Lecture 3: Distribution Flashcards

1
Q

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

A

-constant slope downwards

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2
Q

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

A

-curved increase and decrease

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3
Q

what causes the offset of the pharmacologic effect for thiopental?

A

-driven by redistribution of drug

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

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4
Q

perfusion rate limited

A

-how quickly drug can be delivered

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5
Q

permeability rate limited

A

-how quickly drug moves across membrane

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6
Q

which condition shows slower tissue distribution

A

permeability rate limited

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7
Q

Convection

A

-rate related to pressure

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8
Q

Diffusion

A

-rate related to concentration

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9
Q

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

A

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

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10
Q

Movement of drug within blood

A

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

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11
Q

Shift tissue binding or plasma protein binding

A

-change distribution of drugs

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12
Q

most drugs in tissue is bound to:

A

-nonspecific sites and not receptors

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13
Q

Sites of action

A

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

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14
Q

Adverse reactions to phenytoin (antiseizure) increases

A

as serum albumin decreaases

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15
Q

drug trapping

A

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

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16
Q

Drug trapping in urine

A

-increases elimination

17
Q

phenytoin

A

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

18
Q

Drug trapping mech

A

-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

19
Q

acidic urine effect on basic drug

A

-increase elimination

20
Q

basic urine effect on acidic drug

A

-increase elimination by trapping

21
Q

properties of capillaries to the brain

A

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

22
Q

Brain barriers

A
  1. Blood-brain
  2. Blood-CSF
  3. Blood-arachnoid barrier
23
Q

Blood-brain barrier

A

-tight junctions

24
Q

blood-CSF barrier

A

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

25
arachnoid barrier
-layers of very tight junctions
26
Distribution of drugs into brain
-plasma -CSF -intersitial -intracellular -lysosome -different pHs of compartments can mean drug trapping
27
Ability of compounds to enter brain from blood
-lipophilicity -glucose and L-DOPA (very polar) are exception and get into brain
28
lipophillic (hydrophobic) drug penetration
-higher -more likely to cross brain bariers -ethanol, nictotine
29
lipophobic (hydrophillic) drug penetration
-LOW -sodium, penicilin, dopamine
30
How drugs can get into CNS
-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)
31
Focused ultrasound
-temporarily open tight junctions of BBB -irradiation vibrates microbubbles = opens junctions -AuNPs can cross depending on size
32
Maternal-Fetal drug distribution
-placenta barrier -most drugs enter fetal circulation -large polar molecules less likely to cross placenta -pH differences may demonstrate ion trapping
33