Absorption

Question 1

What type of structures are animal cell membranes?

Answer 1

phospholipid bilayers

Question 2

What is lipophilicity?

Answer 2

lipid solubility of drug; most important characteristic allowing it to diffuse across cell mbs

Question 3

What factor other than lipophilicity is important in allowing a drug to diffuse across cell mb?

Answer 3

molecular size

Question 4

How do chemicals cross cell mbs?

Answer 4

1. passive transport (simple diffusion)
2. filtration (bulk flow)
3. facilitated diffusion
4. active transport

Question 5

What is passive transport (simple diffusion)?

Answer 5

chem follows concentration gradient across cell mb; termed transcellular diffusion

Question 6

What is filtration (bulk flow)?

Answer 6

passive transport through cell junctions due to pressure gradient; termed paracellular transport

Question 7

what is facilitated diffusion?

Answer 7

also passive transport following concentration gradient, but requires transporter to assist movement across mb

Question 8

what is active transport?

Answer 8

movement against concentration gradient, requires ATP

Question 9

What is most common way that drugs cross cell mbs?

Answer 9

passive transport

Question 10

What on either side of the mb determines direction of diffusion?

Answer 10

concentration gradient

Question 11

In order for drug mc to passively diffuse across cell mb, it must be…?

Answer 11

lipophilic (lipid soluble)

Question 12

Pharmaceuticals can be categorized into 2 types of chemicals, influencing their absorption:

Answer 12

1. lipophilic organic chemicals
2. weak organic acids & bases

Question 13

What are lipid organic chemicals?

Answer 13

about 25% of drugs are organic molecules w/ varying degrees of lipid solubility

Question 14

what are weak organic acids & bases?

Answer 14

about 75% of drugs are weak acids & bases; such chems exist in both ionized & nonionized forms in soln, & relative proportion of ionized vs nonionized form depends on pKa of drug & pH of solution; ONLY NONIONIZED FORM OF DRUG CAN PASSIVELY DIFFUSE ACROSS CELL MBS

Question 15

What can the Henderson-Hasselbach eqn be used to determine?

Answer 15

ratio of nonionized vs ionized form of drug

Question 16

What is the Henderson-Hasselbach eqn?

Answer 16

Log ([protonated]/[nonprotonated]) = pKa - pH

Question 17

Remind me what pKa is:

Answer 17

number that measures strength of an acid or tendency of mc to keep a proton.
calculated as negative base-10 log of acid dissociation constant (Ka).
lower pKa value indicates a stronger acid, meaning acid dissociates more completely in water.

Question 18

protonated form of an acid is?

Answer 18

nonionized (HA)

Question 19

Protonated form of a base is?

Answer 19

ionized (BH+)

Question 20

weak acids (HA) donate … to form …

Answer 20

proton (H+), anions (A-)

Question 21

weak bases (B) accept … to form …

Answer 21

a proton, cations (HB+)

Question 22

what form of drug can readily penetrate cell mbs?

Answer 22

nonionized

Question 23

pKa of weak acid or base is …

Answer 23

… pH @ which there are equal amts of protonated form & nonprotonated form

Question 24

What is nonionized in what?

Answer 24

like is nonionized in like!
(weak base is more nonionized in basic soln & weak acid is more non-ionized in acidic soln)

Question 25

would benzoic acid (pKa =4, acid) be ionized @ neutral pH?

Answer 25

yes

Question 26

would aniline (pKa =5, base) be ionized @ neutral pH?

Answer 26

no

Question 27

What is clinical significance of a drug that is a weak base being 10 times more ionized in breast milk (more acidic) than plasma?

Answer 27

More ionized means more protonated. Clinical significance is concept of "ion trapping". as nonionized form diffuses into breast milk, more acidic pH causes more of drug to be ionized, & thus "trapped". treating mammary gland infection (mastitis) w/ an antimicrobial drug that is a weak base will result in increased drug concentration @ site of infection & increase efficacy.

Question 28

What is filtration (bulk flow) of a drug?

Answer 28

- drug moves w/ H2O through gap jxns btwn cells due to pressure gradient (ex: blood press)

Question 29

how big are the gaps btwn most cells?

Answer 29

4 nm

Question 30

how big are the gaps btwn most blood vessel endothelial cells?

Answer 30

2 nm

Question 31

how big are the gaps in glomerulus?

Answer 31

70 nm

Question 32

How big are gaps in CNS?

Answer 32

0 nm

Question 33

what is the most important characteristic about a drug in order for it to move via filtration (bulk flow)?

Answer 33

size of drug mc

Question 34

What is the importance of facilitated diffusion of a drug?

Answer 34

- important for nutrients & electrolytes; certain drugs can compete for these systems - mjr families are the organic anion transporters (OATs) & organic cation transporters (OCTs) - important for excretion too

Question 35

How is active transport related to drugs?

Answer 35

- important for excretion: brain, liver, & kidney all have active transport systems - all are "ATP-binding cassette" (ABC) prots; major families are multi-drug resistance prots (MDRs & MRPs) & breast cancer resistance prot (BCRP) - names originated from high expression in certain cancer cells, severely limiting chemotherapeutic treatments - referred to as "lipophilic vacuum cleaners"