Lecture 3: Distribution

Question 1

concentration vs time cuves: drug distributes to and is restrivted to these tissues (INITIAL COMPARTMENT)

Answer 1

-constant slope downwards

Question 2

concentration vs time cuves: drug distributes to tissues at different rates (AFTER FULL DISTRIBUTION)

Answer 2

-curved increase and decrease

Question 3

what causes the offset of the pharmacologic effect for thiopental?

Answer 3

-driven by redistribution of drug

-hits peak concentration in brain then redistributes concentration to lean tissue

Question 4

perfusion rate limited

Answer 4

-how quickly drug can be delivered

Question 5

permeability rate limited

Answer 5

-how quickly drug moves across membrane

Question 6

which condition shows slower tissue distribution

Answer 6

permeability rate limited

Question 7

Convection

Answer 7

-rate related to pressure

Question 8

Diffusion

Answer 8

-rate related to concentration

Question 9

which method of transport is likely to be important for monoclonal antibodies?

Answer 9

-convection
-increase pressure = increase gaps to push big molecules out

Question 10

Movement of drug within blood

Answer 10

-drug can be free, bound, inside cells, etc
-only free drugs can get across membranes

Question 11

Shift tissue binding or plasma protein binding

Answer 11

-change distribution of drugs

Question 12

most drugs in tissue is bound to:

Answer 12

-nonspecific sites and not receptors

Question 13

Sites of action

Answer 13

-plasma (epithelial barrier)
-intersitial space (cappilary barrier)
-intracellular (membrane barrier)

Question 14

Adverse reactions to phenytoin (antiseizure) increases

Answer 14

as serum albumin decreaases

Question 15

drug trapping

Answer 15

-changing equilibrium between compartments by using differences in ptoyonation states/pH environments

Question 16

Drug trapping in urine

Answer 16

-increases elimination

Question 17

phenytoin

Answer 17

-anti seizure
-binds to albumin
-if reduce albumin = adverse reactions
-changes ability of drug to move between compartments

Question 18

Drug trapping mech

Answer 18

-drive drug out of blood and into urine
-unionized drug can pass to compartment with pH that will ionize it
-ionized drug cannot cross back

Question 19

acidic urine effect on basic drug

Answer 19

-increase elimination

Question 20

basic urine effect on acidic drug

Answer 20

-increase elimination by trapping

Question 21

properties of capillaries to the brain

Answer 21

-tight junctions (little permeation)
-negative head groups (limit acid diffusion)
-high Pgp concentration (high efflux activity)

Question 22

Brain barriers

Answer 22

1. Blood-brain
2. Blood-CSF
3. Blood-arachnoid barrier

Question 23

Blood-brain barrier

Answer 23

-tight junctions

Question 24

blood-CSF barrier

Answer 24

-fenestrated (gaps) cells
-layer of tight junctions beneath

Question 25

arachnoid barrier

Answer 25

-layers of very tight junctions

Question 26

Distribution of drugs into brain

Answer 26

-plasma -CSF -intersitial -intracellular -lysosome -different pHs of compartments can mean drug trapping

Question 27

Ability of compounds to enter brain from blood

Answer 27

-lipophilicity -glucose and L-DOPA (very polar) are exception and get into brain

Question 28

lipophillic (hydrophobic) drug penetration

Answer 28

-higher -more likely to cross brain bariers -ethanol, nictotine

Question 29

lipophobic (hydrophillic) drug penetration

Answer 29

-LOW -sodium, penicilin, dopamine

Question 30

How drugs can get into CNS

Answer 30

-physiochem properties -use existing transporter -direct administration into CNS (yeouch how much u supposed to put in there) -disturb barrier (yikes that lets other stuff in)

Question 31

Focused ultrasound

Answer 31

-temporarily open tight junctions of BBB -irradiation vibrates microbubbles = opens junctions -AuNPs can cross depending on size

Question 32

Maternal-Fetal drug distribution

Answer 32

-placenta barrier -most drugs enter fetal circulation -large polar molecules less likely to cross placenta -pH differences may demonstrate ion trapping