ADME 4

Question 1

how long does it take for a drug to distribute throughout the body?

Answer 1

1 minute

Question 2

is drug distribution evenly distributed?

Answer 2

no, Blood supply is richer to some areas of the body than others

Question 3

what are the reversible-interactions with blood constituents?

Answer 3

plasma proteins –
erthyrocytes–
tissue membranes

Question 4

what blood flow is highly perfused?

Answer 4

lung/kidney/liver/brain

Question 5

what blood flow is poorly prefused?

Answer 5

fat/ muscle/ bone

Question 6

a cell is no more than how far away from a capillary?

Answer 6

20-30 mm

Question 7

what cannot pass through capillaries?

Answer 7

plasma proteins

Question 8

what are the 3 types of capillaries?

Answer 8

contiuous, fenstrated,siduous

Question 9

what are the 3 main features of capillaries?

Answer 9

Endothelial cells provide an uninterrupted lining allowing only  smaller molecules (H2O, ions, urea, etc) to diffuse throughtight junctions
Pores (60-80nm diameter) spanned by a diaphragm of radially oriented fibrils allowing small molecules and limited amounts of protein to diffuse
Larger openings (30-40 μmdiameter)•allow red and white blood cells (7.5μm -25μm diameter) and various serum proteins to pass

Question 10

what is the purpose of the blood brain barrier?

Answer 10

maintains homeostasis of the brain

Question 11

what does the BBB protect against?

Answer 11

non-CNS active hormones and transmitters

Question 12

how does the BBB protect the brain?

Answer 12

it has tightly-fitted cells that do not contain pores

capillaries are coated in a fatty barrier

Question 13

how does drugs entering the CNS penetrate the BBB?

Answer 13

penetrate through tightly-fitted cells that do not contain pores and capillaries that are coated in a fatty barrier

Question 14

is diffusion of small hydrophobic molecules possible through the BBB?

Answer 14

yes

Question 15

do polar molecules leave the CNS - enter/leave early

Answer 15

yes

Question 16

what is the volume of distribution?

Answer 16

A measure of the tendency of a drug to move out of the blood plasma to another site (e.g. tissues, organs)

Question 17

what does the presence of an absorbent do?

Answer 17

The presence of adsorbent reduces drug concentration

Question 18

what are the 3 main categories of bodily water?

Answer 18

Extracellular Fluid
Intracellular fluid (~30-40% )
Transcellular fluid (2.5%)

Question 19

what are the two forms that drugs exist in?

Answer 19

bound and unbound

Question 20

how will drugs that are acid or bases exist in equilibrium?

Answer 20

will exist in equilibrium with the ir ionised forms(pH and pKa dependant)

Question 21

which form of the drug can move between compartments?

Answer 21

free drug

Question 22

what do drugs bound to the plasma department

Answer 22

Binds so strongly to plasma albumin that its Vdis used to measure plasma volume (~0.05 L kg-1body weight)

Question 23

what is the VD for most polar molecules and for drugs distributed in an extracellular compartment

Answer 23

0.2 L kg-1

Question 24

do polar compounds enter cells easily?

Answer 24

no due to low lipid solubility

Question 25

what is the vd of relatively lipid soluble drugs/distribution throughout bodily water?

Answer 25

0.55 L kg-1

Question 26

what is the Vd of the distribution intracellularly?

Answer 26

Many drugs with Vd> ~ 0.55 L kg-1

Question 27

what is the effect of binding the drug outside the plasma or partitioning?

Answer 27

into fat increases Vd beyond total body water.

Question 28

what does a small medium and large Vd indicate

Answer 28

small: Small Vd Mainly in plasma, little in tissues
medium: Medium Vd Similar concs. in plasma and tissues
large: large Vd Mainly in tissues, little in plasma

Question 29

what happens when protein binding occurs?

Answer 29

resulting drug-macromolecule complex does not cross membranes
reversible/ non-specific/ comp for sites

Question 30

what happens with drug interactions in drug distribution?

Answer 30

highly bound drug is partially displaced by another drug or chemical–
large increase in free drug concentration may lead to increase in therapeutic or toxic effect until steady-state re-established

Question 31

what is the most important plasma protein and why?

Answer 31

albunium, binds both anionic (acidic) and cationic (basic) drugs

Question 32

the amount of drug bound to the protein depends on 3 factors:

Answer 32

concentration of free drug
–affinity of drug for binding site
–concentration of protein

Question 33

what is the effect of protein binding on drug action?

Answer 33

Increases the amount of drug that has to be absorbed before a therapeutic level of unbound drug is reached
–May cause elimination of a drug to be delayed

Question 34

what is Warfarin?

Answer 34

Acidic, low VD(7 L)
–warfarin is strongly bound to plasma proteins (albumin), ~90%
–patient stabilised on ~10% of dose

Question 35

what competes with warfarin? and how?

Answer 35

Warfarin and aspirin compete for same albumin proteins–through co-administration of aspirin, warfarin may be displaced from plasma proteins
•Increases effective dose
•Decrease in clotting time

Question 36

what does Phenylbutazone displace and how?

Answer 36

displaces warfarin
–selectively inhibits metabolism of the active S-isomer
–prolongs prothrombintime and may result in increased bleeding

Question 37

what does Quinidine, verapamil and amiodarone displace?

Answer 37

displace digoxin
–reduce renal excretion
–may lead to dysrhythmias through digoxin toxicity

Question 38

what is drug-plasma binding?

Answer 38

Surface of drug plasma protein binds with drug molecules

Question 39

what are the binding forces present in the drug-plasma binding?

Answer 39

ionic interaction–hydrogen bonding–hydrophobic interactions–dipole-dipole interactions–p-pinteraction–p-cationinteraction