reduced absorption, drug won’t be in bowels long enough

Slow motility –> Reduced absorption as takes long to reach SI

Question 10

Do drugs have to be charged or uncharged to cross membrane?

Answer 10

Uncharged (and lipid soluble)

Question 11

What is the degree of ionisation dependent on?

Answer 11

pH of their environment

Question 12

What happens to drugs in stomach (ionisation wise)?

Answer 12

Stomach very acidic - acids become more ionised but bases become more unionised

Acids are proton donors, bases are proton acceptors

Basic drugs will cross membrane more easily than acidic ones in stomach

Question 13

What happens to drugs in small intestine (ionisation wise)?

Answer 13

Acidic drugs cross membrane more easily than basic drugs

Question 14

What happens to strong acids and bases in water?

Answer 14

Dissociate 100%

Question 15

Why do you not need a higher dose for drugs delivered via injection?

Answer 15

Delivered straight into systemic circulation - bypasses liver (1st pass metabolism)

Question 16

What is distribution?

Answer 16

The process by which the drug is transferred reversibly from one location to another within the body:
• From the general circulation into the tissues as concentrations in blood increase
• From the tissues into blood as blood concentrations decrease

Question 17

How does distribution mainly occur?

Answer 17

Mainly by passive diffusion of unionised form across cell membrane

Question 18

Describe conc after IV injection?

Answer 18

High plasma conc and drug rapidly equilibrates with well perfused tissue –> gives high conc in tissue

Question 19

What is the volume of distribution?

Answer 19

Theoretical volume that would be necessary to contain the total amount of an administered drug that it is observed in the blood plasma

If drug stays in plasma, its volume of distribution is smaller than if it is distributed widely in tissues (large volume = distributed to all tissues)

Question 20

What is the volume of distribution used to determine?

Answer 20

• Used to determine the dose necessary for a desired blood concentration of a drug
• Also used for estimating a blood concentration in the treatment of overdose

Question 21

What proteins act as drug carriers?

Answer 21

Albumins and glycoproteins (reversible)

Question 22

If a drug is bound/unbound to protein what are effects?

Answer 22

Bound –> inert
Unbound –> free to have effect

Plasma protein binding affects distribution

Question 23

What must drug bind to to have effect?

Answer 23

Right receptor in tissue

Question 24

How does regional blood flow affect distribution?

Answer 24

o If area is well perfused, more drug to region (liver, heart, kidney)
o Skin, skeletal muscle and fat are poorly perfused organs, drug needs to be given more often or for longer period of time to have effect here

Question 25

What does the administration of a drug that becomes highly bound to a patient who is already taking a drug that is highly protein bound cause?

Answer 25

Displacement of drug already bound which produces increased unbound concentration of drug and biological activity

Question 26

If a drug is widely distributed in tissues, how does the increase in unbound drug affect plasma conc?

Answer 26

The increase in unbound drug is rapidly redistributed to body tissues and unbound plasma concentration rapidly returns to negligible amount

Question 27

If a drug is only 20% bound (poorly albumin bound), what does a reduction of 5% in bound drug cause?

Answer 27

Unbound plasma concentration increases from 80% to 85% (negligible)

Question 28

If a drug is 95% bound (more strongly albumin bound), what does a reduction of 5% in bound drug cause?

Answer 28

* Any changes in concentration has big effect, leads to side effe ts * Unbound plasma concentration increases from 5% to 10% (significant)

Question 29

When are changes in plasma protein binding significant?

Answer 29

Significant for drugs which are greater than 90% bound to plasma proteins

Question 30

What are cell membranes composed of?

Answer 30

Phospholipid bilayer

Question 31

What molecules can cross cell membranes?

Answer 31

Only those not bound to proteins

Question 32

How do molecules cross cell membranes by passive diffusion?

Answer 32

 Molecules move from area of high conc to low conc |  Ion channels may facilitate passive diffusion down conc gradient

Question 33

How do molecules cross cell membranes by facilitated diffusion?

Answer 33

 Molecules combine with membrane-bound carrier protein  Movement still dependent on conc gradient  Slightly faster than passive

Question 34

How do molecules cross cell membranes by active transport?

Answer 34

 Requires energy |  Molecule transported can be transported against conc gradient

Question 35

How do molecules cross cell membranes by pinocytosis?

Answer 35

 Compound engulfed by cell membrane and vesicle formed  Vesicle taken into cell - Molecule released

Question 36

How does absorption differ in children and elderly?

Answer 36

Children --> unreliable in neonates and greater transcutaneous absorption Elderly --> in general unchanged

Question 37

How does distribution differ in children and elderly?

Answer 37

Children & Elderly --> fat components of body mass tends to be proportionately greater, acting as reservoir