Lecture 2: Ionization of Drugs

Question 1

Ionization state

Answer 1

-impacts solubility, absorption, binding to receptor

Question 2

Charged molecules

Answer 2

more soluble, less likely to cross lipid membranes

Question 3

pH

Answer 3

affects ionization
HA –> A- + H+
BH+ –> B + H+

Question 4

Ionizable functional groups

Answer 4

-weak acids and bases

Question 5

Ionizable groups with pKa < 7

Answer 5

-arylcarboxylic acid
-arylamine
-aromatic amines
-alkylcarboxylic acid

Question 6

ionizable groups with pKa > 7

Answer 6

-alkyl amines
-phenol
-guanidine

Question 7

nonionizable groups

Answer 7

-alkyl alcohol
-alkyl aldehyde
-ether
-ester
-ketone
-amide
-quarternary amine

Question 8

Drug examples

Answer 8

SLIDE 6

Question 9

Henderson-Hasselbach equation

Answer 9

pH= pKa + log [A-]/[HA]

Question 10

when pH < pKa

Answer 10

[A-] < [HA]
-protonated

Question 11

when pH > pKa

Answer 11

[A-] > [HA]
-deprotonated

Question 12

when [A-]/[HA]

Answer 12

[HA] = [A-]

Question 13

Acetaminophen

Answer 13

STRUCTURE

Question 14

Water

Answer 14

-polar solvent that dissolves polar molecules
-H bond donors and acceptors
-ionic groups

Question 15

Solubility

Answer 15

-like dissolves like
-can be improved by changing pH

Question 16

1g Procaine

Answer 16

needs 200mL water

Question 17

1g procaine-HCl

Answer 17

needs 1 mL water

Question 18

At pH 7.4, what is the ratio of ibuprofen in the acid form (neutral) to
that in the base form (negatively-charged)? pKa= 4.4

Answer 18

1:1000

Question 19

Membrane permeability

Answer 19

-GI tract, blood brain barrier, lipid membranes
-most drugs absorbed by passive diffusion

Question 20

Absorption rate

Answer 20

related to the drugs liphophilicity

Question 21

lipopholic drugs

Answer 21

absorbed more efficiently

Question 22

Transport across membrane

Answer 22

-intercellular junctions
-lipid cell membranes
-transporters
-endo and exocytosis

Question 23

Passive diffusion of ionizable drugs (cant cross lipid bilayer)

Answer 23

-more efficient at pH where drug is neutral
-even while mostly ionized it still moves through bilayer slowly
-equilibrium

Question 24

diffusion rate

Answer 24

proportional to amount of neutral drug

Question 25

Location of absorption

Answer 25

-most in jejunum (pH 5-7) -acidic drugs in stomach (pH 1-3)

Question 26

A drug is an organic base (RNH2) with a pKa of 9.0. Assume the stomach has a pH of 1.5, and the small intestine has a pH of 6.5. Where will the drug be preferentially absorbed?

Answer 26

Small Intestine

Question 27

Can a drug with a permanent charge (e.g. quaternary amine) be absorbed?

Answer 27

No

Question 28

Which of the following drugs is negatively charged at pH 7.4?

Answer 28

drugs with pKa<7.4

Question 29

Most drugs are absorbed from the GI tract to the blood stream by _______________.

Answer 29

passive diffusion

Question 30

Which of the following statements is most accurate about passive diffusion of

Answer 30

Eventually, the concentrations of the drug become equal in both sides of the membrane.

Question 31

At pH 7.5, what is the ratio of this drug (pKa = 9.5) in the acid form (neutral) to that in the base form (negatively-charged)?

Answer 31

100:1

Question 32

Which of the following shows a functional group whose ionization status is not affected by the pH?

Answer 32

quarternary amine