Pharmacokinetics

Question 1

What is the definition of pharmacokinetics?

Answer 1

Study of movement of a drug into and out of the body

What the body does to the drug

Question 2

What sorts of things can effect drug pharmacokinetics?

Answer 2

Renal function, liver function, GI function, CV function, disease, alcohol intake, pregnancy etc

Question 3

What is the mnemonic for the pharmacokinetic process?

Answer 3

ADME

Absorption
Distribution
Metabolism
Elimination

Question 4

Explain the difference between initial plasma concentrations of drugs that are given orally vs given IV

Answer 4

IV drugs - immediate peak plasma concentration

Oral drugs - takes time to be absorbed first so takes longer to reach peak plasma concentration

Question 5

What is the therapeutic window?

Answer 5

Range of doses in which a therapeutic response is caused without adverse effects

Question 6

What is Cmax?

Answer 6

Peak plasma concentration

Question 7

What is Tmax?

Answer 7

Time in which peak plasma concentration (Cmax) is reached

Question 8

What is bioavailability?

Answer 8

The fraction of a dose which enters the circulation to have an active effect

Question 9

What is the bioavailbility for an intravenous bolus?

Answer 9

100% (all enters bloodstream)

Note that for other routes, compare amount reaching the body comartment by that route with IV bioavailability

Question 10

On a plasma concentration/time graph, what equates to the bioavailability?

Answer 10

Area under the curve

Question 11

How would you calculate oral bioavailability (F) from a graph?

Answer 11

F = Area under the curve (oral) / Area under the curve (IV)

Question 12

What factors can affect bioavailability?

Answer 12

Drug formulation, age, whether its being taken with food, vomiting, malabsorption, first pass effect

Question 13

What is first pass metabolism?

Answer 13

Metabolism that occurs before the drug enters the systemic circulation

Question 14

Where can first pass metabolism occur?

Answer 14

Liver (via portal system)
Gut lumen
Gut wall

Question 15

Give an example of a drug that undergoes first pass metabolism in the liver

Answer 15

Propanolol, GTN

Question 16

Give an example of a drug that undergoes first pass metabolism in the gut

Answer 16

Benzylpenicillin, insulin

Question 17

What two key factors influence drug distribution?

Answer 17

Protein binding and volume of distribution

Question 18

What is the effect of protein binding on drugs?

Answer 18

They are inactive and can’t be eliminated; most drugs must be free to have a pharmacological effect

Question 19

What factors can influence protein binding?

Answer 19

Hypoalbuminaemia (eg malnutrition), pregnancy, renal failure, displacement by other drugs

Question 20

What is the volume of distribution (Vd)?

Answer 20

A measure of how widely a drug is distributed in body tissues (proportional to half life)

Question 21

How do you calculate Vd?

Answer 21

Vd = Dose/[Drug]t0

Question 22

What is half life proportional to?

Answer 22

Volume of distribution

Question 23

What can tissue distribution be affected by?

Answer 23

Specific receptor sites in tissues, regional blood flow, lipid solubility, disease states, drug interactions

Question 24

What is a pro drug?

Answer 24

A drug that is metabolised into a pharmacologically active drug

Question 25

Give an example of an inactive pro drug

Answer 25

Enalaprilat (inactive) to enalapril (active)

Question 26

What are the main cytochrome p450 isoenzymes?

Answer 26

CYP2D6, 2C9, 2C19, 3A4

Question 27

Give an example of CYP enzyme inhibition

Answer 27

Cimetidine inhibits a CYP which slows the metabolism of warfarin

Question 28

What does CYP2D6 metabolise?

Answer 28

Codeine, beta blockers, tricyclics

Question 29

What is CYP2D6 inhibited by?

Answer 29

Fluoxetine, paroexetine, haloperidol, quinidine

Question 30

How does age affect drug metabolism?

Answer 30

Metabolism reduced in elderly and children

Question 31

What is the main route of drug elimination?

Answer 31

Through the kidney | can also be through lungs, breast milk, swear, tears, bile, saliva

Question 32

Which 3 processes determine the renal excretion of a drug?

Answer 32

Glomerular filtration, passive tubular reabsorption, active tubular secretion

Question 33

What is an example of a drug that is actively secreted in the nephron?

Answer 33

Penicillin

Question 34

How does half life relate to clearance?

Answer 34

Inversely proportional

Question 35

What effect does a reduction in clearance (or GFR) have on half life?

Answer 35

Increases half life

Question 36

What is 1st order kinetics?

Answer 36

Rate of elimination is proportional to drug level - constant fraction of drug eliminated in unit time

Question 37

What is zero order kinetics?

Answer 37

Rate of elimination is a constant

Question 38

Why do most drugs exhibit zero order kinetics at high doses?

Answer 38

Because the receptors/enzymes become saturated

Question 39

Which drugs are more likely to result in toxicity: first order or zero order?

Answer 39

Zero order - fixed rate of elimination per unit time

Question 40

What is steady state?

Answer 40

The situation where the overall intake of a drug is fairly in dynamic equilibrium with its elimination. In practice, it is generally considered that steady state is reached when a time of 4 to 5 times the half-life for a drug after regular dosing is started.

Question 41

How many half lives are required to reach steady state?

Answer 41

4-5 half lives - from CpSS it also takes 4-5 half lives to eliminate most of the drug

Question 42

What is a loading dose?

Answer 42

An initial higher dose of a drug - used in acute cases, in drugs with long half life

Question 43

Give an example of a drug that usually requires a loading dose

Answer 43

Digoxin

Question 44

How do you calculate loading dose?

Answer 44

LD = Vd x target concentration of drug

Question 45

What is half life proportional to in terms of clearance?

Answer 45

t1/2 = 1/Clearance (GFR)