Pharmacokinetics - Absorption and Distribution

Question 1

Pharmacokinetics

Answer 1

what the body does to the drug

Question 2

ADME

Answer 2

absorption
distribution
metabolism
excretion

Question 3

What are the minimum requirements for clinical efficacy?

Answer 3

• absorption: overcome physiological barriers
• distribution: achieve the target with appropriate conc
  (overcome internal physiological barriers)

Question 4

If a drug is not readily absorbed,

Answer 4

it can be difficult to get its concentration up to the therapeutic level

Question 5

If a drug is absorbed well but distributed to compartments where it is not needed, then

Answer 5

the drug may not have much effect

Question 6

If a drug is not metabolised well, then

Answer 6

too much of the drug may be circulating

Question 7

if a drug is not excreted quickly enough, then

Answer 7

it may exist at dangerous levels in the body

Question 8

Advantages of an oral route of administration of drugs

Answer 8

• convenient
• acceptable
• no special skills
• variety of pharmaceutical solutions for different
  patients

Question 9

Three categories of factors influencing absorption:

Answer 9

• pharmaceutical properties
• physicochemical properties
• physiological properties

Question 10

Factors influencing absorption: pharmaceutical properties:

Answer 10

• pharmaceutical form

Question 11

Factors influencing absorption: physicochemical properites:

Answer 11

• solubility
• pH drug (acidic drugs are better absorbed in the
  stomach; alkaline drugs better in the intestine)
• molecular weight

Question 12

Factors influencing absorption: physiological properties:

Answer 12

• surface area ( stomach vs intestine; massaging area
  after IM admin)
• contract time (mouth vs stomach vs intestine)
• concentration of the drug on the absorption site
• absorption site (blood flow, pH)
• interactions (drug-drug, drug-food)
• transport systems (glycoprotein P, amino acids,
  transporters)

Question 13

Factors influencing absorption: oral route:

Answer 13

• drug stability in the digestive tract
• presence of food/other drugs/interactions
• alteration in gastric emptying and intestinal motility
• physicochemical properties suitable for crossing
  membranes
• resistance to drug metabolism (first pass metabolism)

Question 14

Oral route

Answer 14

Question 15

Clinical relevance: drug interactions:

Answer 15

Question 16

Bioavailability definition

Answer 16

the fraction of (oral) administered drug which reaches the systemic circulation of the patient as an intact drug

Question 17

Bioavailability equation

Answer 17

oral area under curve/ IV area under curve

AUC = determines the total amount of drug in the systemic circulation

Question 18

If a drug has an oral bioavailability of 20%, the oral dose needed for therapeutic effectiveness will be how different to the corresponding IV dose?

Answer 18

oral dose needs to be 5x the IV dose

Question 19

What does bioavailability take into account?

Answer 19

• both absorption and metabolic degredation by enzymes in the gut wall and liver

Question 20

Absorption and bioavailability

Answer 20

Question 21

a change in motility changes the amount of absorption of a drug.

true or false?

Answer 21

false
changes the rate of absorption of a drug

Question 22

first pass metabolism

Answer 22

Question 23

administration and absorption

Answer 23

Question 24

administration and AUC

Answer 24

Question 25

A 55-year gentleman admitted to Emergency department with chest pain. He has a history of angina. Amongst his other medications he reports that he has some GTN (glyceryl trinitrate) tablets which he was told to use when required for chest pain. On questioning he tells you that he does not use them as he does not find any benefit from them when he swallows them.

Answer 25

GTN if taken orally is 100% metabolised by first pass metabolism

Question 26

Distribution: four compartmental model:

Answer 26

Question 27

How does distribution of drugs occur?

Answer 27

- most drugs transfer by passive diffusion - across capillary walls down a conc grad - into interstitial fluid until conc of free drug in interstitium is equal to that in plasma

Question 28

Volume of distribution

Answer 28

a measure of how widely a drug is distributed between various body fluids and tissues

Question 29

Volume of distribution equation

Answer 29

amount of drug in the body (dose)/ measured plasma conc) Cp

Question 30

For drugs that accumulate outside the plasma compartment, Vd may be

Answer 30

greater than the volume of total body water

Question 31

Factors influencing distribution

Answer 31

- drug physicochemical properties (solubility) - drug protein binding - drug particle size - blood flow - pH - lipid solubility - plasma protein binding

Question 32

Lipid Solubility and volume of distribution:

Answer 32

- drugs can have a higher or lower lipid/water solubility - water soluble are mainly confined to the blood and body water compartments = lower Vd - lipid soluble drugs are widely distributed to tissues = higher Vd

Question 33

routes that avoid first pass metabolism

Answer 33

- IV - IM - IS - inhaled - transdermal

Question 34

Plasma protein binding and Vd

Answer 34

drugs highly bound to proteins remain in plasma hence not as much in other compartments so a lower Vd

Question 35

Plasma protein binding:

Answer 35

- reversible and saturable - unbound or free fraction distributes - unbound portion is responsible for clinical effect

Question 36

Advantage of plasma protein binding drugs

Answer 36

- half-life is longer - less tablets to take

Question 37

plasma protein binding

Answer 37

Question 38

Plasma protein binding: most important protein:

Answer 38

albumin

Question 39

amount of drug that binds to a protein depends on:

Answer 39

- concentration of free drug - affinity for the binding sites - concentration of protein

Question 40

Factors that increase the fraction of unbound drug:

Answer 40

- saturability - displacement - late pregnancy - renal impairment - low plasma albumin

Question 41

Process of the transfer of the drug from the site of administration into the systemic circulation is the definition for: - absorption - distribution - excretion - metabolism - volume of distributino

Answer 41

absorption

Question 42

If you want to convert an IV dose to an oral dose, and the drug has an oral bioavailability of 25%, how much higher would the oral dose need to be? - 2x - 3x -4x -5x -10x - same dose

Answer 42

4x higher than IV dose

Question 43

A water soluble drug would have a volume of distribution higher or lower when compared with a lipid soluble drug?

Answer 43

lower Vd