Lecture 2: Ionization of Drugs Flashcards

1
Q

Ionization state

A

-impacts solubility, absorption, binding to receptor

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2
Q

Charged molecules

A

more soluble, less likely to cross lipid membranes

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3
Q

pH

A

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

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4
Q

Ionizable functional groups

A

-weak acids and bases

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5
Q

Ionizable groups with pKa < 7

A

-arylcarboxylic acid
-arylamine
-aromatic amines
-alkylcarboxylic acid

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6
Q

ionizable groups with pKa > 7

A

-alkyl amines
-phenol
-guanidine

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7
Q

nonionizable groups

A

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

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8
Q

Drug examples

A

SLIDE 6

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9
Q

Henderson-Hasselbach equation

A

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

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10
Q

when pH < pKa

A

[A-] < [HA]
-protonated

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11
Q

when pH > pKa

A

[A-] > [HA]
-deprotonated

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12
Q

when [A-]/[HA]

A

[HA] = [A-]

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13
Q

Acetaminophen

A

STRUCTURE

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14
Q

Water

A

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

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15
Q

Solubility

A

-like dissolves like
-can be improved by changing pH

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16
Q

1g Procaine

A

needs 200mL water

17
Q

1g procaine-HCl

A

needs 1 mL water

18
Q

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

A

1:1000

19
Q

Membrane permeability

A

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

20
Q

Absorption rate

A

related to the drugs liphophilicity

21
Q

lipopholic drugs

A

absorbed more efficiently

22
Q

Transport across membrane

A

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

23
Q

Passive diffusion of ionizable drugs (cant cross lipid bilayer)

A

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

24
Q

diffusion rate

A

proportional to amount of neutral drug

25
Q

Location of absorption

A

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

26
Q

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?

A

Small Intestine

27
Q

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

A

No

28
Q

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

A

drugs with pKa<7.4

29
Q

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

A

passive diffusion

30
Q

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

A

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

31
Q

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)?

A

100:1

32
Q

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

A

quarternary amine