Pharmacokinetics

Question 1

What is pharmacokinetics?

Answer 1

The effect of the body on drugs

Question 2

What are the four main processes in pharmacokinetics?

Answer 2

Absorption, distribution, metabolism and elimination

Question 3

What are some examples of enteral drug administration?

Answer 3

(Delivery into GI tract)

Oral, sublingual, rectal

Question 4

What are some examples of parenteral drug administration?

Answer 4

Intravenous, intramuscular, subcutaneous

Question 5

What is the length and diameter of the small intestine?

Answer 5

6-7m length, 2.5cm diameter

Question 6

What is the total surface area for absorption in the small intestine?

Answer 6

30-35m^2

Question 7

What does the constant GI movement do to the drug?

Answer 7

Mixing - presents drug molecules to GI eptihelia

Question 8

What is the typical transit time through the small intestine?

Answer 8

3-5 hours

Varying motility = 1-10 hours

Question 9

What is a common mechanism for the absorption of lipophilic drugs?

Answer 9

Passive diffusion - diffuse directly down concentration gradient into GI capillaries

Question 10

What is PKa?

Answer 10

The pH at which 50% of the species is ionised

Question 11

What drugs can be absorbed via passive diffusion?

Answer 11

Lipophilic

Weak acids/bases (eg valproate - anti-epileptic)

Question 12

Where are SLCs highly expressed?

Answer 12

GI, hepatic and renal epithelia

Question 13

How can molecules or solutes with net ionic charge within GI pH range can be carried across GI epithelia by what?

Answer 13

Solute Carriers

Question 14

How is fluoxetine absorbed?

Answer 14

Co-transported with Na+ ion

Question 15

How is B lactam antibiotics/penicillin absorbed?

Answer 15

Co-transported with H+ ion

Question 16

What factors can affect drug absorption?

Answer 16

GI length/SA
Drug lipophilicity/pKa
Density of SLC expression in GI
First pass metabolism

Question 17

What is first pass metabolism?

Answer 17

A phenomenon of drug metabolism whereby the concentration of a drug is greatly reduced before it reaches the systemic circulation

Question 18

How does first pass metabolism affect drug absorption?

Answer 18

In gut lumen: enzymes can denature some drugs

In gut wall/liver: cytochrome P450s and conjugating

Question 19

What are phase I and II enzymes?

Answer 19

Phase I - cytochrome P450s

Phase II - conjugating enzymes

Question 20

What is bioavailability?

Answer 20

Proportion of a drug which enters the circulation when introduced into the body and so is able to have an active effect.

Question 21

If a drug is given intravenously, what is the bioavailability?

Answer 21

100% as there are no physical barriers to overcome

Question 22

What is the equation for oral bioavailability (F)?

Answer 22

F = amount reaching systemic circulation/total drug given IV

Question 23

What are the factors affecting drug distribution?

Answer 23

• Drug lipophilicity (if lipophilic, can move across membranes)
• Capillary permeability
• Drug pKa and local pH
• Presence of OATs/OCTs
• Degree of drug binding to plasma/tissue proteins

Question 24

What kinds of proteins could drugs bind to in circulation?

Answer 24

Eg albumin, globulins, lipoproteins, acid glycoproteins

Question 25

What does binding of drugs to plasma/tissue proteins do?

Answer 25

Decreases free drug available for binding, acts as 'reservoir' Binding can be up to 100% (aspirin is around 50%)

Question 26

What is the total body fluid in an average human?

Answer 26

42 litres

Question 27

How much fluid is extracellular in an average human?

Answer 27

14 litres

Question 28

How much fluid is plasma in an avergae human?

Answer 28

3 litres

Question 29

What is apparent volume of distribution? (Vd)

Answer 29

The theoretical volume that would be necessary to contain the total amount of an administered drug at the same concentration that it is observed in the blood plasma.

Question 30

What do smaller Vd values mean?

Answer 30

Less penetration of interstitial/intracellular fluid compartment

Question 31

What do larger Vd values mean?

Answer 31

Greater penetration of interstitial/intracelullar fluid compartment

Question 32

What is the equation for volume of distribution?

Answer 32

Vd = drug dose/concentration of plasma drug

Question 33

Where does drug metabolism mostly take place?

Answer 33

Liver via phase I and II enzymes

Question 34

What ionic charge do metabolised drugs have?

Answer 34

Increased ionic charge

Question 35

What are drugs activated by phase I metabolism called?

Answer 35

Prodrugs

Question 36

What is an example of a prodrug?

Answer 36

Codeine to morphine (higher affinity for opioid receptor)

Question 37

How do phase II enzymes enhance hydrophilicity?

Answer 37

Further increase ionic charge - add to phase I

Question 38

How do phase II enzymes catalyse?

Answer 38

Sulphation, glucorinadation, glutathione conjugation, methylation, N-acetylation

Question 39

How do phase I enzymes catalyse?

Answer 39

Redox, dealkylation, hydroxylation

Question 40

What does phase I and II metabolism do?

Answer 40

Increase ionic charge to enable rapid elimination from the body. Metabolism usually renders pharmacologically inactive.

Question 41

What factors affect drug metabolism?

Answer 41

Age, sex, general health, other drugs, genetic polymorphism

Question 42

What is Carbamezepine (CBZ) and what does it induce?

Answer 42

Anti-epileptic metabolised by CYP3A4 - induces CYP3A4 - lowering its own levels affecting control of epilepsy

Question 43

What is an example of CYP450 inhibition?

Answer 43

Grapefruit juice

Question 44

Where is the main route of drug elimination?

Answer 44

Kidney (but other routes include bile, lung, breat milk, sweat, tears)

Question 45

What are the three processes in renal excretion?

Answer 45

- Glomerular filtration - Active tubular secretion - Passive tubular secretion

Question 46

What is clearance?

Answer 46

Rate of elimination of a drug from the body

Question 47

What is total body clearance?

Answer 47

Total body clearance = hepatic clearance + renal clearance

Question 48

What is clearance measured in?

Answer 48

ml/min

Question 49

What is drug half life?

Answer 49

The amount of time over which the concentration a drug in plasma decreases to one half of that concentration value it had when it was first measured

Question 50

What is half life dependent on?

Answer 50

Vd and CL

Question 51

What happens to half life if CL stays the same and Vd increases?

Answer 51

Half life increases

Question 52

What happens to half life if CL increases and Vd stays the same?

Answer 52

Half life decreases

Question 53

What is the clinical importance of zero order kinetics?

Answer 53

Drugs at or near therapeutic dose with saturation kinetics - more likely to result in ADRs/toxicity.