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PHRM 835 > Drug Distribution - 2 > Flashcards

Drug Distribution - 2 Flashcards

1
Q

Passive diffusion

  • ___ concentration
    gradient
  • ___ saturable
  • Most common
A
  • down
  • not
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2
Q

Paracellular transport is for hydro___ , ___ (size) molecules

A

hydrophilic, small

goes in between cells (not through their membrane)

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3
Q

Facilitated diffusion

  • ___ concentration gradient
  • Via ___
  • Saturable
  • ___ (OATP)
  • Drug example: ___
A
  • down
  • carriers
  • organic aniontransporting polypeptides
  • pravastatin
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4
Q

Active transport

  • ___ concentration gradient
  • Via ___
  • Uses ___ (energy)
  • Saturable
  • P- ___
  • Drug example: ___
A
  • against
  • transporter
  • ATP
  • glycoprotein
  • Vincristine (chonky)

P-glycoprotein will kick drugs out at the cell sing ATP

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5
Q

T or F: Carrier-mediated transport is saturated at high drug concentrations

A

true

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6
Q

Factors determining diffusion

molecular ___
* poor permeability for ___ molecules

lipo___
* poor permeability for ___ molecules

A
  • size, large
  • lipophilicity, hydrophilic
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7
Q

definition

LogP

A

Indicator of compound lipophilicity. The larger, the more lipophilic

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8
Q

Factors determining diffusion

Charge
* poor permeability for ___ molecules

A

charged

Must be unionized to pass membrane

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9
Q

Perfusion-rate limitation

For lipophilic compounds:
Rate-limiting step for drug distribution is…

A

the amount of blood carrying drugs away

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10
Q

Permeability-rate limitation

Hydrophilic compounds: Rate-limiting step for drug distribution is …

A

the slow rate of drug passing the cell membrane

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11
Q

Rate-limiting factor in tissue distribution

T or F: lipophilic compounds are permeability rate limited

A

False; hydrophilic compoounds are permeability rate limited. lipophilic compounds are perfusion-rate limited

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12
Q

Rate-limiting factor in tissue distribution

T or F: lipophilic compounds are permeability rate limited

A

False; hydrophilic compoounds are permeability rate limited. lipophilic compounds are perfusion-rate limited

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12
Q

Rate-limiting factor in tissue distribution

T or F: lipophilic compounds are permeability rate limited

A

False; hydrophilic compoounds are permeability rate limited. lipophilic compounds are perfusion-rate limited

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13
Q

Rate-limiting factor in tissue distribution: Example

Propofol
* General anesthesia-inducing agent
* Nonpolar lipophilic compound (logP 3.79)
* Distribution is perfusion-rate limited
Q: Which of the following two tissue would show faster propofol distribution?

A

The brain

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14
Q

What are the major drug binding plasma proteins?

A
  • albumin
  • a1-acid glycoprotein
  • lipoproteins
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15
Q

Albumin

  • The most abundant plasma protein ( ___ % of human plasma proteins)
  • Produced in the ___
  • Binds free ___ acids, hormones and weakly ___ (anionic) drugs
  • Main function is to maintain the ___ pressure of blood
  • Serum levels are decreased in ___ and ___ diseases
A
  • 50%
  • liver
  • fatty, acidic
  • oncontic
  • liver, kidney
16
Q

α1 -Acid glycoprotein (AAG) and lipoproteins

  • Also known as ___
  • Produced in the ___
  • Binds primarily weakly ___ (cationic) drugs such as tertiary and quaternary amines
  • Serum levels ___ during acute phase reaction, e.g., inflammation and burns
  • Serum levels are ___ in liver and kidney diseases
A
  • orosomucoid
  • liver
  • basic
  • increase
  • decrease
17
Q

Lipoproteins

  • Lipophyllic protein and/or a complex of ____ and ___
  • Includes ___ and ___
  • Binds ___ drugs.
  • Altered in some disease states, including ___ disease.
A
  • proteins and lipids
  • HDL and LDL
  • lipophilic drugs
  • heart
18
Q

Free drug hypothesis: Effects of protein binding on drug transport

Only ___ drug can exit capillaries to reach extravascular sites of
action, cross cell membrane via diffusion, and bind to transporters

A

free (unbound)

19
Q

Reversible nature of protein binding

T or F: Plasma protein binding of drugs is reversible

A

true

20
Q

T or F: Free (unbound) drug concentrations are the same on both sides of the membrane at equilibrium

A

true

21
Q

Plasma vs Blood

  • In most PK studies, we measure drug concentrations in ____
  • Plasma is the ___ component of blood, in which the blood cells are suspended (yellow colored)
  • Plasma makes up about ___ % (50-60%) of total blood volume
  • Plasma contains many vital proteins including ___ , ___ and ___
A
  • plasma
  • liquid
  • 55%
  • fibrinogen, globulins, and albumin
22
Q

Serum

  • Blood is allowed to ___. Clotting occurs, and it settles at the bottom of the tube
  • The ___ fluid is called serum
  • Serum is devoid of blood cells, ___ , and ___ factors
  • Serum contains plasma proteins, such as ___
A
  • coagulate
  • supernatant
  • fibrin, clotting
  • albumin
23
Q

Unbound fraction (fu)

Total drug concentration (C): Measure drug concentration after sample processing to ___ both protein-bound and free drug molecules

Free drug concentration (Cu): Measure drug concentration after sample processing to ___ protein-bound drug molecules

Unbound fraction (fu) = Cu/C

A
  • extract
  • exclude
24
Q

Ultrafiltration method

A
25
Q

True/False: In the example, the measured drug concentration reflects “total” drug concentration (i.e., C, not Cu)

A

True

25
Q

True/False: In the example, the measured drug concentration reflects “total” drug concentration (i.e., C, not Cu)

A

True

26
Q

Determinants of Vd

What is the equation for this?
amount in the body = amount in plasma + amount outside plasma

A
27
Q

Determinants of Vd

What equation reflects this?
Volume of distribution increases when fu is increased.
Volume of distribution decreases when fuT is increased.

A
28
Q

Vd of propranolol ___ when fu is
increased due to ___ plasma
protein binding in patients with chronic hepatic diseases

A
  • increases, decreased
29
Q

Determinants of Vd: tissue binding

  • Digoxin plasma protein binding is 25% ___
  • Digoxin binds to cardiac Na+/K+ ___
  • Digoxin has large Vd (7 L/kg) due to extensive ___ binding
A
  • cardiomyocytes
  • ATPase
  • tissue
30
Q

practice questions

T or F: Ionized compounds show poorer membrane permeability than un-ionized compounds

A

true

31
Q

practice questions

T or F: Lipophilic compounds tend to show greater membrane permeability

A

true

32
Q

practice questions

T or F: Lipophilic compounds tend to show permeability rate-limited distribution

A

False; perfusion

33
Q

practice questions

T or F: Decreased plasma protein binding of high protein-bound drugs will likely increase Vd

A

true

34
Q

T or F: Vd is expected to be small for a drug that exhibits strong binding to tissue components

A

false

PHRM 835 (14 decks)

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