Lecture 2: Ionization of Drugs Flashcards
Ionization state
-impacts solubility, absorption, binding to receptor
Charged molecules
more soluble, less likely to cross lipid membranes
pH
affects ionization
HA –> A- + H+
BH+ –> B + H+
Ionizable functional groups
-weak acids and bases
Ionizable groups with pKa < 7
-arylcarboxylic acid
-arylamine
-aromatic amines
-alkylcarboxylic acid
ionizable groups with pKa > 7
-alkyl amines
-phenol
-guanidine
nonionizable groups
-alkyl alcohol
-alkyl aldehyde
-ether
-ester
-ketone
-amide
-quarternary amine
Drug examples
SLIDE 6
Henderson-Hasselbach equation
pH= pKa + log [A-]/[HA]
when pH < pKa
[A-] < [HA]
-protonated
when pH > pKa
[A-] > [HA]
-deprotonated
when [A-]/[HA]
[HA] = [A-]
Acetaminophen
STRUCTURE
Water
-polar solvent that dissolves polar molecules
-H bond donors and acceptors
-ionic groups
Solubility
-like dissolves like
-can be improved by changing pH