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Kinetics > Lecture 3: Distribution > Flashcards

Lecture 3: Distribution Flashcards

1
Q

Drug Transport Process

A

-paracellular
-transcellular
-carrier mediated

-go from lumen to blood

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2
Q

passive diffusion

A

-down concentration gradient
-not saturated
-most common

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3
Q

Facilitated Diffusion

A

-down concentration
-carriers
-saturable

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4
Q

Active transport

A

-AGAINST concentration
-via TRANSPORTER
-use ATP
-saturable

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5
Q

Passive transport

A

-diffusion
-faciliatated diffusion (carrier mediated)

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6
Q

Factors determining diffusion

A

-molecular size
-lipophilicity
-charge

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7
Q

Smaller molecules permeability

A

high

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8
Q

lipophilic molecules permeability

A

high

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9
Q

Log P

A

-higher = more lipophilic

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10
Q

charge molecule permeability

A

POOR

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11
Q

(True/false) Salicylic acid will exhibit better crossing through the lipid bilayer at higher pH (e.g., in a
basic condition)

A

-FALSE
-it is charged at higher pH

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12
Q

Rate-limiting factors

A

-perfusion-rate limiting
-permeability-rate limiting

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13
Q

perfusion rate-limiting factors

A

-lipophilic compounds
-limited by amount of blood carrying drugs away
-faster distribution

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14
Q

Permeability-rate limiting factors

A

-hydrophilic compunds
-limited by slow rate of passing the cell membrane
-will not distribute as well

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15
Q

Would brain (0.5 perfusion rate) or muscle (0.025 perfusion rate) show faster distribution of propofol (nonpolar lipophilic compound with perfusion-rate limitation)

A

brain

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16
Q

major drug binding plasma proteins

A

-albumin
-a1-acid glycoprotein
-lipoproteins

17
Q

albumin

A

-most abundant plasma protein (50%)
-produced in liver
-binds fatty acids, hormones, and weakly acidic drugs

18
Q

albumin function

A

-maintain oncotic pressure of blood

19
Q

albumin serum levels

A

decreased in liver and kidney disease

20
Q

a1-acid glycoprotein (AAG)

A

-aka orosomucoid
-produced in liver
-binds weakly basic drugs (3’ or 4’ amines)

21
Q

a1-acid serum levels

A

-increase during acute phase reaction (inflammation and. burns)
-DECREASED in liver and kidney disease

22
Q

Lipoproteins

A

-lipophilic protein or complex of protiens and lipids
-HDL, LDL
-binds hydrophobic drugs
-altered in heart disease state

23
Q

Free drug Hypothesis

A

-only free drugs:

-exit capillaries
-cross membrane via diffusion
-bind transporters

24
Q

Plasma protein-binding

A

is reversible

25
Q

Free drug concentration

A

-same on both sides of membrane at equilibrium

26
Q

Plasma

A

-liquid component of blood where blood cells are suspended (yellow)
-makes up 55% blood volume
-contains fibrinogen, globulins, albumin

27
Q

Serum

A

-blood allowed to coagulate, clot, and settle at bottom of tube
-supernatant fluid
-devoid of blood cells, fibrins, and clotting factors
-contains plasma proteins

28
Q

Unbound fraction (fu)

A

Free drug concentration (Cu)/Total drug concentration (C)

29
Q

Ultrafiltration

A

-allow only free drug to be filtered
-allow estimate of unbound fraction

30
Q

Determinants of Vd

A

-increase when fu increases
-decrease when FuT increases

31
Q

Ionized compounds show poorer membrane permeability than un-ionized compounds

A

TRUE

32
Q

Lipophilic compounds tend to show greater membrane permeability

A

TRUE

33
Q

Lipophilic compounds tend to show permeability rate-limited distribution

A

-FALSE
-PERFUSION rate-limited

34
Q

Decreased plasma protein binding of high protein-bound drugs will likely increase Vd

A

TRUE

35
Q

Vd is expected to be small for a drug that exhibits strong binding to tissue components

A

FALSE
-it will be large

36
Q

fut

A

-unbound drug fraction in tissues
-Vd will be smaller for more unbound franstion

Kinetics (22 decks)

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