Session 10.4 Pharmacokinetics 2

Question 1

what is bioavailability

Answer 1

the fraction of a defined dose which reaches its way into a specific body compartment - usually CVS/circulation

through IV = 100% as no physical/metabolic barriers to overcome… so used as a reference/comparison for other routes

Question 2

how is oral bio availability measured

Answer 2

measure the 2 graphs (plasma conc v time):
total area under curve = IV route
total area under curve = oral route

F (0 no drug through-1)= amount reaching systemic circulation via oral route/total given by IV

Question 3

what is bioavailability do

Answer 3

informs choice of administration route by how much enters systemic circulation

Question 4

what is the first stage of drug distribution

Answer 4

bulk flow - from heart via arteries to capillaries
diffusion - capillaries to interstitial fluid to cell membranes to targets
BUT there may be barriers to diffusion such as other interactions and non target binding

Question 5

what does drug distribution look at

Answer 5

where it could reach and interact with both therapeutic and non therapeutic targets as well as other molecules such as proteins and lipids

Question 6

how does diffusion across capillaries affect drug distribution

Answer 6

different capillary types - continuous, fenestrated, sinusoid - variation in entry increases for lipophilic molecules, could aid drug entry to interstitital fluid or unaid it. one way it could aid is the capillary membrane has OAT and OCT

Question 7

a drug can be

Answer 7

hydrophilic - carries net charge at physiological pH…dependent on transport mechanisms
or lipophilic - easily pass

Question 8

what are the factors affecting drug distribution

Answer 8

drug molecule
capillary permeability
drug pKa and local pH
presence of OAT/OCT - in capillary or traget tissue membrane
interaction with proteins

Question 9

what proteins do drugs bind to

Answer 9

albumen - globulins

lipoproteins - acid glycoproteins

Question 10

how do drugs binding to protein affect drug distribution

Answer 10

only free drug molecules can bind to target sites, so if bound to protein by weak electrostatic forces eg:HSA with multiple binding sites- unable to bind so less free drug available for binding
these plasma/tissue ptoein bound drugs acts as dynamic resevoir
there are varying number of binding sites for given drug, some drugs want to bind to same site on same albumen…competition which affects free plasma cnc and pharmacodynamics

Question 11

drug molecules

Answer 11

are solutes in body fluid compartments

Question 12

plasma water

Answer 12

plasma water … 3l/3.5

Question 13

extracellular water

Answer 13

plasma water and intersitital water … 14l

Question 14

total body water

Answer 14

plasma water, intersitital water, intracellular water…42l

Question 15

drugs move from

Answer 15

plasma -> intersitital -> intracellular

Question 16

increasing penetration by drug into interstitial and intracellular fluid compartments

Answer 16

decreased plasma drug concentration

increased Vd

Question 17

some drugs

Answer 17

easily enter intracellular

or stay in plasma

Question 18

what barrier is found between plasma and interstitial and what is present there

Answer 18

capillary membrane barrier which has carrier OAT and OCT

Question 19

what barrier is found between interstitial and intracellular and what is present there

Answer 19

carrier OCT/OAT - if not lipophilic need to get into intracellular space to enter target tissue
or drug targets if lipophilic

Question 20

what is volume of distribution (Vd)

Answer 20

modelled that all compartments are one compartment and says drug distributes throughout body at time 0 which it doesnt, it takes time = PRETEND
referenced to plasma concentration
dependent on factors that affect transport across barrier, if aid = larger volume of distribution

Question 21

smaller Vd value

Answer 21

less penetration of interstitial/intracellular fluid compartments

Question 22

how is Vd measured

Answer 22

drug dose/plasma concentration of drug at time of 0
if lots of litres = high penetration
if units in litres = assume 70kg body
id units in litres/kg = to patients body weight

Question 23

Vd can be affected by

Answer 23

lots of clinical conditions - pregancy, marked changes in body weight, renal failure, cancer, anaesthetic etc

Question 24

how is Vd affected by high BMI

Answer 24

given lipopholic drug - distribute across all adipose tissue, so more drug required to reach brain

Question 25

how is Vd affected by low BMI

Answer 25

lipophilic drugs not taken up by other compartments so must give a lower dose of drug

Question 26

how does renal failure affect Vd

Answer 26

drug circulating may be removed slowly so hang around in body longer

Question 27

how does being younger affect Vd

Answer 27

as child - 75% body water

expression of OAT and OCT different as well as phase 1 and 2 enzymes