clincal pharmacokinetics

Question 1

what do we need to know about absorption of a drug?

Answer 1

• what fraction of the dose is absorbed through intestinal wall
• what fraction gets through liver into systemic circulation

Question 2

what is the symbol F?

Answer 2

bioavailability

Question 3

what is the bioavailability of caffeine?

Answer 3

approximately 100% so F=1

Question 4

what do we need to know about distribution of the drug?

Answer 4

how extensively does the drug distribute into the tissues of the body which depends on:
- physiochemical characteristics
- plasma protein binding
- tissue binding
-molecular weight

• size of patient

Question 5

how to calculate max concentration?

Answer 5

F x dose (mg) / volume of distribution (L)

Question 6

when do you not need to worry about bioavailability?

Answer 6

when it is IV loading because it goes straight into the bloodstream

Question 7

what is clearance?

Answer 7

the volume of the plasma cleared of drug per unit time
- depends on size and organ function

Question 8

what does the dosing rate equal?

Answer 8

excretion rate

Question 9

how to calculate dosing rate using steady state conc and clearance?

Answer 9

Dosing rate= Cav (mg/L) x Cl (L/h) / F

Question 10

how to calculate stead state conc if there is a dosing interval

Answer 10

Cav (mg/L) = F x dose(mg) / Cl (L/h) x dosing interval (h)

Question 11

what is the elimination rate constant?

Answer 11

ratio of clearance/ volume of distribution

Question 12

how to calculate the concentration after a certain amount of time in the body

Answer 12

Ct = D/V exp (^-k.t)

Question 13

what is the elimination half life?

Answer 13

time taken for the concentration to fall by half

Question 14

how to calculate elimination half life?

Answer 14

0.693/ k

Question 15

how many significant figures do you use for elimination constant?

Answer 15

3

Question 16

how to calculate the concentration of infusion?

Answer 16

ct = infusion rate / CL (1-e^-k x Tinf)

Question 17

how to calculate the steady state concentration of infusion?

Answer 17

Css= IR/CL

Question 18

What is the concentration time profile of an elderly patient?

Answer 18

Higher Css and takes longer to get to steady state, decline is slower (takes longer to eliminate drug)

Question 19

what are physiochemical factors that influence bioavailability?

Answer 19

• solubility and dissolution
• stability in acid
• ionised/unionised form
• formulation

Question 20

what are physiological and pathological factors affecting bioavailability?

Answer 20

• metabolism and transporter activity in intestinal wall
• first pass metabolism in the liver
• other drugs/ foods
• other disease states

Question 21

what is an example of absolute bioavailability?

Answer 21

IV route

Question 22

how to calculate absolute bioavailability?

Answer 22

F = AUC oral/ AUC IV

Question 23

how to calculate absolute bioavailability of the doses are different ?

Answer 23

F = AUC oral/ AUC IV x dose iv/dose oral

Question 24

what does bioequivalence studies compare?

Answer 24

• AUCS
• Cmax values
• T max values

Question 25

what is epidural injection?

Answer 25

into epidural space (anaesthesia)

Question 26

what is intracerebral injection?

Answer 26

directly into brain

Question 27

what is intraventrical injection?

Answer 27

directly into ventricles in brain

Question 28

what is inta-atrial injection?

Answer 28

into an artery

Question 29

what is intra-articular injection?

Answer 29

into joint space (osteoarthritis)

Question 30

what is intracardiac injection?

Answer 30

directly into heart

Question 31

what is intraocular injections?

Answer 31

into eye

Question 32

what is intraosseous injection?

Answer 32

directly into bone

Question 33

what is intraperitoneal injection?

Answer 33

into peritoneal cavity

Question 34

what is intrathecal injection?

Answer 34

into spinal cavity (anaesthesia, chemotherapy)

Question 35

what is first order absorption?

Answer 35

constant proportion per time units/h

Question 36

what is zero order absorption?

Answer 36

- constant amount per time (units mg/h) then stops - when input stops, the conc declines exponentially

Question 37

what is ka?

Answer 37

absorption rate constant

Question 38

what happens when absorption rate is greater than elimination rate?

Answer 38

plasma conc increases with time

Question 39

what is the peak conc?

Answer 39

absorption rate equals the elimination rate

Question 40

what happens when absorption rate is less than elimination rate?

Answer 40

plasma concentration decreases with time

Question 41

when does absorption occur to after the peak?

Answer 41

at least 5x absorption half lives have passed (97% absorbed)

Question 42

what does a high ka value mean in term of the graph?

Answer 42

fast absorption (steeper graph)

Question 43

what factors determine first order absorption?

Answer 43

Dose, availability, salt/ molar correction Input rate (Ka), elimination rate (k=Cl/v) Time after administration

Question 44

what does the time to reach max conc depend on?

Answer 44

absorption rate (formulation) elimination rate (patient characteristics)