Pharmacokinetics

Question 1

Pharmacokinetics

Answer 1

Effect of drug on body

Question 2

Why does ADME need to be calculated?

Answer 2

Ensure dose results in correct plasma concentration in all individuals

Question 3

Absorption

Answer 3

Transfer of exogenous compounds from site of administrations o systemic circulation

Question 4

What must a drug be able to do to be absorbed?

What molecules are the best for this?

Answer 4

Cross cell membranes = lipid soluble and unionised

Question 5

Where to more drugs get absorbed

a) oral route - stomach
b) oral route - SI

Answer 5

b

Question 6

What heavily control rate of absorption in the stomach?

Answer 6

Rate of gastric emptying

Question 7

Why is the SI a more common site of absorption?

Answer 7

Large, highly vascularised SA

Enterocytes on epithelium contain metabolising enzymes and transporters

Question 8

Advantages of oral admin

Answer 8

Cheap

No skill = patient can do it

Question 9

Disadvantages of oral admin

Answer 9

Slower rate fo absorption
Dependent on pH
1st pass metabolism

Question 10

4 factors affecting GI absorption

What do they all impact?

Answer 10

Rate of gastric emptying
pH (poor absorption of strong acids/bases)
Physcio-chemical interactions (tetracycline binds to Ca rich foods)
Particle size and formation

Bioavailability

Question 11

Bioavailability?

Answer 11

Fraction of administered dose entering circulation

Question 12

1st pass metabolism?

Answer 12

Metabolism in intestine and liver before reaching systemic circulation

Question 13

How is absorption calculated from concentration time graph?

Answer 13

Area under the curve

Question 14

Bioavailability (F) of IV vs any other route?

Answer 14

IV - F = 1
Any other F<1
No first pass metabolism in IV

Question 15

Limitations of bioavailability?

Answer 15

Doesn’t consider individual variation e.g. gut motility

Question 16

Cmax and Tmax?

Answer 16

Maximum concentration after admin

Time that Cmax occurs

Question 17

Advantages of sublingual administration?

Answer 17

Fast response
Utilises drainage from mouth the sup vena cava so goes straight to intestine
Avoids its pass metabolism

Question 18

Why is rectal/vaginal a possible route?

Answer 18

Bypasses first pass metabolism
Rich blood supply
Useful for someone how is vomiting/diarrhoea

Question 19

Advantages of IV admin?

Answer 19

Bypass 1st pass metabolsim

Rapid response - straight into systemic

Question 20

Disadvantages of IV?

Answer 20

Painful
Needs a professional
Adverse reactions
expensive
Infection

Question 21

Advantages of intramuscular admin?

Answer 21

Local effect = good fro LA

Faster absorption than oral

Question 22

3 ways a drug can pass through membrane (diffusion)?

Answer 22

Passive diffusion down concentration gradient
Diffusion through aqueous channel
Carriers

Question 23

Many drugs are weak acids/bases.

What does this mean about ionisation state?

Answer 23

Unionised and ionised form dependent on pH

Question 24

How is strength of acid calculated?

Answer 24

pKa

Question 25

When pH=pKa how much of drug is ionised?

Answer 25

50%

Question 26

At what pH is a weak acid and weak base unionised?

Answer 26

Weak acid unionised at low pH (acidic) | Weak base unionised at high pH (basic)

Question 27

pH partitioning?

Answer 27

Acidic drugs accumulate in basic areas (where they are ionised so cannot pass through membranes) Basic drugs accumulate in acidic areas

Question 28

Aspirin is a weak acid | Is it mostly ionised or unsigned in the stomach?

Answer 28

Unionised

Question 29

Distribution

Answer 29

Reversible transfer from systemic circulation to tissue

Question 30

What is distribution dependent upon?

Answer 30

Ability to cross membrane, blood flow to tissues, extend of plasma binding proteins

Question 31

When equilibrium between tissue and plasma is reached, plasma concentration decreases as elimination begins. What occurs to tissue?

Answer 31

As plasma concentration decreases, drug diffuses back into plasma down the concentration gradient, this gets eliminated keeping the plasma concentration low so it keeps diffusing out = eliminated at same rate as plasma

Question 32

What effects rate of distribution?

Answer 32

Membrane permeability | Vascularisation

Question 33

What effects extent of distribution?

Answer 33

pKa of drug Lipid solubility Plasma binding protein Tissue binding

Question 34

What happens to drugs with high molecular weight or degree of plasma protein binding?

Answer 34

They are not distributed well because they cannot pass through the membrane

Question 35

What does amount of plasma protein binding depend upon?

Answer 35

Concentration of free drug and concentration of plasma protein Affinity for the free drug to the protein

Question 36

What causes tissue binding?

Answer 36

Composition of drug e.g. lipid soluble drugs bind to fat | Cellular components e.g. tetracycline binds teeth and bone as they contain Ca2+

Question 37

What distribution parameter shows distribution between plasma and tissue?

Answer 37

Vd = volume of distribution

Question 38

How is Vd calculated?

Answer 38

Total amount of drug in body/concentration of drug in plasma

Question 39

If the drug is confined to plasma Vd = a) low b) high

Answer 39

a

Question 40

If drug is not lipid soluble so is distributed in extracellular compartments the Vd will be a) higher than drug confined to plasma but lower than a well distributed drug b) lower than drug in plasma but higher than a well distributed drug?

Answer 40

a